课件：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,R. Ross. Atherosclerosis. NEJM 340:115-126, 1999,Atherosclerosis,Site specific: Bifurcations Branching vessels Curvatures Decreased shear stress and increased turbulence Plaque formation and rupture,Unstable plaque. R.Ross NEJM 340:115-126, 1999.,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, Waldenstroms Macroglobulinemia,Hypercoagualbility: Hereditary/Acquired,Factor V Leiden Prothrombin 20210 Protein C Protein S Anti-thrombin III Dysfibrinogenemia,Hyperhomocysteinemia PAI-I Platelet glycoprotein IIb/IIIa,Factor V Leiden,Mutation at position 506 rendering FV insensitive to degradation by activated protein C. Autosomal dominant; 5% Caucasian population. Heterozygote - 7x increased risk for venous thrombosis Homozygote - 80x increased risk Often found in association with other risk factors - protein C and S deficiencies,Prothrombin 20210 Mutation,Mutation results in increased synthesis of prothrombin resulting in elevated plasma levels of biochemically normal prothrombin Autosomal dominant; 1-2% of population Increased risk of venous thrombosis - 2x,Protein C Deficiency,Autosomal dominant Mutation results in mild to severe deficiency; increase risk for venous thrombosis homozygote = purpura fulminans 0.2% of US population Acquired - DIC, liver disease, oral contraceptives, oral anticoagulant use,Protein S Deficiency,Autosomal dominant Increased risk of venous thrombosis Acquired deficiencies - DIC, liver disease. coumarin therapy, pregnancy (2nd and 3rd trimesters), estrogen replacement therapy, L-asparginase chemotherapy,Hyperhomocysteinemia,Increased levels are associated with increased risk of arterial and venous thrombosis. Multiple effects on endothelial cells - decreased thrombomodulin, increased TF activity, inhibition of NO and TPA,Hyperhomocysteinemia,Primary - mutation of MTHFR gene Acquired - vitamin B12, B6 or folic acid deficiency, hypothyroidism, isoniazid, methotrexate, theophylline,Hereditary Thrombophilia,Consider if : family history of thrombosis history of recurrent thrombosis thrombosis at a young age no acquired predisposing factors for thrombosis,Malignancy,Risk for thrombosis is multifactorial. Predominantly venous thrombosis - stasis, tumor invasion of vessels, chemotherapy effects superimposed on acquired or primary defects in hemostasis. Distinct procoagulant (cysteine protease) found in many patients which can activate FX directly.,Antiphospholipid Antibody Syndrome,Autoimmune disorder, either primary or secondary, associated with an increased risk for arterial and venous thrombosis. Antibody is to cardiolipin in APA (ELISA assay); antibody is to beta 2 glycoprotein 1 and platelet phospholipids in patients with lupus anticoagulants (aPTT and/or PT).,Thrombus,Size, shape and morphology Mural thrombus Infected thrombus bacterial endocarditis Verrucous thrombus Libman-Sacks endocarditis,Thrombus,Natural history: Resolution Propagation Fragmentation/embolization Organization,Resolution,Propagation complete occlusion,F,Fragmentation and Embolization,Organization Fibroblast proliferation,Organization Endothelial cell differentiation,Resolution,Organization - Rethrombosis,Thrombus,Clinical presentation: Arterial coronary, carotid and femoral Acute MI, Angina CVA, TIA Claudication Venous superficial veins, deep veins Thrombophlebitis, swollen, painful extremity Pulmonary embolus,后面内容直接删除就行 资料可