Hemolytic disorders

This video features Michael DeBaun, MD and Taha Bat, MD discussing delayed hemolytic transfusion reactions (DHTR) and hyperhemolysis in sickle cell disease (SCD) patients. The session aims to educate healthcare providers on recognizing, diagnosing, treating, and preventing these challenging complications. It covers recognizing clinical and laboratory features, understanding pathophysiology and risk factors, establishing a diagnostic approach, reviewing treatment strategies including supportive therapy, immunosuppression, and complement inhibitors, and discussing preventive strategies like extended antigen matching and transfusion planning. The discussion highlights the under-recognized nature of hyperhemolysis, the importance of accurate red blood cell antigen matching, and the challenges posed by racial mismatch in blood donation. Additionally, a unique case of ceftriaxone-induced immune hemolytic anemia is presented.

Key Learning Points:

• DHTR and hyperhemolysis are serious, under-recognized complications in sickle cell disease (SCD) patients
• Extended red blood cell antigen matching, including C, E, and c antigens, is crucial to prevent alloimmunization in SCD transfusions
• Diagnosis involves comprehensive lab tests (CBC, bilirubin, LDH, DAT, hemoglobin electrophoresis) to confirm hemolysis
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In this session, Sigbjørn Berentsen, MD and Taha Bat, MD explore the immunologic basis and clinical management of cold agglutinin disease (CAD). They explain how cold-reacting IgM antibodies trigger red cell agglutination and complement activation at lower temperatures, lead to hemolysis, and cause cold-induced symptoms. The session also differentiates primary vs secondary CAD and outlines both supportive and targeted treatments.

Key Learning Points:

• In CAD, IgM autoantibodies bind red cells at low temperatures and activate complement, leading to intravascular or extravascular hemolysis.
• CAD is categorized as primary (often clonal B-cell etiology) or secondary (commonly triggered by infections or lymphoid malignancies).
• Clinically, patients may present with acrocyanosis, cold-induced symptoms, back/abdomen pain, and signs of hemolysis (jaundice, dark urine).
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In this session, Sigbjørn Berentsen, MD and Taha Bat, MD discuss warm autoimmune hemolytic anemia (wAIHA), highlighting immunopathogenesis, clinical features, diagnosis, and therapy. They compare it with other hemolytic anemias, and outline the standard and emerging treatment strategies.

Key Learning Points:

• wAIHA is driven by IgG autoantibodies binding red cell antigens at body temperature, leading predominantly to extravascular hemolysis (usually in spleen).
• Clinical presentation includes anemia symptoms (fatigue, pallor), jaundice, increased reticulocytes, and often splenomegaly.
• Direct antiglobulin (Coombs) test is typically positive for IgG (and sometimes complement).
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In this session, Thomas Coates, MD and Ibrahim Ibrahim, MD provide an in-depth discussion about the state of gene therapy for sickle cell disease. They outline how gene therapy — by genetically correcting or ameliorating the mutation responsible for SCD in hematopoietic (blood-forming) stem cells — is transitioning from theoretical to actual clinical application. They caution, however, that while gene therapy offers hope for a “cure,” it's not a magic bullet. Concerns remain around long-term safety, durability of therapeutic effects, and equitable access. The speakers stress that even after gene therapy, patients may still require traditional supportive care and monitoring for complications. Finally, they call for strong research infrastructure — including long-term follow-up studies, registries, and multidisciplinary care teams — as critical to properly evaluate and deliver gene therapies to SCD patients.

Key Learning Points:

• Gene therapy is becoming a realistic curative option for sickle cell disease, offering an alternative to bone marrow transplant.
• Long-term outcomes are still unknown, making ongoing monitoring and safety follow-up essential.
• Not all patients will qualify, and issues of access, cost, and equity remain major concerns.
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