Bernard-Soulier syndrome: Difference between revisions

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   MeshID        = D001606 |
   MeshID        = D001606 |
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{{SI}}
{{SI}}
{{CMG}} {{shyam}}; {{AE}} {{VKG}}


{{CMG}}; {{AE}} {{VKG}}
{{SK}}BSS, giant platelet syndrome; hemorrhagic parous thrombocytic dystrophy; macrothrombocytopenia, familial Bernard-Soulier type; platelet glycoprotein Ib deficiency; [[Von Willebrand factor]] receptor deficiency.


{{SK}}
==Overview==
Bernard-Soulier syndrome (BSS) belongs to one the rare [[hereditary]] [[platelet]] disorders. Bernard-Soulier syndrome characteristically is defined by the presence of giant [[Platelet|platelets]] and [[thrombocytopenia]]. Bernard-Soulier syndrome (BSS) was first discovered in 1948. Bernard-Soulier syndrome may be classified into 4 subtypes. Bernard-Soulier syndrome is the result of the absence or decreased [[expression]] of the [[Glycoprotein Ib|GPIb]]/IX/V complex on the surface of the [[Platelet|platelets]]. Bernard-Soulier syndrome may be caused by abnormality in the [[Gene|genes]] for [[glycoprotein]] Ib/IX/V. The [[prevalence]] of Bernard-Soulier syndrome is approximately 1 per 100,000 individuals worldwide. The initial [[laboratory]] test to be done is [[Complete blood count|blood cell count]]<nowiki/>s and [[blood smear]]<nowiki/>s. There are no established [[Risk factor|risk factors]] for Bernard-Soulier syndrome. There is sufficient evidence to recommend routine [[Screening (medicine)|screening]] for Bernard-Soulier syndrome with newer technologies in current clinical practice. If left untreated, patients with Bernard-Soulier syndrome may progress to develop [[bleeding]] manifestations like [[mucocutaneous]] bleeding, which can be prolonged and severe. Patients with Bernard-Soulier syndrome usually remarkable for dysfunctional [[Platelet|platelets]]. There is no specific treatment for Bernard-Soulier syndrome, the mainstay of therapy is supportive care.


==Overview==


==Historical Perspective==
==Historical Perspective==
* Bernard-Soulier syndrome (BSS)/ [[Hemorrhage]] Parous [[thrombocytic]] [[dystrophy]]/ [[Congenital]] [[hemorrhagic]] parous [[thrombocytic]] [[dystrophy]] is very rare disease as few as only ~100 cases have been reported in the [[Literature review|literature]].<ref name="Lanza20064">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref>
* Bernard-Soulier syndrome (BSS)/ [[Hemorrhage]] parous [[thrombocytic]] [[dystrophy]]/ [[Congenital]] [[hemorrhagic]] parous [[thrombocytic]] [[dystrophy]] is very rare disease and it occurs less than 1 case per million population. It as few as only ~100 cases have been reported in the [[Literature review|literature]].<ref name="Lanza20064">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref>
*  
*  


* Bernard-Soulier syndrome (BSS) was first discovered in 1948 in a young male by Jean Bernard and Jean-Pierre Soulier who are [[Hematologist|hematologists]] from french.<ref name="pmid17109744">{{cite journal |vauthors=Lanza F |title=Bernard-Soulier syndrome (hemorrhagiparous thrombocytic dystrophy) |journal=Orphanet J Rare Dis |volume=1 |issue= |pages=46 |date=November 2006 |pmid=17109744 |pmc=1660532 |doi=10.1186/1750-1172-1-46 |url=}}</ref>
* Bernard-Soulier syndrome (BSS) was first discovered in 1948 by Jean Bernard and Jean-Pierre Soulier who were French [[Hematologist|hematologists]].<ref name="pmid17109744">{{cite journal |vauthors=Lanza F |title=Bernard-Soulier syndrome (hemorrhagiparous thrombocytic dystrophy) |journal=Orphanet J Rare Dis |volume=1 |issue= |pages=46 |date=November 2006 |pmid=17109744 |pmc=1660532 |doi=10.1186/1750-1172-1-46 |url=}}</ref>
* Bernard-Soulier syndrome (BSS) follows [[autosomal recessive]] [[trait]] and often associated with [[consanguinity]].<ref name="pmid8904201">{{cite journal |vauthors=de la Salle C, Lanza F, Cazenave JP |title=Biochemical and molecular basis of Bernard-Soulier syndrome: a review |journal=Nouv Rev Fr Hematol |volume=37 |issue=4 |pages=215–22 |date=1995 |pmid=8904201 |doi= |url=}}</ref><ref name="pmid7873390">{{cite journal |vauthors=de la Salle C, Baas MJ, Lanza F, Schwartz A, Hanau D, Chevalier J, Gachet C, Briquel ME, Cazenave JP |title=A three-base deletion removing a leucine residue in a leucine-rich repeat of platelet glycoprotein Ib alpha associated with a variant of Bernard-Soulier syndrome (Nancy I) |journal=Br. J. Haematol. |volume=89 |issue=2 |pages=386–96 |date=February 1995 |pmid=7873390 |doi= |url=}}</ref>
* Bernard-Soulier syndrome (BSS) is an [[autosomal recessive]] [[disease]] and is often associated with [[consanguinity]].<ref name="pmid8904201">{{cite journal |vauthors=de la Salle C, Lanza F, Cazenave JP |title=Biochemical and molecular basis of Bernard-Soulier syndrome: a review |journal=Nouv Rev Fr Hematol |volume=37 |issue=4 |pages=215–22 |date=1995 |pmid=8904201 |doi= |url=}}</ref><ref name="pmid7873390">{{cite journal |vauthors=de la Salle C, Baas MJ, Lanza F, Schwartz A, Hanau D, Chevalier J, Gachet C, Briquel ME, Cazenave JP |title=A three-base deletion removing a leucine residue in a leucine-rich repeat of platelet glycoprotein Ib alpha associated with a variant of Bernard-Soulier syndrome (Nancy I) |journal=Br. J. Haematol. |volume=89 |issue=2 |pages=386–96 |date=February 1995 |pmid=7873390 |doi= |url=}}</ref>
* Nurden and Caen, In 1975 reported that [[Platelet|platelets]] showed absence of major surface [[membrane]] [[glycoprotein]] complex.<ref name="NurdenPhillips2006">{{cite journal|last1=Nurden|first1=A. T.|last2=Phillips|first2=D. R.|last3=George|first3=J. N.|title=Platelet membrane glycoproteins: historical perspectives|journal=Journal of Thrombosis and Haemostasis|volume=4|issue=1|year=2006|pages=3–9|issn=15387933|doi=10.1111/j.1538-7836.2005.01549.x}}</ref><ref name="pmid2293505">{{cite journal |vauthors=Beardsley DS |title=Platelet membrane glycoproteins: role in primary hemostasis and component antigens |journal=Yale J Biol Med |volume=63 |issue=5 |pages=469–75 |date=1990 |pmid=2293505 |pmc=2589352 |doi= |url=}}</ref><ref name="pmid6284798">{{cite journal |vauthors=Clemetson KJ, McGregor JL, James E, Dechavanne M, Lüscher EF |title=Characterization of the platelet membrane glycoprotein abnormalities in Bernard-Soulier syndrome and comparison with normal by surface-labeling techniques and high-resolution two-dimensional gel electrophoresis |journal=J. Clin. Invest. |volume=70 |issue=2 |pages=304–11 |date=August 1982 |pmid=6284798 |pmc=371237 |doi= |url=}}</ref>
* Nurden and Caen reported in 1975 that [[Platelet|platelets]] in patients with BSS had absence of major surface [[membrane]] [[glycoprotein]] complex.<ref name="NurdenPhillips2006">{{cite journal|last1=Nurden|first1=A. T.|last2=Phillips|first2=D. R.|last3=George|first3=J. N.|title=Platelet membrane glycoproteins: historical perspectives|journal=Journal of Thrombosis and Haemostasis|volume=4|issue=1|year=2006|pages=3–9|issn=15387933|doi=10.1111/j.1538-7836.2005.01549.x}}</ref><ref name="pmid2293505">{{cite journal |vauthors=Beardsley DS |title=Platelet membrane glycoproteins: role in primary hemostasis and component antigens |journal=Yale J Biol Med |volume=63 |issue=5 |pages=469–75 |date=1990 |pmid=2293505 |pmc=2589352 |doi= |url=}}</ref><ref name="pmid6284798">{{cite journal |vauthors=Clemetson KJ, McGregor JL, James E, Dechavanne M, Lüscher EF |title=Characterization of the platelet membrane glycoprotein abnormalities in Bernard-Soulier syndrome and comparison with normal by surface-labeling techniques and high-resolution two-dimensional gel electrophoresis |journal=J. Clin. Invest. |volume=70 |issue=2 |pages=304–11 |date=August 1982 |pmid=6284798 |pmc=371237 |doi= |url=}}</ref>
==Classification==
==Classification==
Bernard soulier syndrome may be classified into 4 subtypes<ref name="pmid21781244">{{cite journal |vauthors=Nurden A, Nurden P |title=Advances in our understanding of the molecular basis of disorders of platelet function |journal=J. Thromb. Haemost. |volume=9 Suppl 1 |issue= |pages=76–91 |date=July 2011 |pmid=21781244 |doi=10.1111/j.1538-7836.2011.04274.x |url=}}</ref><ref name="pmid14734152">{{cite journal |vauthors=Ramasamy I |title=Inherited bleeding disorders: disorders of platelet adhesion and aggregation |journal=Crit. Rev. Oncol. Hematol. |volume=49 |issue=1 |pages=1–35 |date=January 2004 |pmid=14734152 |doi= |url=}}</ref><ref name="pmid11844132">{{cite journal |vauthors=Nurden AT, Nurden P |title=Inherited defects of platelet function |journal=Rev Clin Exp Hematol |volume=5 |issue=4 |pages=314–34; quiz following 431 |date=December 2001 |pmid=11844132 |doi= |url=}}</ref><ref name="Lanza20063">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref><ref name="pmid8519770">{{cite journal |vauthors=Yagi M, Edelhoff S, Disteche CM, Roth GJ |title=Human platelet glycoproteins V and IX: mapping of two leucine-rich glycoprotein genes to chromosome 3 and analysis of structures |journal=Biochemistry |volume=34 |issue=49 |pages=16132–7 |date=December 1995 |pmid=8519770 |doi= |url=}}</ref><ref name="pmid8021244">{{cite journal |vauthors=Yagi M, Edelhoff S, Disteche CM, Roth GJ |title=Structural characterization and chromosomal location of the gene encoding human platelet glycoprotein Ib beta |journal=J. Biol. Chem. |volume=269 |issue=26 |pages=17424–7 |date=July 1994 |pmid=8021244 |doi= |url=}}</ref>  
Bernard Soulier syndrome is classified into 4 subtypes:<ref name="pmid21781244">{{cite journal |vauthors=Nurden A, Nurden P |title=Advances in our understanding of the molecular basis of disorders of platelet function |journal=J. Thromb. Haemost. |volume=9 Suppl 1 |issue= |pages=76–91 |date=July 2011 |pmid=21781244 |doi=10.1111/j.1538-7836.2011.04274.x |url=}}</ref><ref name="pmid14734152">{{cite journal |vauthors=Ramasamy I |title=Inherited bleeding disorders: disorders of platelet adhesion and aggregation |journal=Crit. Rev. Oncol. Hematol. |volume=49 |issue=1 |pages=1–35 |date=January 2004 |pmid=14734152 |doi= |url=}}</ref><ref name="pmid11844132">{{cite journal |vauthors=Nurden AT, Nurden P |title=Inherited defects of platelet function |journal=Rev Clin Exp Hematol |volume=5 |issue=4 |pages=314–34; quiz following 431 |date=December 2001 |pmid=11844132 |doi= |url=}}</ref><ref name="Lanza20063">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref><ref name="pmid8519770">{{cite journal |vauthors=Yagi M, Edelhoff S, Disteche CM, Roth GJ |title=Human platelet glycoproteins V and IX: mapping of two leucine-rich glycoprotein genes to chromosome 3 and analysis of structures |journal=Biochemistry |volume=34 |issue=49 |pages=16132–7 |date=December 1995 |pmid=8519770 |doi= |url=}}</ref><ref name="pmid8021244">{{cite journal |vauthors=Yagi M, Edelhoff S, Disteche CM, Roth GJ |title=Structural characterization and chromosomal location of the gene encoding human platelet glycoprotein Ib beta |journal=J. Biol. Chem. |volume=269 |issue=26 |pages=17424–7 |date=July 1994 |pmid=8021244 |doi= |url=}}</ref>  


{| class="wikitable"
{|
|+
! style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Phenotype'''
!'''Phenotype'''
! style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Genomic Location'''
!'''Location'''
! style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Inheritance'''
!'''Inheritance'''
! style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Gene'''
!'''Gene'''
! style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Locus'''  
!'''Locus'''  
'''MIM number'''
'''MIM number'''
|-
|-
|Bernard-Soulier syndrome, type A1  
| style="background:#DCDCDC;" align="center" + |Bernard-Soulier syndrome, type A1  
|17p13.2
| style="background:#DCDCDC;" align="center" + |17p13.2
|Autosomal Recessive
| style="background:#DCDCDC;" align="center" + |Autosomal Recessive
|[[GP1BA]]
| style="background:#DCDCDC;" align="center" + |[[GP1BA]]
|606672
| style="background:#DCDCDC;" align="center" + |606672
|-
|-
|Bernard-Soulier syndrome, type B
| style="background:#DCDCDC;" align="center" + |Bernard-Soulier syndrome, type B
|22q11.21
| style="background:#DCDCDC;" align="center" + |22q11.21
|Autosomal Recessive
| style="background:#DCDCDC;" align="center" + |Autosomal Recessive
|[[GP1BB]]
| style="background:#DCDCDC;" align="center" + |[[GP1BB]]
|138720
| style="background:#DCDCDC;" align="center" + |138720
|-
|-
|Bernard-Soulier syndrome, type C
| style="background:#DCDCDC;" align="center" + |Bernard-Soulier syndrome, type C
|3q21.3
| style="background:#DCDCDC;" align="center" + |3q21.3
|Autosomal Recessive
| style="background:#DCDCDC;" align="center" + |Autosomal Recessive
|GP9
| style="background:#DCDCDC;" align="center" + |GP9
|173515
| style="background:#DCDCDC;" align="center" + |173515
|-
|-
|Giant platelet disorder, isolated
| style="background:#DCDCDC;" align="center" + |Giant platelet disorder, isolated
|22q11.21
| style="background:#DCDCDC;" align="center" + |22q11.21
|Autosomal Recessive
| style="background:#DCDCDC;" align="center" + |Autosomal Recessive
|[[GP1BB]]
| style="background:#DCDCDC;" align="center" + |[[GP1BB]]
|138720
| style="background:#DCDCDC;" align="center" + |138720
|}
|}


