溶血性贫血 课件讲座

1、2021/8/121烦恼有何惧怕，既然躲不掉，就调好心态与它共存。心向阳光，何惧风霜。烦恼有何惧怕，既然躲不掉，就调好心态与它共存。心向阳光，何惧风霜。茫茫人海你我相遇就是缘分，欢迎下载！茫茫人海你我相遇就是缘分，欢迎下载！溶血性贫血溶血性贫血Hemolytic AnemiaHemolytic AnemiaH HE EM MO OL LY YT TI IC C A AN NE EM MI IA A ( (r re ed du uc ce ed d R RB BC C l li if fe e s sp pa an n) )vAnemia of increased destructionAnem

2、ia of increased destructionNormochromic, normochromic anemiaNormochromic, normochromic anemiaShortened RBC survivalShortened RBC survivalReticulocytosis-Response to Reticulocytosis-Response to increased RBC destructionincreased RBC destructionIncreased indirect bilirubinIncreased indirect bilirubinI

3、ncreased LDHIncreased LDHMechanismsMechanisms and Causes and CausesvINTRACORPUSCULAR HEMOLYSISINTRACORPUSCULAR HEMOLYSISMembrane AbnormalitiesMembrane AbnormalitiesMetabolic AbnormalitiesMetabolic AbnormalitiesHemoglobinopathiesHemoglobinopathiesvEXTRACORPUSCULAR HEMOLYSISEXTRACORPUSCULAR HEMOLYSISN

4、onimmune Nonimmune ImmuneImmuneMembrane DefectsMembrane DefectsvMicroskeletal defectsMicroskeletal defectsHereditary spherocytosisHereditary spherocytosisvIncreased sensitivity to complementIncreased sensitivity to complementParoxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuriaEnzym

5、opathiesEnzymopathiesvGlucose 6-Phosphate Dehydrogenase Glucose 6-Phosphate Dehydrogenase DeficiencyDeficiencyvPyruvate Kinase DeficiencyPyruvate Kinase DeficiencyHemoglobinopathiesHemoglobinopathiesvHemoglobinopathyHemoglobinopathyvThalassemiaThalassemiaExtracorpuscular HemolysisExtracorpuscular He

6、molysisNonimmuneNonimmunevInfectiousInfectiousvChemicalChemicalvThermalThermalvOsmoticOsmoticExtracorpuscular Hemolysis Extracorpuscular Hemolysis ImmuneImmunevAll require antigen-antibody reactionsAll require antigen-antibody reactionsvTypes of reactions dependent on:Types of reactions dependent on

7、:Class of AntibodyClass of AntibodyNumber & Spacing of antigenic sites on cellNumber & Spacing of antigenic sites on cellAvailability of complementAvailability of complementEnvironmental TemperatureEnvironmental TemperatureFunctional status of reticuloendothelial systemFunctional status of r

8、eticuloendothelial systemvManifestationsManifestationsIntravascular hemolysisIntravascular hemolysisExtravascular hemolysisExtravascular hemolysisExtracorpuscular Hemolysis Extracorpuscular Hemolysis ImmuneImmunevAntibodies combine with RBC, & eitherAntibodies combine with RBC, & eitherActiv

9、ate complement cascade, &/orActivate complement cascade, &/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

10、occurs1.1.If 2, &/or if complement is only If 2, &/or 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

11、 RBC, causing extravascular RBC destructionextravascular RBC destructionClassificationClassificationvIntravascularIntravascularvE Extravascularxtravascular2021/8/1212v9、 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-

12、63/6/2022 8:03:47 PMv11、人总是珍惜为得到。、人总是珍惜为得到。2022-3-62022-3-62022-3-6Mar-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

13、-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。2022-3-62022-3-62022-3-62022-3-6clinical featuresclinical featuresvchronicchronicvpallorpallor 、 jaundicejaun

14、dice 、 splenomegalysplenomegalyvcholelithiasischolelithiasisvaplastic crisisaplastic crisisvacuteacutevalgoralgor、hyperpyrexiahyperpyrexia、sore waistsore waistvhemoglobinuriahemoglobinuriavjaundicejaundice、anaemiaanaemialaboratory examinationlaboratory examinationvI In nc cr re ea as se ed d R RB BC

