University of Wisconsin Hematology

Hemolytic anemias

General

  1. Vallelian et al. Hemolysis, free hemoglobin toxicity, and scavenger protein therapeutics. Blood 2020;140:1837
  2. Brodsky RA. Complement in hemolytic anemia. Blood 2015;126:1259(PNH, aHUS, cold agglutinin disease)
  3. Shih et al. Haptoglobin testing in hemolysis: Measurement and interpretation. Am J Hematol 2013;89:443
  4. Dvanajscak et al.Hemolysis-associated hemoglobin cast nephropathy results from a range of clinicopathologic disorders. Kidney Int 2019;96:1400
  5. Gavrilaki et al. Advancing therapeutic complement inhibition in hematologic diseases: PNH and beyond. Blood 2022;139:3571

Autoimmune

  1. Berentsen and Barcellini. Autoimmune hemolytic anemias. NEJM 2021;385:1407
  2. Brodsky RA. Warm autoimmune hemolytic anemia. NEJM 2019;381:647
  3. Barcellini et al. How I treat warm autoimmune hemolytic anemia. Blood 2021;137:1283
  4. Fattizzo et al. Autoimmune hemolytic anemia during pregnancy and puerperium: an international multicenter experience. Blood 2023;141:2016
  5. Liesveld et al. Variability of the erythropoietic response in autoimmune hemolytic anemia: analysis of 109 cases. Blood 1987; 69:820
  6. Barcellini et al. Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients. Blood 2014;124:2930(Suggests rituximab preferable to splenectomy as second-line treatment)
  7. Dierickx et al. The role of rituximab in adults with warm antibody autoimmune hemolytic anemia. Blood 2015;125:3223
  8. Barcellini et al. Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biologic studies. Blood 2012;119:3691(100 mg weekly x 4 doses, 100% response rate in warm AIHA)
  9. Fattizio et al. Low-dose rituximab in autoimmune hemolytic anemia: 10 years after. Blood 2019;133:996(Confirms utility of rituximab in patients with warm AIHA whose hemolysis worsenss during steroid taper)
  10. Gómez-Almaguer et al. Low-dose rituximab and alemtuzumab combination therapy for patients with steroid-refractory autoimmune cytopenias. Blood 2010;116:4783
  11. Crowther et al. Evidence-based focused review of the treatment of idiopathic warm immune hemolytic anemia in adults. Blood 2011;118:4036
  12. Michel et al. The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. Blood 2009;114:3167(50% had associated autoimmune, lymphoproliferative or immunodeficiency disease)
  13. Seif et al. Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-institutional study. Blood 2010; 115:2142 (> 5% double-negative T cells in peripheral blood a strong predictor of ALPS)
  14. Dowdell et al. Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome. Blood 2010;115:5164
  15. Hadjadj et al. Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes. Blood 2019;134:9
  16. Bride et al. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood 2016;127:17(Pediatric study, patients had multilineage immune cytopenia due to ALPS, CVID, Evans syndrome or SLE)
  17. Kumar et al. mTOR inhibition attenuates cTfh cell dysregulation and chronic T-cell activation in multilineage immune cytopenias. Blood 2023;141:238 (Pediatric patients)
  18. Ratnasingam et al. Bortezomib-based antibody depletion for refractory autoimmune hematological diseases. Blood Adv 2016;1:31(Bortezomib effective in a variety of autoimmune conditions including AIHA, acquired factor VIII inhibitor, and TTP)
  19. Rother et al. The Clinical Sequelae of Intravascular Hemolysis and Extracellular Plasma Hemoglobin. A Novel Mechanism of Human Disease. JAMA 2005;293:1653
  20. Chiao et al. Risk of Immune Thrombocytopenic Purpura and Autoimmune Hemolytic Anemia Among 120 908 US Veterans With Hepatitis C Virus Infection. Arch Intern Med 2009;169:357
  21. Cappellini M. Coagulation in the pathophysiology of hemolytic anemias. Hematology 2007;74
  22. Fattizzo et al. Intravascular hemolysis and multitreatment predict thrombosis in patients with autoimmune hemolytic anemia. J Thromb Haemost 2022;20:1852
  23. Wooley et al. Post-Babesiosis Warm Autoimmune Hemolytic Anemia. NEJM 2017;376:939(6/18 asplenic patients with Babesiosis developed AIHA 2-4 weeks after diagnosis of infection)
  24. Roman et al. Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia. Blood 2025;145:397

