Hemorrhagic diseases MD & PHD Professor Aijun Liao Department of Hematology Shengjing Hospital of China Medical UniversityCell phone: 18940259833Classification of hemorrhagic diseases 1. Abnormality of blood vessel 2. Abnormality of platelets 3 . Abnormality of coagulationMechanism of cougulationCoagulation factors FIFI，fibrinogenfibrinogenFIIFII，prothrombinprothrombin FIIIFIII，tissue factortissue factor，tissue tissue thromboplastinthromboplastinFIVFIV，CaCa+FV, labile factorFV, labile factorFVII, stable factorFVII, stable factorFVIII, FVIII, antihemophilicantihemophilic globulin, AHG globulin, AHGFIX, plasma FIX, plasma thromboplastinthromboplastin component,PTCcomponent,PTC， Christmas factorChristmas factorFX, Stuart-FX, Stuart-ProweProwe factor factorFXI, plasma FXI, plasma thromboplastinthromboplastin anticedent,PTAanticedent,PTAFXII, Hageman FactorFXII, Hageman FactorFXIII, fibrin FXIII, fibrin stablizingstablizing factor factorPKPKHMWK HMWK Coagulation cascadetheoryThe mechanism of anticoagulation and fibrinolysisThe system of anticoagulation *Antithrombin (AT) *Protein C system *Tissue factor pathway inhibitor (TFPI) *HeparinFibrinolysis system *Plasminogen (PLG) *t-PA *u-PA *Plasmin-related inhibitorCoagulation=Anticoagulation Laboratory examination for hemorrhagic diseases 1. Platelet count 2. Bleeding time(BT) 3. Clot retraction test 4. Capillary fragility test If above items are abnormal ,that means abnormality of blood vessel or platelet . 5. Clotting time(CT) 6. Plasma prothrombin time (PT) 7. Thrombin clotting time(TT) 8. Activation partial thromboplastin time(APTT) Kaolin partial thromboplastin time(KPTT) If above items are abnormal, that means abnormality of coagulation.PT FVII deficiencyAPTT hemophilia or FXI deficiency PT deficiency of FV, FX, APTT FII, or fibrinogen abnormalities. Acquired deficiencies of plasma coagulation are more frequent than congenital disorder; the most common disorders include : -Hemorrhagic diathesis of liver disease; -Disseminated intravascular coagulation (DIC), -Vitamin K deficiency of more than one clotting factor.treatmentRequires replacement of the deficient protein using recombinant or purified plasma derived products or fresh plasma. Disseminated Intravascular CoagulationDICDefinitionThe syndrome of DIC is a pathological state in the development of diseases. DIC is always secondary to another disorder. It never occurs as a primary disease.EtiologyInfectious diseases: 43% *bacteria infection *virus *protozoon malariaEtiologyMalignant tumor : 34%Pathologic obsterics: 12%Operation and trauma: 5%Systemic diseasePathogenesis1.Damage of tissue release of tissue factor into blood activate extrinsic coagulation pathway2.Damage of vascular epitheliaintrinsic coagulation system3.Platelet activate4.Activate fibrinolysindisturbance of coagulation and fibrinolysisCoagulationAnticoagulation CoagulationAnticoagulationThe disturbance of balance between coagulation and anticoagulationPathology and pathophysiologyMicrothrombosis-the fundamental and specific change of pathologyAbnormality of coagulation *hypercoagulable stage *consumptive hypocoagulable stage *secondary hyperfibrinolytic stageDisturbance of microcirculationClinical manifestationsBleeding tendencyShock or disturbance of microcirculationEmbolism of microvasculatureMicroangiopathic hemolysisManifestations of primary disease.Clinical manifestationsBleeding tendencyShock or disturbance of microcirculationEmbolism of microvasculatureMicroangiopathic hemolysisManifestations of primary disease.Clinical manifestationsBleeding tendencyShock or disturbance of microcirculationEmbolism of microvasculatureMicroangiopathic hemolysisManifestations of primary disease.DICClinical manifestationsBleeding tendencyShock or disturbance of microcirculationEmbolism of microvasculatureMicroangiopathic hemolysisManifestations of primary disease.Lab examination1.platelet count2.quantitative of plasma fibrinogen 1.5g/L or dynamic decrease, in liver disease 1.0g/L( in malignant tumor 4g/L3.3p test (+) or plasma FDP 20mg/L(60mg/L in liver disease) or D-dimer (+) or increased4.PT: prolonged or shorten more than 3s ( in liver disease 5s) or dynamic change5.plasminogen decreased 6.AT III decreased.7.plasma FVIII:C 50%(in liver disease it must be +) Diagnosis1. Primary disease of DIC2. At least 2 items of clinical manifestation. Anticoagulant treatment is effective3. At least 3 items of lab examination(+) TreatmentEliminate the inducing factors and causes of DIC and treat primary diseaseAnticoagulation therapy : Heparin-APTT prolonged 60%-100% is very goodReplenish coagulation factors and plateletsAntifibrinolysis therapy : EACA PAMBA Idiopathic thrombocytopenic purpura (ITP)also known as Primary immune thrombocytopenia (ITP)Etiology and Pathogenesis (1) Infection (2) Immunity factors: PA IgG and PB IgG (3) Spleen factor (4) Other factor : estrogenClinical manifestation(1) Onset Acute type Chronic type 1) Children women 2) Abrupt insidious 3) History of upper (-) respiratory tract infection 4) Petechiae menorrhea Organ bleeding 5) PLT 20109/L 50109/L 左右 (2) Hemorrhagic symptompetechiae , purpura, hematuriagastrointestinal tract hemorrhagegum bleedingmenorrheaintracranial hemorrhage (3)Sign 1) Purpura2) The spleen usually can not be palpable or enlargement Laboratory examination(1) Platelet count Acute ITP 30mg/day. 3)The use of glucocorticoid is contraindicated. 4) Isotope labeled platelet increases in spleen. (3) Immunosuppression: 46WS 1) VCR :1mg once each week.iv or iv drop 3 6WS 2) CTX 3) 6MP 4) CsA 5) Rituximab(4) Severe cases: 1)PLT20 109/L2) Severe and extensive bleeding3)intracranial hemorrhage4) operation at presentTreatment of severe cases1) supportive treatments PLT or fresh blood transfusion in severe cases ,PLT 20 109/L 2) Gamma globulins :0.20.4/kg.d, 5 days, iv drop3) Plasma change: PA IgG decrease4) large dosage methylprednisolone: 1.o g/d. iv drop. 3 5days.Experimental and novel agentsH. pylori eradicationAnti-DDapsone TPOThrombopoietin Receptor Agonists:, Romiplostim, EltrombopagKey pointCommon Causes of DIClInfection disease (Gram-negative sepsis)lMalignant tumor (leukemia, lymphoma, cancers of liver, lung, pancreas, prostate and stomach)lObstetric complications (abruption placentae, pre-eclampsia, amniotic fluid embolism)lOperation and traumalSystemic diseaseKey pointLaboratory tests for DIC diagnosis lPlatelet counts100109/L, or a rapid declinelFibrinogen1.5g/L, 4g/L, or a rapid declinelFibrin degradation product (FDP)20mg/L, and/or D-dimer increaselProlongation or shorten of PT (more than 3s) and/or APTT (more than 10s)Key pointWhich situation cannot you use antifibrinolytic drugs, such as EACA?lhematuriaKey pointTreatment of ITPlPlatelet transfusionlSteriodslIVIglSplenectomylImmunosuppresantslThrombopoietin Receptor Agonists 谢谢 谢谢 ！