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By John W. Hallett Jr. MD FACS, Joseph L. Mills MD FACS, Jonathan Earnshaw DM FRCS, Jim A. Reekers MD PhD, Thom Rooke MD

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Extra info for Comprehensive Vascular and Endovascular Surgery: Expert Consult - Online and Print, 2nd Edition

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The central fibrinolytic enzyme is plasmin, a serine protease generated by the proteolytic cleavage of the proenzyme plasminogen. Its main substrates include fibrin, fibrinogen, and other coagulation factors. 32 Activation of plasminogen occurs through four major mechanisms. In the presence of thrombin, vascular endothelial cells produce and release tPA, as well as α2-antiplasmin, a natural inhibitor of excess fibrin-bound plasmin. 12 In contrast to free-circulating tPA, fibrinbound tPA is an efficient activator of plasminogen.

In addition, arterial flow across the stenosis results in platelet deposition at its apex, the point of maximal shear force. at venous confluences, saccules, and valve pockets. 49 With progression, leukocytes (initially neutrophils and subsequently monocytes) extravasate into the vein wall in response to the chemokine gradient generated by the initial thrombotic event, ultimately resulting in transmural venous inflammation. A balance between proinflammatory and anti-inflammatory cytokines and chemokines determines the ultimate vein wall response.

Although direct endothelial injury, blood stasis, and changes in its composition leading to hypercoagulable states are known risk factors in venous thrombosis, the inciting event involves the formation of thrombus from local procoagulant events, such as small endothelial ­ disruptions Thrombosis and inflammation P-selectin Extrinsic pathway activation Platelet Release of tissue-factor-rich microparticles Platelet-leukocyte interactions Platelet activation P-selectin expression Thrombosis P-/E-selectin receptor Injury Stasis Hypercoagulability Leukocyteleukocyte interactions Leukocyte activation Leukocyte Endothelial activation P-/E-selectin expression Endothelial-leukocyte interactions P-/E-selectin Endothelial cell Figure 3-6.

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