Thrombocytopenia laboratory findings: Difference between revisions

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__NOTOC__
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{{Thrombocytopenia}}
{{Thrombocytopenia}}
{{CMG}}, {{AE}}Farbod Zahedi Tajrishi, M.D.
{{CMG}}, {{AE}}[https://www.wikidoc.org/index.php/User:Farbod_Zahedi_Tajrishi <nowiki>Farbod Zahedi Tajrishi, M.D. [2]</nowiki>]
==Overview==
==Overview==
On a [[Complete blood count|CBC]], platelet count < 150,000 per µm<sup>3</sup> is considered as [[thrombocytopenia]]. [[Pseudothrombocytopenia]], meaning a falsely reported [[Thrombocytopenia|low platelet count]], should be ruled out before confirming thrombocytopenia and performing further diagnostic tests. A [[Blood film|peripheral blood smear]] and/or repeating the [[Complete blood count|CBC]] using a non-[[EDTA]] [[anticoagulant]] help to do so. Other laboratory findings on CBC and PBS are usually of great benefit and could narrow down the wide range of differential diagnoses for thrombocytopenia. Further laboratory testing are only recommended when these tests are already performed and suggestive of a condition. As [[thrombocytopenia]] is closely associated with [[Human Immunodeficiency Virus (HIV)|HIV]] and [[Hepatitis C|HCV]] infections, adults with new-onset thrombocytopenia should be evaluated for these two conditions     


