Dr. D is a 48-year-old with diabetes, obesity, hypertension, and obstructive sleep apnea, who was in his usual state of health until 2 weeks prior to

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1 Dr. D is a 48-year-old with diabetes, obesity, hypertension, and obstructive sleep apnea, who was in his usual state of health until 2 weeks prior to admission. He developed progressive dyspnea on exertion, darkening of his urine and progressive yellowing of his skin and eyes. He runs a biotechnology company and had his hematocrit spun in his office which was low, and this peripheral smear:

2 What test(s) would you order next? A. PNH Screen B. Serum protein electrophoresis C. ADAMSTS level D. Direct antiglobulin test

3 He presented to an outside emergency room at Holy Cross on 4/27/12. There he had a hemoglobin of 6.6, was given 2 units of blood, treated with steroids. He was also found to have an anti-e antibody and warm agglutinins. He was treated with steroids with improvement initially and was discharged on 4/30/12. However, when he went home, he had worsening of his symptoms and was readmitted, received Solu-Medrol and 3 units of additional transfusion. He was transferred to Hopkins for further management, calling in the transfer himself as he was certain that Hopkins would have a better donor supply. Select the most true statement: A. JHU has unique access to a wider donor pool due to its extensive campus and number 2 status compared to regional hospitals B. The majority of his hemolysis is extravascular C. JHU will be able to provide crossmatch compatible blood D. Direct antiglobulin test will likely be positive for C3

4 A 66 year old woman presents with a hemolytic anemia and this blood smear. Select the true statement: A. She has IgG on the surface of her red cells B. This is a consequence of a delayed hemolytic transfusion reaction C. She has complement detectable on her red cells D. The blood bank has identified IgM on her red cells

5 Autoimmune Hemolytic Anemia: The View From The Blood Bank Karen E. King, M.D. Medical Director, HATS Associate Medical Director, Transfusion Medicine

6 Objectives Review serologic findings for this patient Discuss the serologic workup of WAIHA Overview of transfusion issues related to WAIHA

7 Information from ARC

8 Information from ARC

9 ARC Recommendations

10

11

12

13

14

15

16 Serologic Evaluation

17 Indirect Antiglobulin Test

18 Direct Antiglobulin Test

19

20

21 Autoimmune Hemolytic Anemia

22 Drug Induced Immune Hemolytic Anemia

23 Causes of a Positive DAT Autoimmune Hemolytic Anemia Alloimmune disorders Nonspecific adsorption of immunoglobulin from a drug Passive antibody therapy Idiopathic/unknown

24 Coombs Negative Warm AIHA Approximately 10% of cases of warm AIHA have a negative DAT More sensitive techniques may detect IgG in some cases The significance of strength of DAT is uncertain

25 Reluctance to Transfuse Laboratory concerns: Approximately 12% 40% of patients with autoantibodies will have underlying alloantibodies Clinical concerns: RBCs for these patients will be crossmatch incompatible We are taught to only transfuse crossmatch compatible RBCs

26 RBC ALLOANTIBODIES IN PATIENTS WITH WARM AUTOANTIBODIES #ANTIBODIES/ % OF SERA REFERENCE #SERA TESTED WITH ALLOABS Morel 8/20 40 Branch and Petz 5/14 36 Wallhermfechtel et al 19/ Laine and Beattie 41/ James et al 13/41 32 Issitt et al (alloadsorptions) 13/34 38 Issitt et al (autoadsorptions) 5/41 12 Leger and Garratty 105/ TOTALS: 209/ % (Branch and Petz. Transfusion 1999;39:6-10.)

27 Transfusion 2002;42:

28 Patients 20 consecutive patients with warm autoantibodies, including: 3 with primary AIHA, 6 with CLL, 4 with MDS 8 of 20 had existing alloantibodies 7 of 8 had multiple alloantibodies Anti E identified in 6 of 8 patients Complete phenotype determined in 12 cases

29 12 Patients with Complete Phenotypes 51 samples, 149 RBCs Total

30 8 Patients Required Adsorption Studies 39 samples, 144 RBCs Total

31 Phenotypically Matched Red Cells Issues: Phenotype failures Can use partial phenotyping to guide adsorption studies Availability of phenotyped RBCs Role for genotyping

32 Dr. C. Lockard Conley Born May 14, 1915 JHU, A.B Columbia, M.D JHH Director of Hematology,

33 Autoimmune Hemolytic Anemia with Reticulocytopenia Crosby and Rappaport, Blood patients with idiopathic AIHA 15 patients with relative reticulocytopenia and hyperplastic erythroid marrows 12 of 15 patients died Poor prognostic indicator

34 Conley et al 5 patients with AIHA, reticulocytopenia and hyperplastic erythroid marrows were transferred from other hospitals with hcts of 8% 10% Transfusions had been withheld due to incompatibility Patients were transfused on arrival Transfusions were felt to be life saving

35 Conley et al

36 Conley et al Reticulocytopenia persisted for several days to more than 6 months Patients required 2 to 84 units RBCs AIHA with reticulocytopenia is a medical emergency JAMA 1980;244: NEJM 1982;306:

37 Summary Although hemolytic anemias are uncommon, AIHA is a common cause of hemolysis. AIHA can occur without a + DAT; healthy people and patients without AIHA can have a + DAT. The reticulocyte count is critical for diagnosis and management of AIHA. The specific type of AIHA is important to permit the appropriate therapy and decrease the likelihood that transfusions will be required. Transfusion can be lifesaving and must be used in patients with severe anemia, even if all blood is incompatible.

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