Stent thrombosis pathophysiology: Difference between revisions

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Stent thrombosis occurs due to variety of factors inducing thombogenesis. Being an invasive procedure, the trauma from coronary stenting can itself cause platelet activation and thombogenic cascade. There is either creation or an enhancement of a thrombogenic milieu by:
==Overview==
Stent thrombosis occurs due to variety of factors inducing [[thombogenesis]]. Being an invasive procedure, the trauma from coronary stenting can itself cause platelet activation and thombogenic cascade. There is either creation or an enhancement of a thrombogenic milieu by:


*creating an environment conducive for platelet activation and/or
*creating an environment conducive for [[platelet activation]] and/or
*creating an environment conducive for instent thrombosis
*creating an environment conducive for instent thrombosis


'''These processes are facilitated by'''
'''These processes are facilitated by'''


*Creating a thrombogenic milieu by
*Creating a thrombogenic milieu by
**Slow coronary  flow  
**Slow [[coronary  flow]],
**local dissection,  
**local [[dissection]],  
**distal untreated critical lesion  
**distal untreated critical lesion  
**poor out flow
**poor out flow
*Persistence of or ceation of substrate for platelet activation
*Persistence of or ceation of substrate for platelet activation
**Exposure of platelet activating factors due to trauma of stenting or ballooning – acutely
**Exposure of platelet activating factors due to trauma of [[stenting]] or [[ballooning]] – acutely
**Persistant incomplete endotheliazation (1,6)
**Persistant incomplete endotheliazation<ref name="pmid17684153">{{cite journal| author=Awata M, Kotani J, Uematsu M, Morozumi T, Watanabe T, Onishi T et al.| title=Serial angioscopic evidence of incomplete neointimal coverage after sirolimus-eluting stent implantation: comparison with bare-metal stents. | journal=Circulation | year= 2007 | volume= 116 | issue= 8 | pages= 910-6 | pmid=17684153 | doi=10.1161/CIRCULATIONAHA.105.609057 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17684153  }} </ref><ref name="pmid10458712">{{cite journal| author=Costa MA, Sabaté M, van der Giessen WJ, Kay IP, Cervinka P, Ligthart JM et al.| title=Late coronary occlusion after intracoronary brachytherapy. | journal=Circulation | year= 1999 | volume= 100 | issue= 8 | pages= 789-92 | pmid=10458712 | doi= | pmc= | url= }} </ref>
**Inadequate platelet inhibition – due to inadeqaue dosing or drug unrespopnsivelness.
**Inadequate [[platelet inhibition]] – due to inadeqaue dosing or drug unrespopnsivelness.
***acutely
***acutely
***subacutely  
***subacutely  
***long term
***long term
*Dosing issues
*Dosing issues
** with anti thrombotic medicagtions (acutely)  
**with anti thrombotic medicagtions (acutely)  
**antiplatelet medications (acutely, subacutly or long term)
**[[antiplatelet]] medications (acutely, subacutly or long term)
**inadequate time for the loading dose to act
**inadequate time for the loading dose to act
**suboptimal/subtherapeutic dosing during the procedure or therafter
**suboptimal/subtherapeutic dosing during the procedure or therafter


*Resistance to antiplatelet medications (2)
*Resistance to antiplatelet medications<ref name="pmid15936599">{{cite journal| author=Wenaweser P, Dörffler-Melly J, Imboden K, Windecker S, Togni M, Meier B et al.| title=Stent thrombosis is associated with an impaired response to antiplatelet therapy. | journal=J Am Coll Cardiol | year= 2005 | volume= 45 | issue= 11 | pages= 1748-52 | pmid=15936599 | doi=10.1016/j.jacc.2005.01.058 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15936599  }} </ref>
**ASA resistance
**[[ASA resistance]]
**Clopidogrel resistance
**[[Clopidogrel resistance]]
*Deranaged homeostasis due to disease creating a prothrombotic diathesis
*Deranaged homeostasis due to disease creating a prothrombotic diathesis
**sepsis
**[[sepsis]]
**blood transfusions
**blood transfusions
**surgery (In one study, following BMS, mortality rate among patients who had non cardiac surgery within two-weeks was 32%, almost exclusively due to ST. (3))
**surgery (In one study, following BMS, mortality rate among patients who had non cardiac surgery within two-weeks was 32%, almost exclusively due to ST.<ref name="pmid10758971">{{cite journal| author=Kałuza GL, Joseph J, Lee JR, Raizner ME, Raizner AE| title=Catastrophic outcomes of noncardiac surgery soon after coronary stenting. | journal=J Am Coll Cardiol | year= 2000 | volume= 35 | issue= 5 | pages= 1288-94 | pmid=10758971 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10758971  }} </ref>
**dehydration
**[[dehydration]]
**Other states which may create hypotensive states. (eg. of anectdotal reports of stent thormbosis with defecation syncope)
**Other states which may create [[hypotensive]] states. (eg. of anectdotal reports of stent thormbosis with defecation syncope)
 
