七年出血性疾病

1、Hemorrhagic diseases,,MD & PHD Professor Aijun Liao Department of Hematology Shengjing Hospital of China Medical UniversityCell phone: 18940259833,Classification of hemorrhagic diseases 1. Abnormalit

2、y of blood vessel 2. Abnormality of platelets 3 . Abnormality of coagulation,Mechanism of cougulation,Coagulation factors,FI，fibrinogenFII，prothrombin FIII，tissue factor，tissue thromboplastinFIV，C

3、a++FV, labile factorFVII, stable factorFVIII, antihemophilic globulin, AHGFIX, plasma thromboplastin component,PTC， Christmas factorFX, Stuart-Prowe factorFXI, plasma thromboplastin anticedent,PTAFXII, Hag

4、eman FactorFXIII, fibrin stablizing factorPKHMWK,Coagulation cascade theory,The mechanism of anticoagulation and fibrinolysis,The system of anticoagulation *Antithrombin (AT) *Protein C system *Tissue

5、 factor pathway inhibitor (TFPI) *Heparin,Fibrinolysis system *Plasminogen (PLG) *t-PA *u-PA *Plasmin-related inhibitor,Coagulation=Anticoagulation,? Laboratory examination for hemorrhagic diseases

6、 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 plat

7、elet .,5. Clotting time(CT) 6. Plasma prothrombin time (PT) 7. Thrombin clotting time(TT) 8. Activation partial thromboplastin time(APTT) Kaolin partial thromboplastin

8、 time(KPTT) ? If above items are abnormal, that means abnormality of coagulation.,PT FVII deficiencyAPTT hemophilia or FXI deficiency PT deficiency of FV, FX,

9、 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 d

10、isease; --Disseminated intravascular coagulation (DIC), --Vitamin K deficiency of more than one clotting factor.,treatment,Requires replacement of the deficient protein using recombinant or

11、 purified plasma derived products or fresh plasma.,Disseminated Intravascular Coagulation,DIC,Definition,The syndrome of DIC is a pathological state in the development of diseases. DIC is always secondary to another dis

12、order. It never occurs as a primary disease.,Etiology,Infectious diseases: 43% **bacteria infection **virus **protozoon malaria,Etiology,Malignant tumor : 34%,,Pathologic obsterics: 12%Operation and

13、trauma: 5%Systemic disease,Pathogenesis,1.Damage of tissue –release of tissue factor into blood –activate extrinsic coagulation pathway2.Damage of vascular epithelia—intrinsic coagulation system3.Platelet activate4.A

14、ctivate fibrinolysin—disturbance of coagulation and fibrinolysis,,,Coagulation>Anticoagulation Coagulation<AnticoagulationThe disturbance of balance between coagulation and anticoagulation,Pathology and pathophysi

15、ology,Microthrombosis---the fundamental and specific change of pathologyAbnormality of coagulation **hypercoagulable stage **consumptive hypocoagulable stage **secondary hyperfibrinolytic stageD

16、isturbance of microcirculation,Clinical manifestations,Bleeding tendencyShock or disturbance of microcirculationEmbolism of microvasculatureMicroangiopathic hemolysisManifestations of primary disease.,Clinical manife

17、stations,Bleeding tendencyShock or disturbance of microcirculationEmbolism of microvasculatureMicroangiopathic hemolysisManifestations of primary disease.,Clinical manifestations,Bleeding tendencyShock or disturbanc

18、e of microcirculationEmbolism of microvasculatureMicroangiopathic hemolysisManifestations of primary disease.,DIC,Clinical manifestations,Bleeding tendencyShock or disturbance of microcirculationEmbolism of microvas

19、culatureMicroangiopathic hemolysisManifestations of primary disease.,Lab examination,1.platelet count2.quantitative of plasma fibrinogen4g/L3.3p test (+) or plasma FDP >20mg/L(>60mg/L in liver disease) or D-dim

