2026-08-10 | Autoimmune hemolytic anemia in the era of immunotherapy: from pathogenesis to therapeutic strategies
Abstract Autoimmune hemolytic anemia (AIHA) is a rare hematologic disorder characterized by the accelerated destruction of red blood cells mediated by autoantibodies and is classified into warm antibody type and cold antibody type. Corticosteroids remain the first-line treatment, whereas rituximab has replaced splenectomy as the standard second-line therapy. However, a considerable proportion of patients still experience relapse or refractory disease. In recent years, with an improved understanding of its pathogenesis, significant advances have been achieved in targeted therapies for AIHA, including complement inhibitors, spleen tyrosine kinase inhibitors, Bruton tyrosine kinase inhibitors, phosphoinositide 3-kinase delta inhibitors, other novel agents, and chimeric antigen receptor T-cell therapy. Future AIHA management will focus on individualized treatment guided by precise stratification, combination strategies, and biomarkers, ultimately achieving a transition from empirical immunosuppression to mechanism-targeted precision medicine.
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2026-08-08 | Treatment of Cold Agglutinin Syndrome Secondary to Chronic Lymphocytic Leukemia With Sutimlimab and Obinutuzumab-Venetoclax.
Cold agglutinin-mediated autoimmune hemolytic anemia (AIHA) is a rare disorder in which IgM autoantibodies lead to complement-dependent hemolysis and cold-induced circulatory symptoms. It is categorized as either cold agglutinin disease (CAD), a primary lymphoproliferative disorder (LPD), or cold agglutinin syndrome (CAS), which occurs secondary to other conditions most commonly infections or lymphoid malignancies. Although the treatment for CAS should be directed toward the underlying condition, the often slower response rates of these treatments, especially in the setting of LPD, could necessitate other strategies for patients with severe hemolytic anemia requiring more rapid control of hemolysis. For patients with CAD, inhibition of the classical complement pathway with the C1s inhibitor sutimlimab has demonstrated significant control of hemolysis, resolution of anemia, and improvement in quality of life. However, little has been published regarding the use of sutimlimab for the treatment of CAS. Here, we describe a patient with CAS secondary to chronic lymphocytic leukemia (CLL) with severe IgM-driven complement-mediated hemolysis who was successfully treated with a combination of sutimlimab and CLL-directed therapy with obinutuzumab-venetoclax. Sutimlimab provided rapid cessation of hemolysis, acting as a bridge while the obinutuzumab-venetoclax addressed the underlying CLL that was presumably responsible for the autoantibody production. This case demonstrates that combining sutimlimab with obinutuzumab-venetoclax is an effective and safe treatment for patients with CAS in the setting of CLL, supporting the use of short-term sutimlimab for CAS as a bridge to more durable treatment for underlying LPD such as CLL.
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2026-08-06 | A Case Study of PSTPIP1-Associated Myeloid-Related Proteinemia Inflammatory Syndrome Masquerading as Inflammatory Bowel Disease.
PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a rare autoinflammatory disorder. Systemic inflammation, cytopenia, and skin lesions are classic features, accompanied by hypercalprotectinemia and hyperzincemia. Gastrointestinal manifestations such as colitis are infrequent. We present the first case in Thailand of PAMI syndrome presenting as refractory colitis. A 23-year-old male presenting with adult-onset refractory colitis and a history of a teenage perianal abscess. Despite the relatively late onset of intestinal symptoms, the patient exhibited a complex clinical picture across multiple domains of inborn errors of immunity, including autoimmune hemolytic anemia, chronic neutropenia, hepatosplenomegaly, and severe cystic acne. Genetic testing revealed a PSTPIP1 mutation (E250K variant), and laboratory results showed pathognomonic hyperzincemia, confirming PAMI syndrome. Treatment with adalimumab led to significant clinical and endoscopic remission. PAMI syndrome should be considered a differential diagnosis in patients with atypical or refractory colitis, particularly when accompanied by systemic clues such as cytopenia, severe acne, or organomegaly. Serum zinc levels serve as a simple, cost-effective screening tool to facilitate prompt diagnosis and can function as a practical biomarker for monitoring the response to therapy.
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2026-08-04 | Early-Onset Direct Antiglobulin Test-Negative Autoimmune Hemolytic Anemia Induced by Pembrolizumab in Perioperative Triple-Negative Breast Cancer: A Case Report.
Hematological immune-related adverse events associated with immune checkpoint inhibitors (ICIs) are rare, and autoimmune hemolytic anemia (AIHA) is particularly uncommon. A 71-year-old woman with stage IIA triple-negative breast cancer received perioperative pembrolizumab with carboplatin and paclitaxel. During the first treatment cycle, she developed acute severe anemia with laboratory findings consistent with hemolysis. Despite a negative direct antiglobulin test (DAT), major alternative causes of hemolysis were considered unlikely, leading to a clinical diagnosis of suspected ICI-associated AIHA. Oral prednisolone (1 mg/kg) promptly resolved hemolysis without recurrence. Pembrolizumab was discontinued; however, imaging demonstrated a clinical complete response, and subsequent surgery confirmed a pathological complete response (pCR). This case demonstrates that AIHA during ICI therapy may occur despite a negative DAT and underscores the importance of prompt recognition and corticosteroid therapy. Favorable oncologic outcomes, including pCR, may still be achieved despite early discontinuation of ICI therapy.
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2026-07-31 | Resolution of severe autoimmune hemolytic anemia and thrombocytopenia associated with Plasmodium vivax malaria without corticosteroid therapy: A case report.
Autoimmune hemolytic anemia is a rare but potentially life-threatening complication of Plasmodium vivax malaria. Most reported cases required corticosteroid therapy in addition to antimalarial treatment. We report the case of a 28-year-old Ethiopian man who presented with fever, pallor, and fatigue. Laboratory evaluation revealed severe anemia (hemoglobin 6 g/dL), thrombocytopenia (88,000/µL), hyperbilirubinemia, and a positive direct antiglobulin test. Peripheral smear confirmed P vivax infection with 2% parasitemia. Comprehensive immunohematological testing, including direct antiglobulin test, elution, adsorption, and extended antigen typing, confirmed immune-mediated hemolysis and excluded alloantibody-related incompatibility. The patient received 3 compatible blood transfusions and was treated with intravenous artesunate followed by primaquine, without corticosteroids or platelet transfusion. By day 5, hemoglobin improved to 10.2 g/dL, platelets normalized, and malaria smears were negative. He was discharged in stable condition. This report highlights an unusual presentation of P vivax malaria complicated by severe autoimmune hemolytic anemia and thrombocytopenia, which resolved with antimalarial therapy alone, without immunosuppressive therapy, including corticosteroids. This finding suggests that corticosteroids may not always be necessary in certain cases and underscores the importance of early recognition and comprehensive immunohematological evaluation in malaria-related cytopenias.
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