PC2154: Too Cool for the Pool: Paroxysmal Cold Hemoglobinuria in a Young Adult

Introduction: Paroxysmal Cold Hemoglobinuria (PCH) accounts for nearly 30% of autoimmune hemolytic anemia (AIHA) in children, most often seen in 1-5 year old children following viral illnesses, or associated with congenital syphilis. It presents clinically with fatigue, jaundice, and hemoglobinuria, with laboratory findings of intravascular hemolysis, and diagnosis can be confirmed with positive Donath-Landsteiner (DL) reaction.

Case Description: An otherwise healthy 20 yo male presented to the emergency department after four days of runny nose with intermittent fevers and worsening dark urine and jaundice. His admitting labs were consistent with hemolysis including hemoglobin (Hgb) of 9.9, total bilirubin of 9.0, DAT Anti-C3 3+ and Anti-IgG weakly positive, and haptoglobin < 8. Shortly after admission he experienced symptomatic orthostatic hypotension and was fluid resuscitated with a non-warmed isotonic fluid bolus. Over the next 36 hours, his Hgb dropped precipitously to 4.7. Given high clinical suspicion for AIHA of unconfirmed etiology and severe and persistent anemia, his hemolysis was treated with steroids, IVIg, and rituximab, as well as aggressive warmed blood transfusions to maintain a Hgb >5. Vital signs remained stable throughout. Cold agglutinin titers were negative, and rapid viral panel, EBV, CMV, and mycoplasma serologies were negative as well as negative SPEP with IF, immunoglobulin levels, FLOW cytometry. . He steadily improved after immunosuppressive therapy. Testing for Donath-Landsteiner antibody was positive, confirming the diagnosis of PCH. The DL reaction is characterized by hemolysis after exposure of patient serum to P-antigen positive donor serum at 4°C followed by 37°C, but not when exposed only at 37°C. This indicates presence of the Donath-Landsteiner antibody which binds to the P-antigen at low temperatures. While no clear inciting infectious etiology was identified, the patient and several of his close contacts had upper-respiratory type symptoms in the days preceding his presentation.

Discussion: PCH is a rare disease but a relatively common pediatric AIHA that manifests with cold exposure, most typically in young children. This patient had a preceding viral illness but was significantly older than a typical patient with PCH, and as such received care in an adult hospital and received workup for multiple causes of autoimmune hemolytic anemia, including extensive evaluation for hematologic malignancy. He remains in remission for his hemolytic anemia after induction with steroids, IVIg, and 4 cycles of rituximab. In pediatric hospitals immunosuppressive agents are typically withdrawn after the diagnosis of PCH is made and patients are provided supportive care of warmed fluids and blood transfusions as needed until hemoglobin begins to uptrend.

Conclusion: The patient did well after treatment and was even able to resume activities such as cold water swimming. Conversation between adult and pediatric hematologists could be useful in diagnosis of and care planning for similar adult patients who present with classically pediatric illness.