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Rochester, MN, United States

Mcbane II R.D.,Section of Hematology Research | Mcbane II R.D.,Foundation Medicine | Gonzalez C.,Section of Hematology Research | Hodge D.O.,Mayo Clinic and Foundation for Education and Research | And 2 more authors.
Journal of Thrombosis and Thrombolysis | Year: 2014

Atherosclerosis reduces platelet survival and thereby increases the percentage of younger platelets in the circulation assuming steady-state thrombocytopoiesis. We hypothesized that younger platelets have an increased propensity for arterial thrombus participation compared to older counterparts. Platelet-rich thrombi were generated by perfusing human heparinized whole blood from normal donors over arterial cross-sections under shear conditions (3,350 s-1) corresponding to significant coronary artery stenosis using a perfusion chamber. Harvested thrombi were disaggregated, stained with thiazole orange, anti-integrin β3, glycoprotein (GP) Ibα, GP IX and P-selectin, and compared to paired whole blood samples from the same donor by flow cytometry. Thiazole orange staining intensity provides a measure of platelet m-RNA content and age. Thiazole orange staining intensity (MN ± SEM) of platelets harvested from thrombi (62 ± 13) was twofold greater compared to paired intra-individual whole blood samples (31 ± 1). Integrin β3 receptor density was also greater for thrombus platelets (12.0 ± 1.0) compared to whole blood platelets (7.0 ± 0.6; p < 0.0001). GPs Ibα and IX were reduced from thrombus platelets possibly reflecting shedding. Younger "reticulated" platelets appear to have a greater propensity for thrombus participation under shear conditions of coronary artery stenosis compared to older counterparts. This predisposition may be explained by an increased receptor density of integrin β3 in younger platelets. By this mechanism, the atherosclerotic process may enhance the individual propensity for arterial thrombosis. © 2013 Springer Science+Business Media New York.

McBane R.D.,Section of Hematology Research | McBane R.D.,Mayo Medical School | Karnicki K.,Section of Hematology Research | Wysokinski W.E.,Section of Hematology Research | Wysokinski W.E.,Mayo Medical School
Journal of Thrombosis and Thrombolysis | Year: 2013

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. © 2013 Springer Science+Business Media New York.

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