Transfusion medicine

A 7 year old boy is referred to pediatric hematology from a general pediatrician for new onset anemia with normal white blood cell (WBC) and platelet count after an upper respiratory infection. Iron studies are normal and there is no family history to suggest hemoglobinopathy, membranopathy or enzyme defect. He is found to be anemic with no other complete blood count (CBC) abnormalities. The pediatric hematologist is concerned about autoimmune hemolytic anemia and orders a direct antiglobulin test (DAT), which is negative and requests a peripheral blood smear, which shows increased spherocytes and polychromasia in the image above.

The pediatric hematologist then orders an enhanced DAT or DAT negative autoimmune hemolytic anemia workup. Which of the following is the most likely cause of the patient's apparent hemolysis and explanation for the negative DAT?

1. Hereditary spherocytosis
2. IgG antibody concentration below the limit of detection of standard DATs
3. Lab error in the original DAT
4. Microangiopathic hemolytic anemia

B. IgG antibody concentration below the limit of detection of standard DATs. This likely represents a case of low level or low affinity IgG autoantibodies below the level of detection of a standard DAT. Answer A is incorrect because the child was previously healthy and there is no familial history of a membranopathy. Answer C, while possible, is unlikely because of the use of check cells for negative reactions at antihuman globulin phase in blood bank as a check and balance on negative results. Additionally, most DAT panels include 3 reagents: polyspecific IgG plus C3, monospecific IgG and monospecific C3. Even if there had been a problem with one of the reagents, the built in redundancy of the polyspecific reagent increases the likelihood of detecting any sort of reactivity in the DAT. Answer D is incorrect because there is no significant evidence to suggest microangiopathic hemolytic anemia; namely, there is no major increase in schistocytes, as compared to spherocytes.

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Reference: DAT negative autoimmune hemolytic anemia

A 55 year old woman with chronic lymphocytic lymphoma (CLL) presented with anemia and reticulocytosis, a negative routine direct antiglobulin test (DAT) for both complement and IgG, a negative red cell antibody screen, elevated lactate dehydrogenase (LDH), severely decreased haptoglobin and indirect hyperbilirubinemia. At this point, which of the following is the recommendation the blood bank medical director will most likely give to the consulting physician when contacted for assistance with evaluation for possible autoimmune hemolytic anemia (AIHA)?

1. Peripheral blood smear
2. Send out testing to immunohematology reference lab (IRL) for DAT negative AIHA
3. Send out testing to IRL for Donath-Landsteiner testing
4. Urinalysis

B. Send out testing to the immunohematology reference lab (IRL) for DAT negative AIHA evaluation. Answers A and D are incorrect because at this point, finding spherocytes on a peripheral blood smear or evidence of hemoglobinuria on urinalysis are unlikely to provide any further information to confirm autoimmune hemolytic anemia, as there is already evidence of in vivo hemolysis. The consulting physician is likely to already have started corticosteroids for the treatment of presumed AIHA and confirmation of a DAT negative AIHA would support staying the course, as would clinical improvement with steroids. Answer C is incorrect because send out testing for a Donath-Landsteiner test would be of lesser value in this patient demographic. Unless the patient had known syphilis, paroxysmal cold hemoglobinuria (PCH) is unlikely in an elderly patient. It is most common in pediatric patients after a viral illness. It is confirmed with a positive Donath-Landsteiner test.

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Reference: DAT negative autoimmune hemolytic anemia