==Pathophysiology==
==Pathophysiology==
* It is thought that bernard soulier syndrome is the result of the absence or decreased [[expression]] of the [[Glycoprotein Ib|GPIb]]/IX/V complex on the surface of the [[Platelet|platelets]].<ref name="Lanza2006">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref><ref name="BerndtAndrews2011">{{cite journal|last1=Berndt|first1=M. C.|last2=Andrews|first2=R. K.|title=Bernard-Soulier syndrome|journal=Haematologica|volume=96|issue=3|year=2011|pages=355–359|issn=0390-6078|doi=10.3324/haematol.2010.039883}}</ref><ref name="FeghhiMunday2016">{{cite journal|last1=Feghhi|first1=Shirin|last2=Munday|first2=Adam D.|last3=Tooley|first3=Wes W.|last4=Rajsekar|first4=Shreya|last5=Fura|first5=Adriane M.|last6=Kulman|first6=John D.|last7=López|first7=Jose A.|last8=Sniadecki|first8=Nathan J.|title=Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion|journal=Biophysical Journal|volume=111|issue=3|year=2016|pages=601–608|issn=00063495|doi=10.1016/j.bpj.2016.06.023}}</ref><ref name="pmid9741630">{{cite journal |vauthors=Savage B, Almus-Jacobs F, Ruggeri ZM |title=Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow |journal=Cell |volume=94 |issue=5 |pages=657–66 |date=September 1998 |pmid=9741630 |doi= |url=}}</ref><ref name="pmid9371310">{{cite journal |vauthors=Clemetson KJ, Clemetson JM |title=Molecular abnormalities in Glanzmann's thrombasthenia, Bernard-Soulier syndrome, and platelet-type von Willebrand's disease |journal=Curr. Opin. Hematol. |volume=1 |issue=5 |pages=388–93 |date=September 1994 |pmid=9371310 |doi= |url=}}</ref><ref name="pmid2614964">{{cite journal |vauthors=Ando Y, Fusegawa H, Kawada T, Tanaka Y, Watanabe K, Kobayashi N |title=[Membrane glycoproteins of human platelets: structures, functions, and abnormalities in Glanzmann's thrombasthenia and Bernard-Soulier syndrome] |language=Japanese |journal=Rinsho Byori |volume=37 |issue=12 |pages=1344–52 |date=December 1989 |pmid=2614964 |doi= |url=}}</ref><ref name="pmid10805283">{{cite journal |vauthors=Hayashi T, Suzuki K |title=Molecular pathogenesis of Bernard-Soulier syndrome |journal=Semin. Thromb. Hemost. |volume=26 |issue=1 |pages=53–9 |date=2000 |pmid=10805283 |doi= |url=}}</ref>
* It is thought that Bernard-Soulier syndrome is the result of the absence or decreased [[expression]] of the [[Glycoprotein Ib|GPIb]]/IX/V complex on the surface of the [[Platelet|platelets]].<ref name="Lanza2006">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref><ref name="BerndtAndrews2011">{{cite journal|last1=Berndt|first1=M. C.|last2=Andrews|first2=R. K.|title=Bernard-Soulier syndrome|journal=Haematologica|volume=96|issue=3|year=2011|pages=355–359|issn=0390-6078|doi=10.3324/haematol.2010.039883}}</ref><ref name="FeghhiMunday2016">{{cite journal|last1=Feghhi|first1=Shirin|last2=Munday|first2=Adam D.|last3=Tooley|first3=Wes W.|last4=Rajsekar|first4=Shreya|last5=Fura|first5=Adriane M.|last6=Kulman|first6=John D.|last7=López|first7=Jose A.|last8=Sniadecki|first8=Nathan J.|title=Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion|journal=Biophysical Journal|volume=111|issue=3|year=2016|pages=601–608|issn=00063495|doi=10.1016/j.bpj.2016.06.023}}</ref><ref name="pmid9741630">{{cite journal |vauthors=Savage B, Almus-Jacobs F, Ruggeri ZM |title=Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow |journal=Cell |volume=94 |issue=5 |pages=657–66 |date=September 1998 |pmid=9741630 |doi= |url=}}</ref><ref name="pmid9371310">{{cite journal |vauthors=Clemetson KJ, Clemetson JM |title=Molecular abnormalities in Glanzmann's thrombasthenia, Bernard-Soulier syndrome, and platelet-type von Willebrand's disease |journal=Curr. Opin. Hematol. |volume=1 |issue=5 |pages=388–93 |date=September 1994 |pmid=9371310 |doi= |url=}}</ref><ref name="pmid2614964">{{cite journal |vauthors=Ando Y, Fusegawa H, Kawada T, Tanaka Y, Watanabe K, Kobayashi N |title=[Membrane glycoproteins of human platelets: structures, functions, and abnormalities in Glanzmann's thrombasthenia and Bernard-Soulier syndrome] |language=Japanese |journal=Rinsho Byori |volume=37 |issue=12 |pages=1344–52 |date=December 1989 |pmid=2614964 |doi= |url=}}</ref><ref name="pmid10805283">{{cite journal |vauthors=Hayashi T, Suzuki K |title=Molecular pathogenesis of Bernard-Soulier syndrome |journal=Semin. Thromb. Hemost. |volume=26 |issue=1 |pages=53–9 |date=2000 |pmid=10805283 |doi= |url=}}</ref>
* The [[Glycoprotein Ib|GPIb]]/IX/V complex is the [[receptor]] for [[von Willebrand factor]] ([[Von Willebrand factor|vWF]]).
* The [[Glycoprotein Ib|GPIb]]/IX/V complex is the [[receptor]] for [[von Willebrand factor]] ([[Von Willebrand factor|vWF]]).
* The [[Glycoprotein Ib|GPIb]]/IX/V complex plays a very important role in [[hemostasis]] and [[thrombosis]].<ref name="YanMo2011">{{cite journal|last1=Yan|first1=Rong|last2=Mo|first2=Xi|last3=Paredes|first3=Angel M.|last4=Dai|first4=Kesheng|last5=Lanza|first5=Francois|last6=Cruz|first6=Miguel A.|last7=Li|first7=Renhao|title=Reconstitution of the Platelet Glycoprotein Ib-IX Complex in Phospholipid Bilayer Nanodiscs|journal=Biochemistry|volume=50|issue=49|year=2011|pages=10598–10606|issn=0006-2960|doi=10.1021/bi201351d}}</ref><ref name="pmid11696542">{{cite journal |vauthors=Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN |title=Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin |journal=J. Biol. Chem. |volume=277 |issue=3 |pages=1662–8 |date=January 2002 |pmid=11696542 |doi=10.1074/jbc.M108319200 |url=}}</ref>
* The [[Glycoprotein Ib|GPIb]]/IX/V complex plays a very important role in [[hemostasis]] and [[thrombosis]].<ref name="YanMo2011">{{cite journal|last1=Yan|first1=Rong|last2=Mo|first2=Xi|last3=Paredes|first3=Angel M.|last4=Dai|first4=Kesheng|last5=Lanza|first5=Francois|last6=Cruz|first6=Miguel A.|last7=Li|first7=Renhao|title=Reconstitution of the Platelet Glycoprotein Ib-IX Complex in Phospholipid Bilayer Nanodiscs|journal=Biochemistry|volume=50|issue=49|year=2011|pages=10598–10606|issn=0006-2960|doi=10.1021/bi201351d}}</ref><ref name="pmid11696542">{{cite journal |vauthors=Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN |title=Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin |journal=J. Biol. Chem. |volume=277 |issue=3 |pages=1662–8 |date=January 2002 |pmid=11696542 |doi=10.1074/jbc.M108319200 |url=}}</ref>
* The [[Glycoprotein Ib|GPIb]]/IX/V complex and [[von Willebrand factor]] ([[Von Willebrand factor|vWF]]) ensure normal primary [[hemostasis]] by initiating [[platelet]] [[adhesion]] at sites of [[vascular]] [[injury]].<ref name="pmid12705329">{{cite journal |vauthors=Clemetson KJ |title=Platelet receptors and their role in diseases |journal=Clin. Chem. Lab. Med. |volume=41 |issue=3 |pages=253–60 |date=March 2003 |pmid=12705329 |doi=10.1515/CCLM.2003.039 |url=}}</ref>
* The [[Glycoprotein Ib|GPIb]]/IX/V complex and [[von Willebrand factor]] ([[Von Willebrand factor|vWF]]) ensure normal primary [[hemostasis]] by initiating [[platelet]] [[adhesion]] at sites of [[vascular]] [[injury]].<ref name="pmid12705329">{{cite journal |vauthors=Clemetson KJ |title=Platelet receptors and their role in diseases |journal=Clin. Chem. Lab. Med. |volume=41 |issue=3 |pages=253–60 |date=March 2003 |pmid=12705329 |doi=10.1515/CCLM.2003.039 |url=}}</ref>
* The [[Glycoprotein Ib|GPIb]]/IX/V complex  binds to [[von Willebrand factor]] ([[Von Willebrand factor|vWF]]) and that makes the initial contact [[adhesion]] of [[Platelet|platelets]] to exposed [[vascular]] [[endothelium]].<ref name="pmid27508443">{{cite journal |vauthors=Feghhi S, Munday AD, Tooley WW, Rajsekar S, Fura AM, Kulman JD, López JA, Sniadecki NJ |title=Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion |journal=Biophys. J. |volume=111 |issue=3 |pages=601–608 |date=August 2016 |pmid=27508443 |pmc=4982925 |doi=10.1016/j.bpj.2016.06.023 |url=}}</ref>
* The [[Glycoprotein Ib|GPIb]]/IX/V complex  binds to [[von Willebrand factor]] ([[Von Willebrand factor|vWF]]). This makes the initial contact, or [[adhesion]], of [[Platelet|platelets]] to exposed [[vascular]] [[endothelium]].<ref name="pmid27508443">{{cite journal |vauthors=Feghhi S, Munday AD, Tooley WW, Rajsekar S, Fura AM, Kulman JD, López JA, Sniadecki NJ |title=Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion |journal=Biophys. J. |volume=111 |issue=3 |pages=601–608 |date=August 2016 |pmid=27508443 |pmc=4982925 |doi=10.1016/j.bpj.2016.06.023 |url=}}</ref>
* The [[Glycoprotein Ib|GPIb]]/IX/V complex  along with [[von Willebrand factor]] ([[Von Willebrand factor|vWF]]) also attach to ruptured [[plaque]] in damaged [[blood vessel]]<nowiki/>s.<ref name="pmid10499919">{{cite journal |vauthors=Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, López JA |title=The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin |journal=J. Exp. Med. |volume=190 |issue=6 |pages=803–14 |date=September 1999 |pmid=10499919 |pmc=2195629 |doi= |url=}}</ref>
* The [[Glycoprotein Ib|GPIb]]/IX/V complex  along with [[von Willebrand factor]] ([[Von Willebrand factor|vWF]]) also attach to ruptured [[plaques]] in damaged [[blood vessel]]<nowiki/>s.<ref name="pmid10499919">{{cite journal |vauthors=Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, López JA |title=The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin |journal=J. Exp. Med. |volume=190 |issue=6 |pages=803–14 |date=September 1999 |pmid=10499919 |pmc=2195629 |doi= |url=}}</ref>
* And this attachment to ruptured [[plaque]] in damaged [[blood vessel]]<nowiki/>s is particularly seen at high shear flow rates (>800s<nowiki/>-1).<ref name="pmid10037692">{{cite journal |vauthors=Cranmer SL, Ulsemer P, Cooke BM, Salem HH, de la Salle C, Lanza F, Jackson SP |title=Glycoprotein (GP) Ib-IX-transfected cells roll on a von Willebrand factor matrix under flow. Importance of the GPib/actin-binding protein (ABP-280) interaction in maintaining adhesion under high shear |journal=J. Biol. Chem. |volume=274 |issue=10 |pages=6097–106 |date=March 1999 |pmid=10037692 |doi= |url=}}</ref><ref name="pmid10845886">{{cite journal |vauthors=Wu YP, Vink T, Schiphorst M, van Zanten GH, IJsseldijk MJ, de Groot PG, Sixma JJ |title=Platelet thrombus formation on collagen at high shear rates is mediated by von Willebrand factor-glycoprotein Ib interaction and inhibited by von Willebrand factor-glycoprotein IIb/IIIa interaction |journal=Arterioscler. Thromb. Vasc. Biol. |volume=20 |issue=6 |pages=1661–7 |date=June 2000 |pmid=10845886 |doi= |url=}}</ref><ref name="pmid9808562">{{cite journal |vauthors=Fredrickson BJ, Dong JF, McIntire LV, López JA |title=Shear-dependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein Ib-IX-V complex |journal=Blood |volume=92 |issue=10 |pages=3684–93 |date=November 1998 |pmid=9808562 |doi= |url=}}</ref>
* This attachment to ruptured [[plaque]] in damaged [[blood vessel]]<nowiki/>s is<nowiki/> particularly seen at high shear flow rates (>800s-1).<nowiki/><ref name="pmid10037692">{{cite journal |vauthors=Cranmer SL, Ulsemer P, Cooke BM, Salem HH, de la Salle C, Lanza F, Jackson SP |title=Glycoprotein (GP) Ib-IX-transfected cells roll on a von Willebrand factor matrix under flow. Importance of the GPib/actin-binding protein (ABP-280) interaction in maintaining adhesion under high shear |journal=J. Biol. Chem. |volume=274 |issue=10 |pages=6097–106 |date=March 1999 |pmid=10037692 |doi= |url=}}</ref><ref name="pmid10845886">{{cite journal |vauthors=Wu YP, Vink T, Schiphorst M, van Zanten GH, IJsseldijk MJ, de Groot PG, Sixma JJ |title=Platelet thrombus formation on collagen at high shear rates is mediated by von Willebrand factor-glycoprotein Ib interaction and inhibited by von Willebrand factor-glycoprotein IIb/IIIa interaction |journal=Arterioscler. Thromb. Vasc. Biol. |volume=20 |issue=6 |pages=1661–7 |date=June 2000 |pmid=10845886 |doi= |url=}}</ref><ref name="pmid9808562">{{cite journal |vauthors=Fredrickson BJ, Dong JF, McIntire LV, López JA |title=Shear-dependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein Ib-IX-V complex |journal=Blood |volume=92 |issue=10 |pages=3684–93 |date=November 1998 |pmid=9808562 |doi= |url=}}</ref>
* In the formation of [[Deep vein thrombosis|deep venous]] [[thrombosis]] [[Glycoprotein Ib|GPIb]]/IX/V complex a<nowiki/>long with [[von Willebrand factor]] ([[Von Willebrand factor|vWF]]) plays a very cri<nowiki/>tical role.<ref name="pmid20959603">{{cite journal |vauthors=Brill A, Fuchs TA, Chauhan AK, Yang JJ, De Meyer SF, Köllnberger M, Wakefield TW, Lämmle B, Massberg S, Wagner DD |title=von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models |journal=Blood |volume=117 |issue=4 |pages=1400–7 |date=January 2011 |pmid=20959603 |pmc=3056477 |doi=10.1182/blood-2010-05-287623 |url=}}</ref><ref name="BrillFuchs2010">{{cite journal|last1=Brill|first1=A.|last2=Fuchs|first2=T. A.|last3=Chauhan|first3=A. K.|last4=Yang|first4=J. J.|last5=De Meyer|first5=S. F.|last6=Kollnberger|first6=M.|last7=Wakefield|first7=T. W.|last8=Lammle|first8=B.|last9=Massberg|first9=S.|last10=Wagner|first10=D. D.|title=von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models|journal=Blood|volume=117|issue=4|year=2010|pages=1400–1407|issn=0006-4971|doi=10.1182/blood-2010-05-287623}}</ref><ref name="De MeyerStoll2011">{{cite journal|last1=De Meyer|first1=S. F.|last2=Stoll|first2=G.|last3=Wagner|first3=D. D.|last4=Kleinschnitz|first4=C.|title=von Willebrand Factor: An Emerging Target in Stroke Therapy|journal=Stroke|volume=43|issue=2|year=2011|pages=599–606|issn=0039-2499|doi=10.1161/STROKEAHA.111.628867}}</ref><ref>{{cite journal|doi=10.1161/CIRCRESAHA.117.311185/-/DC1}}</ref><ref name="BiedermannCannegieter2016">{{cite journal|last1=Biedermann|first1=J. S.|last2=Cannegieter|first2=S. C.|last3=Roest|first3=M.|last4=van der Meer|first4=F. J. M.|last5=Reitsma|first5=P. H.|last6=Kruip|first6=M. J. H. A.|last7=Lijfering|first7=W. M.|title=Platelet reactivity in patients with venous thrombosis who use rosuvastatin: a randomized controlled clinical trial|journal=Journal of Thrombosis and Haemostasis|volume=14|issue=7|year=2016|pages=1404–1409|issn=15387933|doi=10.1111/jth.13343}}</ref><ref name="FuchsBrill2012">{{cite journal|last1=Fuchs|first1=T. A.|last2=Brill|first2=A.|last3=Wagner|first3=D. D.|title=Neutrophil Extracellular Trap (NET) Impact on Deep Vein Thrombosis|journal=Arteriosclerosis, Thrombosis, and Vascular Biology|volume=32|issue=8|year=2012|pages=1777–1783|issn=1079-5642|doi=10.1161/ATVBAHA.111.242859}}</ref>
* In the formation of [[Deep vein thrombosis|deep venous]] [[thrombosis]] [[Glycoprotein Ib|GPIb]]/IX/V complex a<nowiki/>long with [[von Willebrand factor]] ([[Von Willebrand factor|vWF]]) plays a very cri<nowiki/>tical role.<ref name="pmid20959603">{{cite journal |vauthors=Brill A, Fuchs TA, Chauhan AK, Yang JJ, De Meyer SF, Köllnberger M, Wakefield TW, Lämmle B, Massberg S, Wagner DD |title=von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models |journal=Blood |volume=117 |issue=4 |pages=1400–7 |date=January 2011 |pmid=20959603 |pmc=3056477 |doi=10.1182/blood-2010-05-287623 |url=}}</ref><ref name="BrillFuchs2010">{{cite journal|last1=Brill|first1=A.|last2=Fuchs|first2=T. A.|last3=Chauhan|first3=A. K.|last4=Yang|first4=J. J.|last5=De Meyer|first5=S. F.|last6=Kollnberger|first6=M.|last7=Wakefield|first7=T. W.|last8=Lammle|first8=B.|last9=Massberg|first9=S.|last10=Wagner|first10=D. D.|title=von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models|journal=Blood|volume=117|issue=4|year=2010|pages=1400–1407|issn=0006-4971|doi=10.1182/blood-2010-05-287623}}</ref><ref name="De MeyerStoll2011">{{cite journal|last1=De Meyer|first1=S. F.|last2=Stoll|first2=G.|last3=Wagner|first3=D. D.|last4=Kleinschnitz|first4=C.|title=von Willebrand Factor: An Emerging Target in Stroke Therapy|journal=Stroke|volume=43|issue=2|year=2011|pages=599–606|issn=0039-2499|doi=10.1161/STROKEAHA.111.628867}}</ref><ref>{{cite journal|doi=10.1161/CIRCRESAHA.117.311185/-/DC1}}</ref><ref name="BiedermannCannegieter2016">{{cite journal|last1=Biedermann|first1=J. S.|last2=Cannegieter|first2=S. C.|last3=Roest|first3=M.|last4=van der Meer|first4=F. J. M.|last5=Reitsma|first5=P. H.|last6=Kruip|first6=M. J. H. A.|last7=Lijfering|first7=W. M.|title=Platelet reactivity in patients with venous thrombosis who use rosuvastatin: a randomized controlled clinical trial|journal=Journal of Thrombosis and Haemostasis|volume=14|issue=7|year=2016|pages=1404–1409|issn=15387933|doi=10.1111/jth.13343}}</ref><ref name="FuchsBrill2012">{{cite journal|last1=Fuchs|first1=T. A.|last2=Brill|first2=A.|last3=Wagner|first3=D. D.|title=Neutrophil Extracellular Trap (NET) Impact on Deep Vein Thrombosis|journal=Arteriosclerosis, Thrombosis, and Vascular Biology|volume=32|issue=8|year=2012|pages=1777–1783|issn=1079-5642|doi=10.1161/ATVBAHA.111.242859}}</ref>
* In an year, on an average 900 000 people in the [[United States]] <nowiki/>suffer from [[deep vein thrombosis]] ([[DVT]]).
* [[Glycoprotein Ib|GPIb]]-IX-V complex is multisubunit in nature consists of 4 [[subunits]].  
* [[Glycoprotein Ib|GPIb]]-IX-V complex is multisubunit in nature consists of 4 [[subunits]].  
* Each of the 4 multisubunit is a member of the [[leucine]]-rich,which contains ~24 [[amino acid]] and are involved in such  processes such as [[cell signaling]], [[cell adhesion]], and development.<ref name="pmid7817399">{{cite journal |vauthors=Kobe B, Deisenhofer J |title=The leucine-rich repeat: a versatile binding motif |journal=Trends Biochem. Sci. |volume=19 |issue=10 |pages=415–21 |date=October 1994 |pmid=7817399 |doi= |url=}}</ref><ref name="pmid7877692">{{cite journal |vauthors=Kobe B, Deisenhofer J |title=A structural basis of the interactions between leucine-rich repeats and protein ligands |journal=Nature |volume=374 |issue=6518 |pages=183–6 |date=March 1995 |pmid=7877692 |doi=10.1038/374183a0 |url=}}</ref>   
* Each of the 4 multisubunit is a member of the [[leucine]]-rich motif, which contains ~24 [[amino acid]] and are involved in such  processes such as [[cell signaling]], [[cell adhesion]], and development.<ref name="pmid7817399">{{cite journal |vauthors=Kobe B, Deisenhofer J |title=The leucine-rich repeat: a versatile binding motif |journal=Trends Biochem. Sci. |volume=19 |issue=10 |pages=415–21 |date=October 1994 |pmid=7817399 |doi= |url=}}</ref><ref name="pmid7877692">{{cite journal |vauthors=Kobe B, Deisenhofer J |title=A structural basis of the interactions between leucine-rich repeats and protein ligands |journal=Nature |volume=374 |issue=6518 |pages=183–6 |date=March 1995 |pmid=7877692 |doi=10.1038/374183a0 |url=}}</ref>   
* In addition to its important role in binding to [[von Willebrand factor]] (VWF), this [[N-terminal]] [[domain]] of [[Glycoprotein Ib|GPIbα]] is a pivotal [[binding site]] for multiple [[ligands]] mediating [[platelet]] interactions with [[matrix]] which are involved in [[thrombosis]] and [[inflammation]].   
* In addition to its important role in binding to [[von Willebrand factor]] (vWF), this [[N-terminal]] [[domain]] of [[Glycoprotein Ib|GPIbα]] is a pivotal [[binding site]] for multiple [[ligands]] mediating [[platelet]] interactions with [[matrix]] which are involved in [[thrombosis]] and [[inflammation]].   
* On activated [[Platelet|platelets]] and [[endothelial]] cells other [[adhesive]] [[ligand]] include [[P-selectin]], αMβ2 /[[CD11b]]/[[CD18]].<ref name="RomoDong1999">{{cite journal|last1=Romo|first1=Gabriel M.|last2=Dong|first2=Jing-Fei|last3=Schade|first3=Alicia J.|last4=Gardiner|first4=Elizabeth E.|last5=Kansas|first5=Geoffrey S.|last6=Li|first6=Chester Q.|last7=McIntire|first7=Larry V.|last8=Berndt|first8=Michael C.|last9=López|first9=José A.|title=The Glycoprotein Ib-IX-V Complex Is a Platelet Counterreceptor for P-Selectin|journal=The Journal of Experimental Medicine|volume=190|issue=6|year=1999|pages=803–814|issn=0022-1007|doi=10.1084/jem.190.6.803}}</ref><ref name="pmid104999192">{{cite journal |vauthors=Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, López JA |title=The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin |journal=J. Exp. Med. |volume=190 |issue=6 |pages=803–14 |date=September 1999 |pmid=10499919 |pmc=2195629 |doi= |url=}}</ref><ref name="Du2007">{{cite journal|last1=Du|first1=Xiaoping|title=Signaling and regulation of the platelet glycoprotein Ib–IX–V complex|journal=Current Opinion in Hematology|volume=14|issue=3|year=2007|pages=262–269|issn=1065-6251|doi=10.1097/MOH.0b013e3280dce51a}}</ref>   
* On activated [[Platelet|platelets]] and [[endothelial]] cells other [[adhesive]] [[ligand]] include [[P-selectin]], αMβ2 /[[CD11b]]/[[CD18]].<ref name="RomoDong1999">{{cite journal|last1=Romo|first1=Gabriel M.|last2=Dong|first2=Jing-Fei|last3=Schade|first3=Alicia J.|last4=Gardiner|first4=Elizabeth E.|last5=Kansas|first5=Geoffrey S.|last6=Li|first6=Chester Q.|last7=McIntire|first7=Larry V.|last8=Berndt|first8=Michael C.|last9=López|first9=José A.|title=The Glycoprotein Ib-IX-V Complex Is a Platelet Counterreceptor for P-Selectin|journal=The Journal of Experimental Medicine|volume=190|issue=6|year=1999|pages=803–814|issn=0022-1007|doi=10.1084/jem.190.6.803}}</ref><ref name="pmid104999192">{{cite journal |vauthors=Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, López JA |title=The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin |journal=J. Exp. Med. |volume=190 |issue=6 |pages=803–14 |date=September 1999 |pmid=10499919 |pmc=2195629 |doi= |url=}}</ref><ref name="Du2007">{{cite journal|last1=Du|first1=Xiaoping|title=Signaling and regulation of the platelet glycoprotein Ib–IX–V complex|journal=Current Opinion in Hematology|volume=14|issue=3|year=2007|pages=262–269|issn=1065-6251|doi=10.1097/MOH.0b013e3280dce51a}}</ref>   
* The [[Glycoprotein Ib|GPIb]]-IX-V complex plays very crucial role in [[coagulation]] especially in intrinsic pathway which has tendency to bind the receptors for [[thrombin]], Factors XI and XII(having the shortest [[Half-life|half life]] of all [[clotting factor]]<nowiki/>s), [[kininogen]] and at last to [[High-molecular-weight kininogen|high molecular weight]] (HMW).<ref name="pmid23336709">{{cite journal |vauthors=Li R, Emsley J |title=The organizing principle of the platelet glycoprotein Ib-IX-V complex |journal=J. Thromb. Haemost. |volume=11 |issue=4 |pages=605–14 |date=April 2013 |pmid=23336709 |pmc=3696474 |doi=10.1111/jth.12144 |url=}}</ref><ref name="pmid104999193">{{cite journal |vauthors=Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, López JA |title=The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin |journal=J. Exp. Med. |volume=190 |issue=6 |pages=803–14 |date=September 1999 |pmid=10499919 |pmc=2195629 |doi= |url=}}</ref>     
* The [[Glycoprotein Ib|GPIb]]-IX-V complex plays very crucial role in [[coagulation]] especially in intrinsic pathway which has tendency to bind the receptors for [[thrombin]], Factors XI and XII (having the shortest [[Half-life|half life]] of all [[clotting factor|clotting facto]]<nowiki/>[[clotting factor|r]]<nowiki/>[[clotting factor|s]]), [[kininogen]] and at last to [[High-molecular-weight kininogen|high molecular weight]] (HMW).<ref name="pmid23336709">{{cite journal |vauthors=Li R, Emsley J |title=The organizing principle of the platelet glycoprotein Ib-IX-V complex |journal=J. Thromb. Haemost. |volume=11 |issue=4 |pages=605–14 |date=April 2013 |pmid=23336709 |pmc=3696474 |doi=10.1111/jth.12144 |url=}}</ref><ref name="pmid104999193">{{cite journal |vauthors=Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, López JA |title=The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin |journal=J. Exp. Med. |volume=190 |issue=6 |pages=803–14 |date=September 1999 |pmid=10499919 |pmc=2195629 |doi= |url=}}</ref>     
* With the help of [[actin]] [[filaments]] ,Trp570, Phe568 and Trp570, [[Glycoprotein Ib|GPIb]]-IX-V plays a crucial role in maintaining the [[Platelet|platelets]] shape.<ref name="pmid15764659">{{cite journal |vauthors=Arya M, Kolomeisky AB, Romo GM, Cruz MA, López JA, Anvari B |title=Dynamic force spectroscopy of glycoprotein Ib-IX and von Willebrand factor |journal=Biophys. J. |volume=88 |issue=6 |pages=4391–401 |date=June 2005 |pmid=15764659 |pmc=1305666 |doi=10.1529/biophysj.104.046318 |url=}}</ref>     
* With the help of [[actin]] [[filaments]], Phe568 and Trp570, [[Glycoprotein Ib|GPIb]]-IX-V plays a crucial role in maintaining the [[Platelet|platelets]] shape.<ref name="pmid15764659">{{cite journal |vauthors=Arya M, Kolomeisky AB, Romo GM, Cruz MA, López JA, Anvari B |title=Dynamic force spectroscopy of glycoprotein Ib-IX and von Willebrand factor |journal=Biophys. J. |volume=88 |issue=6 |pages=4391–401 |date=June 2005 |pmid=15764659 |pmc=1305666 |doi=10.1529/biophysj.104.046318 |url=}}</ref>     
* [[Glycoprotein Ib|GPIb]]-IX-V/[[Von Willebrand factor|VWF]] [[adhesion]] was enhanced by [[Nicotinamide adenine dinucleotide phosphate|NADPH]]([[Nicotinamide adenine dinucleotide phosphate]]) [[oxidase]], (p47 subunit), PI 3-[[kinase]], Hic-5, [[TRAF4]](TNF receptor-associated factor 4) Lyn, and [[Syk]](Spleen tyrosine kinase) [[Protein|proteins]].<ref name="ShibanumaMori2012">{{cite journal|last1=Shibanuma|first1=Motoko|last2=Mori|first2=Kazunori|last3=Nose|first3=Kiyoshi|title=HIC-5: A Mobile Molecular Scaffold Regulating the Anchorage Dependence of Cell Growth|journal=International Journal of Cell Biology|volume=2012|year=2012|pages=1–8|issn=1687-8876|doi=10.1155/2012/426138}}</ref><ref name="pmid275084432">{{cite journal |vauthors=Feghhi S, Munday AD, Tooley WW, Rajsekar S, Fura AM, Kulman JD, López JA, Sniadecki NJ |title=Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion |journal=Biophys. J. |volume=111 |issue=3 |pages=601–608 |date=August 2016 |pmid=27508443 |pmc=4982925 |doi=10.1016/j.bpj.2016.06.023 |url=}}</ref><ref name="pmid20946164">{{cite journal |vauthors=Arthur JF, Shen Y, Gardiner EE, Coleman L, Murphy D, Kenny D, Andrews RK, Berndt MC |title=TNF receptor-associated factor 4 (TRAF4) is a novel binding partner of glycoprotein Ib and glycoprotein VI in human platelets |journal=J. Thromb. Haemost. |volume=9 |issue=1 |pages=163–72 |date=January 2011 |pmid=20946164 |doi=10.1111/j.1538-7836.2010.04091.x |url=}}</ref><ref name="pmid25415317">{{cite journal |vauthors=Carrim N, Walsh TG, Consonni A, Torti M, Berndt MC, Metharom P |title=Role of focal adhesion tyrosine kinases in GPVI-dependent platelet activation and reactive oxygen species formation |journal=PLoS ONE |volume=9 |issue=11 |pages=e113679 |date=2014 |pmid=25415317 |pmc=4240642 |doi=10.1371/journal.pone.0113679 |url=}}</ref><ref name="ArthurShen2011">{{cite journal|last1=Arthur|first1=J. F.|last2=Shen|first2=Y.|last3=Gardiner|first3=E. E.|last4=Coleman|first4=L.|last5=Kenny|first5=D.|last6=Andrews|first6=R. K.|last7=Berndt|first7=M. C.|title=TNF receptor-associated factor 4 (TRAF4) is a novel binding partner of glycoprotein Ib and glycoprotein VI in human platelets|journal=Journal of Thrombosis and Haemostasis|volume=9|issue=1|year=2011|pages=163–172|issn=15387933|doi=10.1111/j.1538-7836.2010.04091.x}}</ref><ref name="pmid24816556">{{cite journal |vauthors=Chapman NM, Houtman JC |title=Functions of the FAK family kinases in T cells: beyond actin cytoskeletal rearrangement |journal=Immunol. Res. |volume=59 |issue=1-3 |pages=23–34 |date=August 2014 |pmid=24816556 |pmc=4125427 |doi=10.1007/s12026-014-8527-y |url=}}</ref><ref name="pmid9257837">{{cite journal |vauthors=Berg NN, Ostergaard HL |title=T cell receptor engagement induces tyrosine phosphorylation of FAK and Pyk2 and their association with Lck |journal=J. Immunol. |volume=159 |issue=4 |pages=1753–7 |date=August 1997 |pmid=9257837 |doi= |url=}}</ref>  
* [[Glycoprotein Ib|GPIb]]-IX-V/[[Von Willebrand factor|VWF]] [[adhesion]] was enhanced by [[Nicotinamide adenine dinucleotide phosphate|NADPH]] ([[Nicotinamide adenine dinucleotide phosphate]]) [[oxidase]], (p47 subunit), PI 3-[[kinase]], Hic-5, [[TRAF4]] (TNF receptor-associated factor 4) Lyn, and [[Syk]] (spleen tyrosine kinase) [[Protein|proteins]].<ref name="ShibanumaMori2012">{{cite journal|last1=Shibanuma|first1=Motoko|last2=Mori|first2=Kazunori|last3=Nose|first3=Kiyoshi|title=HIC-5: A Mobile Molecular Scaffold Regulating the Anchorage Dependence of Cell Growth|journal=International Journal of Cell Biology|volume=2012|year=2012|pages=1–8|issn=1687-8876|doi=10.1155/2012/426138}}</ref><ref name="pmid275084432">{{cite journal |vauthors=Feghhi S, Munday AD, Tooley WW, Rajsekar S, Fura AM, Kulman JD, López JA, Sniadecki NJ |title=Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion |journal=Biophys. J. |volume=111 |issue=3 |pages=601–608 |date=August 2016 |pmid=27508443 |pmc=4982925 |doi=10.1016/j.bpj.2016.06.023 |url=}}</ref><ref name="pmid20946164">{{cite journal |vauthors=Arthur JF, Shen Y, Gardiner EE, Coleman L, Murphy D, Kenny D, Andrews RK, Berndt MC |title=TNF receptor-associated factor 4 (TRAF4) is a novel binding partner of glycoprotein Ib and glycoprotein VI in human platelets |journal=J. Thromb. Haemost. |volume=9 |issue=1 |pages=163–72 |date=January 2011 |pmid=20946164 |doi=10.1111/j.1538-7836.2010.04091.x |url=}}</ref><ref name="pmid25415317">{{cite journal |vauthors=Carrim N, Walsh TG, Consonni A, Torti M, Berndt MC, Metharom P |title=Role of focal adhesion tyrosine kinases in GPVI-dependent platelet activation and reactive oxygen species formation |journal=PLoS ONE |volume=9 |issue=11 |pages=e113679 |date=2014 |pmid=25415317 |pmc=4240642 |doi=10.1371/journal.pone.0113679 |url=}}</ref><ref name="ArthurShen2011">{{cite journal|last1=Arthur|first1=J. F.|last2=Shen|first2=Y.|last3=Gardiner|first3=E. E.|last4=Coleman|first4=L.|last5=Kenny|first5=D.|last6=Andrews|first6=R. K.|last7=Berndt|first7=M. C.|title=TNF receptor-associated factor 4 (TRAF4) is a novel binding partner of glycoprotein Ib and glycoprotein VI in human platelets|journal=Journal of Thrombosis and Haemostasis|volume=9|issue=1|year=2011|pages=163–172|issn=15387933|doi=10.1111/j.1538-7836.2010.04091.x}}</ref><ref name="pmid24816556">{{cite journal |vauthors=Chapman NM, Houtman JC |title=Functions of the FAK family kinases in T cells: beyond actin cytoskeletal rearrangement |journal=Immunol. Res. |volume=59 |issue=1-3 |pages=23–34 |date=August 2014 |pmid=24816556 |pmc=4125427 |doi=10.1007/s12026-014-8527-y |url=}}</ref><ref name="pmid9257837">{{cite journal |vauthors=Berg NN, Ostergaard HL |title=T cell receptor engagement induces tyrosine phosphorylation of FAK and Pyk2 and their association with Lck |journal=J. Immunol. |volume=159 |issue=4 |pages=1753–7 |date=August 1997 |pmid=9257837 |doi= |url=}}</ref>
*   
 
