溶血性贫血教学课件

1、2021/7/91溶血性贫血溶血性贫血Hemolytic AnemiaHemolytic Anemia2021/7/92HEMOLYTIC ANEMIAHEMOLYTIC ANEMIA ( (reduced reduced RBCRBC life span life span) )vAnemia of increased destructionAnemia of increased destructionNormochromic, normochromic anemiaNormochromic, normochromic anemiaShortened RBC survivalShortene

2、d RBC survivalReticulocytosis-Response to Reticulocytosis-Response to increased RBC destructionincreased RBC destructionIncreased indirect bilirubinIncreased indirect bilirubinIncreased LDHIncreased LDH2021/7/93Mechanisms and CausesMechanisms and CausesvINTRACORPUSCULAR HEMOLYSISINTRACORPUSCULAR HEM

3、OLYSISMembrane AbnormalitiesMembrane AbnormalitiesMetabolic AbnormalitiesMetabolic AbnormalitiesHemoglobinopathiesHemoglobinopathiesvEXTRACORPUSCULAR HEMOLYSISEXTRACORPUSCULAR HEMOLYSISNonimmune Nonimmune ImmuneImmune2021/7/94Membrane DefectsMembrane DefectsvMicroskeletal defectsMicroskeletal defect

4、sHereditary spherocytosisHereditary spherocytosisvIncreased sensitivity to complementIncreased sensitivity to complementParoxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuria2021/7/95EnzymopathiesEnzymopathiesvGlucose 6-Phosphate Dehydrogenase Glucose 6-Phosphate Dehydrogenase Defici

5、encyDeficiencyvPyruvate Kinase DeficiencyPyruvate Kinase Deficiency2021/7/96HemoglobinopathiesHemoglobinopathiesvHemoglobinopathyHemoglobinopathyvThalassemiaThalassemia2021/7/97Extracorpuscular HemolysisExtracorpuscular HemolysisNonimmuneNonimmunevInfectiousInfectiousvChemicalChemicalvThermalThermal

6、vOsmoticOsmotic2021/7/98Extracorpuscular Hemolysis Extracorpuscular Hemolysis 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

7、sites on cellNumber & Spacing of antigenic sites on cellAvailability of complementAvailability of complementEnvironmental TemperatureEnvironmental TemperatureFunctional status of reticuloendothelial systemFunctional status of reticuloendothelial systemvManifestationsManifestationsIntravascular h

8、emolysisIntravascular hemolysisExtravascular hemolysisExtravascular hemolysis2021/7/99Extracorpuscular Hemolysis Extracorpuscular Hemolysis ImmuneImmunevAntibodies combine with RBC, & eitherAntibodies combine with RBC, & eitherActivate complement cascade, &/orActivate complement cascade,

9、 &/orOpsonize RBC for immune systemOpsonize RBC for immune systemvIf 1, if all 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, &/o

10、r if complement is only partially fixed, macrophages recognize partially fixed, macrophages 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

11、 destruction2021/7/910ClassificationClassificationvIntravascularIntravascularvE Extravascularxtravascular2021/7/911v9、 人的价值，在招收诱惑的一瞬间被决定。人的价值，在招收诱惑的一瞬间被决定。2022-3-62022-3-6Sunday, March 06, 2022v10、低头要有勇气，抬头要有低气。、低头要有勇气，抬头要有低气。2022-3-62022-3-62022-3-63/6/2022 8:03:38 PMv11、人总是珍惜为得到。、人总是珍惜为得到。2022-3-6

12、2022-3-62022-3-6Mar-226-Mar-22v12、人乱于心，不宽余请。、人乱于心，不宽余请。2022-3-62022-3-62022-3-6Sunday, March 06, 2022v13、生气是拿别人做错的事来惩罚自己。、生气是拿别人做错的事来惩罚自己。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、一个人炫耀什么，说明他内心缺少什么。、一个人炫耀什么，说明他内心缺少什么。2022年年