==Mechanisms and pathophysiology of ST in BMS==
 
After BMS implantation, near-complete endothelization has been shown to occur by 3 to 4 months. (4)
 
This coincides with the reduction of risk of ST. (ref)
 
==Mechanisms and pathophysiology of ST in DES==
 
*Delayed endothelialization of the stented segement serving as a nidus for thrombosis (1,5,7)
*Antineoplastic therapy and delayed endothelialization had been an issue with late ST seen with brachytherapy. (6)
**Coronary brachytherpy use has all but disappeared since the introduction of DES.
*An angioscopic study of stented coronary segments showed that neointimal coverage was complete only in 2 out of 15 patients  with sirolimus stents and all of 22 BMS at three to six months. There were thrombi in most of the stented segments which were not seen on angiography which were more common with incomplete neointimal coverage. (1,7) In a study involving serial angioscopy after sirolimus-eluting stent (SES) implantation at 4, 11, and 21.2 ±2.2 months showed that neointimal coverage after sirolimus-eluting stent implantation was incomplete even at that late stage.  
*In a post mortem analysis, DES, compared to BMS had delayed endothelial healing. This group was more likely to have ST. (8)
*A post mortem analysis of a patient dying from an unrelated cause but who also had a DES implanted, revealed poor endothelial cell junction formation and micro-thrombi of focal platelet aggregation at 16 months after rapamycin stent implantation. (9)
*Inflammatory response to the stent material serving as a nidus for thrombosis
**Evidence of an inflammatory response was present in nearly 9% of the sirolimus eluting stents (SES) and paclitaxel eluting stents (PES) by the demonstration of late aquired stent malaposition (LASMA) which was more than what was seen with BMS . (10,11)
*Hypersensitivity reaction around the stent material in DES serving as nidus for ST
**Cypher and Taxus DES were shown to provoke chronic eosinophilic infiltration and inflammation of the arterial wall potentially predisposing patients for thrombosis. (12,12,13,14,15,16)
Both red and white thrombi have been demonstrated within sirolimus eluting stents (SES) as a cause of late stent thrombosis. (1)




==Mechanisms and pathophysiology of ST==


===back to [[Coronary stent thrombosis]] main page===
'''ST in Bare Metal Stent (BMS):'''


===References===
After [[BMS]] implantation, near-complete [[endothelization]] has been shown to occur by 3 to 4 months.<ref name="pmid14504181">{{cite journal| author=Farb A, Burke AP, Kolodgie FD, Virmani R| title=Pathological mechanisms of fatal late coronary stent thrombosis in humans. | journal=Circulation | year= 2003 | volume= 108 | issue= 14 | pages= 1701-6 | pmid=14504181 | doi=10.1161/01.CIR.0000091115.05480.B0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14504181  }} </ref>
{{refbegin|2}}
(1) Masaki Awata, Jun-ichi Kotani et al; Serial Angioscopic Evidence of Incomplete Neointimal Coverage After Sirolimus-Eluting Stent Implantation. Comparison With Bare-Metal Stents Circulation published online Aug 7, 2007


(2) Wenaweser, P, Dorffler-Melly, J, Imboden, K, et al. Stent thrombosis is associated with an impaired response to antiplatelet therapy. J Am Coll Cardiol 2005; 45:1748
This coincides with the reduction of risk of ST.


(3) Kaluza GL, Joseph J, Lee JR, Raizner ME, Raizner AE. Catastrophic outcomes of non-cardiac surgery soon after coronary stenting. J Am Coll Cardiol 2000;35:1288 –94.