==Laboratory Findings==
==Laboratory Findings==
Line 17: Line 18:
* '''Exposure of blood samples to the [[EDTA]] anticoagulant in the collection tube'''
* '''Exposure of blood samples to the [[EDTA]] anticoagulant in the collection tube'''
Note that a small proportion of the general population (~0.1%) have [[EDTA]]-dependent anti-platelet [[Autoantibody|autoantibodies]] that can also result in platelet clumping. EDTA induces the dissociation of [[Glycoprotein IIb/IIIa|GPIIb/IIIa]], which in turn exposes a concealed [[epitope]] on platelet membrane [[Glycoprotein IIb/IIIa|GPIIb/IIIa]]. This [[epitope]] causes the production of the aforementioned anti-platelet [[Autoantibody|autoantibodies]].<ref name="pmid6422738">{{cite journal| author=Savage RA| title=Pseudoleukocytosis due to EDTA-induced platelet clumping. | journal=Am J Clin Pathol | year= 1984 | volume= 81 | issue= 3 | pages= 317-22 | pmid=6422738 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6422738  }}</ref><ref name="pmid6422167">{{cite journal| author=Payne BA, Pierre RV| title=Pseudothrombocytopenia: a laboratory artifact with potentially serious consequences. | journal=Mayo Clin Proc | year= 1984 | volume= 59 | issue= 2 | pages= 123-5 | pmid=6422167 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6422167  }}</ref><ref name="pmid6797491">{{cite journal| author=Pegels JG, Bruynes EC, Engelfriet CP, von dem Borne AE| title=Pseudothrombocytopenia: an immunologic study on platelet antibodies dependent on ethylene diamine tetra-acetate. | journal=Blood | year= 1982 | volume= 59 | issue= 1 | pages= 157-61 | pmid=6797491 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6797491  }}</ref><ref name="pmid8089218">{{cite journal| author=Casonato A, Bertomoro A, Pontara E, Dannhauser D, Lazzaro AR, Girolami A| title=EDTA dependent pseudothrombocytopenia caused by antibodies against the cytoadhesive receptor of platelet gpIIB-IIIA. | journal=J Clin Pathol | year= 1994 | volume= 47 | issue= 7 | pages= 625-30 | pmid=8089218 | doi= | pmc=502090 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8089218  }}</ref><ref name="pmid9397495">{{cite journal| author=Bartels PC, Schoorl M, Lombarts AJ| title=Screening for EDTA-dependent deviations in platelet counts and abnormalities in platelet distribution histograms in pseudothrombocytopenia. | journal=Scand J Clin Lab Invest | year= 1997 | volume= 57 | issue= 7 | pages= 629-36 | pmid=9397495 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9397495  }}</ref><ref name="pmid9704616">{{cite journal| author=Fiorin F, Steffan A, Pradella P, Bizzaro N, Potenza R, De Angelis V| title=IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to platelet membrane glycoprotein IIb. | journal=Am J Clin Pathol | year= 1998 | volume= 110 | issue= 2 | pages= 178-83 | pmid=9704616 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9704616  }}</ref>
Note that a small proportion of the general population (~0.1%) have [[EDTA]]-dependent anti-platelet [[Autoantibody|autoantibodies]] that can also result in platelet clumping. EDTA induces the dissociation of [[Glycoprotein IIb/IIIa|GPIIb/IIIa]], which in turn exposes a concealed [[epitope]] on platelet membrane [[Glycoprotein IIb/IIIa|GPIIb/IIIa]]. This [[epitope]] causes the production of the aforementioned anti-platelet [[Autoantibody|autoantibodies]].<ref name="pmid6422738">{{cite journal| author=Savage RA| title=Pseudoleukocytosis due to EDTA-induced platelet clumping. | journal=Am J Clin Pathol | year= 1984 | volume= 81 | issue= 3 | pages= 317-22 | pmid=6422738 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6422738  }}</ref><ref name="pmid6422167">{{cite journal| author=Payne BA, Pierre RV| title=Pseudothrombocytopenia: a laboratory artifact with potentially serious consequences. | journal=Mayo Clin Proc | year= 1984 | volume= 59 | issue= 2 | pages= 123-5 | pmid=6422167 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6422167  }}</ref><ref name="pmid6797491">{{cite journal| author=Pegels JG, Bruynes EC, Engelfriet CP, von dem Borne AE| title=Pseudothrombocytopenia: an immunologic study on platelet antibodies dependent on ethylene diamine tetra-acetate. | journal=Blood | year= 1982 | volume= 59 | issue= 1 | pages= 157-61 | pmid=6797491 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6797491  }}</ref><ref name="pmid8089218">{{cite journal| author=Casonato A, Bertomoro A, Pontara E, Dannhauser D, Lazzaro AR, Girolami A| title=EDTA dependent pseudothrombocytopenia caused by antibodies against the cytoadhesive receptor of platelet gpIIB-IIIA. | journal=J Clin Pathol | year= 1994 | volume= 47 | issue= 7 | pages= 625-30 | pmid=8089218 | doi= | pmc=502090 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8089218  }}</ref><ref name="pmid9397495">{{cite journal| author=Bartels PC, Schoorl M, Lombarts AJ| title=Screening for EDTA-dependent deviations in platelet counts and abnormalities in platelet distribution histograms in pseudothrombocytopenia. | journal=Scand J Clin Lab Invest | year= 1997 | volume= 57 | issue= 7 | pages= 629-36 | pmid=9397495 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9397495  }}</ref><ref name="pmid9704616">{{cite journal| author=Fiorin F, Steffan A, Pradella P, Bizzaro N, Potenza R, De Angelis V| title=IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to platelet membrane glycoprotein IIb. | journal=Am J Clin Pathol | year= 1998 | volume= 110 | issue= 2 | pages= 178-83 | pmid=9704616 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9704616  }}</ref>
* '''Platelet satellitism'''; i.e. rosette formation of platelets around [[White blood cells|WBCs]] (whether normal WBCs or [[Lymphoma|lymphoma cells]]).<ref name="pmid11293905">{{cite journal| author=Cesca C, Ben-Ezra J, Riley RS| title=Platelet satellitism as presenting finding in mantle cell lymphoma. A case report. | journal=Am J Clin Pathol | year= 2001 | volume= 115 | issue= 4 | pages= 567-70 | pmid=11293905 | doi=10.1309/75CQ-V7UX-4QX8-WXE7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11293905  }}</ref> [48-52].  
* '''Platelet satellitism'''; i.e. rosette formation of platelets around [[White blood cells|WBCs]] (whether normal WBCs or [[Lymphoma|lymphoma cells]]).<ref name="pmid11293905">{{cite journal| author=Cesca C, Ben-Ezra J, Riley RS| title=Platelet satellitism as presenting finding in mantle cell lymphoma. A case report. | journal=Am J Clin Pathol | year= 2001 | volume= 115 | issue= 4 | pages= 567-70 | pmid=11293905 | doi=10.1309/75CQ-V7UX-4QX8-WXE7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11293905  }}</ref><ref name="pmid21889383">{{cite journal| author=Montague N, Blackwelder P, Alsayegh H, Ochoa R, Vial X, Byrne GE| title=Platelet satellitism and dual surface immunoglobulin light-chain expression in circulating splenic marginal zone lymphoma cells. | journal=Ann Diagn Pathol | year= 2013 | volume= 17 | issue= 1 | pages= 117-22 | pmid=21889383 | doi=10.1016/j.anndiagpath.2011.06.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21889383  }}</ref><ref name="pmid22701880">{{cite journal| author=Bobba RK, Doll DC| title=Platelet satellitism as a cause of spurious thrombocytopenia. | journal=Blood | year= 2012 | volume= 119 | issue= 18 | pages= 4100 | pmid=22701880 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22701880  }}</ref><ref name="pmid22674424">{{cite journal| author=Podda GM, Pugliano M, Femia EA, Mezzasoma AM, Gresele P, Carpani G et al.| title=The platelet count in EDTA-anticoagulated blood from patients with thrombocytopenia may be underestimated when measured in routine laboratories. | journal=Am J Hematol | year= 2012 | volume= 87 | issue= 7 | pages= 727-8 | pmid=22674424 | doi=10.1002/ajh.23216 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22674424  }}</ref>