13、3月月2022-3-62022-3-62022-3-63/6/2022v16、业余生活要有意义，不要越轨。、业余生活要有意义，不要越轨。2022-3-62022-3-6March 6, 2022v17、一个人即使已登上顶峰，也仍要自强不息。、一个人即使已登上顶峰，也仍要自强不息。2022-3-62022-3-62022-3-62022-3-62021/7/912clinical featuresclinical featuresvchronicchronicpallor pallor 、 jaundice jaundice 、 splenomegalysplenomegalycholelith

14、iasischolelithiasisaplastic crisisaplastic crisisvacuteacutealgoralgor、hyperpyrexiahyperpyrexia、sore waistsore waisthemoglobinuriahemoglobinuriajaundicejaundice、anaemiaanaemia2021/7/913laboratory examinationlaboratory examinationvIncreased RBC destructionIncreased RBC destructionvE Erythroid hyperpl

15、asiarythroid hyperplasia2021/7/9142021/7/915diagnosis and diagnosis and differential diagnosisdifferential diagnosisvhemolysis or not?hemolysis or not?vtype of hemolysistype of hemolysisvanother anemia?another anemia?vanother jaundice with anemia?another jaundice with anemia?vanother jaundice withou

16、t anemia?another jaundice without anemia?2021/7/916TreatmentTreatmentvRemove the causes Remove the causes vImmunosupressiveImmunosupressive drug drugvW Washed RBC transfusionashed RBC transfusionvSplenectomySplenectomyvSymptomatic treatmentSymptomatic treatment2021/7/917Hereditary SpherocytosisHered

17、itary SpherocytosisvDefective or absent spectrin Defective or absent spectrin moleculemoleculevLeads to loss of RBC membrane, Leads to loss of RBC membrane, leading to spherocytosisleading to spherocytosisvDecreased deformability of cellDecreased deformability of cellvIncreased osmotic fragilityIncr

18、eased osmotic fragilityvExtravascular hemolysis in spleenExtravascular hemolysis in spleen2021/7/918Hereditary SpherocytosisHereditary SpherocytosisvPathophysiologyPathophysiology-RBC-RBC membrane protein membrane protein defects (spectrin deficiency) resulting defects (spectrin deficiency) resultin

19、g cytoskeleton instabilitycytoskeleton instabilityvFamilly historyFamilly historyvClinical featuresClinical featuressplenomegalysplenomegaly2021/7/919Hereditary SpherocytosisHereditary SpherocytosisvLaboratory featuresLaboratory features - hemolytic anemia - hemolytic anemia - blood smear-microspher

20、ocytes - blood smear-microspherocytes - abnormal osmotic fragility test - abnormal osmotic fragility test - positive autohemolysis test - positive autohemolysis test - prevention of increased - prevention of increased autohemolysis by including autohemolysis by including glucose inglucose in incubat

21、ion medium incubation medium vTreatmentTreatment-splenectomysplenectomy2021/7/920Hereditary SpherocytosisHereditary Spherocytosis2021/7/921Hereditary Spherocytosis Hereditary Spherocytosis Osmotic FragilityOsmotic Fragility0204060801000.30.40.50.6NaCl (% of normal saline)% HemolysisNormalHS2021/7/92

22、2Paroxysmal 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 which arises from a somatic mutation in a hematopoietic stem cell. mutation in a hematopoietic stem c

23、ell. 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 This defect renders the red cells highly susceptible to complement mediated lysis susceptible to

24、 complement mediated lysis resulting in the characteristic hemolysis.resulting in the characteristic hemolysis.2021/7/923Paroxysmal Nocturnal Hemoglobinuria Paroxysmal Nocturnal Hemoglobinuria (PNH)(PNH)vPathogenesisPathogenesis - an acquired clonal disease, arising from a - an acquired clonal disea

25、se, 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 abnormalityabnormality - deficiency of the GPI anchored membrane - deficiency of the GPI anc

26、hored 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 hemolysis - intravascular hemolysis2021/7/924urine aliquot of PNHurine aliquot of PNH2021/7/

27、925clinical manifestationclinical manifestationvpancytopeniapancytopeniavpassage of dark brown urine in the passage of dark brown urine in the morningmorningvvenous thrombosis(Budd-Chiari venous thrombosis(Budd-Chiari Syndrome)Syndrome)2021/7/926Laboratory featuresLaboratory featuresvPancytopeniaPan