*   
==Causes==
==Causes==
* Bernard-Soulier syndrome may be caused by abnormality in the [[Gene|genes]] for [[glycoprotein]] Ib/IX/V.<ref name="pmid12871266">{{cite journal |vauthors=Ruggeri ZM |title=Von Willebrand factor, platelets and endothelial cell interactions |journal=J. Thromb. Haemost. |volume=1 |issue=7 |pages=1335–42 |date=July 2003 |pmid=12871266 |doi= |url=}}</ref><ref name="pmid11513727">{{cite journal |vauthors=Ulsemer P, Strassel C, Baas MJ, Salamero J, Chasserot-Golaz S, Cazenave JP, De La Salle C, Lanza F |title=Biosynthesis and intracellular post-translational processing of normal and mutant platelet glycoprotein GPIb-IX |journal=Biochem. J. |volume=358 |issue=Pt 2 |pages=295–303 |date=September 2001 |pmid=11513727 |pmc=1222061 |doi= |url=}}</ref><ref name="pmid2253772">{{cite journal |vauthors=Hickey MJ, Deaven LL, Roth GJ |title=Human platelet glycoprotein IX. Characterization of cDNA and localization of the gene to chromosome 3 |journal=FEBS Lett. |volume=274 |issue=1-2 |pages=189–92 |date=November 1990 |pmid=2253772 |doi= |url=}}</ref><ref name="pmid8407908">{{cite journal |vauthors=Lanza F, Morales M, de La Salle C, Cazenave JP, Clemetson KJ, Shimomura T, Phillips DR |title=Cloning and characterization of the gene encoding the human platelet glycoprotein V. A member of the leucine-rich glycoprotein family cleaved during thrombin-induced platelet activation |journal=J. Biol. Chem. |volume=268 |issue=28 |pages=20801–7 |date=October 1993 |pmid=8407908 |doi= |url=}}</ref><ref name="pmid3353370">{{cite journal |vauthors=Lopez JA, Chung DW, Fujikawa K, Hagen FS, Davie EW, Roth GJ |title=The alpha and beta chains of human platelet glycoprotein Ib are both transmembrane proteins containing a leucine-rich amino acid sequence |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue=7 |pages=2135–9 |date=April 1988 |pmid=3353370 |pmc=279943 |doi= |url=}}</ref>
* Bernard-Soulier syndrome may be caused by abnormalities in the [[Gene|genes]] for [[glycoprotein]] Ib/IX/V.<ref name="pmid12871266">{{cite journal |vauthors=Ruggeri ZM |title=Von Willebrand factor, platelets and endothelial cell interactions |journal=J. Thromb. Haemost. |volume=1 |issue=7 |pages=1335–42 |date=July 2003 |pmid=12871266 |doi= |url=}}</ref><ref name="pmid11513727">{{cite journal |vauthors=Ulsemer P, Strassel C, Baas MJ, Salamero J, Chasserot-Golaz S, Cazenave JP, De La Salle C, Lanza F |title=Biosynthesis and intracellular post-translational processing of normal and mutant platelet glycoprotein GPIb-IX |journal=Biochem. J. |volume=358 |issue=Pt 2 |pages=295–303 |date=September 2001 |pmid=11513727 |pmc=1222061 |doi= |url=}}</ref><ref name="pmid2253772">{{cite journal |vauthors=Hickey MJ, Deaven LL, Roth GJ |title=Human platelet glycoprotein IX. Characterization of cDNA and localization of the gene to chromosome 3 |journal=FEBS Lett. |volume=274 |issue=1-2 |pages=189–92 |date=November 1990 |pmid=2253772 |doi= |url=}}</ref><ref name="pmid8407908">{{cite journal |vauthors=Lanza F, Morales M, de La Salle C, Cazenave JP, Clemetson KJ, Shimomura T, Phillips DR |title=Cloning and characterization of the gene encoding the human platelet glycoprotein V. A member of the leucine-rich glycoprotein family cleaved during thrombin-induced platelet activation |journal=J. Biol. Chem. |volume=268 |issue=28 |pages=20801–7 |date=October 1993 |pmid=8407908 |doi= |url=}}</ref><ref name="pmid3353370">{{cite journal |vauthors=Lopez JA, Chung DW, Fujikawa K, Hagen FS, Davie EW, Roth GJ |title=The alpha and beta chains of human platelet glycoprotein Ib are both transmembrane proteins containing a leucine-rich amino acid sequence |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue=7 |pages=2135–9 |date=April 1988 |pmid=3353370 |pmc=279943 |doi= |url=}}</ref>
* The genes for [[glycoprotein]] Ib/IX/V code for [[proteins]] that are usally found on the surface of [[Platelet|platelets]], the [[glycoprotein]] Ib/IX/V receptor.<ref name="pmid127053292">{{cite journal |vauthors=Clemetson KJ |title=Platelet receptors and their role in diseases |journal=Clin. Chem. Lab. Med. |volume=41 |issue=3 |pages=253–60 |date=March 2003 |pmid=12705329 |doi=10.1515/CCLM.2003.039 |url=}}</ref>
* The [[Gene|genes]] for [[glycoprotein]] Ib/IX/V encode for [[proteins]] that are usually found on the surface of [[Platelet|platelets]], the [[glycoprotein]] Ib/IX/V receptor.<ref name="pmid127053292">{{cite journal |vauthors=Clemetson KJ |title=Platelet receptors and their role in diseases |journal=Clin. Chem. Lab. Med. |volume=41 |issue=3 |pages=253–60 |date=March 2003 |pmid=12705329 |doi=10.1515/CCLM.2003.039 |url=}}</ref>
* [[Platelet|Platelets]] do not adhere to damaged [[endothelium]] due to lack of [[receptors]].
* [[Platelet|Platelets]] do not adhere to damaged [[endothelium]] due to lack of [[receptors]].
* [[Mutation|Mutations]] are found in ''BP1b-alpha (MW 135 kDa)'', ''Gp1b-beta (MW 26 kDa)'' and ''GP9'' (MW 20 kDa) but not on ''[[GP5|GP5(MW 82 kDa)]].''<ref name="pmid3303030">{{cite journal |vauthors=Lopez JA, Chung DW, Fujikawa K, Hagen FS, Papayannopoulou T, Roth GJ |title=Cloning of the alpha chain of human platelet glycoprotein Ib: a transmembrane protein with homology to leucine-rich alpha 2-glycoprotein |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue=16 |pages=5615–9 |date=August 1987 |pmid=3303030 |pmc=298913 |doi= |url=}}</ref><ref name="pmid2628181">{{cite journal |vauthors=Wenger RH, Wicki AN, Kieffer N, Adolph S, Hameister H, Clemetson KJ |title=The 5' flanking region and chromosomal localization of the gene encoding human platelet membrane glycoprotein Ib alpha |journal=Gene |volume=85 |issue=2 |pages=517–24 |date=December 1989 |pmid=2628181 |doi= |url=}}</ref>
* [[Mutation|Mutations]] are found in ''BP1b-alpha (MW 135 kDa)'', ''Gp1b-beta (MW 26 kDa)'' and ''GP9'' (MW 20 kDa) but not on ''[[GP5|GP5 (MW 82 kDa)]].''<ref name="pmid3303030">{{cite journal |vauthors=Lopez JA, Chung DW, Fujikawa K, Hagen FS, Papayannopoulou T, Roth GJ |title=Cloning of the alpha chain of human platelet glycoprotein Ib: a transmembrane protein with homology to leucine-rich alpha 2-glycoprotein |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue=16 |pages=5615–9 |date=August 1987 |pmid=3303030 |pmc=298913 |doi= |url=}}</ref><ref name="pmid2628181">{{cite journal |vauthors=Wenger RH, Wicki AN, Kieffer N, Adolph S, Hameister H, Clemetson KJ |title=The 5' flanking region and chromosomal localization of the gene encoding human platelet membrane glycoprotein Ib alpha |journal=Gene |volume=85 |issue=2 |pages=517–24 |date=December 1989 |pmid=2628181 |doi= |url=}}</ref>