- A [[Blood film|peripheral blood smear]] and/or repeating the [[Complete blood count|CBC]] using a non-[[EDTA]] [[anticoagulant]] help distinguish pseudothrombocytopenia. After ruling out pseudothrombocytopenia, one of these findings may be present in the [[Complete blood count|CBC]]:  
- A [[Blood film|peripheral blood smear]] and/or repeating the [[Complete blood count|CBC]] using a non-[[EDTA]] [[anticoagulant]] help distinguish pseudothrombocytopenia. After ruling out pseudothrombocytopenia, one of these findings may be present in the [[Complete blood count|CBC]]:  


{| class="wikitable"
{| class="wikitable"
!laboratory finding
!Laboratory finding
!examples of associated conditions
!Examples of associated conditions
!
!Further explanations
|-
|-
|isolated thrombocytopenia
|isolated thrombocytopenia
Line 30: Line 31:
* normal variation
* normal variation
* [[Idiopathic thrombocytopenic purpura|ITP]]
* [[Idiopathic thrombocytopenic purpura|ITP]]
|
|<nowiki>-</nowiki>
|-
|-
|thrombocytopenia + anemia
|thrombocytopenia + anemia
Line 56: Line 57:
* chronic inflammation
* chronic inflammation
* malignancy
* malignancy
|
|<nowiki>-</nowiki>
|-
|-
|thrombocytopenia + anemia + leukopenia (pancytopenia)
|thrombocytopenia + anemia + leukopenia (pancytopenia)
|
|<nowiki>-</nowiki>
|
|<nowiki>-</nowiki>
|-
|-
|[[pseudothrombocytopenia]]
|[[pseudothrombocytopenia]]
|
|<nowiki>-</nowiki>
|
|<nowiki>-</nowiki>
|}
|}


