DISORDERS OF HEMOSTASIS Dept of Hematology Zhong Shan Hospital, FuDan University Prof JIAN-MIN XU
DISORDERS OF HEMOSTASIS Dept.of Hematology ZhongShan Hospital,FuDan University Prof. JlAN-MIN XU
General Considerations Disorders of hemostasis defects in platelet number or function problems in fibrin clot(coagulation) Bleeding due to platelet disorders is typically mucosal or dermatologic include epistaxis, gum bleeding menorrhagia, gastrointestinal bleeding purpura, and petechiae
General Considerations • Disorders of hemostasis defects in platelet number or function problems in fibrin clot (coagulation) • Bleeding due to platelet disorders is typically mucosal or dermatologic include epistaxis, gum bleeding, menorrhagia, gastrointestinal bleeding, purpura, and petechiae
General Considerations Petechiae are seen almost exclusively in conditions of thrombocytopenia and not platelet dysfunction Bleeding due to coagulopathy may occur as deep muscle hematomas as well as skin bleeding Spontaneous hemarthroses are seen only in severe hemophilia
General Considerations • Petechiae are seen almost exclusively in conditions of thrombocytopenia and not platelet dysfunction. • Bleeding due to coagulopathy may occur as deep muscle hematomas as well as skin bleeding. • Spontaneous hemarthroses are seen only in severe hemophilia
General Considerations Definition disorder of hemostasis spontaneous bleeding abnormal bleeding following trauma Machanism vessel wall defect thrombocytopenia, platelet disfunction coagulation disorder
General Considerations • Definition: disorder of hemostasis spontaneous bleeding abnormal bleeding following trauma • Machanism ： vessel wall defect thrombocytopenia, platelet disfunction coagulation disorder
Normal hemostasis and coagulation hemostasis 1. Vessel wall (1)vessel spasm: reflex spasm SHT↑ slow down blood flow (2) subendothelial connective tissue encouraging platelet adhesion, activation aggregation (3)releasing TF, activating FXIl triggering intrinsic and extrinsic pathway (4) pression of haematoma
Normal hemostasis and coagulation • hemostasis: 1. Vessel wall： （1）vessel spasm: reflex spasm S-HT↑ slow down blood flow （2）subendothelial connective tissue： encouraging platelet adhesion, activation, aggregation （3）releasing TF, activating FⅫ： triggering intrinsic and extrinsic pathway （4）pression of haematoma
Normal hemostasis and coagulation 2. platelet: (1) adhesion to subendothelial connective tissue by gpib、WF (2) aggregation formation of platelet thrombus by GPib/Ⅲa (3) release phosphatide-Arachidonic Acid -TXA2 further platelet activation and adhesion vIolent vessel spasm
Normal hemostasis and coagulation 2. platelet： （1）adhesion： to subendothelial connective tissue by GPⅠb、vWF （2）aggregation ： formation of platelet thrombus by GPⅡb/Ⅲa （3）release： phosphatide-Arachidonic Acid -TXA2 further platelet activation and adhesion violent vessel spasm
Normal hemostasis and coagulation 3. coagulation: (1) Rearrangement of platelet membrane phosphatidate-PF3 (2) Tissue injury- TF release (3) Subendothelial connective tissue-Ⅻ-Ⅻa triggering intrinsic and extrinsic pathway- White thrombus-red thrombus
Normal hemostasis and coagulation 3. coagulation: （1） Rearrangement of platelet membrane phosphatidate-PF3 （2） Tissue injury- TF release （3） Subendothelial connective tissue-Ⅻ-Ⅻa triggering intrinsic and extrinsic pathwaywhite thrombus-red thrombus
Normal hemostasis and coagulation coagulation: 1. nature: a cascade of enzymes activation not active before activated 2. component 1.12 coagulation factor: 11 in plasma(tissue factor) protein( exclude Ca code with|、‖、Ⅲ、Ⅳetc 2 PK 3. HMWK
Normal hemostasis and coagulation • coagulation： 1. nature: a cascade of enzymes activation not active before activated 2. component: 1. 12 coagulation factor: 11 in plasma (tissue factor) protein ( exclude Ca++ ) code with Ⅰ、Ⅱ、Ⅲ、Ⅳ etc. 2. PK 3. HMWK
Normal hemostasis and coagulation 3. course (1) thromboplastin intrinsic:ⅫXa—X-XIaX IXa+Ⅷ山+ca+PF3 extrinsic: IlI-Vll+Ca XXa+V+Ca+PF3 (2) thrombin: prothrombin thromboplastin+ Cathrombin
Normal hemostasis and coagulation 3. course： （1）thromboplatin intrinsic: Ⅻ-Ⅻa——Ⅺ-Ⅺa-Ⅸ- Ⅸa+Ⅷ+Ca+PF3 extrinsic: III-VII+Ca Ⅹ-Ⅹa+Ⅴ+Ca+PF3 （2）thrombin：prothrombinthromboplatin+Cathrombin
Xa因子的核心作用 内源性系统 外源性系统 XIla 胞的促凝血 XIa 原激酶 VIla IXa Ca2+ VIlla Ca PL Xa X Xa Va Ca2+ 凝血酶 PL 纤维蛋白原 溶解性纤维蛋序一纤维蛋白(凝块) Boneuet al Sang Thrombose Vaisseaux. 1998; 10: 291-313
Boneu et al. Sang Thrombose Vaisseaux. 1998;10:291-313. II VIIa 细胞的促凝血酶 原激酶 Ca2+ Xa XIa 内源性系统 外源性系统 X IX XIIIa XI XII XIIa 纤维蛋白原 溶解性纤维蛋白 纤维蛋白（凝块） Xa Va PL Ca2+ VII 凝血酶 IIa IXa VIIIa Ca2+ PL Xa因子的核心作用