WARM AGGLUTIN AUTOIMMUNE HEMOLYTIC ANEMIA ASSOCIATED WITH EPSTEIN BARR VIRUS

Abstract

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is a relatively rare disorder (1-3 per 100 000) characterized by antibody production against autologous erythrocytes [1]. We present a novel case of warm agglutinin, autoimmune hemolytic anemia associated with Epstein-Barr Virus (EBV). CASE PRESENTATION: A 79-year-old woman with hypothyroidism was referred from the outpatient clinic after labs showed hemoglobin (Hgb) of 6.7 mg/dL. She complained of fatigue and dyspnea for 5 days. She had yellowing of skin and dark urine for 2 days. Vitals showed a blood pressure of 87/27 mmHg with a heart rate of 87 bpm. Repeat Hgb was 4.7 g/dL associated with mean corpuscular volume 111.6 fL. White cell count was elevated at 18. Leukocyte Alkaline Phosphatase score was elevated at 50. Direct Coombs test was positive with IgG and anti-C3 with warm agglutins. Haptoglobin was <10mg/dL, Lactate dehydrogenase 900U/L, and ferritin 1747. She received 3 units of packed red blood cells (RBC) and was started on corticosteroids. Peripheral blood smear showed left shift with increased bands, and megaloblastic granulocytes. Serum B12 level was 63ng/mL (N >200). Intrinsic factor was within normal limits. Ebstein Barr Virus IgG titers were elevated at 50 times limit upper limit of normal. All other tests for infectious causes of AIHA were negative. She was not on any medications known to cause AIHA. The patient reported resolution of symptoms by admission day 2. Hgb improved to baseline at 9.4 mg/dL and repeat MCV was 94.8 fL. The patient was subsequently discharged with B12 supplementation and continued to be symptom-free 4 weeks later. DISCUSSION: AIHA has a broad differential, with etiologies including medications, viruses, and hematological malignancies. EBV has a well-established connection with cold agglutin AIHA. IgM antibodies formed against EBV can cross-react against erythrocytes, reacting at 1-3 degrees Celsius, hence classified as cold agglutinin hemolytic anemia. However, it is not known if EBV can also induce warm agglutination. An extensive literature review returned a single report of fatal AIHA due to IgG warm agglutination exacerbated by EBV [2]. AIHA may have also be exacerbated by irregular erythropoiesis. Megaloblastic erythrocytes may have unique membrane antigens that present easier targets for circulating antibodies, thus driving hemolysis [3].Macrocytosis was likely due to B12 deficiency in this case, however other autoimmune diseases like pernicious anemia may be associated with AIHA, and warrant investigation. LAP score was also done to differentiate between reactive leukocytosis vs hematological malignancies such as chronic myelogenous leukemia, which also causes AIHA. CONCLUSIONS: EBV is classically associated with cold agglutin AIHA, although this case suggests that warm agglutination is possible. Macrocytic anemia may also worsen AIHA. Further studies are needed to delineate causation. REFERENCE #1: Hill A, Hill QA. Autoimmune hemolytic anemia. Hematology Am Soc Hematol Educ Program. 2018;2018(1):382-389. doi:10.1182/asheducation-2018.1.382 REFERENCE #2: Fadeyi EA, Simmons JH, Jones MR, Palavecino EL, Pomper GJ. Fatal autoimmune hemolytic anemia due to immunoglobulin g autoantibody exacerbated by epstein-barr virus. Lab Med. 2015 Winter;46(1):55-9. doi: 10.1309/LM9OWRF64OGQODEA. PMID: 25617394. REFERENCE #3: Vucelic V, Stancic V, Ledinsky M, Getaldic B, Sovic D, Dodig J, Grbac L, Gacina P, Rincic G, Carzavec D. Combined megaloblastic and immunohemolytic anemia associated--a case report. Acta Clin Croat. 2008 Dec;47(4):239-43. PMID: 19388472. DISCLOSURES: No relevant relationships by Mateus Fernandes, source=Web Response