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 ConsiderationsPetechiae 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 ConsiderationsDefinition: disorder of hemostasis spontaneous bleeding abnormal bleeding following trauma Machanism ： vessel wall defect thrombocytopenia, platelet disfunction coagulation disorderNormal 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 F： triggering intrinsic and extrinsic pathway （4）pression of haematomaNormal hemostasis and coagulation2. platelet：（1）adhesion： to subendothelial connective tissue by GPb、vWF（2）aggregation ： formation of platelet thrombus by GPb/a（3）release： phosphatide-Arachidonic Acid -TXA2 further platelet activation and adhesion violent vessel spasmNormal hemostasis and coagulation3.coagulation:（1） Rearrangement of platelet membrane phosphatidate-PF3 （2） Tissue injury- TF release（3） Subendothelial connective tissue-a triggering intrinsic and extrinsic pathway-white thrombus-red thrombusNormal hemostasis and coagulationcoagulation：1.nature: a cascade of enzymes activation not active before activated2.component:1.12 coagulation factor: 11 in plasma (tissue factor) protein ( exclude Ca+ ) code with 、 etc.2.2.PKPK3.3.HMWKHMWKNormal hemostasis and coagulation3. course：（1）thromboplatin intrinsic: -a-a- a+Ca+PF3 extrinsic: III-VII+Ca -a+Ca+PF3（2）thrombin：prothrombinthromboplatin+CathrombinBoneu et al. Sang Thrombose Vaisseaux. 1998;10:291-313.IIVIIa细胞细胞的促的促凝血酶凝血酶原激酶原激酶Ca2+XaXIa内源性系统内源性系统内源性系统内源性系统外源性系统外源性系统外源性系统外源性系统XIXXIIIaXIXIIXIIa溶解溶解性性纤维蛋白纤维蛋白纤维蛋白纤维蛋白原原纤维蛋白纤维蛋白（凝块）（凝块）XaVaPLCa2+VII凝血酶凝血酶IIaIXaVIIIaCa2+PL Xa因子的核心作用Normal hemostasis and coagulation（3）fibrin：fibrinogenthrombinfibrin monomer-polymerXIIIapolymer（4）function of thrombin： coagulation：activate、 strengthen 、 platelet：aggregation, release fibrinolysis：activate plasminogenNormal hemostasis and coagulationAnticoagulant system：1. anticoagulin：（1）each coagulate factor and their complex has its own inhibitor（2）important： AT-：70% anticoagulant activity serine proteinase inhibitor a. a. a. a. DKNormal hemostasis and coagulation（3）protein C system： PCTMAPC+PS sterilize Va. VIIIa. Inhibit PAIPhysiology and Pathology APCI a,trypsinize， TM+thrombin activator sterilize a，a PC APC release plasminogen Ca+ fibrolysis Ca+ PS modulate the activation of c acceleration inhibition APC：Activated Protein C Normal hemostasis and coagulationfibrinolysis：1. plasminogenplasminogen activator plasmin （PAI）（）（a a2-AP）2. fibrinolysis： fibrinogenfragmentX fragmentY fragmentE （FDP）polypeptideABC fragmentD fragmentD Abnormality 1. Vessel wall： heredity：Telangiectasis aquired：deficiency of Vit C、 Vit P hypersensitivity：anaphylactoid purpura else： Abnormality2. Platelet：（1）thrombocytopenia： production：AA, leukemia, infection, drug destruction ：ITP exhaust：TTP、HUS、DIC Abnormality （2）thrombocythemia ： primary：Primary hemorrhagic thrombocythemia secondary：CML, splenectomy , infection trauma（3）function deficiency： heredity ：thrombasthenia secondary：drug, renal failure liver diseaseAbnormality 3. Coagulation：（1）heredity：hemophilia、willabrand disease（2）aquired：liver disease、renal failure、 VitK deficiency、 DIC（3）anticoagulant agents：、-Ab、drugDiagnosis History and physical exam(PE): 1.history：cause, sex、heredity background course 2.PE：petechial bleeding (organ, muscle, joint cavity)DiagnosisLab examination： 1.filter： vessel, platelet: BT、plt、CRT coagulation：CT、APTT、PT、TTDiagnosis2.particular:（1）platelet： morphology：bulk、scatter、gathering adhesion、aggregation： inducer：Adr、ADP、collagen、ristocetin thrombasthenia thrombus diseaseDiagnosis（2）Coagulation： APTT+CT：VIII. IX. XI PTCT：V. VII. X. II TT：fibrinogen、anticoagulant agents Coagulant factor test：quantity activationPrevention and Therapy1. Prevention： drug：aspirin, persantin, indomethacin disease: liver disease ,renal failure heredity：prevent traumer 、operationPrevention and Therapy2. hemostasis ：（1）supplyment：coagulant factor、fresh plasma、blood、platelet（2）drug： vessel：VitC、VitP、Carbazochrome 、Pred platelet：Etamsylate 、 Pred coagulation：VitK、prothrombin complex fibrinolysis：EACA,PAMBA,Tranexamic Acid （3）local：oppression、decrease movement