Cytomegalovirus-Induced Coombs-Positive Hemolysis or Drug-Induced Hemolysis in an Immunocompetent Young Adult

Coombs-positive hemolytic anemia induced by cytomegalovirus (CMV) infection is a rare phenomenon, often not life-threatening in immunocompetent young adults. To date, the pathogenesis of CMV-induced severe hemolysis is still unknown. Here, we discuss a case of a 22-year-old male without significant past medical history who presented with severe hemolytic anemia that required four units of packed red blood cells. Urinalysis showed microscopic hematuria but urine culture and drug screen reported normal findings. Hemoccult result at the bedside was negative. Abdominal ultrasound and computed tomography (CT) imaging all resulted in normal findings except for splenomegaly measured 18 cm. Hematology was consulted which showed a positive direct Coombs antibody test with 3+ IgG and 3+ complement. Peripheral blood smear showed no evidence of schistocytes or occasional teardrop cells but showed toxic granulations and neutrophils indicating an underlying infection. The patient had a bone marrow biopsy which showed erythroid hyperplasia with a slight increase in sideroblast cells; but revealed no evidence of lymphoma, leukemia, or dysplasia. Infectious workup reported negative findings for HIV and hepatitis panel. However, Epstein-Barr virus (EBV) IgM antibodies to viral capsid antigen (VCA) was reported with a value of greater than 160 U/mL. Polymerase chain reaction (PCR) testing for cytomegalovirus (CMV) DNA detected high titers with 481269 IU/mL. The patient initially received intravenous immunoglobulin (IVIG) therapy for five days, antiviral medication for seven days, and high dose therapeutic corticosteroids resulting in stabilization of his blood hemoglobin (Hb) level. Infections commonly underlie secondary autoimmune hemolytic anemia (AIHA), or it can also be a result of therapy that further exacerbates the course of AIHA. Possible CMV manifestations inducing severe hemolytic anemia in immunocompetent individuals have received inadequate attention. CMV serology studies are not collected regularly in patients with hemolysis, so the incidence of this disorder might be under-reported. Thus, clinicians should take initiative to consider an underlying infection in the differential diagnosis of hemolytic anemia before opting for invasive procedures such as bone marrow biopsy. Randomized control trials are needed for a conclusive treatment specific to hemolytic anemia induced by CMV.