Stent thrombosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editors-In-Chief: Smita Kohli, M.D.; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.
Pathophysiology
Stent thrombosis (ST) 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 in-stent thrombosis
These processes are facilitated by
- Creating a thrombogenic milieu by
- Slow coronary flow,
- Local dissection,
- Distal untreated critical lesion
- Poor out flow
- Persistence of, or creation 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 inadequate dosing or drug unresponsiveness.
- Acutely
- Subacutely
- Long term
- Dosing issues
- With anti thrombotic medications (acutely)
- Antiplatelet medications (acutely, sub-acutely or long term)
- Inadequate time for the loading dose to act
- Suboptimal/sub-therapeutic dosing during the procedure or thereafter
- Resistance to antiplatelet medications[3]
- Aspirin resistance
- Clopidogrel resistance
- Deranged 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 anecdotal reports of stent thrombosis with defecation syncope)
Pathophysiology of 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.
Pathophysiology of ST in Drug Eluting Stent (DES)
Factors that serve as nidus for development stent thrombosis are:
- Delayed endothelialization[6][1][7].
- 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 brachytherapy 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
- ↑ 1.0 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.
- ↑ 2.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 7.0 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.
- ↑ 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.
- ↑ 9.0 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.
- ↑ 10.0 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.
- ↑ 11.0 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.
- ↑ 12.0 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.
- ↑ 13.0 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.
- ↑ 14.0 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.
- ↑ 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.
- ↑ 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.