Line 71: Line 72:
* outpatients with isolated mild [[thrombocytopenia]] ([[platelet]] count = 100,000 to 149,000 per µL), since [[platelet]] counts will improve in some of these patients without any interventions. <ref name="pmid16401142">{{cite journal| author=Stasi R, Amadori S, Osborn J, Newland AC, Provan D| title=Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia. | journal=PLoS Med | year= 2006 | volume= 3 | issue= 3 | pages= e24 | pmid=16401142 | doi=10.1371/journal.pmed.0030024 | pmc=1326262 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16401142  }}</ref>
* outpatients with isolated mild [[thrombocytopenia]] ([[platelet]] count = 100,000 to 149,000 per µL), since [[platelet]] counts will improve in some of these patients without any interventions. <ref name="pmid16401142">{{cite journal| author=Stasi R, Amadori S, Osborn J, Newland AC, Provan D| title=Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia. | journal=PLoS Med | year= 2006 | volume= 3 | issue= 3 | pages= e24 | pmid=16401142 | doi=10.1371/journal.pmed.0030024 | pmc=1326262 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16401142  }}</ref>
* [[asymptomatic]] patients (eg, no signs of [[bleeding]] and no [[Comorbidity|comorbidities]]) with moderate [[thrombocytopenia]] ([[platelet]] count = 50,000 to 100,000 per µL)
* [[asymptomatic]] patients (eg, no signs of [[bleeding]] and no [[Comorbidity|comorbidities]]) with moderate [[thrombocytopenia]] ([[platelet]] count = 50,000 to 100,000 per µL)
* [[symptomatic]] patients (eg, those with signs of [[bleeding]])
* severe [[thrombocytopenia]] ([[platelet]] count<50,000 per µL)
* Patients with combined [[thrombocytopenia]] and [[leukocytosis]] as well as those with [[pancytopenia]]


=== '''Peripheral blood smear''' ===
=== '''Peripheral blood smear''' ===
 Review of the peripheral blood smear is used to exclude pseudothrombocytopenia and to evaluate morphologic abnormalities of blood cells that could be useful in determining the cause of thrombocytopenia.
[[Blood film|Peripheral blood smear]] is a useful test to exclude [[pseudothrombocytopenia]] and even to determine the underlying cause of [[thrombocytopenia]]. Abnormal cell morphologies on a [[Blood film|PBS]] could be diagnostic; for instance:


As an example, giant platelets (picture 5) may suggest a congenital platelet disorder (eg, MYH-9-related disorders, Bernard Soulier syndrome [BSS]); these may be counted as red blood cells by some automated counters. (See "Congenital and acquired disorders of platelet function", section on 'Giant platelet disorders'.) 
{| class="wikitable"
 
!Finding on PBS
Abnormal RBC and WBC morphologies may suggest a specific condition.
!suggested diagnosis
 
|-
Examples include the following:
|'''Giant [[Platelet|platelets]]'''
 
|congenital platelet disorders such as [[Bernard-Soulier syndrome]]
●Schistocytes (picture 7) suggest a microangiopathic process (eg, DIC, TTP, HUS, DITMA).
|-
 
|'''[[Red blood cell|Schistocytes]]'''
●Nucleated RBCs (picture 8), and Howell-Jolly bodies (picture 9), may be seen post-splenectomy or occasionally in patients with poor splenic function.
|[[Microangiopathic hemolytic anemia|microangiopathic]] processes:
 
* [[Disseminated intravascular coagulation|DIC]]
●Spherocytes (picture 10 and picture 11) suggest immune-mediated hemolytic anemia or hereditary spherocytosis.
* [[Thrombotic thrombocytopenic purpura|TTP]]
 
* [[Hemolytic-uremic syndrome|HUS]]
●Leukoerythroblastic findings (picture 12), teardrop cells (picture 13), nucleated RBCs, or immature granulocytes suggest an infiltrative process in the bone marrow.
* Drug-induced
 
|-
●Leukocytosis with a predominance of bands (left shift) and/or toxic granulations suggest infection (picture 14).
|'''Nucleated RBCs and [[Howell-Jolly body|Howell-Jolly bodies]]'''
 
|
●Immature WBCs (eg, myeloblasts) (picture 15) or dysplastic WBCs (picture 16) suggest leukemia or myelodysplasia.
* after [[splenectomy]]
 
