Evidence-based focused review of the treatment of idiopathic warm immune hemolytic anemia in adults

Abstract

Case presentationsCase 1. Robert Davies, a 50-year-old man, presents with tiredness and lethargy. Examination demonstrates pallor and jaundice. Investigations reveal anemia that is consistent with warm autoimmune hemolytic anemia (AIHA; Figure 1). He has no evidence of any other autoimmune disease or chronic lymphocytic leukemia (CLL) and is not taking any medications; these factors suggest idiopathic AIHA. How should he be treated?* AIHA is an uncommon but potentially fatal condition. It results from autoantibodies with specificity against RBC Ags leading to the premature removal of red cells from the circulation. Anemia may occur if the rate of red cell removal exceeds the ability of the BM to produce new red cells. AIHA may be secondary to drugs or underlying conditions such as CLL, infections, or autoimmune disorders. This guideline will deal specifically with idiopathic AIHA, and will not discuss secondary AIHA.Several of the treatments in this article are not licensed for the treatment of AIHA and come with little evidence, so clinicians and patients should be informed of known risks.A decision was made a priori to limit this review to published data only. Where there is no published evidence, or only expert opinion, we suggest referring to the recent Blood "How I treat" article on AIHA. 1 Medline, Embase, and the Cochrane Library were searched for relevant articles, along with reference lists of identified articles. Search strategies are found in supplemental Data (available on the Blood Web site; see the Supplemental Materials link at the top of the online article). Identified articles were then screened for inclusion. English-language articles were included only if they provided useful extractable data on adult (Ͼ 18 years) patients with idiopathic AIHA. Secondary AIHA, cold hemagglutinin disease, and patients with concomitant thrombocytopenia (Evans syndrome) were excluded.Secondary AIHA was defined as AIHA in the presence of other autoimmune conditions, hematologic malignancies, or drugs known to cause AIHA, or where the authors of the article described the anemia as secondary. Conference abstracts were not searched. To reduce the number of articles, it was decided a priori that if a randomized controlled trial (RCT) was found, then nonrandomized controlled studies and case series would be excluded. If no RCT was found, only nonrandomized controlled studies would be included. If there were no nonrandomized controlled studies then case series with Ͼ 10 participants would be included; if there were no case series with Ͼ 10 participants then any case series would be included. Case reports were excluded. This is similar to the method used in the recent American Society of Hematology (ASH) Immune Thrombocytopenia Guidelines. 2 Articles meeting the inclusion criteria underwent data extraction and quality assessment using pre-prepared forms (example found in supplemental data). Searching, data extraction, and quality assessment were all done in duplicate. The guidelines were given a Grading of Recommendation...

Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single‐center experience with 60 patients

“…Adult wAIHA is a rare and potentially life-threatening autoimmune disease with mainly empirical management [6]. In the last 10 years and since the era of rituximab, no or only a few large series (i.e., including more than 50 cases) focusing on adult wAIHA have been reported.…”

“…Consequently, the sole presence of high ANA titers without clinical features of SLE and/or positive anti-DNA antibodies does not discount searching for an underlying lymphoma [19]. Corticosteroids remain the cornerstone of first-line treatment [6,7], but two patients with primary wAIHA were watched only and remained without treatment because they had partially compensated wAIHA with stable and moderate anemia. Beyond corticosteroids, the use of rituximab off-label in the past decade has emerged as the preferred second-line and corticosteroid-sparing option, most often before splenectomy in corticosteroid-dependent wAIHA.…”

“…The management of wAIHA is still mainly empirical and based on expert opinion and corticosteroids remain the cornerstone of therapy [6,7]. However, since 2000, rituximab has been increasingly used as second-or third-line treatment first in children and then in adults [8][9][10][11].…”

Treatment of autoimmune hemolytic anemias

“…However, no controlled clinical trials have yet been performed that can guide the choice of treatment. 24 It is current opinion that the sequence of second-line therapy in primary warm AIHA should be splenectomy, rituximab, and thereafter any of the immunosuppressive drugs. Nevertheless, the choice of second-line therapies depends on the physician's personal experience, the patient's age and comorbidity, and patient preference.…”

“…2 A drawback of splenectomy is the lack of reliable predictors of the outcome, since its effectiveness is not related to disease duration, response to steroids nor the extent of splenic sequestration. 24 Moreover, splenectomy may be associated with surgical complications (pulmonary embolism, intra-abdominal bleeding, abdominal abscess, abdominal wall hematoma), although laparoscopic intervention has lowered the surgical risk compared to conventional surgery (0.5-1.6% vs. 6%). 25 The most feared complication after splenectomy is overwhelming sepsis due to encapsulated bacteria, with a risk of 3.3-5% and a mortality rate of up to 50%, 26,27 even after the introduction of pre-operative vaccination against pneumococci, meningococci, and hemophilus.…”