溶血性貧血 課件

1、溶血性貧血溶血性貧血Hemolytic AnemiaHemolytic AnemiaHEMOLYTIC ANEMIAHEMOLYTIC ANEMIA ( (reduced reduced RBCRBC life span life span) )vAnemia of increased destructionAnemia of increased destructionNormochromic, normochromic anemiaNormochromic, normochromic anemiaShortened RBC survivalShortened RBC survivalReti

2、culocytosis-Response to Reticulocytosis-Response to increased RBC destructionincreased RBC destructionIncreased indirect bilirubinIncreased indirect bilirubinIncreased LDHIncreased LDHMechanismsMechanisms and Causes and CausesvINTRACORPUSCULAR HEMOLYSISINTRACORPUSCULAR HEMOLYSISMembrane Abnormalitie

3、sMembrane AbnormalitiesMetabolic AbnormalitiesMetabolic AbnormalitiesHemoglobinopathiesHemoglobinopathiesvEXTRACORPUSCULAR HEMOLYSISEXTRACORPUSCULAR HEMOLYSISNonimmune Nonimmune ImmuneImmuneMembrane DefectsMembrane DefectsvMicroskeletal defectsMicroskeletal defectsHereditary spherocytosisHereditary

4、spherocytosisvIncreased sensitivity to complementIncreased sensitivity to complementParoxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuriaEnzymopathiesEnzymopathiesvGlucose 6-Phosphate Dehydrogenase Glucose 6-Phosphate Dehydrogenase DeficiencyDeficiencyvPyruvate Kinase DeficiencyPyru

5、vate Kinase DeficiencyHemoglobinopathiesHemoglobinopathiesvHemoglobinopathyHemoglobinopathyvThalassemiaThalassemiaExtracorpuscular HemolysisExtracorpuscular HemolysisNonimmuneNonimmunevInfectiousInfectiousvChemicalChemicalvThermalThermalvOsmoticOsmoticExtracorpuscular Hemolysis Extracorpuscular Hemo

6、lysis ImmuneImmunevAll require antigen-antibody reactionsAll require antigen-antibody reactionsvTypes of reactions dependent on:Types of reactions dependent on:Class of AntibodyClass of AntibodyNumber & Spacing of antigenic sites on cellNumber & Spacing of antigenic sites on cellAvailability

7、 of complementAvailability of complementEnvironmental TemperatureEnvironmental TemperatureFunctional status of reticuloendothelial systemFunctional status of reticuloendothelial systemvManifestationsManifestationsIntravascular hemolysisIntravascular hemolysisExtravascular hemolysisExtravascular hemo

8、lysisExtracorpuscular Hemolysis Extracorpuscular Hemolysis ImmuneImmunevAntibodies combine with RBC, & eitherAntibodies combine with RBC, & eitherActivate complement cascade, &/orActivate complement cascade, &/orOpsonize RBC for immune systemOpsonize RBC for immune systemvIf 1, if al

9、l of complement cascade is If 1, if all of complement cascade is fixed to red cell, intravascular cell fixed to red cell, intravascular cell lysis occurslysis occurs1.1.If 2, &/or if complement is only If 2, &/or if complement is only partially fixed, macrophages recognize partially fixed, m

10、acrophages recognize Fc receptor of Ig &/or C3b of Fc receptor of Ig &/or C3b of complement & phagocytize RBC, causing complement & phagocytize RBC, causing extravascular RBC destructionextravascular RBC destructionClassificationClassificationvIntravascularIntravascularvE Extravascul

11、arxtravascular2021/5/711v9、 人的價值，在招收誘惑的一瞬間被決定。人的價值，在招收誘惑的一瞬間被決定。2022-3-62022-3-6Sunday, March 06, 2022v10、低頭要有勇氣，抬頭要有低氣。、低頭要有勇氣，抬頭要有低氣。2022-3-62022-3-62022-3-63/6/2022 8:02:36 PMv11、人總是珍惜為得到。、人總是珍惜為得到。2022-3-62022-3-62022-3-6Mar-226-Mar-22v12、人亂于心，不寬余請。、人亂于心，不寬余請。2022-3-62022-3-62022-3-6Sunday, Marc

12、h 06, 2022v13、生氣是拿別人做錯的事來懲罰自己。、生氣是拿別人做錯的事來懲罰自己。2022-3-62022-3-62022-3-62022-3-63/6/2022v14、抱最大的希望，作最大的努力。、抱最大的希望，作最大的努力。2022年年3月月6日星期日日星期日2022-3-62022-3-62022-3-6v15、一個人炫耀什么，說明他內(nèi)心缺少什么。、一個人炫耀什么，說明他內(nèi)心缺少什么。2022年年3月月2022-3-62022-3-62022-3-63/6/2022v16、業(yè)余生活要有意義，不要越軌。、業(yè)余生活要有意義，不要越軌。2022-3-62022-3-6March 6