15、 C d de es st tr ru uc ct ti io on nvE Er ry yt th hr ro oi id d h hy yp pe er rp pl la as si ia avR Re ed du uc ce ed d R RB BC Cl li if fe e s sp pa an nvI In nd di ir re ec ct t h hy yp pe er rb bi il li ir ru ub bi in ne em mi ia avR Re et ti ic cu ul lo oc cy yt to os si is svE Er ry yt th hr r

16、o ob bl la as st ts s, , a an ni is so op po oi ik ki il lo oc cy yt to os si is, s, s sp ph he er ro oc cy yt te es si in n b bl lo oo od d s sm me ea ar r vE Er ry yt th hr ro oi id d h hy yp pe er rp pl la as si ia ai in n b bo on ne e m ma ar rr ro ow wdiagnosis and diagnosis and differential di

17、agnosisdifferential diagnosisvhemolysis or not?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 th

18、e causes vImmunosupressiveImmunosupressive drug drugvW Washed RBC transfusionashed RBC transfusionvSplenectomySplenectomyvSymptomatic treatmentSymptomatic treatmentHereditary SpherocytosisHereditary SpherocytosisvDefective or absent spectrin Defective or absent spectrin moleculemoleculevLeads to los

19、s of RBC membrane, Leads to loss of RBC membrane, leading to spherocytosisleading to spherocytosisvDecreased deformability of cellDecreased deformability of cellvIncreased osmotic fragilityIncreased osmotic fragilityvExtravascular hemolysis in spleenExtravascular hemolysis in spleenHereditary Sphero

20、cytosisHereditary SpherocytosisvPathophysiologyPathophysiology-RBC-RBC membrane protein membrane protein defects (spectrin deficiency) resulting defects (spectrin deficiency) resulting cytoskeleton instabilitycytoskeleton instabilityvFamilly historyFamilly historyvClinical featuresClinical featuress

21、plenomegalysplenomegalyHereditary SpherocytosisHereditary SpherocytosisvLaboratory featuresLaboratory features - hemolytic anemia - hemolytic anemia - blood smear-microspherocytes - blood smear-microspherocytes - abnormal osmotic fragility test - abnormal osmotic fragility test - positive autohemoly

22、sis test - positive autohemolysis test - prevention of increased - prevention of increased autohemolysis by including autohemolysis by including glucose inglucose in incubation medium incubation medium vTreatmentTreatment-splenectomysplenectomyHereditary SpherocytosisHereditary SpherocytosisHeredita

23、ry Spherocytosis Hereditary Spherocytosis Osmotic 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

24、anemia which arises from a somatic anemia which 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 de

25、fect. This defect renders the red cells highly 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

26、 Nocturnal Hemoglobinuria (PNH)(PNH)vP Pa at th ho og ge en ne es si is s - - a an n a ac cq qu ui ir re ed d c cl lo on na al l d di is se ea as se, e, a ar ri is si in ng g f fr ro om m a a s so om ma at ti ic c m mu ut ta at ti io on n i in n a a s si in ng gl le e a ab bn no or rm ma al l s st t

27、e em m c ce el ll l - - g gl ly yc co os sy yl l- -p ph ho os sp ph ha at ti id dy yl l- - i in no os si it to ol l ( (G GP PI) I) a an nc ch ho or r a ab bn no or rm ma al li it ty y - - d de ef fi ic ci ie en nc cy y o of f t th he e G GP PI I a an nc ch ho or re ed d m me em mb br ra an ne e p pr

28、 ro ot te ei in ns s( (C CD D5 55 5 a an nd d C CD D5 59)9) - - r re ed d c ce el ll ls s a ar re e m mo or re e s se en ns si it ti iv ve e t to o t th he e l ly yt ti ic c e ef ff fe ec ct t o of f c co om mp pl le em me en nt t - - i in nt tr ra av va as sc cu ul la ar r h he em mo ol ly ys si is

29、 surine 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)Syndrome)Laboratory featuresLabora

30、tory featuresvP Pa an nc cy yt to op pe en ni ia avC Ch hr ro on ni ic c u ur ri in na ar ry y i ir ro on n l lo os ss svS Se er ru um m i ir ro on n c co on nc ce en nt tr ra at ti io on n d de ec cr re ea as se ed dvH He em mo og gl lo ob bi in nu ur ri ia avH He em mo os si id de er ri in nu ur r