20、er (+) 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 +),,,,Diagnosis

21、1. Primary disease of DIC2. At least 2 items of clinical manifestation. Anticoagulant treatment is effective3. At least 3 items of lab examination(+),,Treatment,Eliminate the inducing factors and causes of DIC an

22、d treat primary diseaseAnticoagulation therapy : Heparin----APTT prolonged 60%-100% is very goodReplenish coagulation factors and plateletsAntifibrinolysis therapy : EACA PAMBA,,Idiopathic thrombocytopenic purpura (I

23、TP),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 : estrogen,Clinical manifesta

24、tion,(1) Onset Acute type Chronic type 1) Children women 2) Abrupt insidious 3) History of upper (-) respiratory

25、tract infection 4) Petechiae menorrhea Organ bleeding 5) PLT< 20×109/L 50×109/L 左右,,(2) Hemorrhagic symptompetechiae , purpura, hematuria

26、gastrointestinal tract hemorrhagegum bleedingmenorrheaintracranial hemorrhage,(3)Sign 1) Purpura2) The spleen usually can not be palpable or enlargement,Laboratory examination(1) Platelet count Acute

27、 ITP <20×109/L Chronic ITP 30----80×109/L(2) BT is prolongation Clot retraction is impaired. Capillary fragility is positive. CT is normal.(3) Bone marrow: The n

28、umber of megakaryocytes are increased or normal with maturation disturbance.,Diagnosis1.Extensive bleeding2.Repeated examinations reveal that platelet count is decreased in peripheral blood.3.Bone marrow4.No he

29、patosplenomegaly5.Cortisone treatment or splenectomy is effective6.Rule out other diseases: Leukemia, AA, ITP, SLE, tumor,Treatment1.Glucocorticoid: first choice 1)Prednisone:1mg ? kg.d gradually decreas

30、ed 2)Dexamethasone:10 —20mg intravenous drip 3) Methylprednisolone :120- 500mg/d, iv drop,(2) Splenectomy can be done:Indication : 1) Glucocorticoid treatment for 3—6 months is not effective.

31、2)Small dosage is easily to relapse. prednisone must >30mg/day. 3)The use of glucocorticoid is contraindicated. 4) Isotope labeled platelet increases in spleen.,,(3) Immunosuppression: 4—6WS

32、 1) VCR :1mg once each week.iv or iv drop 3— 6WS 2) CTX 3) 6—MP 4) CsA 5) Rituximab,(4) Severe cases: PLT<20× 109/L Severe and extensive bleedingintracranial hemorrhage4) operation at pres

33、ent,Treatment of severe cases,1) supportive treatments PLT or fresh blood transfusion in severe cases ,PLT< 20× 109/L 2) Gamma globulins :0.2—0.4/kg.d, 5 days, iv drop3) Plasma change: PA IgG decre

34、ase4) large dosage methylprednisolone: 1.o g/d. iv drop. 3 — 5days.,Experimental and novel agents,H. pylori eradicationAnti-DDapsone TPOThrombopoietin Receptor Agonists:, Romiplostim, Eltrombopag,Key point,C

35、ommon Causes of DICInfection disease (Gram-negative sepsis)Malignant tumor (leukemia, lymphoma, cancers of liver, lung, pancreas, prostate and stomach)Obstetric complications (abruption placentae, pre-eclampsia, amnio

36、tic fluid embolism)Operation and traumaSystemic disease,Key point,Laboratory tests for DIC diagnosis Platelet counts≤100×109/L, or a rapid declineFibrinogen＜1.5g/L, ＞4g/L, or a rapid declineFibrin degradation p

37、roduct (FDP)＞20mg/L, and/or D-dimer increaseProlongation or shorten of PT (more than 3s) and/or APTT (more than 10s),Key point,Which situation cannot you use antifibrinolytic drugs, such as EACA?hematuria,Key point,Tre