13、, 2022v17、一個人即使已登上頂峰，也仍要自強不息。、一個人即使已登上頂峰，也仍要自強不息。2022-3-62022-3-62022-3-62022-3-6clinical featuresclinical featuresvchronicchronicpallorpallor 、 jaundicejaundice 、 splenomegalysplenomegalycholelithiasischolelithiasisaplastic crisisaplastic crisisvacuteacutealgoralgor、hyperpyrexiahyperpyrexia、sore wa

14、istsore waisthemoglobinuriahemoglobinuriajaundicejaundice、anaemiaanaemialaboratory examinationlaboratory examinationvIncreased RBC destructionIncreased RBC destructionvE Erythroid hyperplasiarythroid hyperplasiadiagnosis and diagnosis and differential diagnosisdifferential diagnosisvhemolysis or not

15、?hemolysis or not?vtype of hemolysistype of hemolysisvanother anemia?another anemia?vanother jaundice with anemia?another jaundice with anemia?vanother jaundice without anemia?another jaundice without anemia?TreatmentTreatmentvRemove the causes Remove the causes vImmunosupressiveImmunosupressive dru

16、g drugvW Washed RBC transfusionashed RBC transfusionvSplenectomySplenectomyvSymptomatic treatmentSymptomatic treatmentHereditary SpherocytosisHereditary SpherocytosisvDefective or absent spectrin Defective or absent spectrin moleculemoleculevLeads to loss of RBC membrane, Leads to loss of RBC membra

17、ne, leading to spherocytosisleading to spherocytosisvDecreased deformability of cellDecreased deformability of cellvIncreased osmotic fragilityIncreased osmotic fragilityvExtravascular hemolysis in spleenExtravascular hemolysis in spleenHereditary SpherocytosisHereditary SpherocytosisvPathophysiolog

18、yPathophysiology-RBC-RBC membrane protein membrane protein defects (spectrin deficiency) resulting defects (spectrin deficiency) resulting cytoskeleton instabilitycytoskeleton instabilityvFamilly historyFamilly historyvClinical featuresClinical featuressplenomegalysplenomegalyHereditary Spherocytosi

19、sHereditary SpherocytosisvLaboratory featuresLaboratory features - hemolytic anemia - hemolytic anemia - blood smear-microspherocytes - blood smear-microspherocytes - abnormal osmotic fragility test - abnormal osmotic fragility test - positive autohemolysis test - positive autohemolysis test - preve

20、ntion of increased - prevention of increased autohemolysis by including autohemolysis by including glucose inglucose in incubation medium incubation medium vTreatmentTreatment-splenectomysplenectomyHereditary SpherocytosisHereditary SpherocytosisHereditary Spherocytosis Hereditary Spherocytosis Osmo

21、tic FragilityOsmotic Fragility0204060801000.30.40.50.6NaCl (% of normal saline)% HemolysisNormalHSParoxysmal Nocturnal Hemoglobinuria Paroxysmal Nocturnal Hemoglobinuria (PNH)(PNH)PNH is an acquired chronic hemolytic PNH is an acquired chronic hemolytic anemia which arises from a somatic anemia whic

22、h arises from a somatic mutation in a hematopoietic stem cell. mutation in a hematopoietic stem cell. Most hematopoitic cell lines may be Most hematopoitic cell lines may be affected by the intrinsic membrane defect. affected by the intrinsic membrane defect. This defect renders the red cells highly

23、 This defect renders the red cells highly susceptible to complement mediated lysis susceptible to complement mediated lysis resulting in the characteristic hemolysis.resulting in the characteristic hemolysis.Paroxysmal Nocturnal Hemoglobinuria Paroxysmal Nocturnal Hemoglobinuria (PNH)(PNH)vPathogene

24、sisPathogenesis - an acquired clonal disease, arising from a - an acquired clonal disease, arising from a somatic mutation in a single abnormal stem cellsomatic mutation in a single abnormal stem cell - glycosyl-phosphatidyl- inositol (GPI) anchor - glycosyl-phosphatidyl- inositol (GPI) anchor abnor

25、malityabnormality - deficiency of the GPI anchored membrane - deficiency of the GPI anchored membrane proteins(CD55 and CD59)proteins(CD55 and CD59) - red cells are more sensitive to the lytic - red cells are more sensitive to the lytic effect of complement effect of complement - intravascular hemol

26、ysis - intravascular hemolysisurine aliquot of PNHurine aliquot of PNHclinical manifestationclinical manifestationvpancytopeniapancytopeniavpassage of dark brown urine in the passage of dark brown urine in the morningmorningvvenous thrombosis(Budd-Chiari venous thrombosis(Budd-Chiari Syndrome)Syndro

27、me)Laboratory featuresLaboratory featuresvPancytopeniaPancytopeniavC Chronic urinary iron losshronic urinary iron lossvS Serum iron concentration decreasederum iron concentration decreasedvHemoglobinuriaHemoglobinuriavHemosiderinuriaHemosiderinuriavP Positive Hamositive Hams test (acid hemolysis tes

