Journal of Thrombosis and Thrombolysis

, Volume 36, Issue 4, pp 442–447

Platelet recruitment to venous stent thrombi

  • Robert D. McBaneII
  • Krzysztof Karnicki
  • Waldemar E. Wysokinski


Thrombosis following venous stent placement is a morbid clinical outcome. Whether to target platelets or coagulation factors for venous stent thromboprophylaxis remains unclear. We sought to determine whether integrin αIIbβ3 antagonism with lamifiban would inhibit platelet recruitment to venous stent thrombosis. Anti-thrombotic efficacy was compared between venous and arterial circulations. Pigs received either lamifiban (0.2 mg/kg bolus plus 0.2 mg/kg/h infusion; n = 6) or saline (n = 12). Carotid arteries were crush injured and then harvested 30 min later to provide an assessment of antithrombotic efficacy in the arterial circulation. Iliac venous stents were then deployed and thrombi allowed to propagate for 2 h before harvesting. Platelet deposition was measured by scintillation detection of autologous 111In-platelets. Venous thrombi were quantified by weight and compared to platelet, Von Willebrand factor (VWF) and fibrinogen content. Arterial platelet deposition (×106/cm2) was reduced >80 % by lamifiban (398 ± 437) compared to controls (1,540 ± 883; p < 0.005). Lamifiban also reduced venous thrombus platelet deposition (139 ± 88 vs. 281 ± 167) however did not prevent thrombosis. In control animals, venous stent platelet deposition correlated with plasma fibrinogen content (R2 = 0.29; p = 0.03). Fibrinogen content correlated directly with venous stent platelet deposition (p = 0.03) but not thrombus weight. Neither venous platelet deposition nor thrombus weights varied by VWF content. Platelet recruitment to venous stent thrombi occurs in part through the integrin αIIbβ3 receptor. Unlike arterial thrombosis, inhibition of this receptor is insufficient to prevent venous stent thrombosis.


