Abstract
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.