==Differentiating Bernard-Soulier syndrome from Other Disease==
==Differentiating Bernard-Soulier syndrome from Other Disease==
* Bernard-Soulier syndrome must be differentiated from<ref name="pmid12745278">{{cite journal |vauthors=Balduini CL, Cattaneo M, Fabris F, Gresele P, Iolascon A, Pulcinelli FM, Savoia A |title=Inherited thrombocytopenias: a proposed diagnostic algorithm from the Italian Gruppo di Studio delle Piastrine |journal=Haematologica |volume=88 |issue=5 |pages=582–92 |date=May 2003 |pmid=12745278 |doi= |url=}}</ref><ref name="pmid15477207">{{cite journal |vauthors=Noris P, Pecci A, Di Bari F, Di Stazio MT, Di Pumpo M, Ceresa IF, Arezzi N, Ambaglio C, Savoia A, Balduini CL |title=Application of a diagnostic algorithm for inherited thrombocytopenias to 46 consecutive patients |journal=Haematologica |volume=89 |issue=10 |pages=1219–25 |date=October 2004 |pmid=15477207 |doi= |url=}}</ref> <ref name="pmid12161364">{{cite journal |vauthors=Balduini CL, Iolascon A, Savoia A |title=Inherited thrombocytopenias: from genes to therapy |journal=Haematologica |volume=87 |issue=8 |pages=860–80 |date=August 2002 |pmid=12161364 |doi= |url=}}</ref> <ref name="pmid14689830">{{cite journal |vauthors=Doubek M, Smejkal P, Dostálová V, Trnavská I, Buliková A, Brychtová Y, Mayer J |title=[Hereditary thrombocytopenia. Differential diagnosis of a case] |language=Czech |journal=Cas. Lek. Cesk. |volume=142 |issue=11 |pages=683–6 |date=2003 |pmid=14689830 |doi= |url=}}</ref><ref name="pmid22886561">{{cite journal |vauthors=Balduini CL, Savoia A |title=Genetics of familial forms of thrombocytopenia |journal=Hum. Genet. |volume=131 |issue=12 |pages=1821–32 |date=December 2012 |pmid=22886561 |doi=10.1007/s00439-012-1215-x |url=}}</ref><ref name="pmid9154320">{{cite journal |vauthors=Bellucci S |title=Megakaryocytes and inherited thrombocytopenias |journal=Baillieres Clin. Haematol. |volume=10 |issue=1 |pages=149–62 |date=February 1997 |pmid=9154320 |doi= |url=}}</ref> <ref name="pmid23510089">{{cite journal |vauthors=Balduini CL, Savoia A, Seri M |title=Inherited thrombocytopenias frequently diagnosed in adults |journal=J. Thromb. Haemost. |volume=11 |issue=6 |pages=1006–19 |date=June 2013 |pmid=23510089 |doi=10.1111/jth.12196 |url=}}</ref>
* Bernard-Soulier syndrome must be differentiated from<ref name="pmid12745278">{{cite journal |vauthors=Balduini CL, Cattaneo M, Fabris F, Gresele P, Iolascon A, Pulcinelli FM, Savoia A |title=Inherited thrombocytopenias: a proposed diagnostic algorithm from the Italian Gruppo di Studio delle Piastrine |journal=Haematologica |volume=88 |issue=5 |pages=582–92 |date=May 2003 |pmid=12745278 |doi= |url=}}</ref><ref name="pmid15477207">{{cite journal |vauthors=Noris P, Pecci A, Di Bari F, Di Stazio MT, Di Pumpo M, Ceresa IF, Arezzi N, Ambaglio C, Savoia A, Balduini CL |title=Application of a diagnostic algorithm for inherited thrombocytopenias to 46 consecutive patients |journal=Haematologica |volume=89 |issue=10 |pages=1219–25 |date=October 2004 |pmid=15477207 |doi= |url=}}</ref> <ref name="pmid12161364">{{cite journal |vauthors=Balduini CL, Iolascon A, Savoia A |title=Inherited thrombocytopenias: from genes to therapy |journal=Haematologica |volume=87 |issue=8 |pages=860–80 |date=August 2002 |pmid=12161364 |doi= |url=}}</ref> <ref name="pmid14689830">{{cite journal |vauthors=Doubek M, Smejkal P, Dostálová V, Trnavská I, Buliková A, Brychtová Y, Mayer J |title=[Hereditary thrombocytopenia. Differential diagnosis of a case] |language=Czech |journal=Cas. Lek. Cesk. |volume=142 |issue=11 |pages=683–6 |date=2003 |pmid=14689830 |doi= |url=}}</ref><ref name="pmid22886561">{{cite journal |vauthors=Balduini CL, Savoia A |title=Genetics of familial forms of thrombocytopenia |journal=Hum. Genet. |volume=131 |issue=12 |pages=1821–32 |date=December 2012 |pmid=22886561 |doi=10.1007/s00439-012-1215-x |url=}}</ref><ref name="pmid9154320">{{cite journal |vauthors=Bellucci S |title=Megakaryocytes and inherited thrombocytopenias |journal=Baillieres Clin. Haematol. |volume=10 |issue=1 |pages=149–62 |date=February 1997 |pmid=9154320 |doi= |url=}}</ref><ref name="pmid23510089">{{cite journal |vauthors=Balduini CL, Savoia A, Seri M |title=Inherited thrombocytopenias frequently diagnosed in adults |journal=J. Thromb. Haemost. |volume=11 |issue=6 |pages=1006–19 |date=June 2013 |pmid=23510089 |doi=10.1111/jth.12196 |url=}}</ref>
** [[Wiskott-Aldrich syndrome]] (small platelets)  
** [[Wiskott-Aldrich syndrome]] (small platelets)  
** X-linked thrombocytopenia (small platelets)
** X-linked thrombocytopenia (small platelets)
** May-Hegglin syndrome(Giant platelets)
** May-Hegglin syndrome (giant platelets)
** Sebastian syndrome(Giant platelets)
** Sebastian syndrome (giant platelets)
** [[Fechtner syndrome]](Giant platelets)
** [[Fechtner syndrome]] (giant platelets)
** Epstein syndrome(Giant platelets)
** Epstein syndrome (giant platelets)
** [[Idiopathic thrombocytopenic purpura]] ([[ITP]])- Most commonly misdiagnosed BSS as [[ITP]].
** [[Idiopathic thrombocytopenic purpura]] ([[ITP]])- most commonly misdiagnosed BSS as [[ITP]]


==Epidemiology and Demographics==
==Epidemiology and Demographics==
* The [[prevalence]] of Bernard-Soulier syndrome is approximately 1 per 100,000 individuals worldwide.<ref name="Lanza20065">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref><ref name="Lanza20066">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref><ref name="pmid171097442">{{cite journal |vauthors=Lanza F |title=Bernard-Soulier syndrome (hemorrhagiparous thrombocytic dystrophy) |journal=Orphanet J Rare Dis |volume=1 |issue= |pages=46 |date=November 2006 |pmid=17109744 |pmc=1660532 |doi=10.1186/1750-1172-1-46 |url=}}</ref><ref name="pmid21699652">{{cite journal |vauthors=Sumitha E, Jayandharan GR, David S, Jacob RR, Sankari Devi G, Bargavi B, Shenbagapriya S, Nair SC, Abraham A, George B, Viswabandya A, Mathews V, Chandy M, Srivastava A |title=Molecular basis of Bernard-Soulier syndrome in 27 patients from India |journal=J. Thromb. Haemost. |volume=9 |issue=8 |pages=1590–8 |date=August 2011 |pmid=21699652 |doi=10.1111/j.1538-7836.2011.04417.x |url=}}</ref>
* The [[prevalence]] of Bernard-Soulier syndrome is approximately 1 per 100,000 individuals worldwide.<ref name="Lanza20065">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref><ref name="Lanza20066">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref><ref name="pmid171097442">{{cite journal |vauthors=Lanza F |title=Bernard-Soulier syndrome (hemorrhagiparous thrombocytic dystrophy) |journal=Orphanet J Rare Dis |volume=1 |issue= |pages=46 |date=November 2006 |pmid=17109744 |pmc=1660532 |doi=10.1186/1750-1172-1-46 |url=}}</ref><ref name="pmid21699652">{{cite journal |vauthors=Sumitha E, Jayandharan GR, David S, Jacob RR, Sankari Devi G, Bargavi B, Shenbagapriya S, Nair SC, Abraham A, George B, Viswabandya A, Mathews V, Chandy M, Srivastava A |title=Molecular basis of Bernard-Soulier syndrome in 27 patients from India |journal=J. Thromb. Haemost. |volume=9 |issue=8 |pages=1590–8 |date=August 2011 |pmid=21699652 |doi=10.1111/j.1538-7836.2011.04417.x |url=}}</ref>
 
* Bernard-Soulier syndrome is very rare; until now only ~100 cases have been reported.
* Bernard-Soulier syndrome usally very rare that till now only ~100 cases have been reported.
 