28、t)s test (acid hemolysis test), , sugar-water testsugar-water testvS Specific immunophenotype ofpecific immunophenotype of blood cells blood cells(CD59, (CD59, CD55)CD55)AttentionAttentionvAA-PNH syndromeAA-PNH syndromeAAPNHAAPNHPNHAAPNHAAPNH with AAPNH with AAAA with PNHAA with PNHTreatmentTreatmen

29、tvavoid causesavoid causesvwashed RBC transfusionwashed RBC transfusionviron therapyiron therapyvallogenic bone marrow allogenic bone marrow transplantationtransplantationG-6-PD DeficiencyG-6-PD Deficiencyvacute hemolytic anemiaacute hemolytic anemiavcongenital nonspherocytic congenital nonspherocyt

30、ic hemolytic anemiahemolytic anemiavneonatal hyperbilirubinemia neonatal hyperbilirubinemia （kernicteruskernicterus）vfavismfavism00.20.40.60.81020406080100120RBC Age (Days)G6PD Activity (%)Normal (GdB)Black Variant (GdA-)Mediterranean (Gd Med)Level needed for protection vs ordinary oxidative stressA

31、utoimmune HemolysisAutoimmune HemolysisvDue to formation of autoantibodies that Due to formation of autoantibodies that attack patientattack patients own RBCs own RBCs svType characterized by ability of Type characterized by ability of autoantibodies to fix complement & site autoantibodies to fi

32、x complement & site of RBC destructionof RBC destructionvOften associated with either Often associated with either lymphoproliferative disease or collagen lymphoproliferative disease or collagen vascular diseasevascular diseaseAutoimmune Hemolytic AnemiaAutoimmune Hemolytic Anemiavwarm-reactive

33、warm-reactive antibodiesantibodiesprimaryprimarysecondarysecondaryvcoldcold-reactive -reactive antibodiesantibodiescold agglutinin cold agglutinin syndromesyndromeparoxysmal cold paroxysmal cold hemoglubinuriahemoglubinuriaAutoimmune hematolysisAutoimmune hematolysisWarm TypeWarm TypevIgG+C3IgG+C3vI

34、gGIgGvC3C3Autoimmune hematolysis Autoimmune hematolysis Warm TypeWarm TypevUsually IgG antibodiesUsually IgG antibodiesvFix complement only to level of C3,if at allFix complement only to level of C3,if at allvImmunoglobulin binding occurs at all tempsImmunoglobulin binding occurs at all tempsvFc rec

35、eptors/C3b recognized by macrophagesFc receptors/C3b recognized by macrophagesvHemolysis primarily extravascularHemolysis primarily extravascularv70% associated with other illnesses70% associated with other illnessesvResponsive to steroids/splenectomyResponsive to steroids/splenectomyClinical manife

36、stationClinical manifestationvanemiaanemia、jaundicejaundice、splenohepatomegaliasplenohepatomegaliavITP+AIHA=Evens syndromeITP+AIHA=Evens syndromeLaboratory examinationLaboratory examinationvBloodBlood：anemiaanemia；RetRet ；e erythroblastsrythroblasts, , anisopoikilocytosisanisopoikilocytosisvBone mar

37、rowBone marrow：e evCoombs TestCoombs TestCoombs Test - DirectCoombs Test - DirectvLooks for immunoglobulin &/or complement of Looks for immunoglobulin &/or complement of surface of red blood cell (normally neither surface of red blood cell (normally neither found on RBC surface)found on RBC

38、surface)vCoombs reagent - combination of anti-human Coombs reagent - combination of anti-human immunoglobulin & anti-human complementimmunoglobulin & anti-human complementvMixed with patientMixed with patients red cells; if s red cells; if immunoglobulin or complement are on surface, immunog

39、lobulin or complement are on surface, Coombs reagent will link cells together and Coombs reagent will link cells together and cause agglutination of RBCscause agglutination of RBCsCoombs Test - IndirectCoombs Test - IndirectvLooks for anti-red blood cell Looks for anti-red blood cell antibodies in t

40、he patientantibodies in the patients serum, s serum, using a panel of red cells with known using a panel of red cells with known surface antigenssurface antigensvCombine patientCombine patients serum with cells from s serum with cells from a panel of RBCa panel of RBCs with known antigenss with know

41、n antigensvAdd CoombsAdd Coombs reagent to this mixture reagent to this mixturevIf anti-RBC antigens are in serum, If anti-RBC antigens are in serum, agglutination occursagglutination occursDiagnosisDiagnosisTreatmentTreatmentvSteroidsSteroidsvSplenectomySplenectomyvI Immunosupressive agents mmunosu

42、pressive agents vT TransfusionransfusionAutoimmune hematolysis Autoimmune hematolysis Cold TypeCold TypevMost commonly IgM mediatedMost commonly IgM mediatedvAntibodies bind best at 30Antibodies bind best at 30 or lower or lowervFix entire complement cascadeFix entire complement cascadevLeads to formation of membrane attack Leads to forma