* splenic malfunction
●Multi-lobed/hypersegmented neutrophils (ie, >5 lobes) (picture 17) suggest a megaloblastic process (eg, B12/folate/copper deficiency).
|-
 
|'''[[Spherocytosis|Spherocytes]]'''
'''HIV and HCV testing''' — Thrombocytopenia has been identified as an important "indicator condition" for HIV infection [20]. Thus, adults with new thrombocytopenia should have HIV testing if not done recently. (See "Hematologic manifestations of HIV infection: Thrombocytopenia and coagulation abnormalities", section on 'Incidence and causes of thrombocytopenia' and "Screening and diagnostic testing for HIV infection".)
|
 
* immune-mediated [[hemolytic anemia]]
Thrombocytopenia may also be seen with hepatitis C virus (HCV) infection; testing is appropriate for adults with thrombocytopenia if not done recently. (See "Screening for chronic hepatitis C virus infection".)
* [[hereditary spherocytosis]]
 
|-
'''Other laboratory testing''' — Aside from the testing mentioned above (CBC, review of peripheral smear, HIV and HCV testing), no additional laboratory testing is absolutely required in a patient with isolated thrombocytopenia. However, additional testing may be warranted in patients with other findings.
|'''Leukoerythroblastic findings, [[Poikilocytosis|teardrop cells]], nucleated RBCs, or immature [[Granulocyte|granulocytes]]'''
 
|[[bone marrow infiltration]]
Examples of findings that may trigger other laboratory testing include the following:
|-
 
|'''[[Bandemia]] (left shift) and/or toxic granulations'''
●Symptoms or findings of systemic autoimmune disorders (eg, systemic lupus erythematosus [SLE], anti-phospholipid syndrome [APS]) may prompt testing for anti-nuclear antibodies or anti-phospholipid antibodies, respectively. We do not test for these in patients with isolated thrombocytopenia and no signs or symptoms suggestive of SLE or APS.
|[[infection]]
 
|-
●Findings of liver disease should prompt measurements of hepatic enzymes and possibly tests of liver synthetic function (eg, albumin, coagulation testing), depending on the severity of the liver disease. (See "Liver biochemical tests that detect injury to hepatocytes" and "Tests of the liver's biosynthetic capacity (eg, albumin, coagulation factors, prothrombin time)".)
|'''Immature/dysplastic [[White blood cells|WBC]]<nowiki/>s'''
|
* [[leukemia]]
* [[Myelodysplastic syndrome|MDS]]
|-
|'''Hypersegmented [[Neutrophil|neutrophils]]'''  
|megaloblastic process
* [[Vitamin B12 deficiency|B12 deficiency]]
* [[folate deficiency]]
* [[copper deficiency]]
|}


●Thrombosis should prompt consideration of DIC, heparin-induced thrombocytopenia (HIT), and APS. Depending on the site of thrombosis and other hematologic findings, paroxysmal nocturnal hemoglobinuria (PNH) may also be a consideration. Testing for these conditions is discussed separately. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia" and "Diagnosis of antiphospholipid syndrome" and "Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in adults" and "Treatment and prognosis of paroxysmal nocturnal hemoglobinuria".)
=== '''HIV and HCV testing''' ===
As [[thrombocytopenia]] is closely associated with [[Human Immunodeficiency Virus (HIV)|HIV]] and [[Hepatitis C|HCV]] infections, adults with new-onset thrombocytopenia should be evaluated for these two conditions.<ref name="pmid17958515">{{cite journal| author=Weksler BB| title=Review article: the pathophysiology of thrombocytopenia in hepatitis C virus infection and chronic liver disease. | journal=Aliment Pharmacol Ther | year= 2007 | volume= 26 Suppl 1 | issue=  | pages= 13-9 | pmid=17958515 | doi=10.1111/j.1365-2036.2007.03512.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17958515  }}</ref><ref name="pmid21325604">{{cite journal| author=Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA et al.| title=The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. | journal=Blood | year= 2011 | volume= 117 | issue= 16 | pages= 4190-207 | pmid=21325604 | doi=10.1182/blood-2010-08-302984 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21325604  }}</ref>


●Microangiopathic changes on the peripheral smear should prompt coagulation testing (eg, PT, aPTT, fibrinogen) and measurement of serum lactate dehydrogenase (LDH) and renal function to evaluate for DIC, TTP, or HUS; with subsequent evaluation based on the results.  
=== '''Further lab tests''' ===
Additional testing is necessary only when there are other findings as well as [[thrombocytopenia]] that suggest specific conditions. For example, findings suggestive of [[SLE]] or [[Autoimmune polyendocrine syndrome|APS]] may lead to appropriate antibody testing or signs of liver disease may prompt for measurements of liver [[enzymes]] and [[Liver function tests|liver function testing]].  




