止血障碍血栓形成.ppt

Disorders of Hemostasis: Thrombosis John Lazarchick, M.D. Director, Hematopathology/Hemostasis August 30, 2001 Hypercoagulability Definition: Alteration in the hemostatic balance between blood fluidity and clot formation. This is due to genetic and acquired disorders which shift this balance toward excessive or inappropriate platelet aggregation and fibrin formation and predispose to thrombosis. Prethrombotic States 10 - inherited abnormalities resulting from mutations affecting the function of coagulant proteins and natural inhibitors 20 - acquired defects that either affect the endothelium, fluid flow or blood components. These defects are often superimposed on 10 defects Hypercoagulability:Prethrombotic States Virchow (1856) Abnormalities of blood vessels Abnormalities of fluid flow Abnormalities of blood components Blood Vessel Abnormalities Endothelial cell antithrombotic properties- PGI2, NO2, TFPI, PAI-1, heparans, thrombomodulin Genetic predisposition and acquired defects in these functions increase the risk of arterial and venous thrombosis Role of dietary excesses, hypertension, diabetes mellitus, obesity, smoking, lipid abnormalities in atherosclerosis Atherosclerosis Endothelial injury and dysfunction LDL cholesterol – oxidized LDL--- foam cells Diabetes mellitus – glycated LDL cholesterol Smoking – free radical production Hypertension – smooth muscle proliferation Genetic alterations – MTHFR mutations Atherosclerosis Site specific: Bifurcations Branching vessels Curvatures Decreased shear stress and increased turbulence Plaque formation and rupture Blood Flow Abnormalities Stasis is the underlying mechanism as the cause of venous or arterial thrombosis Conditions - immobilization, surgery, congestive heart failure, pregnancy, obesity. Increased blood viscosity RBCs - polycythemias, sickle cells WBCs – myeloproliferative disorders especially CML Platelets - primary thrombocytosis Paraproteins - Myeloma, Waldenstrom’s Macroglobulinemia Hypercoagu