(4) Farb A, Burke AP, Kolodgie FD, Virmani R. Pathological mechanisms of fatal late coronary stent thrombosis in humans. Circulation. 2003;108: 1701–1706.
'''ST in Drug Eluting Stent (DES):'''


(5) Edoardo Camenzind, MD; P. Gabriel Steg, MD; William Wijns, MD Stent Thrombosis Late After Implantation of First Generation Drug-Eluting Stents A Cause for Concern Circulation. 2007;115:1440-1455.  
Factors that serve as nidus for development stent thrombosis are:
*Delayed [[endothelialization]]<ref name="pmid17344324">{{cite journal| author=Camenzind E, Steg PG, Wijns W| title=Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. | journal=Circulation | year= 2007 | volume= 115 | issue= 11 | pages= 1440-55; discussion 1455 | pmid=17344324 | doi=10.1161/CIRCULATIONAHA.106.666800 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17344324  }} </ref><ref name="pmid17684153">{{cite journal| author=Awata M, Kotani J, Uematsu M, Morozumi T, Watanabe T, Onishi T et al.| title=Serial angioscopic evidence of incomplete neointimal coverage after sirolimus-eluting stent implantation: comparison with bare-metal stents. | journal=Circulation | year= 2007 | volume= 116 | issue= 8 | pages= 910-6 | pmid=17684153 | doi=10.1161/CIRCULATIONAHA.105.609057 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17684153  }} </ref><ref name="pmid16697331">{{cite journal| author=Kotani J, Awata M, Nanto S, Uematsu M, Oshima F, Minamiguchi H et al.| title=Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic findings. | journal=J Am Coll Cardiol | year= 2006 | volume= 47 | issue= 10 | pages= 2108-11 | pmid=16697331 | doi=10.1016/j.jacc.2005.11.092 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16697331  }} </ref>.


(6) Circ 1999 Costa Late coronary occlusion after intra cor brachytherapy.pdf
*Inflammatory response to the stent material<ref>Leon MB, Abizaid A, Moses JW. Subgroup analysis from the Cypher clinical trials. In: The Cypher Stent: A New Gold Standard in the Treatment of Coronary Artery Disease. New York, NY: Cardiovascular Research Foundation; 2003:54–57.</ref><ref name="pmid15710761">{{cite journal| author=Tanabe K, Serruys PW, Degertekin M, Grube E, Guagliumi G, Urbaszek W et al.| title=Incomplete stent apposition after implantation of paclitaxel-eluting stents or bare metal stents: insights from the randomized TAXUS II trial. | journal=Circulation | year= 2005 | volume= 111 | issue= 7 | pages= 900-5 | pmid=15710761 | doi=10.1161/01.CIR.0000155607.54922.16 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15710761  }} </ref>.
Costa MA, Sabate M, van der Giessen WJ, et al. Late coronary occlusion after intracoronary brachytherapy. Circulation 1999;100: 789–92.


(7)Kotani, J, Awata, M, Nanto, S, et al. Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic findings. J Am Coll Cardiol 2006; 47:2108.
*Hypersensitivity reaction around the stent material in DES serving as nidus for ST<ref name="pmid14744976">{{cite journal| author=Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T et al.| title=Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? | journal=Circulation | year= 2004 | volume= 109 | issue= 6 | pages= 701-5 | pmid=14744976 | doi=10.1161/01.CIR.0000116202.41966.D4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14744976  }} </ref><ref name="pmid16386683">{{cite journal| author=Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J et al.| title=Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. | journal=J Am Coll Cardiol | year= 2006 | volume= 47 | issue= 1 | pages= 175-81 | pmid=16386683 | doi=10.1016/j.jacc.2005.07.071 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16386683  }} </ref><ref name="pmid16814667">{{cite journal| author=Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E et al.| title=Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. | journal=J Am Coll Cardiol | year= 2006 | volume= 48 | issue= 1 | pages= 193-202 | pmid=16814667 | doi=10.1016/j.jacc.2006.03.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16814667  }} </ref><ref name="pmid15963413">{{cite journal| author=Ong AT, McFadden EP, Regar E, de Jaegere PP, van Domburg RT, Serruys PW| title=Late angiographic stent thrombosis (LAST) events with drug-eluting stents. | journal=J Am Coll Cardiol | year= 2005 | volume= 45 | issue= 12 | pages= 2088-92 | pmid=15963413 | doi=10.1016/j.jacc.2005.02.086 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15963413  }} </ref><ref name="pmid15464315">{{cite journal| author=Grube E, Lansky A, Hauptmann KE, Di Mario C, Di Sciascio G, Colombo A et al.| title=High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary revascularization: one-year results from the SCORE randomized trial. | journal=J Am Coll Cardiol | year= 2004 | volume= 44 | issue= 7 | pages= 1368-72 | pmid=15464315 | doi=10.1016/j.jacc.2004.06.054 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15464315  }} </ref>.


