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Hemolytic Anemia (Aiha) Clinical Hemolysis Indicators

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Hemolytic Anemia (Aiha) Clinical Hemolysis Indicators October 15, 2013 GME Morning report Harmesh Naik, MD. AUTO IMMUNE HEMOLYTIC ANEMIA (AIHA) CLINICAL HEMOLYSIS INDICATORS Anemia High reticulocyte counts Elevated LDH level Unconjugated (indirect) hyper bilirubinemia Reduced haptoglobin level Hemoglobinuria COMPARISON Autoimmune hemolytic anemia Hereditary spherocytosis Hemolysis Hemolysis Spherocytes Spherocytes Splenomegaly Splenomegaly DAT positive DAT negative No Family history Family history TYPE OF ANTIBODY Auto antibody – generally seen in AIHA- detected generally by DAT Allo antibody – generally seen after transfusion of donor RBCs containing antigen – detected generally by IAT ANTI GLOBULIN TEST (COOMB’S TEST) Developed by Coombs in 1945 THE DIRECT ANTIGLOBULIN TEST (DAT) AND INDIRECT ANTIGLOBULIN TEST (IAT). Zarandona J M , and Yazer M H CMAJ 2006;174:305-307 DIRECT COOMB’S TEST (DAT) Detects IgG or complement coating on surface of circulating RBCs Detects In Vivo sensitization of RBCs Useful in differentiating immune mediated hemolysis Generally detects auto-antibodies in AIHA DIRECT COOMB’S TEST (DAT) Auto antibodies in AIHA are generally IgG antibodies with high affinity for human RBCs at 37*C 9body temperature) As a result most of antibody is bound to RBCs and very little is free in plasma So DAT can find RBC bound antibody effectively INDIRECT COOMB’S TEST (IAT OR ANTIBODY SCREENING) Detects antibodies in serum (IgG antibodies in serum) Detects in vitro sensitization of RBCs COLD AUTO ANTIBODY Spontaneous agglutination after incubation of patient serum at 16*C Generally an IgM antibody POSITIVE DAT: NOW WHAT? DAT +ve No clinical Clinical hemolysis hemolysis Investigate Stop cause POSITIVE DAT WITH HEMOLYSIS DAT +ve AND Clinical hemolysis Anti IgG Anti complement antibody antibody Warm antibody Cold antibody AIHA AIHA Eluate containing antibody agglutinates all RBCs DIRECT COOMB’S TEST (DAT): METHOD First done with poly specific antihuman globulin reagent If positive run it with monospecific reagent to detect type of coating antibody – IgG or IgA or IgM or C3C or C3D If complement deposition – C3C or C3D is detected in absence of auto antibody – still need to rule out Cold antibody IgM or warm IgA (rare) or warm IgM (rare) or biphasic antibody IgM is hard to detect because of removal during washing DIRECT COOMB’S TEST (DAT): ELUTION Positive DAT – to identify warm antibody with specificity – separate antibody form RBC by elution Eluate is tested with standard RBC panel Most warm antibodies are non specific Sometimes specific antibody can be identified (anti C or anti Rh or anti kell) Cold IgM can be directed against anti I or Anti H Biphasic are sometimes against anti P Use specific blood products when indicated (example use C negative blood in anti C patient) DAT AND IAT : COMMON RESULTS DAT IAT Condition Comment + -- AIHA Auto-antibody + + AIHA Auto-antibody RBC bound and free -- + Prior transfusion Allo antibody Fetal to maternal transfer of RBCs RECENTLY TRANSFUSED PATIENT Positive DAT in patient may reflect binding of allo antibody (produced in transfused patient as result of antigen on donor RBCs) to donor RBCs still present in patient's circulation – suggests delayed transfusion reaction Can be confused with auto antibody Further characterization can determine if DAT positive antibody directed against donor RBCs or autolgous RBCs ALLO IMMUNIZATION FROM PRIOR TRANSFUSION: UNEXPECTED ANTIBODY +ve DAT • Transfusion of donor red • Allo antibody in serum can cells to a patient be detected by Indirect • Antigen on donor cells but • Allo antibody coats donor coomb’s test not present on recipient antigen positive RBCs but • Re transfusion of same triggers antibody formation not patients own RBCs donor antigen containing lacking antigen RBCs may trigger more • Results in positive DAT in antibody formation in 7-10 patient days and delayed reaction Allo Hemolysis with immunization next transfusion TRANSFUSIONS IN AIHA PATIENT: INDICATIONS Chronic anemia in asymptomatic patients- do not need transfusion Patients who are symptomatic at rest or cardiac patients with symptoms can be transfused to maintain clinically acceptable hemoglobin until hemolysis is treated Transfused RBCs may have short survival and might be destroyed TRANSFUSIONS IN AIHA PATIENT: FINDING RIGHT BLOOD PRODUCT Most auto-antibodies react with all potential donor RBCs Cross matching is difficult Detection of coexisting allo antibody in patient’s serum (IAT) is time consuming and difficult Serocompatible blood is found rarely if auto antibody is specific for certain blood group antigen One must choose donor RBCs that are LEAST INCOMPATIBLE with patients serum in cross match testing TRANSFUSIONS IN AIHA PATIENT: WHO IS AT RISK OF REACTION Allo antibody is more likely to cause severe transfusion reaction than auto antibody Patients with prior transfusions or history of pregnancy might contain allo antibodies – careful testing is necessary for this group Never transfused or never pregnant patients are unlikely to have allo antibody – no need to delay transfusion for this group TRANSFUSIONS IN AIHA PATIENT: PRECAUTIONS Do not hold up transfusion in severely anemic symptomatic patient Use LEAST INCOMPATIBLE blood product Monitor patient very closely for transfusion reaction .
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