Atypical presentation of relapsed multiple myeloma with microangiopathic hemolytic anemia

Abstract Introduction: Multiple myeloma (MM) is a neoplastic plasma cell dyscrasia. Anemia in MM is typically due to anemia of chronic disease. However, microangiopathic hemolytic anemia (MAHA), defined by fragmentation and intravascular hemolysis of red blood cells (RBCs) in small vessels, is a rare and potentially life-threatening manifestation. Diagnosis is based on peripheral smear evidence of schistocytes, supported by elevated reticulocyte count, lactate dehydrogenase (LDH), unconjugated bilirubin, and low haptoglobin. Causes of MAHA in MM may include chemotherapy-induced toxicity, infection associated with hemolytic uremic syndrome (HUS), or disease progression. Prompt diagnosis is essential to prevent irreversible organ damage and reduce mortality. Case Description: A 61-year-old female with IgG lambda-restricted MM and 90% bone marrow plasma cell infiltration at initial diagnosis presented with two weeks of nausea, vomiting, diarrhea, decreased oral intake, and low urine output. Her disease had progressed through multiple lines of therapy: CyBorD followed by Lenalidomide maintenance, D-Kd with Daratumumab maintenance, and most recently DaraH-Kd. Prior to this submission, bone biopsy revealed 50% plasma cells, and she was found to be iron deficient. On admission, she was anemic with hemoglobin of 7.7 g/dL and had acute kidney injury with Cr 20 mg/dL and BUN 180 mg/dL. Her hemoglobin dropped to 6.3 g/dL without signs of bleeding. Hemolysis work up revealed: LDH 936 U/L, haptoglobin <3.5 mg/dL, reticulocyte count 12%, total bilirubin 0.5 mg/dL with a negative Coombs test, platelet count was 150k. Serial peripheral smears demonstrated schistocytes, consistent with MAHA. Additional findings included: total protein 7.0 g/dL, kappa free light chains 1.0 mg/L, kappa/lambda ratio 0.01, paraprotein 0.75 g/dL, and ADAMTS13 level of 85%. Serum protein electrophoresis identified a monoclonal spike in the gamma globulin region. The infectious work up was negative. Given the acute renal failure, hemolysis, and peripheral smear findings, the patient was empirically treated for MAHA secondary to MM progression with plasma exchange (three sessions), high-dose dexamethasone (40 mg for 4 days), and CyBorD. Renal replacement therapy was also initiated. Clinically, the patient responded with improvement in renal function, hemoglobin levels and repeat bone marrow biopsy showing only 10% of plasma cells. Discussion: This case highlights a rare presentation of MM progression as MAHA without evidence of AIHA. Despite ongoing monthly DaraH-Kd maintenance therapy and a recent bone marrow showing 50% plasma cells, the acute deterioration prompted a multidisciplinary evaluation. Once AIHA, infection-associated HUS, and drug-induced MAHA were excluded, a presumptive diagnosis of MM-related MAHA was made. A decisive approach with prompt plasmapheresis and anti-myeloma therapy led to hematologic and renal recovery. Conclusion: Progressive MM presenting as MAHA is a rare but critical diagnosis. Recognizing MM as a potential cause of hemolysis, especially when other etiologies are excluded, is essential to initiating appropriate systemic therapy. This case highlights the importance of keeping a broad working differential, timely intervention, and multidisciplinary collaboration in managing complex presentations of relapsed MM.