Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells worldwide and typically presents in childhood or early adulthood following exposure to oxidative stressors. Late-life diagnosis is uncommon and may be overlooked in patients without exposure to classic hemolytic triggers. We report the case of a 70-year-old man with intermittent, mild macrocytic anemia who was ultimately diagnosed with G6PD deficiency. This case highlights how G6PD deficiency may remain clinically silent for decades, discusses reasons for delayed diagnosis, and emphasizes the importance of considering inherited hemolytic disorders in older adults with unexplained macrocytic anemia.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ dysfunction, with high untreated mortality that can be effectively reduced with timely plasma exchange (PLEX) and immunosuppressive therapy. However, several conditions can produce a clinically similar pseudo-TMA picture, among which severe vitamin B12 deficiency is an underrecognized and potentially treatable mimic that occurs due to ineffective intramedullary erythropoiesis, megaloblastic fragmentation of structurally abnormal erythrocytes, and pancytopenia in the absence of true endothelial injury or ADAMTS13 deficiency. We present a 74-year-old female patient who presented with altered mental status, bradycardia, and severe hemolytic anemia, in whom PLEX was initiated for suspected TTP but failed to improve platelet counts despite four sessions, ultimately prompting a workup that showed B12 deficiency due to pernicious anemia, confirmed by an elevated methylmalonic acid (MMA) and low serum B12, with complete hematologic recovery following cyanocobalamin repletion.

Red blood cell (RBC) transfusion is a cornerstone of life-sustaining therapy, yet it is profoundly challenged in autoimmune hemolytic anemia (AIHA). In this disorder, a diverse array of autoantibodies targets both the autologous and transfused RBCs, leading to their rapid clearance. This limitation is especially severe during hemolytic crises, rendering conventional transfusion ineffective and eliminating a critical therapeutic option. To overcome this, we developed a biocompatible strategy by utilizing a microbial transglutaminase that first anchors to the RBC membrane and then crosslinks a polysialic acid (PSA) network onto the cell surface. This created an immunologically inert shield that broadly masks surface antigens from pathogenic antibodies. Crucially, this "stealth" modification preserved the RBCs' native biological functions, including essential gas exchange, while conferring robust resistance to antibody-mediated hemolysis. In vitro, the engineered RBCs were protected from antibody binding and macrophage phagocytosis. This protection translated to a significantly prolonged circulation time in AIHA murine models and demonstrated excellent biocompatibility in an allogeneic transfusion setting. Our findings underscore the significant potential of this platform to enable effective, life-saving transfusion therapies for AIHA and other antibody-mediated disorders.

Thalassemia is one of the most common and harmful single-gene recessive disorders in the clinic. It is characterized by impaired or absent production of one globin chain of hemoglobin in adults. The most common form is beta-thalassemia, which is associated with defects in the production of beta-globin chain, resulting in an imbalance in the ratio of alpha-globin to beta-globin. As a result, unbound free alpha-globin chains precipitated in red blood cell precursors, resulting in iron overload, ineffective red blood cell production, and changes in mesenchymal stem cells, osteoblasts, osteoclasts, and other associated cells. Among them, iron overload and ineffective red blood cell production will destroy the bone marrow microenvironment, which will cause further damage to the hematopoietic system. Therefore, the correction of the bone marrow microenvironment plays an important role in the treatment of thalassemia. This review summarizes studies on the destruction of the bone marrow microenvironment in beta-thalassemia, treatment options for improving the microenvironment and stem cell transplantation.

Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, and pregnancy is a recognized trigger, particularly in the third trimester and postpartum period. We report a 29-year-old primigravida at 33 weeks' gestation who presented with severe acute kidney injury (AKI), thrombocytopenia, anemia, elevated lactate dehydrogenase, and hyperbilirubinemia with otherwise normal liver enzymes. The ADAMTS13 activity was normal, and autoimmune serologies were negative. She required urgent hemodialysis and underwent emergency cesarean section for maternal indications; however, renal failure persisted postpartum with dialysis dependence. Kidney biopsy demonstrated thrombotic microangiopathy with arteriolar fibrin thrombi. Genetic testing identified a heterozygous pathogenic splice-site variant in complement factor H, supporting the diagnosis of complement-mediated aHUS. Complement inhibition with eculizumab was initiated approximately five weeks after presentation and later transitioned to ravulizumab. Despite delayed therapy and initial dialysis dependence, she achieved dialysis independence five weeks after initiation of complement blockade, with partial renal recovery and normalization of platelet count. This case emphasizes the need to consider complement-mediated TMA in pregnant patients with severe renal dysfunction disproportionate to liver enzyme abnormalities and demonstrates that meaningful renal recovery remains possible even when dialysis is required, and complement inhibition is not initiated immediately.

Renin-angiotensin-aldosterone system inhibitors (RAASi) are suggested for treating albuminuria in patients with sickle cell disease (SCD). RAASi may exacerbate anemia in the general and diabetic population through unclear mechanisms. The impact of RAASi on anemia in chronic hemolytic disorders, such as SCD, is unknown. In a cross-sectional analysis of 658 Walk-PHaSST participants, RAASi use was independently associated with lower hemoglobin concentrations adjusting for age, sex, SCD genotype, estimated glomerular filtration rate, and erythroid-stimulating agent and hydroxyurea use (β -0.46±0.21; P=0.032). In two longitudinal cohorts (UIC, n=24; multicenter losartan clinical trial, n=32), RAASi therapy led to a reduction in hemoglobin concentrations compared with pre-treatment values by -0.44±0.14g/dL (P=0.006) and -0.53±0.17g/dL (P=0.005), respectively. SCD mice treated with losartan demonstrated lower hemoglobin concentrations after 6- and 14-weeks (P<0.001) and lower absolute reticulocyte counts by 14-weeks (P=0.03) versus control mice without changes in circulating erythropoietin, IL-12p70, IL-3, or IGF-1 levels. Bone marrow cells from losartan-treated SCD mice had lower colony forming units (P≤0.09) with rescue of erythroid colony formation after exogenous erythropoietin supplementation (P=0.02). Bone marrow histopathology demonstrated reduced erythroid relative to myeloid ratios in losartan-treated versus untreated SCD mice. Hemoglobin levels should be closely monitored when using RAASi in this high-risk population.

A 51-year-old woman presented with severe headache and severe anemia. She was diagnosed with autoimmune hemolytic anemia (AIHA) and treated with prednisolone and red blood cell transfusion. During the clinical course, the patient developed acute transient neurological symptoms. Magnetic resonance angiography revealed multifocal segmental narrowing of the cerebral arteries, which improved spontaneously on follow-up. The clinical and radiological findings were consistent with reversible cerebral vasoconstriction syndrome (RCVS). This case highlights that multiple factors, including active hemolysis, red blood cell transfusion, and corticosteroid therapy, may contribute to the development of RCVS.