(8) Joner, M, Finn, AV, Farb, A, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 2006; 48:193.
*Antineoplastic therapy and delayed endothelialization had been an issue with late ST seen with [[brachytherapy]]<ref name="pmid10458712">{{cite journal| author=Costa MA, Sabaté M, van der Giessen WJ, Kay IP, Cervinka P, Ligthart JM et al.| title=Late coronary occlusion after intracoronary brachytherapy. | journal=Circulation | year= 1999 | volume= 100 | issue= 8 | pages= 789-92 | pmid=10458712 | doi= | pmc= | url= }} </ref>.
**Coronary [[brachytherpy]] use has all but disappeared since the introduction of [[DES]].


(9) Guagliumi G, Farb A, Musumeci G, Valsecchi O, Tespili M, Motta T, Virmani R. Images in cardiovascular medicine: sirolimus-eluting stent implanted in human coronary artery for 16 months: pathological findings. Circulation. 2003;107:1340 –1341.


(10) Leon MB, Abizaid A, Moses JW. Subgroup analysis from the Cypher clinical trials. In: The Cypher Stent: A New Gold Standard in the Treatment of Coronary Artery Disease. New York, NY: Cardiovascular Research Foundation; 2003:54–57.
==Clinical Trial Data==
*An angioscopic study of stented coronary segments showed that neointimal coverage was complete only in 2 out of 15 patients  with [[sirolimus]] stents and all of 22 [[BMS]] at three to six months. There were thrombi in most of the stented segments which were not seen on angiography which were more common with incomplete neointimal coverage.<ref name="pmid17684153">{{cite journal| author=Awata M, Kotani J, Uematsu M, Morozumi T, Watanabe T, Onishi T et al.| title=Serial angioscopic evidence of incomplete neointimal coverage after sirolimus-eluting stent implantation: comparison with bare-metal stents. | journal=Circulation | year= 2007 | volume= 116 | issue= 8 | pages= 910-6 | pmid=17684153 | doi=10.1161/CIRCULATIONAHA.105.609057 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17684153  }} </ref><ref name="pmid16697331">{{cite journal| author=Kotani J, Awata M, Nanto S, Uematsu M, Oshima F, Minamiguchi H et al.| title=Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic findings. | journal=J Am Coll Cardiol | year= 2006 | volume= 47 | issue= 10 | pages= 2108-11 | pmid=16697331 | doi=10.1016/j.jacc.2005.11.092 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16697331  }} </ref> In a study involving serial angioscopy after sirolimus-eluting stent (SES) implantation at 4, 11, and 21.2 ±2.2 months showed that neointimal coverage after sirolimus-eluting stent implantation was incomplete even at that late stage.  


(11) Tanabe K, Serruys PW, Colombo A et al, for the TAXUS II Study Group. Incomplete stent apposition after implantation of paclitaxel-eluting stents or bare metal stents: insights from the randomized TAXUS II trial. Circulation. 2005;111:900–905.
*In a post mortem analysis, [[DES]], compared to [[BMS]] had delayed endothelial healing. This group was more likely to have [[ST]].<ref name="pmid16814667">{{cite journal| author=Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E et al.| title=Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. | journal=J Am Coll Cardiol | year= 2006 | volume= 48 | issue= 1 | pages= 193-202 | pmid=16814667 | doi=10.1016/j.jacc.2006.03.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16814667  }} </ref>
*A post mortem analysis of a patient dying from an unrelated cause but who also had a DES implanted, revealed poor endothelial cell junction formation and micro-thrombi of focal platelet aggregation at 16 months after rapamycin stent implantation.<ref name="pmid12628958">{{cite journal| author=Guagliumi G, Farb A, Musumeci G, Valsecchi O, Tespili M, Motta T et al.| title=Images in cardiovascular medicine. Sirolimus-eluting stent implanted in human coronary artery for 16 months: pathological findings. | journal=Circulation | year= 2003 | volume= 107 | issue= 9 | pages= 1340-1 | pmid=12628958 | doi= | pmc= | url= }} </ref>