Cold agglutinin disease

  1. Berentsen S. How I treat cold agglutinin disease. Blood 2021;137:1295
  2. Swiecicki et al. Cold agglutinin disease. Blood 2013;122:1114
  3. Berentsen et al. Cold agglutinin disease revisited: a multinational, observational study of 232 patients. Blood 2020;136:480(Rituximab/bendamustine had 78% response rate)
  4. Berentsen et al.  Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients.  Blood 2004;103:2925
  5. Berentsen et al. Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial. Blood 2017;130:537 (40% CR, 31% PR; durable responses, modest toxicity)
  6. Berentsen et al. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood 2010;116:3180
  7. Shi et al. TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins. Blood 2014;123:4015
  8. Röth et al. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial. Blood 2022;140:980
  9. Rossi et al. Short course of bortezomib in anemic patients with relapsed cold agglutinin disease: a phase 2 prospective GIMEMA study. Blood 2018;132:547(About 30% of patients showed CR or PR)
  10. Röth et al. Eculizumab in cold agglutinin disease (DECADE): an open-label, prospective, bicentric, nonrandomized phase 2 trial. Blood Adv 2018;2:2543(Reduced hemolysis & transfusion need but not cold-induced symptoms)
  11. Jäger et al. Inhibition of complement C1s improves severe hemolytic anemia in cold agglutinin disease: a first-in-human trial. Blood 2019;133:893
  12. Roman et al. Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia. Blood 2025;145:397
  13. Röth et al. Sutimlimab in Cold Agglutinin Disease. NEJM 2021;384:1323(C1 inhibition causes rapid improvement in CAD)
  14. D’Sa et al. Safety, tolerability, and activity of the active C1s antibody riliprubart in cold agglutinin disease: a phase 1b study. Blood 2024;143:713 (Single IV dose gave sustained response lasting at least 15 weeks)

Drug-induced hemolytic anemia

  1. Garratty G. Drug-induced immune hemolytic anemia. Hematology 2009:73
  2. Maquet et al. Drug-induced immune hemolytic anemia: detection of new signals and risk assessment in a nationwide cohort study. Blood Adv 2024;8:817

Hemolysis due to infection

  1. Haldar and Mohandas. Malaria, erythrocytic infection, and anemia. Hematology 2009:87

Red cell enzyme deficiencies

  1. Luzzatto et al .Glucose-6-phosphate dehydrogenase deficiency. Blood 2020;136:1225
  2. Beutler E. Glucose-6-phosphate dehydrogenase deficiency: a historical perspective. Blood 2008;111:16
  3. Prchal and Gregg. Red cell enzymes. Hematology 2005:19
  4. van Wijk and van Solinge. The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis. Blood 2005;106:4034
  5. Cocco et al. Mortality in a cohort of men expressing the glucose-6-phosphate dehydrogenase deficiency. Blood 1998;91:706
  6. Pamba et al. Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase–deficient children receiving dapsone. Blood 2012;120:4123
  7. Luzzatto and Arese. Favism and Glucose-6-Phosphate Dehydrogenase Deficiency. NEJM 2017;378:60
  8. Grace and Barcellini. Management of pyruvate kinase deficiency in children and adults. Blood 2020;136:1241
  9. Grace et al. Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study. Blood 2018;131:2183
  10. Grace et al. Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency. NEJM 2019;381:933
  11. Al-Samkari et al. Mitapivat versus Placebo for Pyruvate Kinase Deficiency. NEJM 2022;386:1432
  12. Glenthøj et al. Mitapivat in adult patients with pyruvate kinase deficiency receiving regular transfusions (ACTIVATE-T): a multicentre, open-label, single-arm, phase 3 trial. Lancet Haematol 2022;9:e724
  13. Ayi et al. Pyruvate kinase deficiency and malaria. NEJM 2008;358:1805(Mutant PK alleles protect against malaria)

Membrane disorders

  1. Risinger and Kalfa. Red cell membrane disorders: structure meets function. Blood 2020;136:1250
  2. Iolascon et al. Advances in understanding the pathogenesis of red cell membrane disorders. Br J Haematol 2019;187:13
  3. Gallagher P. Red Cell Membrane Disorders. Hematology 2005:13-18
  4. Glogowska et al. Mutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis. Blood 2015;126:1281