* The severity of Bernard-Soulier syndrome increases with [[age]].
* The severity of Bernard-Soulier syndrome increases with [[age]].
 
* Bernard-Soulier syndrome more commonly affects [[Infant|infants]] than children and older people.
* Bernard-Soulier syndrome commonly affects [[Infant|infants]] than younger and older people.
* Bernard-Soulier syndrome usually affects individuals from Japan, Europe and North America.
 
* Males and females are affected with equal frequency.
* Bernard-Soulier syndrome usually affects individuals of the Japan, Europe and North America.
* The majority of Bernard-Soulier syndrome cases are reported in whites of European ancestry.
 
* In bernard-soulier syndrome patients males and females are affected with equal frequency.
 
* The majority of bernard-soulier syndrome cases are reported in whites of European ancestry.


==Risk Factors==
==Risk Factors==
* There are no established [[Risk factor|risk factors]] for Bernard-Soulier syndrome.
* There are no established [[Risk factor|risk factors]] for Bernard-Soulier syndrome.
* [[Autosomal recessive]] genetic pattern was followed by Bernard-Soulier syndrome.
* [[Autosomal recessive]] genetic pattern is characteristic of Bernard-Soulier syndrome.
* Risk of Bernard-Soulier syndrome patients can be a [[carrier]] when they receive the following
* Bernard-Soulier syndrome patients can be [[carriers]] when they receive one normal [[gene]] and one [[abnormal]] [[gene]].
** One normal [[gene]] and one abnormal gene  
* Risk of Bernard-Soulier syndrome in a child is 25% to 50% with each [[pregnancy]] when two carrier parents both pass the [[abnormal]] gene.
* Risk of Bernard-Soulier syndrome in a child is 25% to 50% with each [[pregnancy]] when  
** Two carrier parents to both pass the [[abnormal]] gene


==Screening==
==Screening==
* There is sufficient evidence to recommend routine screening for Bernard-Soulier syndrome with newer technologies in current clinical practice like the following.<ref name="pmid10588464">{{cite journal |vauthors=Cattaneo M, Lecchi A, Agati B, Lombardi R, Zighetti ML |title=Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion |journal=Thromb. Res. |volume=96 |issue=3 |pages=213–7 |date=November 1999 |pmid=10588464 |doi= |url=}}</ref><ref name="pmid9579642">{{cite journal |vauthors=Mammen EF, Comp PC, Gosselin R, Greenberg C, Hoots WK, Kessler CM, Larkin EC, Liles D, Nugent DJ |title=PFA-100 system: a new method for assessment of platelet dysfunction |journal=Semin. Thromb. Hemost. |volume=24 |issue=2 |pages=195–202 |date=1998 |pmid=9579642 |doi=10.1055/s-2007-995840 |url=}}</ref>
* There is sufficient evidence to recommend routine [[Screening (medicine)|screening]] for Bernard-Soulier syndrome with newer technologies in current clinical practice like the following.<ref name="pmid10588464">{{cite journal |vauthors=Cattaneo M, Lecchi A, Agati B, Lombardi R, Zighetti ML |title=Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion |journal=Thromb. Res. |volume=96 |issue=3 |pages=213–7 |date=November 1999 |pmid=10588464 |doi= |url=}}</ref><ref name="pmid9579642">{{cite journal |vauthors=Mammen EF, Comp PC, Gosselin R, Greenberg C, Hoots WK, Kessler CM, Larkin EC, Liles D, Nugent DJ |title=PFA-100 system: a new method for assessment of platelet dysfunction |journal=Semin. Thromb. Hemost. |volume=24 |issue=2 |pages=195–202 |date=1998 |pmid=9579642 |doi=10.1055/s-2007-995840 |url=}}</ref>
'''PFA-100(Platelet Function Analyzer)'''
'''PFA-100(Platelet Function Analyzer)'''
*The most common screening test used for screening the patients with BSS <ref name="pmid11260277">{{cite journal |vauthors=Favaloro EJ |title=Utility of the PFA-100 for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations |journal=Haemophilia |volume=7 |issue=2 |pages=170–9 |date=March 2001 |pmid=11260277 |doi= |url=}}</ref><ref name="pmid12172459">{{cite journal |vauthors=Favaloro EJ |title=Clinical application of the PFA-100 |journal=Curr. Opin. Hematol. |volume=9 |issue=5 |pages=407–15 |date=September 2002 |pmid=12172459 |doi= |url=}}</ref><ref name="pmid19214910">{{cite journal |vauthors=Favaloro EJ |title=Clinical utility of the PFA-100 |journal=Semin. Thromb. Hemost. |volume=34 |issue=8 |pages=709–33 |date=November 2008 |pmid=19214910 |doi=10.1055/s-0029-1145254 |url=}}</ref><ref name="pmid9278200">{{cite journal |vauthors=Marshall PW, Williams AJ, Dixon RM, Growcott JW, Warburton S, Armstrong J, Moores J |title=A comparison of the effects of aspirin on bleeding time measured using the Simplate method and closure time measured using the PFA-100, in healthy volunteers |journal=Br J Clin Pharmacol |volume=44 |issue=2 |pages=151–5 |date=August 1997 |pmid=9278200 |pmc=2042813 |doi= |url=}}</ref>
*The most common [[Screening (medicine)|screening test]] used for screening the patients with BSS <ref name="pmid11260277">{{cite journal |vauthors=Favaloro EJ |title=Utility of the PFA-100 for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations |journal=Haemophilia |volume=7 |issue=2 |pages=170–9 |date=March 2001 |pmid=11260277 |doi= |url=}}</ref><ref name="pmid12172459">{{cite journal |vauthors=Favaloro EJ |title=Clinical application of the PFA-100 |journal=Curr. Opin. Hematol. |volume=9 |issue=5 |pages=407–15 |date=September 2002 |pmid=12172459 |doi= |url=}}</ref><ref name="pmid19214910">{{cite journal |vauthors=Favaloro EJ |title=Clinical utility of the PFA-100 |journal=Semin. Thromb. Hemost. |volume=34 |issue=8 |pages=709–33 |date=November 2008 |pmid=19214910 |doi=10.1055/s-0029-1145254 |url=}}</ref><ref name="pmid9278200">{{cite journal |vauthors=Marshall PW, Williams AJ, Dixon RM, Growcott JW, Warburton S, Armstrong J, Moores J |title=A comparison of the effects of aspirin on bleeding time measured using the Simplate method and closure time measured using the PFA-100, in healthy volunteers |journal=Br J Clin Pharmacol |volume=44 |issue=2 |pages=151–5 |date=August 1997 |pmid=9278200 |pmc=2042813 |doi= |url=}}</ref>
*PFA-100 helps in differentiate between  
*[[PFA-100]] helps in differentiate between  
**Aspirin-induced defect and
**[[Aspirin]]-induced defect and
**Severe platelet dysfunction
**Severe [[platelet]] dysfunction
*In other bleeding disorders like storage pool disorders PFA-100 is less sensitive.
*In other [[bleeding]] disorders like storage pool disorders [[PFA-100]] is less sensitive.
'''Ultegra'''
'''Ultegra'''
*Ultegra an automated whole blood assay.
*Ultegra an automated whole blood [[assay]].
*Ultegra is very easy to use and can be done at the bedside.
*Ultegra is very easy to use and can be done at the bedside.
*Ultegra helps in measuring [[platelet aggregation]] based on how strong activated [[Platelet|platelets]] binding to [[fibrinogen]].
*Ultegra helps in measuring [[platelet aggregation]] based on how strong activated [[Platelet|platelets]] binding to [[fibrinogen]].


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
* If left untreated, patients with Bernard-Soulier syndrome may progress to develop [[bleeding]] manifestations like [[mucocutaneous]] bleeding, which can be prolonged and severe.<ref name="pmid28131619">{{cite journal |vauthors=Boeckelmann D, Hengartner H, Greinacher A, Nowak-Göttl U, Sachs UJ, Peter K, Sandrock-Lang K, Zieger B |title=Patients with Bernard-Soulier syndrome and different severity of the bleeding phenotype |journal=Blood Cells Mol. Dis. |volume=67 |issue= |pages=69–74 |date=September 2017 |pmid=28131619 |doi=10.1016/j.bcmd.2017.01.010 |url=}}</ref>
 
* Common [[Complication (medicine)|complications]] of Bernard-Soulier syndrome include ante, intra, or [[postpartum hemorrhage]] in pregnant patients.<ref name="pmid8336744">{{cite journal |vauthors=Greinacher A, Zellner A, Brangenberg R, Kiefel V, Mueller-Eckhardt C |title=[Bernard-Soulier syndrome. An important differential diagnosis in chronic thrombocytopenia with bleeding complications] |language=German |journal=Monatsschr Kinderheilkd |volume=141 |issue=6 |pages=483–6 |date=June 1993 |pmid=8336744 |doi= |url=}}</ref>
OR
* [[Prognosis]] is generally good in patients with Bernard-Soulier syndrome is but it is largely based on the severity of the condition.
 
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
 
OR
 
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
===Diagnostic Study of Choice===
* The initial [[laboratory]] test to be done is [[Complete blood count|blood cell count]]<nowiki/>s and [[blood smear]]<nowiki/>s.
* The diagnostic study of choice for Bernard-Soulier syndrome is [[Ristocetin induced platelet agglutination|ristocetin]]-induced [[agglutination]].<ref name="JenkinsPhillips1976">{{cite journal|last1=Jenkins|first1=C S|last2=Phillips|first2=D R|last3=Clemetson|first3=K J|last4=Meyer|first4=D|last5=Larrieu|first5=M J|last6=Lüscher|first6=E F|title=Platelet membrane glycoproteins implicated in ristocetin-induced aggregation. Studies of the proteins on platelets from patients with Bernard-Soulier syndrome and von Willebrand's disease.|journal=Journal of Clinical Investigation|volume=57|issue=1|year=1976|pages=112–124|issn=0021-9738|doi=10.1172/JCI108251}}</ref><ref name="KelseyChristopoulos1994">{{cite journal|last1=Kelsey|first1=H|last2=Christopoulos|first2=C|last3=Gray|first3=A A|last4=Machin|first4=S J|title=Acquired pseudo-pseudo Bernard-Soulier syndrome complicating Gaucher's disease.|journal=Journal of Clinical Pathology|volume=47|issue=2|year=1994|pages=162–165|issn=0021-9746|doi=10.1136/jcp.47.2.162}}</ref><ref name="pmid7579348">{{cite journal |vauthors=Li C, Martin SE, Roth GJ |title=The genetic defect in two well-studied cases of Bernard-Soulier syndrome: a point mutation in the fifth leucine-rich repeat of platelet glycoprotein Ib alpha |journal=Blood |volume=86 |issue=10 |pages=3805–14 |date=November 1995 |pmid=7579348 |doi= |url=}}</ref><ref name="pmid78733902">{{cite journal |vauthors=de la Salle C, Baas MJ, Lanza F, Schwartz A, Hanau D, Chevalier J, Gachet C, Briquel ME, Cazenave JP |title=A three-base deletion removing a leucine residue in a leucine-rich repeat of platelet glycoprotein Ib alpha associated with a variant of Bernard-Soulier syndrome (Nancy I) |journal=Br. J. Haematol. |volume=89 |issue=2 |pages=386–96 |date=February 1995 |pmid=7873390 |doi= |url=}}</ref>
 
* [[Ristocetin]] is a drug that increases [[Adhesin|adherence]] between [[Von Willebrand factor|VWF]] and GP1b, and this aggregation is not seen in Bernard-Soulier syndrome.
* The [[diagnosis]] of Bernard-Soulier syndrome is based on the presence of a large [[Platelet|platelets]] (diameter 4–10 μ m) with a rounded shape.
 
* One of the diagnoses of Bernard-Soulier syndrome is based on the [[bleeding time]], which include
** Moderately [[bleeding time]]: 5–10 min
** Severe [[bleeding time]]: >20 min
* On [[blood smear]] manual counting is necessary as the large [[Platelet|platelets]] is often mistaken by [[Lymphocyte|lymphocytes]].
* Another unique diagnosing test for Bernard-Soulier syndrome is [[Ristocetin induced platelet agglutination|ristocetin]]-induced agglutination.
* [[Ristocetin]] is a drug that increases [[Adhesin|adherence]] between [[Von Willebrand factor|VWF]] and GP1b and is not seen in Bernard-Soulier syndrome.
* [[Factor VIII|FVIII]]-[[von Willebrand factor]] levels are measured.
* [[Aggregation]] responses to [[thrombin]] is decreased.
* In Bernard-Soulier syndrome patients on testing we can observe the defect in [[prothrombin]] consumption and can help in the [[diagnosis]].
* Defect in [[prothrombin]] consumption is due to effective binding of FXI due to a lack of [[Glycoprotein Ib|GPIb]] and decrease in [[Glycoprotein Ib|GPIb]]-[[fibrin]]-dependent [[thrombin]].
 
*CD42 a-d a [[Monoclonal antibodies|monoclonal antibody]] detected in [[flow cytometry]] is also helps in the diagnosis and confirmation of the diagnosis in the patients with Bernard-Soulier syndrome.
*[[Genetic]] abnormalities testing also aid in the diagnosing the patients with bernard soulier syndrome.
*[[Immunoblotting]] also helps in diagnosing bernard soulier syndrome.
*Other new tests like [[platelet]] [[glycoprotein]] analysis by [[SDS]]-[[polyacrylamide]] [[gel]] separation are the news tests in the research which proves that in the diagnosis of the patients with bernard soulier syndrome.