(12) Virmani R, Guagliumi G, Farb A, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation 2004;109:701–5.
*Evidence of an inflammatory response was present in nearly 9% of the [[sirolimus]] eluting stents (SES) and [[paclitaxel]] eluting stents (PES) by the demonstration of late aquired stent malaposition (LASMA) which was more than what was seen with [[BMS]]<ref>Leon MB, Abizaid A, Moses JW. Subgroup analysis from the Cypher clinical trials. In: The Cypher Stent: A New Gold Standard in the Treatment of Coronary Artery Disease. New York, NY: Cardiovascular Research Foundation; 2003:54–57.</ref><ref name="pmid15710761">{{cite journal| author=Tanabe K, Serruys PW, Degertekin M, Grube E, Guagliumi G, Urbaszek W et al.| title=Incomplete stent apposition after implantation of paclitaxel-eluting stents or bare metal stents: insights from the randomized TAXUS II trial. | journal=Circulation | year= 2005 | volume= 111 | issue= 7 | pages= 900-5 | pmid=15710761 | doi=10.1161/01.CIR.0000155607.54922.16 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15710761  }} </ref>.


(13) Nebeker JR, Virmani R, Feldman MD et al, Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. J Am Coll Cardiol. 2006; 47:175–181.
*Cypher and Taxus [[DES]] were shown to provoke chronic [[eosinophilic]] infiltration and inflammation of the arterial wall potentially predisposing patients for thrombosis<ref name="pmid14744976">{{cite journal| author=Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T et al.| title=Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? | journal=Circulation | year= 2004 | volume= 109 | issue= 6 | pages= 701-5 | pmid=14744976 | doi=10.1161/01.CIR.0000116202.41966.D4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14744976  }} </ref><ref name="pmid16386683">{{cite journal| author=Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J et al.| title=Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. | journal=J Am Coll Cardiol | year= 2006 | volume= 47 | issue= 1 | pages= 175-81 | pmid=16386683 | doi=10.1016/j.jacc.2005.07.071 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16386683  }} </ref><ref name="pmid16814667">{{cite journal| author=Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E et al.| title=Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. | journal=J Am Coll Cardiol | year= 2006 | volume= 48 | issue= 1 | pages= 193-202 | pmid=16814667 | doi=10.1016/j.jacc.2006.03.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16814667  }} </ref><ref name="pmid15963413">{{cite journal| author=Ong AT, McFadden EP, Regar E, de Jaegere PP, van Domburg RT, Serruys PW| title=Late angiographic stent thrombosis (LAST) events with drug-eluting stents. | journal=J Am Coll Cardiol | year= 2005 | volume= 45 | issue= 12 | pages= 2088-92 | pmid=15963413 | doi=10.1016/j.jacc.2005.02.086 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15963413  }} </ref><ref name="pmid15464315">{{cite journal| author=Grube E, Lansky A, Hauptmann KE, Di Mario C, Di Sciascio G, Colombo A et al.| title=High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary revascularization: one-year results from the SCORE randomized trial. | journal=J Am Coll Cardiol | year= 2004 | volume= 44 | issue= 7 | pages= 1368-72 | pmid=15464315 | doi=10.1016/j.jacc.2004.06.054 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15464315  }} </ref>


(14) Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol. 2006;48:193–202.
*Both red and white thrombi have been demonstrated within [[sirolimus]] eluting stents (SES) as a cause of late stent thrombosis<ref name="pmid17684153">{{cite journal| author=Awata M, Kotani J, Uematsu M, Morozumi T, Watanabe T, Onishi T et al.| title=Serial angioscopic evidence of incomplete neointimal coverage after sirolimus-eluting stent implantation: comparison with bare-metal stents. | journal=Circulation | year= 2007 | volume= 116 | issue= 8 | pages= 910-6 | pmid=17684153 | doi=10.1161/CIRCULATIONAHA.105.609057 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17684153  }} </ref>


(15) JACC 2005 Ong LAST Late angiographic ST DES.pdf
Ong, AT, McFadden, EP, Regar, E, et al. Late angiographic stent thrombosis (LAST) events with drug-eluting stents. J Am Coll Cardiol 2005; 45:2088.


