溶血性贫血英文版课件

1、溶血性贫血Hemolytic Anemia华山医院血液科陈勤奋HEMOLYTIC ANEMIA (reduced RBC life span) Anemia of increased destructionNormochromic, normochromic anemiaShortened RBC survivalReticulocytosis-Response to increased RBC destructionIncreased indirect bilirubinIncreased LDHMechanisms and CausesINTRACORPUSCULAR HEMOLYSISM

2、embrane AbnormalitiesMetabolic AbnormalitiesHemoglobinopathiesEXTRACORPUSCULAR HEMOLYSISNonimmune ImmuneMembrane DefectsMicroskeletal defectsHereditary spherocytosisIncreased sensitivity to complementParoxysmal nocturnal hemoglobinuriaEnzymopathiesGlucose 6-Phosphate Dehydrogenase DeficiencyPyruvate

3、 Kinase DeficiencyHemoglobinopathiesHemoglobinopathyThalassemiaExtracorpuscular HemolysisNonimmuneInfectiousChemicalThermalOsmoticExtracorpuscular Hemolysis ImmuneAll require antigen-antibody reactionsTypes of reactions dependent on:Class of AntibodyNumber & Spacing of antigenic sites on cellAvailab

4、ility of complementEnvironmental TemperatureFunctional status of reticuloendothelial systemManifestationsIntravascular hemolysisExtravascular hemolysisExtracorpuscular Hemolysis ImmuneAntibodies combine with RBC, & eitherActivate complement cascade, &/orOpsonize RBC for immune systemIf 1, if all of

5、complement cascade is fixed to red cell, intravascular cell lysis occursIf 2, &/or if complement is only partially fixed, macrophages recognize Fc receptor of Ig &/or C3b of complement & phagocytize RBC, causing extravascular RBC destructionClassificationIntravascularExtravascularclinical featuresch

6、ronicpallor 、 jaundice 、 splenomegalycholelithiasisaplastic crisisacutealgor、hyperpyrexia、sore waisthemoglobinuriajaundice、anaemialaboratory examinationIncreased RBC destructionReduced RBC life spanIndirect hyperbilirubinemiaErythroid hyperplasiaReticulocytosisErythroblasts, anisopoikilocytosis, sph

7、erocytes in blood smear Erythroid hyperplasia in bone marrowdiagnosis and differential diagnosishemolysis or not?type of hemolysisanother anemia?another jaundice with anemia?another jaundice without anemia?TreatmentRemove the causes Immunosupressive drugWashed RBC transfusionSplenectomySymptomatic t

8、reatmentHereditary SpherocytosisDefective or absent spectrin moleculeLeads to loss of RBC membrane, leading to spherocytosisDecreased deformability of cellIncreased osmotic fragilityExtravascular hemolysis in spleenHereditary SpherocytosisPathophysiology-RBC membrane protein defects (spectrin defici

9、ency) resulting cytoskeleton instabilityFamilly historyClinical featuressplenomegalyHereditary SpherocytosisLaboratory features - hemolytic anemia - blood smear-microspherocytes - abnormal osmotic fragility test - positive autohemolysis test - prevention of increased autohemolysis by including gluco

10、se in incubation medium Treatment-splenectomyHereditary SpherocytosisHereditary Spherocytosis Osmotic FragilityParoxysmal Nocturnal Hemoglobinuria (PNH)PNH is an acquired chronic hemolytic anemia which arises from a somatic mutation in a hematopoietic stem cell. Most hematopoitic cell lines may be a

11、ffected by the intrinsic membrane defect. This defect renders the red cells highly susceptible to complement mediated lysis resulting in the characteristic hemolysis.Paroxysmal Nocturnal Hemoglobinuria (PNH)Pathogenesis - an acquired clonal disease, arising from a somatic mutation in a single abnorm

12、al stem cell - glycosyl-phosphatidyl- inositol (GPI) anchor abnormality - deficiency of the GPI anchored membrane proteins(CD55 and CD59) - red cells are more sensitive to the lytic effect of complement - intravascular hemolysis urine aliquot of PNHclinical manifestationpancytopeniapassage of dark b

13、rown urine in the morningvenous thrombosis(Budd-Chiari Syndrome)Laboratory featuresPancytopeniaChronic urinary iron lossSerum iron concentration decreasedHemoglobinuriaHemosiderinuriaPositive Hams test (acid hemolysis test), sugar-water testSpecific immunophenotype of blood cells(CD59, CD55)Attentio

14、nAA-PNH syndromeAAPNHPNHAAPNH with AAAA with PNHTreatmentavoid causeswashed RBC transfusioniron therapyallogenic bone marrow transplantationG-6-PD Deficiencyacute hemolytic anemiacongenital nonspherocytic hemolytic anemianeonatal hyperbilirubinemia （kernicterus）favismLevel needed for protection vs o

15、rdinary oxidative stressAutoimmune HemolysisDue to formation of autoantibodies that attack patients own RBCsType characterized by ability of autoantibodies to fix complement & site of RBC destructionOften associated with either lymphoproliferative disease or collagen vascular diseaseAutoimmune Hemol

16、ytic Anemiawarm-reactive antibodiesprimarysecondarycold-reactive antibodiescold agglutinin syndromeparoxysmal cold hemoglubinuriaAutoimmune hematolysisWarm TypeIgG+C3IgGC3Autoimmune hematolysis Warm TypeUsually IgG antibodiesFix complement only to level of C3,if at allImmunoglobulin binding occurs a

17、t all tempsFc receptors/C3b recognized by macrophagesHemolysis primarily extravascular70% associated with other illnessesResponsive to steroids/splenectomyClinical manifestationanemia、jaundice、splenohepatomegaliaITP+AIHA=Evens syndromeLaboratory examinationBlood：anemia；Ret；erythroblasts, anisopoikil

18、ocytosisBone marrow：erythroid hyperplasia Coombs TestCoombs Test - DirectLooks for immunoglobulin &/or complement of surface of red blood cell (normally neither found on RBC surface)Coombs reagent - combination of anti-human immunoglobulin & anti-human complementMixed with patients red cells; if imm

19、unoglobulin or complement are on surface, Coombs reagent will link cells together and cause agglutination of RBCsCoombs Test - IndirectLooks for anti-red blood cell antibodies in the patients serum, using a panel of red cells with known surface antigensCombine patients serum with cells from a panel of RBCs with known antigensAdd Coombs reagent to this mixtureIf anti-RBC antigens are in serum, agglutination occursDiagnosisTreatme