Paroxysmal cold hemoglobinuria associated with monoclonal b-cell lymphocytosis in an elderly patient: A rare case report Free

Introduction:

Paroxysmal cold hemoglobinuria (PCH) is a rare cause of autoimmune hemolytic anemia

(AIHA), most frequently observed in children following viral infections. It is mediated by

Donath–Landsteiner (DL) antibodies, which induce intravascular hemolysis upon cold

exposure and rewarming. The occurrence of PCH in adults is uncommon, and its co

existence with monoclonal B-cell lymphocytosis (MBL), a premalignant clonal B-cell

disorder is extremely rare, with few documented cases. This report highlights a unique

diagnostic intersection and expands the differential for chronic anemia with hemolytic

indices in elderly patients.

Case Description:

An 86-year-old male with a history of chronic anemia, atrial fibrillation, and transient

ischemic attack presented for evaluation of fatigue and longstanding anemia. Labs showed

hemoglobin 8.9–12.0 g/dL over several years, persistently undetectable haptoglobin,

elevated indirect bilirubin, and reticulocytosis. Iron, B12, and folate were normal.

Peripheral smear showed normocytic anemia without schistocytes or burr cells. Initial

direct antiglobulin test (DAT) was negative; however, a super DAT was positive for cold

agglutinins (titer 1:64), and Donath–Landsteiner antibody testing confirmed the diagnosis

of PCH. Bone marrow biopsy revealed a small clonal CD5+, kappa-restricted B-cell

population consistent with MBL. The patient was treated with weekly rituximab infusions

for four weeks. No transfusions, corticosteroids, or IVIG were required. He remained

clinically stable during and after treatment.

Discussion:

This case underscores the diagnostic complexity and rarity of PCH in elderly patients and its

unusual co-presentation with MBL. While PCH is more often seen in children and usually

post-viral, adult cases require a high index of suspicion due to nonspecific symptoms and

often-negative DAT results. MBL, although often asymptomatic, may contribute to immune

dysregulation and has been rarely associated with AIHA. The pathophysiology of PCH

involves the DL antibody, an IgG autoantibody that binds RBCs at low temperatures and

activates complement upon warming, leading to hemolysis. Early recognition of this

biphasic mechanism is key. While rituximab was used effectively in our case, cold

avoidance and treatment of underlying infections remain the cornerstone of therapy in

typical cases. The patient's favorable response without escalation of therapy highlights the potential for

targeted management in such rare presentations. This report contributes to the limited

literature on PCH–MBL overlap and supports thorough hematologic workup in elderly

patients with unexplained hemolysis.