Autoimmunhämolytische Anämien

Autoimmunhämolytische Anämien stellen eine Untergruppe der hämolytischen Anämien dar. Auch wenn es sich um seltene Erkrankungen handelt, ist eine zügige Diagnosestellung wichtig, um betroffene Patienten schnell in spezialisierte hämatologische Zentren und Praxen vorzustellen. Dieser Beitrag soll einen kurzen Überblick über die verschiedenen Unterformen, die Diagnostik sowie Therapieansätze geben.

Abstract

Autoimmune haemolytic anemia (AIHA) is defined as the immune-mediated destruction of red blood cells. In most cases, antibodies that target surface antigens on erythrocytes lead to their premature degradation in the spleen or, less commonly, in the liver. The term includes a heterogenous group of diseases, which differ largely in pathophysiology and treatment. The two most common entities are warm AIHA and cold AIHA. Diagnostic testing involves the analysis of haemolytic markers like lactate dehydrogenase, haptoglobin and unconjugated bilirubin as well as a hemoglobin and reticulocytes. In case of a haemolytic anemia, further testing like a blood smear and a direct antiglobulin test should follow. As diagnostic testing and treatment of AIHA are complex, affected patients should always be referred to a hematologist.

In warm AIHA, mainly IgG autoantibodies bind to their antigen on the erythrocyte surface at body temperature, leading to their premature destruction in the spleen. First line treatment options include the administration of steroids which mitigate the destruction of red blood cells by macrophages in the spleen. In contrast, IgM autoantibodies in cold AIHA lead to intravasal agglutination of erythrocytes and complement activation. The IgM antibodies have their highest affinity below body temperature which is why patients experience symptoms mainly in cold-exposed body areas. Although the IgM antibodies dissolve at body temperature, the complement-loaded erythrocytes are destroyed in the liver. Therapeutic options include protection from cold and immunosuppressive agents or complement inhibition.

Schlüsselwörter

Autoimmunhämolytische Anämie - Coombs-Test - wAIHA - cAIHA - Kälteagglutin-Krankheit

Key words

autoimmune haemolytic anemia - Coombs test - warm AIHA - cold AIHA - cold agglutinin disease

Publication History

Article published online:
20 September 2022

• Literatur

• 1 Randen U, Gunhild T, Anne T. et al. Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma. Haematologica 2014; 99: 497-504
• 2 Das SS, Chakrabarty R, Zaman RU. Immunohematological and clinical characterizations of mixed autoimmune hemolytic anemia. Asian J Transfus Sci 2018; 12: 99-104
• 3 Jäger U, Barcellini W, Broome CM. et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood Reviews 2020; 41: 100648
• 4 Flores G, Cunningham-Rundles C, Newland AC. et al. Efficacy of intravenous immunoglobulin in the treatment of autoimmune hemolytic anemia: results in 73 patients. Am J Hematol 1993; 44: 237-242
• 5 McLeod BC. Evidence based therapeutic apheresis in autoimmune and other hemolytic anemias. Curr Opin Hematol 2007; 14: 647-654
• 6 Barcellini W, Fattizzo B. How I treat warm autoimmune hemolytic anemia. Blood 2021; 137: 1283-1294
• 7 Birgens H, Frederiksen H, Hasselbalch HC. et al. A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia. Br J Haematol 2013; 163: 393-399
• 8 Michel M, Terriou L, Roudot-Thoraval F. et al. A randomized and double-blind controlled trial evaluating the safety and efficacy of rituximab for warm auto-immune hemolytic anemia in adults (the RAIHA study). Am J Hematol 2017; 92: 23-27
• 9 Berentsen S, Barcellini W. Autoimmune Hemolytic Anemias. N Engl J Med 2021; 385: 1407-1419
• 10 Hill A, Hill QA. Autoimmune hemolytic anemia. Hematology Am Soc Hematol Educ Program 2018; 2018: 382-389
• 11 Barbara DW, Mauermann WJ, Neal JR. et al. Cold agglutinins in patients undergoing cardiac surgery requiring cardiopulmonary bypass. J Thorac Cardiovasc Surg 2013; 146: 668-680
• 12 Hill QA, Stamps R, Massey E. et al. The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol 2017; 176: 395-411
• 13 Berentsen S, Barcellini W, D’Sa S. et al. Cold agglutinin disease revisited: a multinational, observational study of 232 patients. Blood 2020; 136: 480-488
• 14 Berentsen S, Randen U, Vågan AM. et al. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood 2010; 116: 3180-3184
• 15 Berentsen S, Randen U, Oksman M. et al. Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial. Blood 2017; 130: 537-541
• 16 Jalink M, Berentsen S, Castillo JJ. et al. Effect of ibrutinib treatment on hemolytic anemia and acrocyanosis in cold agglutinin disease/cold agglutinin syndrome. Blood 2021; 138: 2002-2005
• 17 Rossi G, Gramegna D, Paoloni F. et al. Short course of bortezomib in anemic patients with relapsed cold agglutinin disease: a phase 2 prospective GIMEMA study. Blood 2018; 132: 547-550
• 18 Röth A, Barcellini W, DʼSa S. et al. Sutimlimab in Cold Agglutinin Disease. N Engl J Med 2021; 384: 1323-1334