Recognition and Management of Transfusion-Associated Immune Hemolytic Crisis in Pregnant Patients with Thalassemia: Analysis of Three Cases and Construction of a Clinical Pathway

Pregnancy complicated by thalassemia, especially in transfusion-dependent thalassemia (TDT) patients, poses major obstetric challenges. Due to physiological hemodilution and a shortened red blood cell (RBC) lifespan, these patients require regular transfusions to maintain stable hemoglobin levels. Long-term transfusions increase the risks of alloimmunization and autoimmune hemolytic anemia (AIHA). These conditions can be misdiagnosed as primary thalassemia or normal pregnancy-related physiological changes due to their non-specific manifestations, thus delaying critical intervention. This raises risks of maternal mortality, thrombosis, heart failure, fetal growth restriction (FGR), and preterm birth. While guidelines recommend multidisciplinary management for pregnant women with thalassemia, there’s no standardized clinical pathway for rapid differentiation between alloimmune and autoimmune hemolysis and initiating targeted intervention after transfusion refractoriness. This study analyzed three cases of pregnancy complicated by thalassemia and immune hemolysis with clinical significance. Based on these cases and guidelines, a management pathway was established emphasizing immediate antibody screening and direct antiglobulin test (DAT, Coombs test) upon signs of transfusion refractoriness to differentiate alloimmunity from AIHA and guide targeted treatment.