31、i ia avP Po os si it ti iv ve e H Ha amms s t te es st t ( (a ac ci id d h he em mo ol ly ys si is s t te es st)t), , s su ug ga ar r- -w wa at te er r t te es st tvS Sp pe ec ci if fi ic c i im mm mu un no op ph he en no ot ty yp pe e o of f b bl lo oo od d c ce el ll ls s( (C CD D5 59, 9, C CD D5

32、55)5)AttentionAttentionvAA-PNH syndromeAA-PNH syndromeAAPNHAAPNHPNHAAPNHAAPNH with AAPNH with AAAA with PNHAA with PNHTreatmentTreatmentvavoid causesavoid causesvwashed RBC transfusionwashed RBC transfusionviron therapyiron therapyvallogenic bone marrow allogenic bone marrow transplantationtransplan

33、tationG-6-PD DeficiencyG-6-PD Deficiencyvacute hemolytic anemiaacute hemolytic anemiavcongenital nonspherocytic congenital nonspherocytic hemolytic anemiahemolytic anemiavneonatal hyperbilirubinemia neonatal hyperbilirubinemia （kernicteruskernicterus）vfavismfavism00.20.40.60.81020406080100120RBC Age

34、 (Days)G6PD Activity (%)Normal (GdB)Black Variant (GdA-)Mediterranean (Gd Med)Level needed for protection vs ordinary oxidative stressAutoimmune HemolysisAutoimmune HemolysisvDue to formation of autoantibodies that Due to formation of autoantibodies that attack patients own RBCsattack patients own R

35、BCsvType characterized by ability of Type characterized by ability of autoantibodies to fix complement & site autoantibodies to fix complement & site of RBC destructionof RBC destructionvOften associated with either Often associated with either lymphoproliferative disease or collagen lymphop

36、roliferative disease or collagen vascular diseasevascular diseaseAutoimmune Hemolytic AnemiaAutoimmune Hemolytic Anemiavwarm-reactive warm-reactive antibodiesantibodiesvprimaryprimaryvsecondarysecondaryvcoldcold-reactive -reactive antibodiesantibodiesvcold agglutinin cold agglutinin syndromesyndrome

37、vparoxysmal cold paroxysmal cold hemoglubinuriahemoglubinuriaAutoimmune hematolysisAutoimmune hematolysisWarm TypeWarm TypevIgG+C3IgG+C3vIgGIgGvC3C3Autoimmune hematolysis Autoimmune hematolysis Warm TypeWarm TypevUsually IgG antibodiesUsually IgG antibodiesvFix complement only to level of C3,if at a

38、llFix complement only to level of C3,if at allvImmunoglobulin binding occurs at all tempsImmunoglobulin binding occurs at all tempsvFc receptors/C3b recognized by macrophagesFc receptors/C3b recognized by macrophagesvHemolysis primarily extravascularHemolysis primarily extravascularv70% associated w

39、ith other illnesses70% associated with other illnessesvResponsive to steroids/splenectomyResponsive to steroids/splenectomyClinical manifestationClinical manifestationvanemiaanemia、jaundicejaundice、splenohepatomegaliasplenohepatomegaliavITP+AIHA=Evens syndromeITP+AIHA=Evens syndromeLaboratory examin

40、ationLaboratory examinationvB Bl lo oo od d：a an ne em mi ia a；R Re et t ；e er ry yt th hr ro ob bl la as st ts s, , a an ni is so op po oi ik ki il lo oc cy yt to os si is svB Bo on ne e m ma ar rr ro ow w：e evC Co oo om mb bs s T Te es st tr ry yt th hr ro oi id d h hy yp pe er rp pl la as si ia a

41、Coombs 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 surface)vCoombs reagent - combination of

42、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 immunoglobulin or complement are on surface, immunoglobulin or complement are on surface, Coo

43、mbs 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 the patients serum, antibodies in the pati

44、ents 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 mix

45、tureAdd Coombs reagent to this mixturevIf anti-RBC antigens are in serum, If anti-RBC antigens are in serum, agglutination occursagglutination occursDiagnosisDiagnosisTreatmentTreatmentvSteroidsSteroidsvSplenectomySplenectomyvI Immunosupressive agents mmunosupressive agents vT TransfusionransfusionA

46、utoimmune 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 formation of membrane attack complex,