===History and Symptoms===
===History and Symptoms===
The majority of patients with bernard soulier syndrome shows the following [[Symptom|symptoms]]:
The majority of patients with Bernard-Soulier syndrome show the following [[Symptom|symptoms]]:
 
Common [[symptoms]] of Bernard-Soulier syndrome patients include:<ref name="pmid21113246">{{cite journal |vauthors=Kirchmaier CM, Pillitteri D |title=Diagnosis and Management of Inherited Platelet Disorders |journal=Transfus Med Hemother |volume=37 |issue=5 |pages=237–246 |date=2010 |pmid=21113246 |pmc=2980508 |doi=10.1159/000320257 |url=}}</ref><ref name="Diz-Kucukkaya2013">{{cite journal|last1=Diz-Kucukkaya|first1=R.|title=Inherited platelet disorders including Glanzmann thrombasthenia and Bernard-Soulier syndrome|journal=Hematology|volume=2013|issue=1|year=2013|pages=268–275|issn=1520-4391|doi=10.1182/asheducation-2013.1.268}}</ref><ref name="BerndtAndrews20113">{{cite journal|last1=Berndt|first1=M. C.|last2=Andrews|first2=R. K.|title=Bernard-Soulier syndrome|journal=Haematologica|volume=96|issue=3|year=2011|pages=355–359|issn=0390-6078|doi=10.3324/haematol.2010.039883}}</ref><ref name="Lanza20062">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref><ref name="BragadottirBirgisdottir2015">{{cite journal|last1=Bragadottir|first1=Gudrun|last2=Birgisdottir|first2=Elisabet R.|last3=Gudmundsdottir|first3=Brynja R.|last4=Hilmarsdottir|first4=Bylgja|last5=Vidarsson|first5=Brynjar|last6=Magnusson|first6=Magnus K.|last7=Larsen|first7=Ole Halfdan|last8=Sorensen|first8=Benny|last9=Ingerslev|first9=Jorgen|last10=Onundarson|first10=Pall T.|title=Clinical phenotype in heterozygote and biallelic Bernard-Soulier syndrome-A case control study|journal=American Journal of Hematology|volume=90|issue=2|year=2015|pages=149–155|issn=03618609|doi=10.1002/ajh.23891}}</ref><ref name="pmid2550101">{{cite journal |vauthors=Berndt MC, Fournier DJ, Castaldi PA |title=Bernard-Soulier syndrome |journal=Baillieres Clin. Haematol. |volume=2 |issue=3 |pages=585–607 |date=July 1989 |pmid=2550101 |doi= |url=}}</ref>
=== Common Symptoms ===
Common [[symptoms]] of bernard soulier syndrome patients include:<ref name="pmid21113246">{{cite journal |vauthors=Kirchmaier CM, Pillitteri D |title=Diagnosis and Management of Inherited Platelet Disorders |journal=Transfus Med Hemother |volume=37 |issue=5 |pages=237–246 |date=2010 |pmid=21113246 |pmc=2980508 |doi=10.1159/000320257 |url=}}</ref><ref name="Diz-Kucukkaya2013">{{cite journal|last1=Diz-Kucukkaya|first1=R.|title=Inherited platelet disorders including Glanzmann thrombasthenia and Bernard-Soulier syndrome|journal=Hematology|volume=2013|issue=1|year=2013|pages=268–275|issn=1520-4391|doi=10.1182/asheducation-2013.1.268}}</ref><ref name="BerndtAndrews20113">{{cite journal|last1=Berndt|first1=M. C.|last2=Andrews|first2=R. K.|title=Bernard-Soulier syndrome|journal=Haematologica|volume=96|issue=3|year=2011|pages=355–359|issn=0390-6078|doi=10.3324/haematol.2010.039883}}</ref><ref name="Lanza20062">{{cite journal|last1=Lanza|first1=François|journal=Orphanet Journal of Rare Diseases|volume=1|issue=1|year=2006|pages=46|issn=17501172|doi=10.1186/1750-1172-1-46}}</ref><ref name="BragadottirBirgisdottir2015">{{cite journal|last1=Bragadottir|first1=Gudrun|last2=Birgisdottir|first2=Elisabet R.|last3=Gudmundsdottir|first3=Brynja R.|last4=Hilmarsdottir|first4=Bylgja|last5=Vidarsson|first5=Brynjar|last6=Magnusson|first6=Magnus K.|last7=Larsen|first7=Ole Halfdan|last8=Sorensen|first8=Benny|last9=Ingerslev|first9=Jorgen|last10=Onundarson|first10=Pall T.|title=Clinical phenotype in heterozygote and biallelic Bernard-Soulier syndrome-A case control study|journal=American Journal of Hematology|volume=90|issue=2|year=2015|pages=149–155|issn=03618609|doi=10.1002/ajh.23891}}</ref><ref name="pmid2550101">{{cite journal |vauthors=Berndt MC, Fournier DJ, Castaldi PA |title=Bernard-Soulier syndrome |journal=Baillieres Clin. Haematol. |volume=2 |issue=3 |pages=585–607 |date=July 1989 |pmid=2550101 |doi= |url=}}</ref>
* [[Nosebleeds]] ([[Epistaxis]])
* [[Nosebleeds]] ([[Epistaxis]])
* Prolonged [[bleeding time]] in some cases it is more than 20 minutes
* Prolonged [[bleeding time]] (in some cases it is more than 20 minutes)
 
* Easy [[bruising]]  
* Easy [[bruising]]  
* Severe [[Menorrhagia]] in females
* Severe [[Menorrhagia]] in females
Line 186: Line 149:
* [[Cutaneous]] [[bleeding]]  
* [[Cutaneous]] [[bleeding]]  
* [[Petechia|Petechiae]]  
* [[Petechia|Petechiae]]  
 
Less common [[Symptom|symptoms]] of Bernard-Soulier syndrome include:<ref name="pmid211132462">{{cite journal |vauthors=Kirchmaier CM, Pillitteri D |title=Diagnosis and Management of Inherited Platelet Disorders |journal=Transfus Med Hemother |volume=37 |issue=5 |pages=237–246 |date=2010 |pmid=21113246 |pmc=2980508 |doi=10.1159/000320257 |url=}}</ref><ref name="BerndtAndrews20112">{{cite journal|last1=Berndt|first1=M. C.|last2=Andrews|first2=R. K.|title=Bernard-Soulier syndrome|journal=Haematologica|volume=96|issue=3|year=2011|pages=355–359|issn=0390-6078|doi=10.3324/haematol.2010.039883}}</ref><ref name="BragadottirBirgisdottir20152">{{cite journal|last1=Bragadottir|first1=Gudrun|last2=Birgisdottir|first2=Elisabet R.|last3=Gudmundsdottir|first3=Brynja R.|last4=Hilmarsdottir|first4=Bylgja|last5=Vidarsson|first5=Brynjar|last6=Magnusson|first6=Magnus K.|last7=Larsen|first7=Ole Halfdan|last8=Sorensen|first8=Benny|last9=Ingerslev|first9=Jorgen|last10=Onundarson|first10=Pall T.|title=Clinical phenotype in heterozygote and biallelic Bernard-Soulier syndrome-A case control study|journal=American Journal of Hematology|volume=90|issue=2|year=2015|pages=149–155|issn=03618609|doi=10.1002/ajh.23891}}</ref>
=== Less Common Symptoms ===
* Occasionally patients present with:
Less common [[Symptom|symptoms]] of bernard soulier syndrome patients include:<ref name="pmid211132462">{{cite journal |vauthors=Kirchmaier CM, Pillitteri D |title=Diagnosis and Management of Inherited Platelet Disorders |journal=Transfus Med Hemother |volume=37 |issue=5 |pages=237–246 |date=2010 |pmid=21113246 |pmc=2980508 |doi=10.1159/000320257 |url=}}</ref><ref name="BerndtAndrews20112">{{cite journal|last1=Berndt|first1=M. C.|last2=Andrews|first2=R. K.|title=Bernard-Soulier syndrome|journal=Haematologica|volume=96|issue=3|year=2011|pages=355–359|issn=0390-6078|doi=10.3324/haematol.2010.039883}}</ref><ref name="BragadottirBirgisdottir20152">{{cite journal|last1=Bragadottir|first1=Gudrun|last2=Birgisdottir|first2=Elisabet R.|last3=Gudmundsdottir|first3=Brynja R.|last4=Hilmarsdottir|first4=Bylgja|last5=Vidarsson|first5=Brynjar|last6=Magnusson|first6=Magnus K.|last7=Larsen|first7=Ole Halfdan|last8=Sorensen|first8=Benny|last9=Ingerslev|first9=Jorgen|last10=Onundarson|first10=Pall T.|title=Clinical phenotype in heterozygote and biallelic Bernard-Soulier syndrome-A case control study|journal=American Journal of Hematology|volume=90|issue=2|year=2015|pages=149–155|issn=03618609|doi=10.1002/ajh.23891}}</ref>
** [[Bastrointestinal]] [[bleeding]]
* And occasionally patients present with [[gastrointestinal]] [[bleeding]]
** [[Bleeding]] after [[childbirth]]
* [[Bleeding]] after [[childbirth]]
** Blood in [[stool]]  
* Blood in [[stool]]  
** Blood in [[vomiting]]
* Blood in [[vomiting]]
** [[Bleeding]] without [[trauma]]
* [[Bleeding]] without [[trauma]]


===Physical Examination===
===Physical Examination===
*Patients with bernard soulier syndrome usually remarkable for dysfunctional platelets  an include
Patients with Bernard-Soulier syndrome usually have:
**Mucosal bleeding
* [[Mucosal]] bleeding
**Bruising
* [[Bruise|Bruising]]


===Laboratory Findings===
===Laboratory Findings===
*<nowiki/><nowiki/> The initial [[laboratory]] test to be done is [[Complete blood count|blood cell count]]<nowiki/>s and [[blood smear]]<nowiki/>s.
*<nowiki/><nowiki/> The initial [[laboratory]] test to be done is [[Complete blood count|blood cell count]]<nowiki/>s and [[blood smear]]<nowiki/>s.<ref name="pmid2725065">{{cite journal |vauthors=Nichols WL, Kaese SE, Gastineau DA, Otteman LA, Bowie EJ |title=Bernard-Soulier syndrome: whole blood diagnostic assays of platelets |journal=Mayo Clin. Proc. |volume=64 |issue=5 |pages=522–30 |date=May 1989 |pmid=2725065 |doi= |url=}}</ref><ref name="pmid7900092">{{cite journal |vauthors=Bunescu A, Lindahl T, Solum NO, Schulman S, Larsson A, Lundahl J, Egberg N |title=Partial expression of GP Ib measured by flow cytometry in two patients with Bernard-Soulier syndrome |journal=Thromb. Res. |volume=76 |issue=5 |pages=441–50 |date=December 1994 |pmid=7900092 |doi= |url=}}</ref><ref name="pmid3096050">{{cite journal |vauthors=De Marco L, Fabris F, Casonato A, Fabris P, Dal Ben MG, Barbato A, Girolami A |title=Bernard-Soulier syndrome: diagnosis by an ELISA method using monoclonal antibodies in 2 new unrelated patients |journal=Acta Haematol. |volume=75 |issue=4 |pages=203–8 |date=1986 |pmid=3096050 |doi=10.1159/000206125 |url=}}</ref><ref name="pmid2693494">{{cite journal |vauthors=Poulsen LO, Johansen P, Jensen MK, Freund L |title=Differentiation between Bernard-Soulier syndrome and immune thrombocytopenia by immunostaining of peripheral blood |journal=J. Clin. Pathol. |volume=42 |issue=12 |pages=1296–7 |date=December 1989 |pmid=2693494 |pmc=502064 |doi= |url=}}</ref><ref name="pmid25501012">{{cite journal |vauthors=Berndt MC, Fournier DJ, Castaldi PA |title=Bernard-Soulier syndrome |journal=Baillieres Clin. Haematol. |volume=2 |issue=3 |pages=585–607 |date=July 1989 |pmid=2550101 |doi= |url=}}</ref><ref name="pmid20725709">{{cite journal |vauthors=Kirchmaier CM, Pillitteri D |title=[Congenital thrombocytopathies] |language=German |journal=Internist (Berl) |volume=51 |issue=9 |pages=1109–14, 1116–7 |date=September 2010 |pmid=20725709 |doi=10.1007/s00108-010-2596-3 |url=}}</ref><ref name="pmid8336744">{{cite journal |vauthors=Greinacher A, Zellner A, Brangenberg R, Kiefel V, Mueller-Eckhardt C |title=[Bernard-Soulier syndrome. An important differential diagnosis in chronic thrombocytopenia with bleeding complications] |language=German |journal=Monatsschr Kinderheilkd |volume=141 |issue=6 |pages=483–6 |date=June 1993 |pmid=8336744 |doi= |url=}}</ref><ref name="pmid19408193">{{cite journal |vauthors=Nurden AT, Fiore M, Pillois X, Nurden P |title=Genetic testing in the diagnostic evaluation of inherited platelet disorders |journal=Semin. Thromb. Hemost. |volume=35 |issue=2 |pages=204–12 |date=March 2009 |pmid=19408193 |doi=10.1055/s-0029-1220328 |url=}}</ref>
* The [[diagnosis]] of Bernard-Soulier syndrome is based on the <nowiki/>presence of a lar<nowiki/>ge [[Platelet|platelets]] (diameter 4–10 μ m) with a rounded shape.
* The [[diagnosis]] of Bernard-Soulier syndrome is based on the <nowiki/>presence of a lar<nowiki/>ge [[Platelet|platelets]] (diameter 4–10 μ m) with a rounded shape.
 
* One of the diagnostic criteria of Bernard-Soulier syndrome is prolonged [[bleeding time]].
* One of the diagnoses of Bernard-Soulier syndrome is based on the [[bleeding time]], which include
** Moderately prolonged [[bleeding time]]: 5–10 min
** Moderately [[bleeding time]]: 5–10 min
** Severely prolonged [[bleeding time]]: >20 min
** Severe [[bleeding time]]: >20 min
* On [[blood smear]] manual counting is necessary as the large [[Platelet|platelets]] are often mistaken as [[Lymphocyte|lymphocytes]].
* On [[blood smear]] manual counting is necessary as the large [[Platelet|platelets]] is often mistaken by [[Lymphocyte|lymphocytes]].
* [[Factor VIII|FVIII]]-[[von Willebrand factor]] levels are measured.
* [[Factor VIII|FVIII]]-[[von Willebrand factor]] levels are measured.
* [[Aggregation]] responses to [[thrombin]] is decreased.
* [[Aggregation]] responses to [[thrombin]] is decreased.
* In Bernard-Soulier syndrome patients on testing we can observe the defect in [[prothrombin]] consumption and can help in the [[diagnosis]].
* In Bernard-Soulier syndrome patients we can observe the defect in [[prothrombin]] consumption.
* Defect in [[prothrombin]] consumption is due to effective binding of FXI due to a lack of [[Glycoprotein Ib|GPIb]] and decrease in [[Glycoprotein Ib|GPIb]]-[[fibrin]]-dependent [[thrombin]].<ref name="pmid116965422">{{cite journal |vauthors=Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN |title=Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin |journal=J. Biol. Chem. |volume=277 |issue=3 |pages=1662–8 |date=January 2002 |pmid=11696542 |doi=10.1074/jbc.M108319200 |url=}}</ref>
* Defect in [[prothrombin]] consumption is due to effective binding of FXI due to a lack of [[Glycoprotein Ib|GPIb]] and decrease in [[Glycoprotein Ib|GPIb]]-[[fibrin]]-dependent [[thrombin]].<ref name="pmid116965422">{{cite journal |vauthors=Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN |title=Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin |journal=J. Biol. Chem. |volume=277 |issue=3 |pages=1662–8 |date=January 2002 |pmid=11696542 |doi=10.1074/jbc.M108319200 |url=}}</ref>
 
*CD42 a-d a [[Monoclonal antibodies|monoclonal antibody]] detected in [[flow cytometry]] also helps in the diagnosis and confirmation of the diagnosis in the patients with Bernard-Soulier syndrome.
*CD42 a-d a [[Monoclonal antibodies|monoclonal antibody]] detected in [[flow cytometry]] is also helps in the diagnosis and confirmation of the diagnosis in the patients with Bernard-Soulier syndrome.
*[[Genetic]] testing also aids in diagnosing patients with Bernard-Soulier syndrome.
*[[Genetic]] abnormalities testing also aid in the diagnosing the patients with bernard soulier syndrome.
*[[Immunoblotting]] also helps in diagnosing patients with Bernard-Soulier syndrome.
*[[Immunoblotting]] also helps in diagnosing bernard soulier syndrome.
*Other new tests like [[platelet]] [[glycoprotein]] analysis by [[SDS]]-[[polyacrylamide]] [[gel]] separation are still being studied.
*Other new tests like [[platelet]] [[glycoprotein]] analysis by [[SDS]]-[[polyacrylamide]] [[gel]] separation are the news tests in the research which proves that in the diagnosis of the patients with bernard soulier syndrome.


===Electrocardiogram===
===Electrocardiogram===
There are no ECG findings associated with Bernard-Soulier syndrome.
* There are no [[ECG]] findings associated with Bernard-Soulier syndrome.


===X-ray===
===X-ray===
There are no x-ray findings associated with bernard soulier syndrome.
* There are no [[x-ray]] findings associated with Bernard-Soulier syndrome.


===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound findings associated with bernard soulier syndrome.
* There are no [[ultrasound]] findings associated with the Bernard-Soulier syndrome.


===CT scan===
===CT scan===
There are no CT scan findings associated with [disease name].
* There are no [[Computed tomography|CT]] scan findings associated with Bernard-Soulier syndrome.
 
OR
 
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===MRI===
===MRI===
There are no MRI findings associated with [disease name].
* There are no [[MRI]] findings associated with the Bernard-Soulier syndrome.


OR
==Treatment==
 
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
 
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
 
OR
 
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].
 