Latest revision as of 00:19, 20 December 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Farbod Zahedi Tajrishi, M.D. [2]

Overview

On a CBC, platelet count < 150,000 per µm3 is considered as thrombocytopenia. Pseudothrombocytopenia, meaning a falsely reported low platelet count, should be ruled out before confirming thrombocytopenia and performing further diagnostic tests. A peripheral blood smear and/or repeating the CBC using a non-EDTA anticoagulant help to do so. Other laboratory findings on CBC and PBS are usually of great benefit and could narrow down the wide range of differential diagnoses for thrombocytopenia. Further laboratory testing are only recommended when these tests are already performed and suggestive of a condition. As thrombocytopenia is closely associated with HIV and HCV infections, adults with new-onset thrombocytopenia should be evaluated for these two conditions

Laboratory Findings

Laboratory tests might include: full blood count (CBC), liver enzymes, renal function, vitamin B12 levels, folic acid levels, erythrocyte sedimentation rate, and peripheral blood smear.

CBC:

On a CBC, platelet count < 150,000 per µm3 is considered as thrombocytopenia. These limits, however, are determined by the 2.5th lower and upper percentile, and a deviation does not necessarily imply any form of disease. The number of platelets in a blood sample also decreases quickly with time and a low platelet count may be caused by a delay between sampling and analysis.

- Pseudothrombocytopenia:

Pseudothrombocytopenia simply means a false low platelet count. It usually occurs when platelet clumps are formed in blood samples and as a result the automated counter devices consider them as other entities (eg. leukocytes) by mistake. Several conditions can cause pseudothrombocyopenia. For instance:

  • Exposure of blood samples to the EDTA anticoagulant in the collection tube

Note that a small proportion of the general population (~0.1%) have EDTA-dependent anti-platelet autoantibodies that can also result in platelet clumping. EDTA induces the dissociation of GPIIb/IIIa, which in turn exposes a concealed epitope on platelet membrane GPIIb/IIIa. This epitope causes the production of the aforementioned anti-platelet autoantibodies.[1][2][3][4][5][6]

- A peripheral blood smear and/or repeating the CBC using a non-EDTA anticoagulant help distinguish pseudothrombocytopenia. After ruling out pseudothrombocytopenia, one of these findings may be present in the CBC:

Laboratory finding Examples of associated conditions Further explanations
isolated thrombocytopenia
  • normal variation
  • ITP
 -
thrombocytopenia + anemia Combined anemia and thrombocytopenia may occur if there has been longstanding bleeding (eg, gastrointestinal). Combined anemia and thrombocytopenia also raises the possibility of systemic disorders.

Note that some of the mentioned conditions can coexist.

thrombocytopenia + leukocytosis
  • infecton/sepsis
  • chronic inflammation
  • malignancy
 -
thrombocytopenia + anemia + leukopenia (pancytopenia) - -
pseudothrombocytopenia - -

Repeat CBC 

A repeat CBC is indicated in the following conditions:

Peripheral blood smear 

Peripheral blood smear is a useful test to exclude pseudothrombocytopenia and even to determine the underlying cause of thrombocytopenia. Abnormal cell morphologies on a PBS could be diagnostic; for instance:

Finding on PBS suggested diagnosis
Giant platelets congenital platelet disorders such as Bernard-Soulier syndrome
Schistocytes microangiopathic processes:
Nucleated RBCs and Howell-Jolly bodies
Spherocytes
Leukoerythroblastic findings, teardrop cells, nucleated RBCs, or immature granulocytes bone marrow infiltration
Bandemia (left shift) and/or toxic granulations infection
Immature/dysplastic WBCs
Hypersegmented neutrophils megaloblastic process

HIV and HCV testing 

As thrombocytopenia is closely associated with HIV and HCV infections, adults with new-onset thrombocytopenia should be evaluated for these two conditions.[12][13]

Further lab tests 

Additional testing is necessary only when there are other findings as well as thrombocytopenia that suggest specific conditions. For example, findings suggestive of SLE or APS may lead to appropriate antibody testing or signs of liver disease may prompt for measurements of liver enzymes and liver function testing.


