Aplastic Crisis in a Woman with Autoimmune Hemolytic Anemia

Parvovirus B19 (B19) infection is associated with a variety of hematologic manifestations that include transient erythroid aplasia in immunocompetent individuals, chronic erythroid aplasia in immunocompromised hosts, aplastic crisis in patients with hemolytic anemia, and nonimmune hydrops fetalis [1]. The abrupt cessation of erythropoiesis following B19 infection in the patient with chronic hemolytic anemia results in a rapid drop in hemoglobin—the so-called aplastic crisis (B19-aplastic crisis). Infection with B19 may unmask an underlying hemolytic disease either inherited or acquired [2, 3]. B19-aplastic crisis has mostly been reported in patients with inherited hemolytic anemia and reports of its occurrence in acquired hemolytic anemia are rare; this is probably related to the number of patients at risk.

Case A 33-yearr-old woman was diagnosed with idiopathic warm autoimmune hemolytic anemia (AIHA) in June 2018; her hemoglobin (Hb) was 6.4 g/dL, mean corpuscular volume 133 fL, mean corpuscular hemoglobin 69.4 pg, mean corrpuscular hemoglobin concentration 51.9 g/dL, total leucocyte count 8.5 × 10⁹/L with normal differential count, platelets 343 × 10⁹/L, and reticulocytes 30%. Blood smear examination showed marked red cell agglutination, polychromasia, and microspherocytes. Serum total bilirubin was 4.0 mg/dL, direct bilirubin 1.8 mg/dL, and lactate dehydrogenase 970 IU/L (120–246 U/L). Tests for HBsAg, hepatitis C antibody, antinuclear antibody and HIV 1 & 2 were negative. She was treated successfully with prednisolone and all treatment was discontinued in December 2018.

On March 29, 2019, laboratory tests performed at another clinic because of new-onset jaundice showed Hb 6.4 g/dL, reticulocytes 15%, serum total bilirubin 4.3 mg/dl and direct bilirubin, 0.5 mg/dl.

She was seen in consultation on April 2, 2019. She was afebrile, pale, and jaundiced. The spleen was palpable 8 cm below the costal margin. The direct Coombs’ test was strongly positive and the indirect Coombs’ was negative. She was diagnosed with relapse of AIHA and begun on prednisone 50 mg orally twice daily.

Four days later, she presented with a 1-day history of fever, drowsiness and weakness. Her temperature was 101.9 °F, pulse 128/min, blood pressure 110/60 mm Hg and SpO₂ 98%. Her Hb was 2.5 g/dL, total leucocyte count 2.8 × 10⁹/L, platelets 169 × 10⁹/L and reticulocytes 0%. Smears of bone marrow aspirate, and trephine biopsy showed severe erythroblastopenia, and giant proerythroblasts suggestive of B19 infection (Fig. 1). Serum was positive for B19 DNA (nested PCR) and B19-IgM (EIA). B19 titer was not determined. She was treated with pulse methylprednisolone 1 gm intravenously daily for 3 days, followed by oral prednisolone 2 mg/kg/d. She was transfused with three units of packed red cells. Her reticulocyte count remained zero for 6 days and was 2% on the seventh hospital day. The following day, her Hb was 5.8 g/dL and reticulocytes 15%. Four weeks later she was asymptomatic; the spleen was palpable 4 cm below the costal margin. Her Hb was 12.5 g/dL, total leukocyte count 6.1 × 10⁹/L and platelets 164 × 10⁹/L; serum was positive for B19 DNA and B19-IgG.

Fig. 1.

Smear of bone marrow aspirate shows giant proerythroblast with intranuclear inclusions and ‘dog-ear’ cytoplasmic pseudopod. Wright- Giemsa stain, original magnification x 1000

The clinical and hematologic data together with positive B19 DNA and B19-IgM established the diagnosis of B19-aplastic crisis in our patient.

Recovery from B19-aplastic crisis typically occurs within a week or two, associated with the development of IgM and IgG antibody to the virus. Patients with a defective immune response (e.g. HIV infection) may develop persistent B19 viremia, chronic erythroid aplasia and severe anemia requiring high-dose intravenous immunoglobulin therapy for recovery.

Corticosteroid therapy is used for its immunosuppressive effect in the first-line treatment of AIHA. It is reassuring that high-dose corticosteroid therapy did not delay recovery from erythroid aplasia in our patient as also reported by others [4, 5].

The rapid development of anemia with virtual absence of reticulocytes in the patient with chronic hemolytic anemia should prompt the diagnostic consideration of B19-aplastic crisis. The immunocompetent patient with B19-aplastic crisis is viremic at presentation and is highly infectious. Prompt recognition of B19-aplastic crisis helps in counseling the patient and contacts. Current guidelines recommend droplet and contact precautions maintained for 7 days. The American Academy of Pediatrics further recommends informing any at-risk pregnant health care professional of potential risks to the fetus from B19 infection and need for appropriate follow-up care.

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Conflict of interest

The Authors have no conflicts of interest to declare.