28、cytopeniavC Chronic urinary iron losshronic urinary iron lossvS Serum iron concentration decreasederum iron concentration decreasedvHemoglobinuriaHemoglobinuriavHemosiderinuriaHemosiderinuriavP Positive Hams test (acid hemolysis test)ositive Hams test (acid hemolysis test), , sugar-water testsugar-w

29、ater testvS Specific immunophenotype ofpecific immunophenotype of blood cells blood cells(CD59, (CD59, CD55)CD55)2021/7/927AttentionAttentionvAA-PNH syndromeAA-PNH syndromeAAPNHAAPNHPNHAAPNHAAPNH with AAPNH with AAAA with PNHAA with PNH2021/7/928TreatmentTreatmentvavoid causesavoid causesvwashed RBC

30、 transfusionwashed RBC transfusionviron therapyiron therapyvallogenic bone marrow allogenic bone marrow transplantationtransplantation2021/7/929G-6-PD DeficiencyG-6-PD Deficiencyvacute hemolytic anemiaacute hemolytic anemiavcongenital nonspherocytic congenital nonspherocytic hemolytic anemiahemolyti

31、c anemiavneonatal hyperbilirubinemia neonatal hyperbilirubinemia （kernicteruskernicterus）vfavismfavism2021/7/93000.20.40.60.81020406080100120RBC Age (Days)G6PD Activity (%)Normal (GdB)Black Variant (GdA-)Mediterranean (Gd Med)Level needed for protection vs ordinary oxidative stress2021/7/931Autoimmu

32、ne HemolysisAutoimmune HemolysisvDue to formation of autoantibodies that Due to formation of autoantibodies that attack patients own RBCsattack patients own RBCsvType characterized by ability of Type characterized by ability of autoantibodies to fix complement & site autoantibodies to fix comple

33、ment & site of RBC destructionof RBC destructionvOften associated with either Often associated with either lymphoproliferative disease or collagen lymphoproliferative disease or collagen vascular diseasevascular disease2021/7/932Autoimmune Hemolytic AnemiaAutoimmune Hemolytic Anemiavwarm-reactiv

34、e warm-reactive antibodiesantibodiesprimaryprimarysecondarysecondaryvcoldcold-reactive -reactive antibodiesantibodiescold agglutinin cold agglutinin syndromesyndromeparoxysmal cold paroxysmal cold hemoglubinuriahemoglubinuria2021/7/933Autoimmune hematolysisAutoimmune hematolysisWarm TypeWarm TypevIg

35、G+C3IgG+C3vIgGIgGvC3C32021/7/934Autoimmune 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 occu

36、rs at all tempsvFc receptors/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/sple

37、nectomy2021/7/935Clinical manifestationClinical manifestationvanemiaanemia、jaundicejaundice、splenohepatomegaliasplenohepatomegaliavITP+AIHA=Evens syndromeITP+AIHA=Evens syndrome2021/7/936Laboratory examinationLaboratory examinationvBloodBlood：anemiaanemia；RetRet ；e erythroblastsrythroblasts, , aniso

38、poikilocytosisanisopoikilocytosisvBone marrowBone marrow：e evCoombs TestCoombs Test2021/7/937Coombs 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

39、(normally neither found on RBC surface)found on RBC surface)vCoombs reagent - combination of anti-human Coombs reagent - combination of anti-human immunoglobulin & anti-human complementimmunoglobulin & anti-human complementvMixed with patients red cells; if Mixed with patients red cells; if

40、immunoglobulin or complement are on surface, immunoglobulin 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 RBCs2021/7/938Coombs Test - IndirectCoombs Test - IndirectvLooks for ant

41、i-red blood cell Looks for anti-red blood cell antibodies in the patients serum, antibodies in the patients serum, using a panel of red cells with known using a panel of red cells with known surface antigenssurface antigensvCombine patients serum with cells Combine patients serum with cells from a panel of RBCs with known from a panel of RBCs with known antigensantigensvAdd Coombs reagent to this mixtureAdd Coombs reagent to this mixturevIf anti-RBC antigens are in serum, If anti-RBC antigens are in serum, agglutination occursagglutinat