PNH

  1. Brodsky R. How I treat paroxysmal nocturnal hemoglobinuria. Blood 2021;137:1304
  2. Parker CJ. Management of Paroxysmal Nocturnal Hemoglobinuria in the Era of Complement Inhibitory Therapy. Hematology 2011;21
  3. Fattizzo et al. Breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria throughout clinical trials: from definition to clinical practice.  Blood 2025;146:411
  4. Notaro and Luzzatto. Breakthrough Hemolysis in PNH with Proximal or Terminal Complement Inhibition. NEJM 2022;387;160
  5. Townsley and Young. Blood consult: paroxysmal nocturnal hemoglobinuria and its complications. Blood 2013;122:2795
  6. Hillmen et al. Natural history of paroxysmal nocturnal hemoglobinuria. NEJM 1995;333:1253
  7. de Latour et al. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood 2008;112:3099
  8. Schmidt et al. Complement and the prothrombotic state. Blood 2022;139:1972
  9. Schrezenmeier et al. Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry. Haematologica 2014;99:922
  10. Parker et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005;106:3699
  11. Kelly et al. Treatment outcomes of complement protein C5 inhibition in 509 UK patients with paroxysmal nocturnal hemoglobinuria. Blood 2024;143:1157  (Eculizumab and ravulizumab safe and effective; premature deaths primarily due to associated marrow failure)
  12. Dunn et al. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med 1999;131:401
  13. Hall et al. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH).  Blood 2003;102:3587
  14. Skeith L. Anticoagulating patients with high-risk acquired thrombophilias. Blood 2018;132:2219 (Discusses DOAC use in APS, HIT, PNH)
  15. van Bijnen et al. Mechanisms and clinical implications of thrombosis in paroxysmal nocturnal hemoglobinuria. J Thromb Haemost 2012;10:1
  16. Hill et al. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood 2013;121:4985
  17. Hillmen et al. The Complement Inhibitor Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. NEJM 2006;355:1233 (About half of recipients became transfusion-independent)
  18. Hillmen et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 2007;110:4123 (85% reduction in rate of thromboembolism)
  19. Brodsky et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood 2008;111:1840 (51% of patients became transfusion independent, QOL improved)
  20. Kelly et al. Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria. NEJM 2015;373:1032
  21. Nishimura et al. Genetic variants in C5 and poor response to eculizumab. NEJM 2014;370:632
  22. Prata et al. Rare germline complement factor H variants in patients with paroxysmal nocturnal hemoglobinuria. Blood 2023;141:1812
  23. Peffault de Latour et al. Assessing complement blockade in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab. Blood 2015;125:775 (CH50 activity is a good measure of complement blockade)
  24. Lin et al. Complement C3dg-mediated erythrophagocytosis: implications for paroxysmal nocturnal hemoglobinuria. Blood 2015;126:891 (C3 mediated RBC destruction can cause persistent hemolysis in eculizumab-treated patients)
  25. Lee et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood 2019;133:530 (Ravulizumab every 8 weeks non-inferior to eculizumab every 2 weeks)
  26. Kulasekararaj et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor–experienced adult patients with PNH: the 302 study. Blood 2019;133:540 (Similar results to above study)
  27. Röth et al. The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria. Blood 2020;135:912 (Every 4-week subcutaneous self-administration)
  28. Hillmen et al. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. NEJM 2021;384:1028 (C3 inhibition gave better hematologic outcomes)
  29. Gerber and Brodsky. Pegcetacoplan for paroxysmal nocturnal hemoglobinuria. Blood 2022;139:3365
  30. de Latour et al. Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial. Lancet Haematol 2022;9:e648
  31. Griffin et al. Experience of compassionate-use pegcetacoplan for paroxysmal nocturnal hemoglobinuria. Blood 2023;141:116 (Describes breakthrough events with this drug)
  32. Griffin et al. Real-world experience of pegcetacoplan in paroxysmal nocturnal hemoglobinuria. Am J Hematol 2024;99:816
  33. Mannes et al. Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity. Blood 2021;137:443 (Strong classical pathway activation can activate C5 despite C3 inhibition)
  34. Risitano et al. Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial. Lancet Haematol 2021;8:e344
  35. Jang et al. Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Blood Adv 2022;6:4450
  36. de Latour et al. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria.  NEJM 2024390;994 (Oral factor B inhibitor reverses anemia in C5 inhibitor-treated patients with PNH, and is effective as a first-line treatment)
  37. Kulasekararaj et al. Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab. Blood 2021;138:1928 (Oral factor D inhibitor added to eculizumab decreased extravascular hemolysis)
  38. Kulasekararaj et al. Long-term efficacy and safety of danicopan as add-on therapy to ravulizumab or eculizumab in PNH with significant EVH. Blood 2025;145:811
  39. Sun and Babushok. Secondary myelodysplastic syndrome and leukemia in acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria. Blood 2020;136:36
  40. James et al. Heme induces rapid endothelial barrier dysfunction via the MKK3/p38MAPK axis. Blood 2020;136:749
  41. Gerber et al. COVID-19 vaccines induce severe hemolysis in paroxysmal nocturnal hemoglobinuria. Blood 2021;137:3670

Other

  1. Trudel et al. Hemolysis contributes to anemia during long-duration space flight. Nat Med 2022;28:59