Quarterly Medical Review
Warm autoimmune hemolytic anemia: Advances in pathophysiology and treatment

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Summary

Autoimmune hemolytic anemia due to warm antibodies (wAIHA) accounts for approximately 70% to 80% of all AIHAs in adults. The pathogenesis of wAIHA is a complex multistep process, the last step of which being the abnormal production of auto-antibodies directed towards red blood cells’ membrane antigens. The recent advances in the understanding of the underlying mechanisms leading to the breakdown of self-tolerance in wAIHA, mainly thanks to the study of animal models are discussed in this review. Treatment of wAIHA has long been empirical and mainly based on corticosteroids. In the last decade however, the efficacy of rituximab as second-line treatment has been demonstrated first in retrospective and more recently throughout prospective studies. Based on these advances, an algorithm for the management of primary adult's wAIHA is proposed in this review.

Section snippets

Pathophysiology

The pathogenesis of wAIHA is a complex multistep process involving not only the auto-antibodies directed towards RBC's membrane antigens but also various effectors of the immune system including the complement system, macrophages as well as B and T-cells [7]. Whereas the mechanisms leading to hemolysis are partially elucidated (antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity are primarily involved), the mechanisms leading to the breakdown of self-tolerance

Treatment of wAIHA

The management of wAIHA has long been and still is mainly empirical or based on retrospective uncontrolled studies [32], [33]. It is only recently that the first 2 prospective studies including one randomized-controlled study focused on adult's wAIHA have been reported.

Systemic lupus erythematosus-associated wAIHA

Autoimmune hemolytic anemia occurs in approximately 5 to 10% of patients with SLE and is more frequently observed in patient of African ancestry [58]. wAIHA may be the sole presenting sign of the disease and may precede the appearance of other disease manifestations by several years. wAIHA in the setting of SLE is often associated with the presence of antiphospholipid antibodies with or without a definite antiphospholipid syndrome and has been associated with a higher risk of thrombosis [58].

Conclusion

wAIHA has long been viewed as a rare autoimmune disease that could be treated empirically mainly by corticosteroids on a long-term. Thanks to some informative observational studies and efforts made in the classification of wAIHA (primary versus secondary) the natural history and prognosis of the disease is henceforth better known. Based on retrospective and more recently on prospective trials, rituximab has emerged in the last decade as the preferred second-line option prior to splenectomy. As

Disclosure of interest

the author has received research support from Roche for a clinical trial in wAIHA.

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