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,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,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 F： triggering intrinsic and extrinsic pathway （4）pression of haematoma,Normal hemostasis and coagulation,2. 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 spasm,Normal hemostasis and coagulation,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 thrombus,Normal hemostasis and coagulation,coagulation： nature: a cascade of enzymes activation not active before activated component: 12 coagulation factor: 11 in plasma (tissue factor) protein ( exclude Ca+ ) code with 、 etc. PK HMWK,Normal hemostasis and coagulation,3. course： （1）thromboplatin intrinsic: -a-a- a+Ca+PF3 extrinsic: III-VII+Ca -a+Ca+PF3 （2）thrombin：prothrombinthromboplatin+Cathrombin,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,溶解性纤维蛋白,纤维蛋白原,纤维蛋白（凝块）,VII,凝血酶 IIa,IXa,VIIIa,Ca2+,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 plasminogen,Normal hemostasis and coagulation,Anticoagulant 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. DK,Normal hemostasis and coagulation,（3）protein C system： PCTMAPC+PS sterilize Va. VIIIa. Inhibit PAI,Physiology 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 coagulation,fibrinolysis： plasminogenplasminogen activator plasmin （PAI）（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：,Abnormality,2. 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 disease,Abnormality,3. Coagulation： （1）heredity：hemophilia、willabrand disease （2）aquired：liver disease、renal failure、 VitK deficiency、 DIC （3）anticoagulant agents：、-Ab、drug,Diagnosis,History and physical exam(PE): 1.history：cause, sex、heredity background course 2.PE：petechial bleeding (organ, muscle, joint cavity),Diagnosis,Lab examination： 1.filter： vessel, platelet: BT、plt、CRT coagulation：CT、APTT、PT、TT,Diagnosis,2.particular: （1）platelet： morphology：bulk、scatter、gathering adhesion、aggregation： inducer：Adr、ADP、collagen、ristocetin thrombasthenia thrombus disease,Diagnosis,（2）Coagulation： APTT+CT：VIII. IX. XI PTCT：V. VII. X. II TT：fibrinogen、anticoagulant agents Coagulant factor test：quantity activation,Prevention and Therapy,1. Prevention： drug：aspirin, persantin, indomethacin disease: liver disease ,renal failure heredity：prevent traumer 、operation,Prevention and Therapy,2. 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