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AUTOIMMUNE HEMOLYTIC ANEMIA - LABORATORY PREDICTERS OF CLINICAL OUTCOME, RESPONSE AND PROGNOSIS

AUTOIMMUNE HEMOLYTIC ANEMIA - LABORATORY PREDICTERS OF CLINICAL OUTCOME, RESPONSE AND PROGNOSIS. DR.SANOOJA PINKI 1 , DR .MATHEW THOMAS 2 (1.Dept of Transfusion Medicine 2. Dept. of Clinical Hematology) KERALA INSTITUTE OF MEDICAL SCIENCES, TRIVANDRUM, KERALA. BACKGROUND.

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AUTOIMMUNE HEMOLYTIC ANEMIA - LABORATORY PREDICTERS OF CLINICAL OUTCOME, RESPONSE AND PROGNOSIS

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  1. AUTOIMMUNE HEMOLYTIC ANEMIA - LABORATORY PREDICTERS OF CLINICAL OUTCOME, RESPONSE AND PROGNOSIS DR.SANOOJA PINKI 1, DR .MATHEW THOMAS2 (1.Dept of Transfusion Medicine 2. Dept. of Clinical Hematology) KERALA INSTITUTE OF MEDICAL SCIENCES, TRIVANDRUM, KERALA

  2. BACKGROUND • Heterogeneous group of disorders characterized by autoantibody mediated destruction of red blood cells (RBCs) • A positive DAT with no other obvious cause of hemolysis- clinical hallmark • Degree of hemolysis-quantity, specificity, thermal amplitude, complement activation and bind tissue macrophages • PRBC Transfusion - severity of hemolysis, progression of anemia & clinical findings

  3. AIMS & OBJECTIVES • To analyze the trends in pre transfusion testing of AIHA cases • To find the association between DAT strength and in vivo hemolysis • To find the effect of PRBC transfusions in the patient outcome

  4. METHODOLOGY 12 MONTHS • IAT • ANTIBODY SCREENING & IDENTIFICATION BLOOD GROUPING DISCREPANCY • DAT IN CTT • MONOSPECIFIC DAT RESOLUTION SENSITISATION EVENT ADSORPTION-ELUTION STUDIES

  5. Severity of Hemolysis-Classification Laboratory parameters taken to describe the severity of hemolysis are: • Hemoglobin <9 g/dl • Percentage of reticulocyte >2% • Total serum Bilirubin >2mg/dl • LDH >500 IU/ml Ref: Wikman et al ; characterization of red cell autoantibodies in consecutive DAT positive patients with respect to invivo hemolysis Ann hematol 84, 150-158 SEVERE HEMOLYSIS – 4 out of 4 MODERATE HEMOLYSIS- 2/3 out of 4

  6. TRANSFUSION • Given to patients who showed clinical manifestations of chronic anemia • Slow transfusion of best compatible unit under close monitoring • Once diagnosed, IV methyl prednisolone (1 mg/kg) along with immunosuppressants were started for 5 to 7 days • Number of cross matches, No : of transfusions, C/T ratio • Mean hemoglobin increment • Transfusion reactions • Response to treatment were also assessed 24 hours post transfusion as well as at discharge

  7. STATISTICAL TOOLS • Data collected will be tabulated using MS Excel and analysed using SPSS version 16.0. • Categorical variables are represented using frequencies and percentages. • Continuous variables are reported using mean and SD. • Association between categorical variables were analysed using Chi square test. • A p value was calculated to understand the significance level

  8. RESULTS 812 REQUESTS 183 POSITIVE • No drug was incriminated as a cause of hemolysis • 1 had direct hyperbilirubinemia due to obstructive jaundice • 1 had thromboembolic complication-ruled out APLA

  9. TYPE OF AUTOANTIBODIES - frequency

  10. PATTERN OF PRE TRANSFUSION TESTING • Most common discrepancy was Type 1V • Association between cold AIHA and grouping discrepancy (p <0.001) • 81.3 % resolved by prewarming • 18.7 % resolved by cold auto adsorption • BLOOD GROUPING 36 % WAIHA RESOLUTION 36 % MIXED 28 % CAD Blood grouping was performed in column agglutination technology (Ortho vision), discrepant samples were repeated in tube method and resolved

  11. DAT ALONE POSITIVE : 34.6 % ; n=9 76.5% (13/17)– had history of sensitization event; so adsorption elution was performed, to differentiate autoantibody from underlying alloantibody. DAT ALONG WITH IAT POSITIVE : 65.4% , n=17 15.3 % (2/13) showed the presence of alloantibody anti c, anti e 15.3 % (2/13) showed autoantibody with specificity –auto anti c and auto anti c, e 69.4 % showed autoantibody with no alloantibody or specificity DAT – CAT VS CTT • 84.6% had CAT GRADE > CTT GRADE • 15.4% had CAT GRADE = CTT GRADE • There was one case where CAT is positive(3+ grade) and CTT is negative • SENSITIVITY of CTT is 96 .4% whereas 100 % with CAT

  12. DAT STRENGTH * INVIVO HEMOLYSIS

  13. TRANSFUSION SUPPORT • 19 out of 26 required Transfusion • All severe patients required transfusion(p=0.001) C:T =4.94 (Auto antibodies alone) • Average PRBC transfusion is 1.58/patient

  14. Effect of PRBC transfusion P=0.05 Mean hospital stay is 5.5 days (idiopathic)

  15. Discussion • Most common Grouping discrepancy was type IV Extra reactions in the serum grouping is due to the free antibodies in serum after binding to autologous RBCs • Association between cold AIHA and blood group discrepancy can be explained by 90% of cold agglutinins are IgM by nature and produce spontaneous agglutination • We observed CAT to be a good alternative to CTT in terms of sensitivity of 100% Hence its better to repeat the DAT in CAT technology, if the patient is having clinical and laboratory evidence of hemolysis and negative DAT in CTT

  16. 15.3 % of the patients developed alloantibodies supports the evidence that , approximately 12 - 40 % of patients with previous sensitization can develop clinically significant alloantibodies • 2 patients had autoantibody with specificity– auto anti c,e& auto anti e Supports the finding that, nearly 50% of all AIHA patients have autoantibodies specific for epitopes on Rh proteins • We have observed a significant correlation between DAT strength and in vivo hemolysis Grade 4 + reaction being associated with high incidence of severe hemolysis • This supports the assumption that the concentration of antibodies is important for the recognition of reticulo endothelial system and in vivo hemolysis

  17. Mean Hb increment after each PRBC transfusion is 0.99; Various studies reported Hb increments ranging from 1.40–1.70 g/dL Implies that Serological incompatibility does not necessarily mean that the RBC will be destroyed in vivo The efficacy of blood transfusion may be explained by the natural limitation of Fc- and C3b-mediated phagocytosis (Ref: Taluk Dar et al) • Our CT ratio was 4.9, comparable to that of Das et al (6.4) could be due to the increased number of crossmatches to get a best compatible unit • High turn around time of PRBC issue can be attributed to the time taken to resolve the blood group discrepancy as well as to get a best compatible unit

  18. CONCLUSION • DAT strength had a correlation with disease severity • Performing the serological investigations at the earliest may help in the early diagnosis and management • Transfusion support should not be denied to any patient because of serological incompatibility • Institutional policy should be made for the transfusion support of AIHA patients

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