OR
 
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


OR
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
==Treatment==
===Medical Therapy===
===Medical Therapy===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
* There is no specific treatment for Bernard-Soulier syndrome; the mainstay of therapy is supportive care.
 
* Pharmacologic medical therapy is recommended among patients with bleeding episodes:<ref name="pmid18278172">{{cite journal |vauthors=Nurden P, Nurden AT |title=Congenital disorders associated with platelet dysfunctions |journal=Thromb. Haemost. |volume=99 |issue=2 |pages=253–63 |date=February 2008 |pmid=18278172 |doi=10.1160/TH07-09-0568 |url=}}</ref>
OR
 
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].


OR
==== Antifibrinolytic agents ====
* ε-[[aminocaproic acid]]
* [[Tranexamic acid]]
* Both are very effective in controlling the [[mucosal]] bleeding


The majority of cases of [disease name] are self-limited and require only supportive care.
==== Platelet transfusion ====
* [[Platelet]] [[transfusion]] is the alternative when the patient is undergoing any surgical procedure.<ref name="FisherChapman1985">{{cite journal|last1=Fisher|first1=Marlene|last2=Chapman|first2=Jeremy R.|last3=Ting|first3=Alan|last4=Morris|first4=Peter J.|title=Alloimmunisation to HLA Antigens following Transfusion
with Leucocyte-Poor and Purified Platelet Suspensions|journal=Vox Sanguinis|volume=49|issue=5|year=1985|pages=331–335|issn=0042-9007|doi=10.1159/000466401}}</ref>


OR
==== Desmopressin acetate (DDAVP) ====
 
* [[Desmopressin]] helps in shorten the [[bleeding time]] by increasing the release of vWF from endothelium.<ref name="pmid1901273">{{cite journal |vauthors=Waldenström E, Holmberg L, Axelsson U, Winqvist I, Nilsson IM |title=Bernard-Soulier syndrome in two Swedish families: effect of DDAVP on bleeding time |journal=Eur. J. Haematol. |volume=46 |issue=3 |pages=182–7 |date=March 1991 |pmid=1901273 |doi= |url=}}</ref>
[Disease name] is a medical emergency and requires prompt treatment.
* [[Desmopressin]] also helps in minor bleeding episodes.
 
* In patients who are suffering with [[congenital]] platelet disorders [[recombinant]] activated [[factor VII]] have been shown useful.
OR
 
The mainstay of treatment for [disease name] is [therapy].
 
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR
 
[Therapy] is recommended among all patients who develop [disease name].
 
OR
 
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
 
OR
 
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
 
OR
 
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
 
OR
 
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].


===Surgery===
===Surgery===
Surgical intervention is not recommended for the management of [disease name].
* Surgical intervention is not recommended for the management of Bernard-Soulier syndrome.
 
OR
 
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
 
OR
 
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
 
OR
 
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
 
OR
 
Surgery is the mainstay of treatment for [disease or malignancy].


===Primary Prevention===
===Primary Prevention===
There are no established measures for the primary prevention of [disease name].
* There are no established measures for the [[primary prevention]] of the Bernard-Soulier syndrome.
 
OR
 
There are no available vaccines against [disease name].
 
OR
 
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
 
OR
 
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].


===Secondary Prevention===
===Secondary Prevention===
There are no established measures for the secondary prevention of [disease name].
* There are no established measures for the [[secondary prevention]] of Bernard-Soulier syndrome.
 
OR
 
Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].


==References==
==References==
Line 356: Line 226:


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Latest revision as of 03:36, 21 December 2018

Bernard-Soulier syndrome
Bernard-Soulier syndrome.
(Image courtesy of Melih Aktan M.D.)
ICD-10 D69.1
ICD-9 287.1
OMIM 231200
DiseasesDB 1356
eMedicine ped/230 
MeSH D001606

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [3]

Synonyms and keywords:BSS, giant platelet syndrome; hemorrhagic parous thrombocytic dystrophy; macrothrombocytopenia, familial Bernard-Soulier type; platelet glycoprotein Ib deficiency; Von Willebrand factor receptor deficiency.

Overview

Bernard-Soulier syndrome (BSS) belongs to one the rare hereditary platelet disorders. Bernard-Soulier syndrome characteristically is defined by the presence of giant platelets and thrombocytopenia. Bernard-Soulier syndrome (BSS) was first discovered in 1948. Bernard-Soulier syndrome may be classified into 4 subtypes. Bernard-Soulier syndrome is the result of the absence or decreased expression of the GPIb/IX/V complex on the surface of the platelets. Bernard-Soulier syndrome may be caused by abnormality in the genes for glycoprotein Ib/IX/V. The prevalence of Bernard-Soulier syndrome is approximately 1 per 100,000 individuals worldwide. The initial laboratory test to be done is blood cell counts and blood smears. There are no established risk factors for Bernard-Soulier syndrome. There is sufficient evidence to recommend routine screening for Bernard-Soulier syndrome with newer technologies in current clinical practice. If left untreated, patients with Bernard-Soulier syndrome may progress to develop bleeding manifestations like mucocutaneous bleeding, which can be prolonged and severe. Patients with Bernard-Soulier syndrome usually remarkable for dysfunctional platelets. There is no specific treatment for Bernard-Soulier syndrome, the mainstay of therapy is supportive care.


Historical Perspective

Classification

Bernard Soulier syndrome is classified into 4 subtypes:[8][9][10][11][12][13]

Phenotype Genomic Location Inheritance Gene Locus

MIM number

Bernard-Soulier syndrome, type A1 17p13.2 Autosomal Recessive GP1BA 606672
Bernard-Soulier syndrome, type B 22q11.21 Autosomal Recessive GP1BB 138720
Bernard-Soulier syndrome, type C 3q21.3 Autosomal Recessive GP9 173515
Giant platelet disorder, isolated 22q11.21 Autosomal Recessive GP1BB 138720

Pathophysiology

Causes

Differentiating Bernard-Soulier syndrome from Other Disease

Epidemiology and Demographics

  • The prevalence of Bernard-Soulier syndrome is approximately 1 per 100,000 individuals worldwide.[65][66][67][68]
  • Bernard-Soulier syndrome is very rare; until now only ~100 cases have been reported.
  • The severity of Bernard-Soulier syndrome increases with age.
  • Bernard-Soulier syndrome more commonly affects infants than children and older people.
  • Bernard-Soulier syndrome usually affects individuals from Japan, Europe and North America.
  • Males and females are affected with equal frequency.
  • The majority of Bernard-Soulier syndrome cases are reported in whites of European ancestry.

Risk Factors

  • There are no established risk factors for Bernard-Soulier syndrome.
  • Autosomal recessive genetic pattern is characteristic of Bernard-Soulier syndrome.
  • Bernard-Soulier syndrome patients can be carriers when they receive one normal gene and one abnormal gene.
  • Risk of Bernard-Soulier syndrome in a child is 25% to 50% with each pregnancy when two carrier parents both pass the abnormal gene.

Screening

  • There is sufficient evidence to recommend routine screening for Bernard-Soulier syndrome with newer technologies in current clinical practice like the following.[69][70]

PFA-100(Platelet Function Analyzer)

Ultegra

Natural History, Complications, and Prognosis

  • If left untreated, patients with Bernard-Soulier syndrome may progress to develop bleeding manifestations like mucocutaneous bleeding, which can be prolonged and severe.[75]
  • Common complications of Bernard-Soulier syndrome include ante, intra, or postpartum hemorrhage in pregnant patients.[76]
  • Prognosis is generally good in patients with Bernard-Soulier syndrome is but it is largely based on the severity of the condition.

Diagnosis

Diagnostic Study of Choice

History and Symptoms

The majority of patients with Bernard-Soulier syndrome show the following symptoms: Common symptoms of Bernard-Soulier syndrome patients include:[81][82][83][84][85][86]

Less common symptoms of Bernard-Soulier syndrome include:[87][88][89]

Physical Examination

Patients with Bernard-Soulier syndrome usually have:

Laboratory Findings

Electrocardiogram

  • There are no ECG findings associated with Bernard-Soulier syndrome.

X-ray

  • There are no x-ray findings associated with Bernard-Soulier syndrome.

Echocardiography or Ultrasound

  • There are no ultrasound findings associated with the Bernard-Soulier syndrome.

CT scan

  • There are no CT scan findings associated with Bernard-Soulier syndrome.

MRI

  • There are no MRI findings associated with the Bernard-Soulier syndrome.

Treatment

Medical Therapy

  • There is no specific treatment for Bernard-Soulier syndrome; the mainstay of therapy is supportive care.
  • Pharmacologic medical therapy is recommended among patients with bleeding episodes:[98]

Antifibrinolytic agents

Platelet transfusion

Desmopressin acetate (DDAVP)

Surgery

  • Surgical intervention is not recommended for the management of Bernard-Soulier syndrome.

Primary Prevention

  • There are no established measures for the primary prevention of the Bernard-Soulier syndrome.

