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Fribrinogen in Thrombus Formation

Fibrinogen, one of the most abundant plasma proteins, plays important roles in blood clotting, fibrinolysis, cellular and matrix interactions, inflammation, wound healing, and neoplasia. We have recently focused our research on multiple functions of fibrinogen that may contribute to both hemostasis and thrombosis, including: 1) binding to platelet integrin αIIbβ3, thus supporting both platelet adhesion and aggregation, 2) fibrin formation, 3) fibrin cross-linking in concert with factor XIIIa, 4)clot consolidation via retraction in concert with platelets, 5) enhanced whole blood viscosity. Fibrinogen also has functions that may limit hemostasis and thrombosis, including the binding of thrombin to fibrin (thus removing it from the systemic circulation), and the binding of components of the fibrinolytic system.

To understand better the relative contributions of these functions to primary hemostasis and arterial thrombosis we study mice lacking fibrinogen, mice lacking the αIIbβ3 binding site (QADGV) in the C-terminus of the fibrinogen γ-chain (γΔ5), and wild type mice treated with the hamster antibody 7E9, which binds to the C-terminus of the fibrinogen γ chain; inhibits platelet adhesion, aggregation, and clot retraction; interferes with fibrin formation and FXIIIa-mediated cross-linking; and facilitates thrombolysis.