陈勤奋－溶血性贫血

null溶血性贫血 Hemolytic Anemia溶血性贫血 Hemolytic Anemia华山医院血液科 陈勤奋HEMOLYTIC ANEMIA (reduced RBC life span) HEMOLYTIC ANEMIA (reduced RBC life span) Anemia of increased destruction Normochromic, normochromic anemia Shortened RBC survival Reticulocytosis--Response to increased RBC destruction Increased indirect bilirubin Increased LDHMechanisms and CausesMechanisms and CausesINTRACORPUSCULAR HEMOLYSIS Membrane Abnormalities Metabolic Abnormalities Hemoglobinopathies EXTRACORPUSCULAR HEMOLYSIS Nonimmune ImmuneMembrane DefectsMembrane DefectsMicroskeletal defects Hereditary spherocytosis Increased sensitivity to complement Paroxysmal nocturnal hemoglobinuriaEnzymopathiesEnzymopathiesGlucose 6-Phosphate Dehydrogenase Deficiency Pyruvate Kinase DeficiencyHemoglobinopathiesHemoglobinopathiesHemoglobinopathy ThalassemiaExtracorpuscular Hemolysis NonimmuneExtracorpuscular Hemolysis NonimmuneInfectious Chemical Thermal OsmoticExtracorpuscular Hemolysis ImmuneExtracorpuscular Hemolysis ImmuneAll require antigen-antibody reactions Types of reactions dependent on: Class of Antibody Number & Spacing of antigenic sites on cell Availability of complement Environmental Temperature Functional status of reticuloendothelial system Manifestations Intravascular hemolysis Extravascular hemolysisExtracorpuscular Hemolysis ImmuneExtracorpuscular Hemolysis ImmuneAntibodies combine with RBC, & either Activate complement cascade, &/or Opsonize RBC for immune system If 1, if all of complement cascade is fixed to red cell, intravascular cell lysis occurs If 2, &/or if complement is only partially fixed, macrophages recognize Fc receptor of Ig &/or C3b of complement & phagocytize RBC, causing extravascular RBC destructionClassificationClassificationIntravascular Extravascularclinical featuresclinical featureschronic pallor 、 jaundice 、 splenomegaly cholelithiasis aplastic crisis acute algor、hyperpyrexia、sore waist hemoglobinuria jaundice、anaemialaboratory examinationlaboratory examinationIncreased RBC destruction Reduced RBC life span Indirect hyperbilirubinemia Erythroid hyperplasia Reticulocytosis Erythroblasts, anisopoikilocytosis, spherocytes in blood smear Erythroid hyperplasia in bone marrow nulldiagnosis and differential diagnosisdiagnosis and differential diagnosishemolysis or not? type of hemolysis another anemia? another jaundice with anemia? another jaundice without anemia?TreatmentTreatmentRemove the causes Immunosupressive drug Washed RBC transfusion Splenectomy Symptomatic treatmentHereditary SpherocytosisHereditary SpherocytosisDefective or absent spectrin molecule Leads to loss of RBC membrane, leading to spherocytosis Decreased deformability of cell Increased osmotic fragility Extravascular hemolysis in spleenHereditary SpherocytosisHereditary SpherocytosisPathophysiology--RBC membrane protein defects (spectrin deficiency) resulting cytoskeleton instability Familly history Clinical features—splenomegalyHereditary SpherocytosisHereditary SpherocytosisLaboratory features - hemolytic anemia - blood smear-microspherocytes - abnormal osmotic fragility test - positive autohemolysis test - prevention of increased autohemolysis by including glucose in incubation medium Treatment--splenectomyHereditary SpherocytosisHereditary SpherocytosisHereditary Spherocytosis Osmotic FragilityHereditary Spherocytosis Osmotic FragilityParoxysmal Nocturnal Hemoglobinuria (PNH)Paroxysmal 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 affected 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)Paroxysmal Nocturnal Hemoglobinuria (PNH)Pathogenesis - an acquired clonal disease, arising from a somatic mutation in a single abnormal 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 PNHurine aliquot of PNHclinical manifestationclinical manifestationpancytopenia passage of dark brown urine in the morning venous thrombosis(Budd-Chiari Syndrome)Laboratory featuresLaboratory featuresPancytopenia Chronic urinary iron loss Serum iron concentration decreased Hemoglobinuria Hemosiderinuria Positive Ham’s test (acid hemolysis test), sugar-water test Specific immunophenotype of blood cells(CD59, CD55) AttentionAttentionAA-PNH syndrome AA→PNH PNH→AA PNH with AA AA with PNHTreatmentTreatmentavoid causes washed RBC transfusion iron therapy allogenic bone marrow transplantationG-6-PD DeficiencyG-6-PD Deficiencyacute hemolytic anemia congenital nonspherocytic hemolytic anemia neonatal hyperbilirubinemia （kernicterus） favismnullLevel needed for protection vs ordinary oxidative stressAutoimmune HemolysisAutoimmune HemolysisDue to formation of autoantibodies that attack patient’s own RBC’s Type characterized by ability of autoantibodies to fix complement & site of RBC destruction Often associated with either lymphoproliferative disease or collagen vascular diseaseAutoimmune Hemolytic AnemiaAutoimmune Hemolytic Anemiawarm-reactive antibodies primary secondary cold-reactive antibodies cold agglutinin syndrome paroxysmal cold hemoglubinuriaAutoimmune hematolysis Warm TypeAutoimmune hematolysis Warm TypeIgG+C3 IgG C3Autoimmune hematolysis Warm TypeAutoimmune hematolysis Warm TypeUsually IgG antibodies Fix complement only to level of C3,if at all Immunoglobulin binding occurs at all temps Fc receptors/C3b recognized by macrophages Hemolysis primarily extravascular 70% associated with other illnesses Responsive to steroids/splenectomyClinical manifestationClinical manifestationanemia、jaundice、splenohepatomegalia ITP+AIHA=Evens syndromeLaboratory examinationLaboratory examinationBlood：anemia；Ret；erythroblasts, anisopoikilocytosis Bone marrow：erythroid hyperplasia Coombs TestCoombs Test - DirectCoombs 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 complement Mixed with patient’s red cells; if immunoglobulin or complement are on surface, Coombs reagent will link cells together and cause agglutination of RBCsCoombs Test - IndirectCoombs Test - IndirectLooks for anti-red blood cell antibodies in the patient’s serum, using a panel of red cells with known surface antigens Combine patient’s serum with cells from a panel of RBC’s with known antigens Add Coombs’ reagent to this mixture If anti-RBC antigens are in serum, agglutination occursDiagnosisDiagnosisTreatmentTreatmentSteroids Splenectomy Immunosupressive agents Transfusion Autoimmune hematolysis Cold TypeAutoimmune hematolysis Cold TypeMost commonly IgM mediated Antibodies bind best at 30º or lower Fix entire complement cascade Leads to formation of membrane attack complex, which leads to RBC lysis in vasculature Typically only complement found on cells 90% associated with other illnesses Poorly responsive to steroids, splenectomy; responsive to plasmapheresisHemolytic anemia SummaryHemolytic anemia SummaryMyriad causes of increased RBC destruction Marrow function usually normal Often requires extra folic acid to maintain hematopoiesis Anything that turns off the bone marrow can result in acute, life-threatening anemia