Integrin αIIbβ3 GP IIb/IIIa Platelets Venous stent thrombosis Lamifiban 


  1. 1.
    Mewissen MW, Seabrook GR, Meissner MH et al (1999) Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology 211:39–49PubMedCrossRefGoogle Scholar
  2. 2.
    AbuRahma AF, Perkins SE, Wulu JT et al (2001) Iliofemoral deep vein thrombosis: conventional therapy versus lysis and percutaneous transluminal angioplasty and stenting. Ann Surg 233:752–760PubMedCrossRefGoogle Scholar
  3. 3.
    Vedantham S, Vesely TM, Sicard GA et al (2004) Pharmacomechanical thrombolysis and early stent placement for iliofemoral deep vein thrombosis. J Vasc Interv Radiol 15:565–574PubMedCrossRefGoogle Scholar
  4. 4.
    Augustinos P, Ouriel K (2004) Invasive approaches to treatment of venous thromboembolism. Circulation 110:I27–I134PubMedCrossRefGoogle Scholar
  5. 5.
    Thomas IH, Zierler BK (2005) An integrative review of outcomes in patients with acute primary upper extremity deep venous thrombosis following no treatment or treatment with anticoagulation, thrombolysis, or surgical algorithms. Vasc Endovasc Surg 39:163–174CrossRefGoogle Scholar
  6. 6.
    Mickley V, Gorich J, Rilinger N et al (1997) Stenting of central venous stenoses in hemodialysis patients: long-term results. Kidney Int 51:277–280PubMedCrossRefGoogle Scholar
  7. 7.
    Blattler W, Blattler IK (1999) Relief of obstructive pelvic venous symptoms with endoluminal stenting. J Vasc Surg 29:484–488PubMedCrossRefGoogle Scholar
  8. 8.
    Enden T, Kløw NE, Sandvik L et al (2009) Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency. J Thromb Haemost 7:1268–1275PubMedCrossRefGoogle Scholar
  9. 9.
    Enden T, Haig Y, Kløw NE, Slagsvold CE, Sandvik L, Ghanima W, Hafsahl G, Holme PA, Holmen LO, Njaastad AM, Sandbæk G, Sandset PM (2012) Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis: a randomised controlled trial. Lancet 379:31–38PubMedCrossRefGoogle Scholar
  10. 10.
    Coleman RW, Clowes AW, George JN et al (2006) Overview of hemostasis. In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ (eds) Hemostasis and thrombosis, 5th edn. Lipincott Williams and Wilkins, Philadelphia, pp 3–16Google Scholar
  11. 11.
    Sevitt S (1974) The structure and growth of valve-pocket thrombi in femoral veins. J Clin Pathol 27:517–528PubMedCrossRefGoogle Scholar
  12. 12.
    Malone PC (1977) A hypothesis concerning the aetiology of venous thrombosis. Med Hypothal 3:189–201CrossRefGoogle Scholar
  13. 13.
    Ruiz-Irastorza G, Crowther M, Branch W et al (2010) Antiphospholipid syndrome. Lancet 3:1–12Google Scholar
  14. 14.
    Greinacher A, Warkentin TE (2006) Recognition, treatment, and prevention of heparin-induced thrombocytopenia: review and update. Thromb Res 118:165–176PubMedCrossRefGoogle Scholar
  15. 15.
    Hovinga JAK, Vesely SK, Terrell DR et al (2010) Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 115:1500–1511CrossRefGoogle Scholar
  16. 16.
    Gruppo Italiano Studio (1995) Polycythemia vera: the natural history of 1213 patients followed for 20 years. Gruppo Italiano Studio Policitemia. Ann Intern Med 123:656–664CrossRefGoogle Scholar
  17. 17.
    Cortelazzo S, Viero P, Finazzi G et al (1990) Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol 8:556–562PubMedGoogle Scholar
  18. 18.
    Burches B, Karnicki K, Wysokinski W et al (2006) Immunohistochemistry of thrombi following iliac venous stenting: a novel model of venous thrombosis. Thromb Haemost 96:618–622PubMedGoogle Scholar
  19. 19.
    Wysokinski W, Karnicki K, McBane RD 2nd (2008) Individual propensity for thrombosis: comparison of venous and arterial circulations. Thromb Res 122(3):390–396PubMedCrossRefGoogle Scholar
  20. 20.
    McBane RD 2nd, Leadley RJ Jr, Baxi SM et al (2008) Iliac venous stenting: antithrombotic efficacy of PD0348292, an oral direct Factor Xa inhibitor, compared with antiplatelet agents in pigs. Arterioscler Thromb Vasc Biol 28:413–418PubMedCrossRefGoogle Scholar
  21. 21.
    Knight LC, Romano JE, Maurer AH (1998) In vitro platelet binding compared with in vivo thrombus imaging using alpha(IIb)beta3-targeted radioligands. Thromb Haemost 80:845–851PubMedGoogle Scholar
  22. 22.
    Alig L, Edenhofer A, Hadvary P et al (1992) Low molecular weight, non-peptide fibrinogen receptor antagonists. J Med Chem 35:4393–4407PubMedCrossRefGoogle Scholar
  23. 23.
    Kouns WC, Kirchhofer D, Hadvary P et al (1992) Reversible conformational changes induced in glycoprotein IIb/IIIa by a potent and selective peptidomimetic inhibitor. Blood 80:2539–2547PubMedGoogle Scholar
  24. 24.
    Chico TJ, Chamberlain J, Gunn J et al (2001) Effect of selective or combined inhibition of integrins alpha(IIb)beta(3) and alpha(v)beta(3) on thrombosis and neointima after oversized porcine coronary angioplasty. Circulation 103:1135–1141PubMedCrossRefGoogle Scholar
  25. 25.
    McBane RD, Wysokinski WE, Chesebro JH et al (1995) Antithrombotic action of endogenous porcine protein C activated with a latent porcine thrombin preparation. Thromb Haemost 74:879–885PubMedGoogle Scholar
  26. 26.
    Posan E, McBane RD, Grill DE et al (2003) Comparison of PFA-100 testing and bleeding time for detecting platelet hypofunction and von Willebrand disease in clinical practice. Thromb Haemost 90:483–490PubMedGoogle Scholar
  27. 27.
    Rossi E, Mondonico P, Lombardi A et al (1988) Method for the determination of functional (clottable) fibrinogen by the new family of ACL coagulometers. Thromb Res 52:453–468PubMedCrossRefGoogle Scholar
  28. 28.
    Eby C, Chance D, Oliver D (1997) A multicenter evaluation of STA-LIATEST VWF: a new latex particle immunoassay for von Willebrand factor antigen. Clin Hemost Rev 11:16–17Google Scholar
  29. 29.
    Pruthi RK, Daniels TM, Heit JA et al (2010) Plasma von Willebrand factor multimer quantitative analysis by in-gel immunostaining and infrared fluorescent imaging. Thromb Res 126:543–549PubMedCrossRefGoogle Scholar
  30. 30.
    Budde U, Schneppenheim R, Eikenboom J et al (2008) Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD). J Thromb Haemost 6:762–771PubMedCrossRefGoogle Scholar
  31. 31.
    Knight LC, Romano JE, Maurer AH (1998) In vitro platelet binding compared with in vivo thrombus imaging using alpha(IIb)beta3-targeted radioligands. Thromb Haemost 80:845–851PubMedGoogle Scholar
  32. 32.
    Herbert JM, Bernat A, Maffrand JP (1992) Importance of platelets in experimental venous thrombosis in the rat. Blood 80:2281–2286PubMedGoogle Scholar
  33. 33.
    Chauhan AK, Kisucka J, Lamb CB et al (2007) von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins. Blood 109:2424–2429PubMedCrossRefGoogle Scholar
  34. 34.
    Brill A, Fuchs TA, Chauhan AK, et al (2011) von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood 117:1400–1407Google Scholar
  35. 35.
    Lopez JA, Dong JF (2004) Cleavage of von Willebrand factor by ADAMTS13 on endothelial cells. Semin Hematol 41:15–23PubMedCrossRefGoogle Scholar
  36. 36.
    Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, Bianchi M, Moia M, Ageno W, Vandelli MR, Grandone E, Prandoni P, WARFASA Investigators (2012) Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 366:1959–1967PubMedCrossRefGoogle Scholar
  37. 37.
    Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, Gibbs H, Hague W, Xavier D, Diaz R, Kirby A, Simes J, ASPIRE Investigators (2012) Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 367:1979–1987PubMedCrossRefGoogle Scholar
  38. 38.
    Kageyama K, Nakajima Y, Shibasaki M et al (2007) Increased platelet, leukocyte, and endothelial cell activity are associated with increased coagulability in patients after total knee arthroplasty. J Thromb Haemost 5:738–745PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Robert D. McBaneII
    • 1
    • 2
    • 3
  • Krzysztof Karnicki
    • 1
  • Waldemar E. Wysokinski
    • 1
    • 2
  1. 1.Section of Hematology ResearchMayo ClinicRochesterUSA
  2. 2.Division of CardiologyMayo ClinicRochesterUSA
  3. 3.Division of Cardiovascular MedicineMayo ClinicRochesterUSA

Personalised recommendations