Immunohistochemistry of thrombi following iliac venous stenting: A novel model of venous thrombosis

Summary

Stenting has become a common intervention for venous occlusive disease. Little is known regarding the composition of venous thrombi complicating stent placement. The optimal design of antithrombotic agents in this setting requires this knowledge. Quantitative immunohistochemistry was undertaken to define the platelet, fibrin(ogen) and leukocyte composition and spatial orientation of venous thrombi following percutaneous iliac stent placement in pigs. Venous stent thrombus size was measured by weight and scintillation detection of autologous ¹¹¹In-platelets. Thrombi were divided in segments (cephalad to caudad), sectioned and stained with monoclonal anti-platelet glycoprotein Ib or polyclonal anti-fibrin(ogen) fluorescent antibodies. Thrombus platelet content was 100-fold greater than paired whole blood samples. The caudal-most segments contained platelet-rich aggregates (p<0.05) with abundant leukocytes (p<0.0001) relative to more cephalad segments. Platelet and fibrin(ogen) content varied over an eight-fold range between segments but were directly correlated with each other (r=0.77; p<0.0001). The platelet co-localization with fibrin(ogen) is consistent with the phospholipid dependence of prothrombin activation. The abundance and caudal distribution of platelet-leukocyte aggregates indicate their preferential accretion from flowing blood early in the genesis of venous stent thrombi. These may represent novel cellular targets for the prevention and treatment of venous thrombosis.

Keywords

Venous thrombosis - vascular stents - platelets

• References

• 1 Thomas ICH, Zierler BK. 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 2005; 39: 163-74.
• 2 Mewissen MW. et al. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology 1999; 211: 39-49.
• 3 AbuRahma AF. et al. Iliofemoral deep vein thrombosis: conventional therapy versus lysis and percutaneous transluminal angioplasty and stenting. Ann Surg 2001; 233: 752-60.
• 4 Vedantham S. et al. Pharmacomechanical thrombolysis and early stent placement for iliofemoral deep vein thrombosis. J Vasc Intervent Radiol 2004; 15: 565-74.
• 5 Augustinos P, Ouriel K. Invasive approaches to treatment of venous thromboembolism. Circulation 2004; 110: I27-34.
• 6 Mickley V. et al. Stenting of central venous stenoses in hemodialysis patients: long-term results. Kidney Int 1997; 51: 277-80.
• 7 Blattler W, Blattler IK. Relief of obstructive pelvic venous symptoms with endoluminal stenting. J Vasc Surg 1999; 29: 484-8.
• 8 Ko GY. et al. Endovascular treatment of hepatic venous outflow obstruction after living-donor liver transplantation. J Vasc Intervent Radiol 2002; 13: 591-9.
• 9 Caldarone CA. et al. Relentless pulmonary vein stenosis after repair of total anomalous pulmonary venous drainage. Ann Thorac Surg 1998; 66: 1514-20.
• 10 McBane RD. et al. Antithrombotic action of endogenous porcine protein C activated with a latent porcine thrombin preparation. Thromb Haemost 1995; 74: 879-85.
• 11 Wysokinski WE. et al. Atrialfibrillation and thrombosis: immunohistochemical differences between in situ and embolized thrombi. J Thromb Haemost 2004; 02: 1637-44.
• 12 Myers Jr DD. et al. Decreased venous thrombosis with an oral inhibitor of P selectin. J Vasc Surg 2005; 42: 329-36.
• 13 Sevitt S. The structure and growth of valve-pocket thrombi in femoral veins. J Clin Path 1974; 27: 517-28.
• 14 Malone PC. A hypothesis concerning the aetiology of venous thrombosis. Med Hypoth 1977; 03: 189-201.
• 15 Schaub RG. et al. Early events in the formation of a venous thrombus following local trauma and stasis. Lab Invest 1984; 51: 218-24.
• 16 Thomas DP. Venous thrombosis and the “Wessler” test. Thromb Haemost 1996; 76: 1-4.
• 17 Neglen P, Raju S. In-stent recurrent stenosis in stents placed in the lower extremity venous outflow tract. J Vasc Surg 2004; 39: 181-7.
• 18 Heckenkamp J. et al. Vascular restenosis. Basic science and clinical implications. J Cardiovasc Surg 2002; 43: 349-57.
• 19 Bjarnason H. et al. Iliofemoral deep venous thrombosis: safety and efficacy outcome during5 years of catheter-directed thrombolytic therapy. J Vasc Intervent Radiol 1997; 08: 405-18.