Secondary Prevention

References

  1. ↑ Lanza, François (2006). Orphanet Journal of Rare Diseases. 1 (1): 46. doi:10.1186/1750-1172-1-46. ISSN 1750-1172. Missing or empty |title= (help)
  2. ↑ Lanza F (November 2006). "Bernard-Soulier syndrome (hemorrhagiparous thrombocytic dystrophy)". Orphanet J Rare Dis. 1: 46. doi:10.1186/1750-1172-1-46. PMC 1660532. PMID 17109744.
  3. ↑ de la Salle C, Lanza F, Cazenave JP (1995). "Biochemical and molecular basis of Bernard-Soulier syndrome: a review". Nouv Rev Fr Hematol. 37 (4): 215–22. PMID 8904201.
  4. ↑ de la Salle C, Baas MJ, Lanza F, Schwartz A, Hanau D, Chevalier J, Gachet C, Briquel ME, Cazenave JP (February 1995). "A three-base deletion removing a leucine residue in a leucine-rich repeat of platelet glycoprotein Ib alpha associated with a variant of Bernard-Soulier syndrome (Nancy I)". Br. J. Haematol. 89 (2): 386–96. PMID 7873390.
  5. ↑ Nurden, A. T.; Phillips, D. R.; George, J. N. (2006). "Platelet membrane glycoproteins: historical perspectives". Journal of Thrombosis and Haemostasis. 4 (1): 3–9. doi:10.1111/j.1538-7836.2005.01549.x. ISSN 1538-7933.
  6. ↑ Beardsley DS (1990). "Platelet membrane glycoproteins: role in primary hemostasis and component antigens". Yale J Biol Med. 63 (5): 469–75. PMC 2589352. PMID 2293505.
  7. ↑ Clemetson KJ, McGregor JL, James E, Dechavanne M, Lüscher EF (August 1982). "Characterization of the platelet membrane glycoprotein abnormalities in Bernard-Soulier syndrome and comparison with normal by surface-labeling techniques and high-resolution two-dimensional gel electrophoresis". J. Clin. Invest. 70 (2): 304–11. PMC 371237. PMID 6284798.
  8. ↑ Nurden A, Nurden P (July 2011). "Advances in our understanding of the molecular basis of disorders of platelet function". J. Thromb. Haemost. 9 Suppl 1: 76–91. doi:10.1111/j.1538-7836.2011.04274.x. PMID 21781244.
  9. ↑ Ramasamy I (January 2004). "Inherited bleeding disorders: disorders of platelet adhesion and aggregation". Crit. Rev. Oncol. Hematol. 49 (1): 1–35. PMID 14734152.
  10. ↑ Nurden AT, Nurden P (December 2001). "Inherited defects of platelet function". Rev Clin Exp Hematol. 5 (4): 314–34, quiz following 431. PMID 11844132.
  11. ↑ Lanza, François (2006). Orphanet Journal of Rare Diseases. 1 (1): 46. doi:10.1186/1750-1172-1-46. ISSN 1750-1172. Missing or empty |title= (help)
  12. ↑ Yagi M, Edelhoff S, Disteche CM, Roth GJ (December 1995). "Human platelet glycoproteins V and IX: mapping of two leucine-rich glycoprotein genes to chromosome 3 and analysis of structures". Biochemistry. 34 (49): 16132–7. PMID 8519770.
  13. ↑ Yagi M, Edelhoff S, Disteche CM, Roth GJ (July 1994). "Structural characterization and chromosomal location of the gene encoding human platelet glycoprotein Ib beta". J. Biol. Chem. 269 (26): 17424–7. PMID 8021244.
  14. ↑ Lanza, François (2006). Orphanet Journal of Rare Diseases. 1 (1): 46. doi:10.1186/1750-1172-1-46. ISSN 1750-1172. Missing or empty |title= (help)
  15. ↑ Berndt, M. C.; Andrews, R. K. (2011). "Bernard-Soulier syndrome". Haematologica. 96 (3): 355–359. doi:10.3324/haematol.2010.039883. ISSN 0390-6078.
  16. ↑ Feghhi, Shirin; Munday, Adam D.; Tooley, Wes W.; Rajsekar, Shreya; Fura, Adriane M.; Kulman, John D.; López, Jose A.; Sniadecki, Nathan J. (2016). "Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion". Biophysical Journal. 111 (3): 601–608. doi:10.1016/j.bpj.2016.06.023. ISSN 0006-3495.
  17. ↑ Savage B, Almus-Jacobs F, Ruggeri ZM (September 1998). "Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow". Cell. 94 (5): 657–66. PMID 9741630.
  18. ↑ Clemetson KJ, Clemetson JM (September 1994). "Molecular abnormalities in Glanzmann's thrombasthenia, Bernard-Soulier syndrome, and platelet-type von Willebrand's disease". Curr. Opin. Hematol. 1 (5): 388–93. PMID 9371310.
  19. ↑ Ando Y, Fusegawa H, Kawada T, Tanaka Y, Watanabe K, Kobayashi N (December 1989). "[Membrane glycoproteins of human platelets: structures, functions, and abnormalities in Glanzmann's thrombasthenia and Bernard-Soulier syndrome]". Rinsho Byori (in Japanese). 37 (12): 1344–52. PMID 2614964.
  20. ↑ Hayashi T, Suzuki K (2000). "Molecular pathogenesis of Bernard-Soulier syndrome". Semin. Thromb. Hemost. 26 (1): 53–9. PMID 10805283.
  21. ↑ Yan, Rong; Mo, Xi; Paredes, Angel M.; Dai, Kesheng; Lanza, Francois; Cruz, Miguel A.; Li, Renhao (2011). "Reconstitution of the Platelet Glycoprotein Ib-IX Complex in Phospholipid Bilayer Nanodiscs". Biochemistry. 50 (49): 10598–10606. doi:10.1021/bi201351d. ISSN 0006-2960.
  22. ↑ Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN (January 2002). "Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin". J. Biol. Chem. 277 (3): 1662–8. doi:10.1074/jbc.M108319200. PMID 11696542.
  23. ↑ Clemetson KJ (March 2003). "Platelet receptors and their role in diseases". Clin. Chem. Lab. Med. 41 (3): 253–60. doi:10.1515/CCLM.2003.039. PMID 12705329.
  24. ↑ Feghhi S, Munday AD, Tooley WW, Rajsekar S, Fura AM, Kulman JD, López JA, Sniadecki NJ (August 2016). "Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion". Biophys. J. 111 (3): 601–608. doi:10.1016/j.bpj.2016.06.023. PMC 4982925. PMID 27508443.
  25. ↑ Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, López JA (September 1999). "The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin". J. Exp. Med. 190 (6): 803–14. PMC 2195629. PMID 10499919.
  26. ↑ Cranmer SL, Ulsemer P, Cooke BM, Salem HH, de la Salle C, Lanza F, Jackson SP (March 1999). "Glycoprotein (GP) Ib-IX-transfected cells roll on a von Willebrand factor matrix under flow. Importance of the GPib/actin-binding protein (ABP-280) interaction in maintaining adhesion under high shear". J. Biol. Chem. 274 (10): 6097–106. PMID 10037692.
  27. ↑ Wu YP, Vink T, Schiphorst M, van Zanten GH, IJsseldijk MJ, de Groot PG, Sixma JJ (June 2000). "Platelet thrombus formation on collagen at high shear rates is mediated by von Willebrand factor-glycoprotein Ib interaction and inhibited by von Willebrand factor-glycoprotein IIb/IIIa interaction". Arterioscler. Thromb. Vasc. Biol. 20 (6): 1661–7. PMID 10845886.
  28. ↑ Fredrickson BJ, Dong JF, McIntire LV, López JA (November 1998). "Shear-dependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein Ib-IX-V complex". Blood. 92 (10): 3684–93. PMID 9808562.
  29. ↑ Brill A, Fuchs TA, Chauhan AK, Yang JJ, De Meyer SF, Köllnberger M, Wakefield TW, Lämmle B, Massberg S, Wagner DD (January 2011). "von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models". Blood. 117 (4): 1400–7. doi:10.1182/blood-2010-05-287623. PMC 3056477. PMID 20959603.
  30. ↑ Brill, A.; Fuchs, T. A.; Chauhan, A. K.; Yang, J. J.; De Meyer, S. F.; Kollnberger, M.; Wakefield, T. W.; Lammle, B.; Massberg, S.; Wagner, D. D. (2010). "von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models". Blood. 117 (4): 1400–1407. doi:10.1182/blood-2010-05-287623. ISSN 0006-4971.
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  32. ↑ . doi:10.1161/CIRCRESAHA.117.311185/-/DC1. Missing or empty |title= (help)
  33. ↑ Biedermann, J. S.; Cannegieter, S. C.; Roest, M.; van der Meer, F. J. M.; Reitsma, P. H.; Kruip, M. J. H. A.; Lijfering, W. M. (2016). "Platelet reactivity in patients with venous thrombosis who use rosuvastatin: a randomized controlled clinical trial". Journal of Thrombosis and Haemostasis. 14 (7): 1404–1409. doi:10.1111/jth.13343. ISSN 1538-7933.
  34. ↑ Fuchs, T. A.; Brill, A.; Wagner, D. D. (2012). "Neutrophil Extracellular Trap (NET) Impact on Deep Vein Thrombosis". Arteriosclerosis, Thrombosis, and Vascular Biology. 32 (8): 1777–1783. doi:10.1161/ATVBAHA.111.242859. ISSN 1079-5642.
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  37. ↑ Romo, Gabriel M.; Dong, Jing-Fei; Schade, Alicia J.; Gardiner, Elizabeth E.; Kansas, Geoffrey S.; Li, Chester Q.; McIntire, Larry V.; Berndt, Michael C.; López, José A. (1999). "The Glycoprotein Ib-IX-V Complex Is a Platelet Counterreceptor for P-Selectin". The Journal of Experimental Medicine. 190 (6): 803–814. doi:10.1084/jem.190.6.803. ISSN 0022-1007.
  38. ↑ Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, López JA (September 1999). "The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin". J. Exp. Med. 190 (6): 803–14. PMC 2195629. PMID 10499919.
  39. ↑ Du, Xiaoping (2007). "Signaling and regulation of the platelet glycoprotein Ib–IX–V complex". Current Opinion in Hematology. 14 (3): 262–269. doi:10.1097/MOH.0b013e3280dce51a. ISSN 1065-6251.
  40. ↑ Li R, Emsley J (April 2013). "The organizing principle of the platelet glycoprotein Ib-IX-V complex". J. Thromb. Haemost. 11 (4): 605–14. doi:10.1111/jth.12144. PMC 3696474. PMID 23336709.
  41. ↑ Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, López JA (September 1999). "The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin". J. Exp. Med. 190 (6): 803–14. PMC 2195629. PMID 10499919.
  42. ↑ Arya M, Kolomeisky AB, Romo GM, Cruz MA, López JA, Anvari B (June 2005). "Dynamic force spectroscopy of glycoprotein Ib-IX and von Willebrand factor". Biophys. J. 88 (6): 4391–401. doi:10.1529/biophysj.104.046318. PMC 1305666. PMID 15764659.
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  44. ↑ Feghhi S, Munday AD, Tooley WW, Rajsekar S, Fura AM, Kulman JD, López JA, Sniadecki NJ (August 2016). "Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion". Biophys. J. 111 (3): 601–608. doi:10.1016/j.bpj.2016.06.023. PMC 4982925. PMID 27508443.
  45. ↑ Arthur JF, Shen Y, Gardiner EE, Coleman L, Murphy D, Kenny D, Andrews RK, Berndt MC (January 2011). "TNF receptor-associated factor 4 (TRAF4) is a novel binding partner of glycoprotein Ib and glycoprotein VI in human platelets". J. Thromb. Haemost. 9 (1): 163–72. doi:10.1111/j.1538-7836.2010.04091.x. PMID 20946164.
  46. ↑ Carrim N, Walsh TG, Consonni A, Torti M, Berndt MC, Metharom P (2014). "Role of focal adhesion tyrosine kinases in GPVI-dependent platelet activation and reactive oxygen species formation". PLoS ONE. 9 (11): e113679. doi:10.1371/journal.pone.0113679. PMC 4240642. PMID 25415317.
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  58. ↑ Balduini CL, Cattaneo M, Fabris F, Gresele P, Iolascon A, Pulcinelli FM, Savoia A (May 2003). "Inherited thrombocytopenias: a proposed diagnostic algorithm from the Italian Gruppo di Studio delle Piastrine". Haematologica. 88 (5): 582–92. PMID 12745278.
  59. ↑ Noris P, Pecci A, Di Bari F, Di Stazio MT, Di Pumpo M, Ceresa IF, Arezzi N, Ambaglio C, Savoia A, Balduini CL (October 2004). "Application of a diagnostic algorithm for inherited thrombocytopenias to 46 consecutive patients". Haematologica. 89 (10): 1219–25. PMID 15477207.
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  61. ↑ Doubek M, Smejkal P, Dostálová V, Trnavská I, Buliková A, Brychtová Y, Mayer J (2003). "[Hereditary thrombocytopenia. Differential diagnosis of a case]". Cas. Lek. Cesk. (in Czech). 142 (11): 683–6. PMID 14689830.
  62. ↑ Balduini CL, Savoia A (December 2012). "Genetics of familial forms of thrombocytopenia". Hum. Genet. 131 (12): 1821–32. doi:10.1007/s00439-012-1215-x. PMID 22886561.
  63. ↑ Bellucci S (February 1997). "Megakaryocytes and inherited thrombocytopenias". Baillieres Clin. Haematol. 10 (1): 149–62. PMID 9154320.
  64. ↑ Balduini CL, Savoia A, Seri M (June 2013). "Inherited thrombocytopenias frequently diagnosed in adults". J. Thromb. Haemost. 11 (6): 1006–19. doi:10.1111/jth.12196. PMID 23510089.
  65. ↑ Lanza, François (2006). Orphanet Journal of Rare Diseases. 1 (1): 46. doi:10.1186/1750-1172-1-46. ISSN 1750-1172. Missing or empty |title= (help)
  66. ↑ Lanza, François (2006). Orphanet Journal of Rare Diseases. 1 (1): 46. doi:10.1186/1750-1172-1-46. ISSN 1750-1172. Missing or empty |title= (help)
  67. ↑ Lanza F (November 2006). "Bernard-Soulier syndrome (hemorrhagiparous thrombocytic dystrophy)". Orphanet J Rare Dis. 1: 46. doi:10.1186/1750-1172-1-46. PMC 1660532. PMID 17109744.
  68. ↑ Sumitha E, Jayandharan GR, David S, Jacob RR, Sankari Devi G, Bargavi B, Shenbagapriya S, Nair SC, Abraham A, George B, Viswabandya A, Mathews V, Chandy M, Srivastava A (August 2011). "Molecular basis of Bernard-Soulier syndrome in 27 patients from India". J. Thromb. Haemost. 9 (8): 1590–8. doi:10.1111/j.1538-7836.2011.04417.x. PMID 21699652.
  69. ↑ Cattaneo M, Lecchi A, Agati B, Lombardi R, Zighetti ML (November 1999). "Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion". Thromb. Res. 96 (3): 213–7. PMID 10588464.
  70. ↑ Mammen EF, Comp PC, Gosselin R, Greenberg C, Hoots WK, Kessler CM, Larkin EC, Liles D, Nugent DJ (1998). "PFA-100 system: a new method for assessment of platelet dysfunction". Semin. Thromb. Hemost. 24 (2): 195–202. doi:10.1055/s-2007-995840. PMID 9579642.
  71. ↑ Favaloro EJ (March 2001). "Utility of the PFA-100 for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations". Haemophilia. 7 (2): 170–9. PMID 11260277.
  72. ↑ Favaloro EJ (September 2002). "Clinical application of the PFA-100". Curr. Opin. Hematol. 9 (5): 407–15. PMID 12172459.
  73. ↑ Favaloro EJ (November 2008). "Clinical utility of the PFA-100". Semin. Thromb. Hemost. 34 (8): 709–33. doi:10.1055/s-0029-1145254. PMID 19214910.
  74. ↑ Marshall PW, Williams AJ, Dixon RM, Growcott JW, Warburton S, Armstrong J, Moores J (August 1997). "A comparison of the effects of aspirin on bleeding time measured using the Simplate method and closure time measured using the PFA-100, in healthy volunteers". Br J Clin Pharmacol. 44 (2): 151–5. PMC 2042813. PMID 9278200.
  75. ↑ Boeckelmann D, Hengartner H, Greinacher A, Nowak-Göttl U, Sachs UJ, Peter K, Sandrock-Lang K, Zieger B (September 2017). "Patients with Bernard-Soulier syndrome and different severity of the bleeding phenotype". Blood Cells Mol. Dis. 67: 69–74. doi:10.1016/j.bcmd.2017.01.010. PMID 28131619.
  76. ↑ 76.0 76.1 Greinacher A, Zellner A, Brangenberg R, Kiefel V, Mueller-Eckhardt C (June 1993). "[Bernard-Soulier syndrome. An important differential diagnosis in chronic thrombocytopenia with bleeding complications]". Monatsschr Kinderheilkd (in German). 141 (6): 483–6. PMID 8336744.
  77. ↑ Jenkins, C S; Phillips, D R; Clemetson, K J; Meyer, D; Larrieu, M J; Lüscher, E F (1976). "Platelet membrane glycoproteins implicated in ristocetin-induced aggregation. Studies of the proteins on platelets from patients with Bernard-Soulier syndrome and von Willebrand's disease". Journal of Clinical Investigation. 57 (1): 112–124. doi:10.1172/JCI108251. ISSN 0021-9738.
  78. ↑ Kelsey, H; Christopoulos, C; Gray, A A; Machin, S J (1994). "Acquired pseudo-pseudo Bernard-Soulier syndrome complicating Gaucher's disease". Journal of Clinical Pathology. 47 (2): 162–165. doi:10.1136/jcp.47.2.162. ISSN 0021-9746.
  79. ↑ Li C, Martin SE, Roth GJ (November 1995). "The genetic defect in two well-studied cases of Bernard-Soulier syndrome: a point mutation in the fifth leucine-rich repeat of platelet glycoprotein Ib alpha". Blood. 86 (10): 3805–14. PMID 7579348.
  80. ↑ de la Salle C, Baas MJ, Lanza F, Schwartz A, Hanau D, Chevalier J, Gachet C, Briquel ME, Cazenave JP (February 1995). "A three-base deletion removing a leucine residue in a leucine-rich repeat of platelet glycoprotein Ib alpha associated with a variant of Bernard-Soulier syndrome (Nancy I)". Br. J. Haematol. 89 (2): 386–96. PMID 7873390.
  81. ↑ Kirchmaier CM, Pillitteri D (2010). "Diagnosis and Management of Inherited Platelet Disorders". Transfus Med Hemother. 37 (5): 237–246. doi:10.1159/000320257. PMC 2980508. PMID 21113246.
  82. ↑ Diz-Kucukkaya, R. (2013). "Inherited platelet disorders including Glanzmann thrombasthenia and Bernard-Soulier syndrome". Hematology. 2013 (1): 268–275. doi:10.1182/asheducation-2013.1.268. ISSN 1520-4391.
  83. ↑ Berndt, M. C.; Andrews, R. K. (2011). "Bernard-Soulier syndrome". Haematologica. 96 (3): 355–359. doi:10.3324/haematol.2010.039883. ISSN 0390-6078.
  84. ↑ Lanza, François (2006). Orphanet Journal of Rare Diseases. 1 (1): 46. doi:10.1186/1750-1172-1-46. ISSN 1750-1172. Missing or empty |title= (help)
  85. ↑ Bragadottir, Gudrun; Birgisdottir, Elisabet R.; Gudmundsdottir, Brynja R.; Hilmarsdottir, Bylgja; Vidarsson, Brynjar; Magnusson, Magnus K.; Larsen, Ole Halfdan; Sorensen, Benny; Ingerslev, Jorgen; Onundarson, Pall T. (2015). "Clinical phenotype in heterozygote and biallelic Bernard-Soulier syndrome-A case control study". American Journal of Hematology. 90 (2): 149–155. doi:10.1002/ajh.23891. ISSN 0361-8609.
  86. ↑ Berndt MC, Fournier DJ, Castaldi PA (July 1989). "Bernard-Soulier syndrome". Baillieres Clin. Haematol. 2 (3): 585–607. PMID 2550101.
  87. ↑ Kirchmaier CM, Pillitteri D (2010). "Diagnosis and Management of Inherited Platelet Disorders". Transfus Med Hemother. 37 (5): 237–246. doi:10.1159/000320257. PMC 2980508. PMID 21113246.
  88. ↑ Berndt, M. C.; Andrews, R. K. (2011). "Bernard-Soulier syndrome". Haematologica. 96 (3): 355–359. doi:10.3324/haematol.2010.039883. ISSN 0390-6078.
  89. ↑ Bragadottir, Gudrun; Birgisdottir, Elisabet R.; Gudmundsdottir, Brynja R.; Hilmarsdottir, Bylgja; Vidarsson, Brynjar; Magnusson, Magnus K.; Larsen, Ole Halfdan; Sorensen, Benny; Ingerslev, Jorgen; Onundarson, Pall T. (2015). "Clinical phenotype in heterozygote and biallelic Bernard-Soulier syndrome-A case control study". American Journal of Hematology. 90 (2): 149–155. doi:10.1002/ajh.23891. ISSN 0361-8609.
  90. ↑ Nichols WL, Kaese SE, Gastineau DA, Otteman LA, Bowie EJ (May 1989). "Bernard-Soulier syndrome: whole blood diagnostic assays of platelets". Mayo Clin. Proc. 64 (5): 522–30. PMID 2725065.
  91. ↑ Bunescu A, Lindahl T, Solum NO, Schulman S, Larsson A, Lundahl J, Egberg N (December 1994). "Partial expression of GP Ib measured by flow cytometry in two patients with Bernard-Soulier syndrome". Thromb. Res. 76 (5): 441–50. PMID 7900092.
  92. ↑ De Marco L, Fabris F, Casonato A, Fabris P, Dal Ben MG, Barbato A, Girolami A (1986). "Bernard-Soulier syndrome: diagnosis by an ELISA method using monoclonal antibodies in 2 new unrelated patients". Acta Haematol. 75 (4): 203–8. doi:10.1159/000206125. PMID 3096050.
  93. ↑ Poulsen LO, Johansen P, Jensen MK, Freund L (December 1989). "Differentiation between Bernard-Soulier syndrome and immune thrombocytopenia by immunostaining of peripheral blood". J. Clin. Pathol. 42 (12): 1296–7. PMC 502064. PMID 2693494.
  94. ↑ Berndt MC, Fournier DJ, Castaldi PA (July 1989). "Bernard-Soulier syndrome". Baillieres Clin. Haematol. 2 (3): 585–607. PMID 2550101.
  95. ↑ Kirchmaier CM, Pillitteri D (September 2010). "[Congenital thrombocytopathies]". Internist (Berl) (in German). 51 (9): 1109–14, 1116–7. doi:10.1007/s00108-010-2596-3. PMID 20725709.
  96. ↑ Nurden AT, Fiore M, Pillois X, Nurden P (March 2009). "Genetic testing in the diagnostic evaluation of inherited platelet disorders". Semin. Thromb. Hemost. 35 (2): 204–12. doi:10.1055/s-0029-1220328. PMID 19408193.
  97. ↑ Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN (January 2002). "Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin". J. Biol. Chem. 277 (3): 1662–8. doi:10.1074/jbc.M108319200. PMID 11696542.
  98. ↑ Nurden P, Nurden AT (February 2008). "Congenital disorders associated with platelet dysfunctions". Thromb. Haemost. 99 (2): 253–63. doi:10.1160/TH07-09-0568. PMID 18278172.
  99. ↑ Fisher, Marlene; Chapman, Jeremy R.; Ting, Alan; Morris, Peter J. (1985). "Alloimmunisation to HLA Antigens following Transfusion with Leucocyte-Poor and Purified Platelet Suspensions". Vox Sanguinis. 49 (5): 331–335. doi:10.1159/000466401. ISSN 0042-9007. line feed character in |title= at position 55 (help)
  100. ↑ Waldenström E, Holmberg L, Axelsson U, Winqvist I, Nilsson IM (March 1991). "Bernard-Soulier syndrome in two Swedish families: effect of DDAVP on bleeding time". Eur. J. Haematol. 46 (3): 182–7. PMID 1901273.
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