徐建民－特發(fā)性血小板減少性紫癜 (2)

1、DISORDERS OF HEMOSTASIS Dept.of Hematology ZhongShan Hospital,FuDan University Prof. JlAN-MIN XU 1General 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

2、 epistaxis, gum bleeding, menorrhagia, gastrointestinal bleeding, purpura, and petechiae 2Thrombocytopenic PurpuraDept.of Hematology ZhongShan Hospital,FuDan University Prof. JlAN-MIN XU 3Brief 1.definition：bleeding of skin、mucous and organs2.cause：（1）production ：drug, tumor, infection, radiation（2）

3、destruction ：ITP,DIC,TTP（3）abnormal distribution：splenomegaly3.classification：primary ,secondary4IDIOPATHIC (AUTOIMMUNE) THROMBOCYTOPENIC PURPURA (ITP)5General Considerations ITP is an autoimmune disorder in which an IgG autoantibody is formed that binds to platelets It is not clear which antigen on

4、 the platelet surface is involved. Although the antiplatelet antibody may bind complement, platelets are not destroyed by direct lysis 6 General Considerations Rather, destruction takes place in the spleen, where splenic macrophages with Fc receptors bind to antibody-coated platelets Since the splee

5、n is the major site both of antibody production and platelet sequestration, splenectomy is highly effective therapy 7 General Considerations1.definition：thrombocyte unrelated to a drug, an infection, or autoimmune disease is generally classified as ITP2.character： shortened span of platelet increase

6、d megakaryocyte in bone marrow3.classification：acute, chronic8Mechanism 1.Immunity （1）acute： postviral infection immune complex (viral Ag and Ab) connect with platelet Fc-R viral components banding with platelet auto Ab generation （2）chronic：not affected by foreign Ag9Mechanism2.liver and spleen：（1）

7、1/3 platelets are held within the spleen（2）spleen produces platelet associated Ab（3）liver and spleen erase platelet：7-11 days in normal persons, 1-3 days in patients10Mechanism 3.else：（1）estrogen: ITP often seen in female patient hold down platelet production augment platelet clearance（2）more delica

8、te capillary wall11 Clinical Findings Symptoms and Signs: occurs ： in childhood, frequently precipitated by viral infection and usually self-limited. In adult form is usually a chronic disease and only infrequently follows a viral infection. 12 Clinical Findings age ： It is a disease of young person

9、s, with peak incidence between ages 20 and 50 sex： there is a 2:1 female predominance 13Clinical Findingspresenting complaint： mucosal or skin bleeding. Common types： epistaxis, oral bleeding, menorrhagia, purpura, and petechiae. Patients are systemically well and not febrile. 14Clinical FindingsOn

10、examination： no abnormal findings other than those related to bleeding. An enlarged spleen should lead one to doubt the diagnosis. Common signs of bleeding are purpura, petechiae, and hemorrhagic bullae in the mouth. 15 Clinical Findings1. occurs ：（1）acute： children, fever viral infection history fe

11、rvent uprise, （2）chronic： young or middle-aged female dormant uprise16 Clinical Findings 2. bleeding：（1）manifestation： a. petechial and purpuric、epistaxis gum bleeding b. menorrhagia、digestive tract、 urotract bleeding c. retina hemorrhageblindness intracranial hemorrhage-death17 Clinical Findings（2）

12、characteristic： a. acute：severe、self-limited (4-6w） seldom relapse b. chronic：less severe、ofter relapse longtermelse：anemia (severe bleeding) mild splenomegaly 18 Laboratory FindingsLaboratory Findings: Peripheral blood： counts： The hallmark is thrombocytopenia, which may be less than 10,000/mL. Oth

13、er counts are usually normal except for occasional mild anemia 19 Laboratory Findingscell morphology： normal except that platelets are slightly enlarged (megathrombocytes). These larger platelets are young platelets produced in response to enhanced platelet destruction. 20 Laboratory FindingsEvanss

14、syndrome： Approximately 10% of patients will have coexistent autoimmune hemolytic anemia will see anemia, reticulocytosis, and spherocytes on peripheral smear. Red blood cell fragmentation should not be seen. 21 Laboratory Findingsbone marrow： appear normal, with a normal or increased number of mega

15、karyocytes. Tests： Coagulation studies will be entirely normal. Quantitate platelet-associated IgG may help the diagnosis，highly sensitive (95%) but very nonspecific(50%)22Essentials of DiagnosisIsolated thrombocytopenia. Other hematopoietic cell lines normal. No systemic illness. Spleen not palpabl

16、e. Normal bone marrow with normal or increased megakaryocytes 23Differential Diagnosis Thrombocytopenia may be produced either by abnormal bone marrow function or by peripheral destruction.bone marrow disorders： diagnoses such as myelodysplasia can only be excluded by examining the bone marrow. 24Di

17、fferential Diagnosis peripheral destruction： Can be ruled out by initial evaluation. Disorders such as DIC、TTP、HUS、hypersplenism, and sepsis are easily excluded by the absence of systemic illness. Patients with isolated thrombocytopenia with no other abnormal findings almost certainly have immune th

18、rombocytopenia. 25Differential Diagnosis Patients should be questioned regarding drug use, especially sulfonamides, quinine, thiazides, cimetidine, gold, and heparin. Heparin is now the most common cause of drug-induced thrombocytopenia in hospitalized patients. SLE、Cll are common causes of secondar

19、y thrombocytopenic purpura, hematologically identical to ITP. 26Treatment Few adults with ITP will have spontaneous remissions, most will require treatment. Prednisone： Primarily by decreasing the affinity of splenic macrophages for antibody-coated platelets. High-dose also reduces the binding of an

20、tibody to the platelet surface. Long-term therapy decrease antibody production 27TreatmentInitial treatment is 12 mg/kg/d. Bleeding will often diminish within 1 day The platelet count will usually begin to rise within a weekResponses are almost always seen within 3 weeks. About 80% of patients will

21、respond, and the platelet count will usually return to normal. 28TreatmentHigh-dose therapy should be continued until the platelet count is normal, and the dose should then be gradually tapered. In most, thrombocytopenia will recur if prednisone is completely withdrawn, and one aims to find a dose t

22、hat will maintain an adequate platelet count. 29TreatmentIt is not necessary for the platelet count to be entirely normal the risk of bleeding is small with platelet counts above 50,000/mL. 30TreatmentSplenectomy： the most definitive treatment for ITP, and most adult patients will ultimately undergo

23、 splenectomy High-dose prednisone therapy should not be continued indefinitely in an attempt to avoid surgery. 31TreatmentIndicated： If patients do not respond to prednisone initially or require unacceptably high doses to maintain an adequate platelet count. Other patients may be intolerant of predn

24、isone or may simply prefer the surgical alternative. 32TreatmentSafety： performed safely even with platelet counts less than 10,000/mL. Efficacy： Eighty percent of patients benefit from splenectomy with either complete or partial remission. 33TreatmentHigh-dose intravenous immunoglobulin Reserved fo

25、r bleeding emergencies or situations such as preparing a severely thrombocytopenic patient for surgery This treatment is expensive34Treatment 400 mg/kg/d for 35 days highly effective in rapidly raising the platelet count. The response rate is 90% The platelet count rises within 15 days. The beneficial effect lasts only 12 weeks.35TreatmentDanazol： patients who fail to respond to prednisone and splenectomy，600 mg/d, with responses obtained in about half of cases.Immunosuppressive agents： employed in r