徐建民－特发性血小板减少性紫癜

1、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

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

3、2）destruction ：ITP,DIC,TTP （3）abnormal distribution：splenomegaly 3.classification：primary ,secondary,IDIOPATHIC (AUTOIMMUNE) THROMBOCYTOPENIC PURPURA (ITP),General Considerations,ITP is an autoimmune disorder in which an IgG autoantibody is formed that binds to platelets It is not clear which antige

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

5、een is the major site both of antibody production and platelet sequestration, splenectomy is highly effective therapy,General Considerations,1.definition：thrombocyte unrelated to a drug, an infection, or autoimmune disease is generally classified as ITP 2.character： shortened span of platelet increa

6、sed megakaryocyte in bone marrow 3.classification：acute, chronic,Mechanism,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 Ag,Mechanism,2.liver and spleen

7、： （1）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 patients,Mechanism,3.else： （1）estrogen: ITP often seen in female patient hold down platelet production augment platelet clearance （2）mor

8、e delicate capillary wall,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.,Clinical Findings,age ： It is a disease of young per

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

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.,Clinical Findings,1. occurs ： （1）acute： children, fever viral infection history fe

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

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

13、counts are usually normal except for occasional mild anemia,Laboratory Findings,cell morphology： normal except that platelets are slightly enlarged (megathrombocytes). These larger platelets are young platelets produced in response to enhanced platelet destruction.,Laboratory Findings,Evanss syndrom

14、e： 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.,Laboratory Findings,bone marrow： appear normal, with a normal or increased number of megakaryocyte

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

16、 bone marrow with normal or increased megakaryocytes,Differential 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.,Differential D

17、iagnosis,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 thrombocytopen

18、ia.,Differential 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 secondary thrombocytop

19、enic purpura, hematologically identical to ITP.,Treatment,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 antibody to the pl

20、atelet surface. Long-term therapy decrease antibody production,Treatment,Initial treatment is 12 mg/kg/d. Bleeding will often diminish within 1 day The platelet count will usually begin to rise within a week Responses are almost always seen within 3 weeks. About 80% of patients will respond, and the

21、 platelet count will usually return to normal.,Treatment,High-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 that will maintain

22、 an adequate platelet count.,Treatment,It is not necessary for the platelet count to be entirely normal the risk of bleeding is small with platelet counts above 50,000/mL.,Treatment,Splenectomy： the most definitive treatment for ITP, and most adult patients will ultimately undergo splenectomy High-d

23、ose prednisone therapy should not be continued indefinitely in an attempt to avoid surgery.,Treatment,Indicated： 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 prednisone or may simply

24、prefer the surgical alternative.,Treatment,Safety： 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.,Treatment,High-dose intravenous immunoglobulin Reserved for bleeding emergencies

25、 or situations such as preparing a severely thrombocytopenic patient for surgery This treatment is expensive,Treatment,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.,Treatment,Danazol： patients who fail to respond to prednisone and splenectomy，600 mg/d, with responses obtained in about half of cases. Immunosuppressive agents： employed