References

  1. ↑ Savage RA (1984). "Pseudoleukocytosis due to EDTA-induced platelet clumping". Am J Clin Pathol. 81 (3): 317–22. PMID 6422738.
  2. ↑ Payne BA, Pierre RV (1984). "Pseudothrombocytopenia: a laboratory artifact with potentially serious consequences". Mayo Clin Proc. 59 (2): 123–5. PMID 6422167.
  3. ↑ Pegels JG, Bruynes EC, Engelfriet CP, von dem Borne AE (1982). "Pseudothrombocytopenia: an immunologic study on platelet antibodies dependent on ethylene diamine tetra-acetate". Blood. 59 (1): 157–61. PMID 6797491.
  4. ↑ Casonato A, Bertomoro A, Pontara E, Dannhauser D, Lazzaro AR, Girolami A (1994). "EDTA dependent pseudothrombocytopenia caused by antibodies against the cytoadhesive receptor of platelet gpIIB-IIIA". J Clin Pathol. 47 (7): 625–30. PMC 502090. PMID 8089218.
  5. ↑ Bartels PC, Schoorl M, Lombarts AJ (1997). "Screening for EDTA-dependent deviations in platelet counts and abnormalities in platelet distribution histograms in pseudothrombocytopenia". Scand J Clin Lab Invest. 57 (7): 629–36. PMID 9397495.
  6. ↑ Fiorin F, Steffan A, Pradella P, Bizzaro N, Potenza R, De Angelis V (1998). "IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to platelet membrane glycoprotein IIb". Am J Clin Pathol. 110 (2): 178–83. PMID 9704616.
  7. ↑ Cesca C, Ben-Ezra J, Riley RS (2001). "Platelet satellitism as presenting finding in mantle cell lymphoma. A case report". Am J Clin Pathol. 115 (4): 567–70. doi:10.1309/75CQ-V7UX-4QX8-WXE7. PMID 11293905.
  8. ↑ Montague N, Blackwelder P, Alsayegh H, Ochoa R, Vial X, Byrne GE (2013). "Platelet satellitism and dual surface immunoglobulin light-chain expression in circulating splenic marginal zone lymphoma cells". Ann Diagn Pathol. 17 (1): 117–22. doi:10.1016/j.anndiagpath.2011.06.001. PMID 21889383.
  9. ↑ Bobba RK, Doll DC (2012). "Platelet satellitism as a cause of spurious thrombocytopenia". Blood. 119 (18): 4100. PMID 22701880.
  10. ↑ Podda GM, Pugliano M, Femia EA, Mezzasoma AM, Gresele P, Carpani G; et al. (2012). "The platelet count in EDTA-anticoagulated blood from patients with thrombocytopenia may be underestimated when measured in routine laboratories". Am J Hematol. 87 (7): 727–8. doi:10.1002/ajh.23216. PMID 22674424.
  11. ↑ Stasi R, Amadori S, Osborn J, Newland AC, Provan D (2006). "Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia". PLoS Med. 3 (3): e24. doi:10.1371/journal.pmed.0030024. PMC 1326262. PMID 16401142.
  12. ↑ Weksler BB (2007). "Review article: the pathophysiology of thrombocytopenia in hepatitis C virus infection and chronic liver disease". Aliment Pharmacol Ther. 26 Suppl 1: 13–9. doi:10.1111/j.1365-2036.2007.03512.x. PMID 17958515.
  13. ↑ Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA; et al. (2011). "The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia". Blood. 117 (16): 4190–207. doi:10.1182/blood-2010-08-302984. PMID 21325604.

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