Case Presentation: A 61-year-old African American female with a history of diabetes mellitus presented with right lower quadrant abdominal pain and melena for 1 week. Her stool was guaiac-positive. CBC with differential and CMP revealed severe normocytic anemia (MCV 88 fL) with a hemoglobin of 5.8 g/dL, leukocytosis (17 × 109/L), thrombocytopenia (118 × 109/L), and acute kidney injury with a creatinine of 4.1 mg/dL (baseline: 1.0 mg/dL). Her coagulation profile showed INR of 1.4, normal PTT and fibrinogen level. Hemolysis workup showed normal LDH and haptoglobin levels. EGD and colonoscopy revealed Forrest III gastric ulcers with no signs of recent bleeding. Patient continued requiring intermittent PRBC transfusion (1 unit every 3 days) with appropriate response during hospital stay. No overt GI bleeding was observed.Production etiologies for anemia were investigated. Peripheral smear showed immature and atypical lymphocytes concerning for hematological malignancies. Flow cytometry suggested chronic lymphocytic lymphoma. Meanwhile, patient’s blood samples were repeatedly reported too viscous for laboratory processing. On further questioning about history, she also complained about intermittent blurry vision and headache with lower extremities neuropathic pain for 1 year. Hyperviscosity syndrome was suspected and treated emergently, detailed as below. Such diagnosis was later confirmed by elevated serum viscosity of 14 centipoises. Other labs include significantly elevated serum IgM level (greater than 5850 mg/dL), serum Kappa to Lambda light chain ratio of less than 0.01, elevated beta-2 microglobulin of 18.7 mg/L, and monoclonal IgM Lambda of 6.74 g/dL. Bone marrow biopsy showed a hypercellular marrow with 50% involved by lymphoplasmacytic lymphoma, 6q23 (MYB) deletion, and absence of amyloid. The patient was diagnosed with WM and was treated with two sessions of plasmapheresis plus a 3-day course of intravenous dexamethasone 40 mg daily with significant relief of visual symptoms and headache. Her hemoglobin levels stablized before discharge without further transfusion. She received chemotherapy as outpatient.
Discussion: Waldenström’s macroglobulinemia (WM) is a distinct clinicopathologic entity demonstrating lymphoplasmacytic lymphoma in the bone marrow with an IgM monoclonal gammopathy in the blood. It commonly presents with constitutional symptoms, bleeding, lymphadenopathy, hepatosplenomegaly, neurological symptoms and hyperviscosity syndrome.
With a incidence about 3 per million persons per year, initial encounter of WM with hyperviscosity in inpatient setting is rare. Early recognition of hyperviscosity syndrome can prompt workup and management of potential oncological emergency. Anemia in WM is multifactorial, including decreased synthesis due to bone marrow replacement, bleeding diathesis and autoimmune hemolytic anemia. Bleeding diathesis is secondary to hyperviscosity, and an interference between IgM, clotting factors and platelet function. The most frequent source of bleeding is chronic oozing from the nose or gums, which can be intermittent and difficult to reveal with endoscopy. Treatment with plasmapheresis for WM-related hyperviscosity syndrome should start before laboratory confirmation of serum viscosity.
Conclusions: WM is an unusual cause of anemia encountered as inpatient. Increasing awareness can prompt management as it can be difficult to diagnose with unspecified symptoms and unrevealing routine workup.