title: Platelet recruitment to venous stent thrombi.
abstract: 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 α(IIb)β3 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 (111)In-platelets. Venous thrombi were quantified by weight and compared to platelet, Von Willebrand factor (VWF) and fibrinogen content. Arterial platelet deposition (×10(6)/cm(2)) 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 (R(2) = 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 α(IIb)β3 receptor. Unlike arterial thrombosis, inhibition of this receptor is insufficient to prevent venous stent thrombosis.
authors.affiliation: Section of Hematology Research, Mayo Clinic, Rochester, MN, 55905, USA, mcbane.robert@mayo.edu.
authors.forename: Robert D
authors.initials: RD
authors.lastname: McBane
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Karnicki
authors.forename: Waldemar E
authors.initials: WE
authors.lastname: Wysokinski
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D005260:Female; D007084:Iliac Vein / Q000378:metabolism / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D015607:Stents; D013552:Swine; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000085:Acetates; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; C084062:lamifiban