(16)Grube E, Lansky A, Hauptmann KE, et al. High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary revascularization: one-year results from the SCORE randomized trial. J Am Coll Cardiol 2004;44:1368 –72.
==References==
{{refend}}
{{reflist|2}}


{{SIB}}
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Stent thrombosis occurs due to variety of factors inducing thombogenesis. Being an invasive procedure, the trauma from coronary stenting can itself cause platelet activation and thombogenic cascade. There is either creation or an enhancement of a thrombogenic milieu by:

  • creating an environment conducive for platelet activation and/or
  • creating an environment conducive for instent thrombosis


These processes are facilitated by

  • Creating a thrombogenic milieu by
  • Persistence of or ceation of substrate for platelet activation
    • Exposure of platelet activating factors due to trauma of stenting or ballooning – acutely
    • Persistant incomplete endotheliazation[1][2]
    • Inadequate platelet inhibition – due to inadeqaue dosing or drug unrespopnsivelness.
      • acutely
      • subacutely
      • long term
  • Dosing issues
    • with anti thrombotic medicagtions (acutely)
    • antiplatelet medications (acutely, subacutly or long term)
    • inadequate time for the loading dose to act
    • suboptimal/subtherapeutic dosing during the procedure or therafter
  • Resistance to antiplatelet medications[3]
  • Deranaged homeostasis due to disease creating a prothrombotic diathesis
    • sepsis
    • blood transfusions
    • surgery (In one study, following BMS, mortality rate among patients who had non cardiac surgery within two-weeks was 32%, almost exclusively due to ST.[4]
    • dehydration
    • Other states which may create hypotensive states. (eg. of anectdotal reports of stent thormbosis with defecation syncope)


Mechanisms and pathophysiology of ST

ST in Bare Metal Stent (BMS):

After BMS implantation, near-complete endothelization has been shown to occur by 3 to 4 months.[5]

This coincides with the reduction of risk of ST.


ST in Drug Eluting Stent (DES):

Factors that serve as nidus for development stent thrombosis are:

  • Inflammatory response to the stent material[8][9].
  • Hypersensitivity reaction around the stent material in DES serving as nidus for ST[10][11][12][13][14].
  • Antineoplastic therapy and delayed endothelialization had been an issue with late ST seen with brachytherapy[2].
    • Coronary brachytherpy use has all but disappeared since the introduction of DES.


Clinical Trial Data

  • An angioscopic study of stented coronary segments showed that neointimal coverage was complete only in 2 out of 15 patients with sirolimus stents and all of 22 BMS at three to six months. There were thrombi in most of the stented segments which were not seen on angiography which were more common with incomplete neointimal coverage.[1][7] In a study involving serial angioscopy after sirolimus-eluting stent (SES) implantation at 4, 11, and 21.2 ±2.2 months showed that neointimal coverage after sirolimus-eluting stent implantation was incomplete even at that late stage.
  • In a post mortem analysis, DES, compared to BMS had delayed endothelial healing. This group was more likely to have ST.[12]
  • A post mortem analysis of a patient dying from an unrelated cause but who also had a DES implanted, revealed poor endothelial cell junction formation and micro-thrombi of focal platelet aggregation at 16 months after rapamycin stent implantation.[15]
  • Evidence of an inflammatory response was present in nearly 9% of the sirolimus eluting stents (SES) and paclitaxel eluting stents (PES) by the demonstration of late aquired stent malaposition (LASMA) which was more than what was seen with BMS[16][9].
  • Cypher and Taxus DES were shown to provoke chronic eosinophilic infiltration and inflammation of the arterial wall potentially predisposing patients for thrombosis[10][11][12][13][14]
  • Both red and white thrombi have been demonstrated within sirolimus eluting stents (SES) as a cause of late stent thrombosis[1]


References

  1. ↑ 1.0 1.1 1.2 1.3 Awata M, Kotani J, Uematsu M, Morozumi T, Watanabe T, Onishi T; et al. (2007). "Serial angioscopic evidence of incomplete neointimal coverage after sirolimus-eluting stent implantation: comparison with bare-metal stents". Circulation. 116 (8): 910–6. doi:10.1161/CIRCULATIONAHA.105.609057. PMID 17684153.
  2. ↑ 2.0 2.1 Costa MA, Sabaté M, van der Giessen WJ, Kay IP, Cervinka P, Ligthart JM; et al. (1999). "Late coronary occlusion after intracoronary brachytherapy". Circulation. 100 (8): 789–92. PMID 10458712.
  3. ↑ Wenaweser P, Dörffler-Melly J, Imboden K, Windecker S, Togni M, Meier B; et al. (2005). "Stent thrombosis is associated with an impaired response to antiplatelet therapy". J Am Coll Cardiol. 45 (11): 1748–52. doi:10.1016/j.jacc.2005.01.058. PMID 15936599.
  4. ↑ Kałuza GL, Joseph J, Lee JR, Raizner ME, Raizner AE (2000). "Catastrophic outcomes of noncardiac surgery soon after coronary stenting". J Am Coll Cardiol. 35 (5): 1288–94. PMID 10758971.
  5. ↑ Farb A, Burke AP, Kolodgie FD, Virmani R (2003). "Pathological mechanisms of fatal late coronary stent thrombosis in humans". Circulation. 108 (14): 1701–6. doi:10.1161/01.CIR.0000091115.05480.B0. PMID 14504181.
  6. ↑ Camenzind E, Steg PG, Wijns W (2007). "Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern". Circulation. 115 (11): 1440–55, discussion 1455. doi:10.1161/CIRCULATIONAHA.106.666800. PMID 17344324.
  7. ↑ 7.0 7.1 Kotani J, Awata M, Nanto S, Uematsu M, Oshima F, Minamiguchi H; et al. (2006). "Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic findings". J Am Coll Cardiol. 47 (10): 2108–11. doi:10.1016/j.jacc.2005.11.092. PMID 16697331.
  8. ↑ Leon MB, Abizaid A, Moses JW. Subgroup analysis from the Cypher clinical trials. In: The Cypher Stent: A New Gold Standard in the Treatment of Coronary Artery Disease. New York, NY: Cardiovascular Research Foundation; 2003:54–57.
  9. ↑ 9.0 9.1 Tanabe K, Serruys PW, Degertekin M, Grube E, Guagliumi G, Urbaszek W; et al. (2005). "Incomplete stent apposition after implantation of paclitaxel-eluting stents or bare metal stents: insights from the randomized TAXUS II trial". Circulation. 111 (7): 900–5. doi:10.1161/01.CIR.0000155607.54922.16. PMID 15710761.
  10. ↑ 10.0 10.1 Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T; et al. (2004). "Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious?". Circulation. 109 (6): 701–5. doi:10.1161/01.CIR.0000116202.41966.D4. PMID 14744976.
  11. ↑ 11.0 11.1 Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J; et al. (2006). "Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project". J Am Coll Cardiol. 47 (1): 175–81. doi:10.1016/j.jacc.2005.07.071. PMID 16386683.
  12. ↑ 12.0 12.1 12.2 Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E; et al. (2006). "Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk". J Am Coll Cardiol. 48 (1): 193–202. doi:10.1016/j.jacc.2006.03.042. PMID 16814667.
  13. ↑ 13.0 13.1 Ong AT, McFadden EP, Regar E, de Jaegere PP, van Domburg RT, Serruys PW (2005). "Late angiographic stent thrombosis (LAST) events with drug-eluting stents". J Am Coll Cardiol. 45 (12): 2088–92. doi:10.1016/j.jacc.2005.02.086. PMID 15963413.
  14. ↑ 14.0 14.1 Grube E, Lansky A, Hauptmann KE, Di Mario C, Di Sciascio G, Colombo A; et al. (2004). "High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary revascularization: one-year results from the SCORE randomized trial". J Am Coll Cardiol. 44 (7): 1368–72. doi:10.1016/j.jacc.2004.06.054. PMID 15464315.
  15. ↑ Guagliumi G, Farb A, Musumeci G, Valsecchi O, Tespili M, Motta T; et al. (2003). "Images in cardiovascular medicine. Sirolimus-eluting stent implanted in human coronary artery for 16 months: pathological findings". Circulation. 107 (9): 1340–1. PMID 12628958.
  16. ↑ Leon MB, Abizaid A, Moses JW. Subgroup analysis from the Cypher clinical trials. In: The Cypher Stent: A New Gold Standard in the Treatment of Coronary Artery Disease. New York, NY: Cardiovascular Research Foundation; 2003:54–57.

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