Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients

Abstract

Key Points• Mixed, atypical, and warm immunoglobulin G plus C AIHA (;30% of cases) more frequently have a severe onset (Hb #6 g/dL) and require multiple therapy lines.• Infections, particularly after splenectomy, acute renal failure, Evans syndrome, and multitreatment, were predictors of fatal outcome.The clinical outcome, response to treatment, and occurrence of acute complications were retrospectively investigated in 308 primary autoimmune hemolytic anemia (AIHA) cases and correlated with serological characteristics and severity of anemia at onset. Patients had been followed up for a median of 33 months (range 12-372); 60% were warm AIHA, 27% cold hemagglutinin disease, 8% mixed, and 5% atypical (mostly direct antiglobulin test negative). The latter 2 categories more frequently showed a severe onset (hemoglobin [Hb] levels £6 g/dL) along with reticulocytopenia. The majority of warm AIHA patients received first-line steroid therapy only, whereas patients with mixed and atypical forms were more frequently treated with 2 or more therapy lines, including splenectomy, immunosuppressants, and rituximab. The cumulative incidence of relapse was increased in more severe cases (hazard ratio 3.08; 95% confidence interval, 1.44-6.57 for Hb £6 g/dL; P < .001). Thrombotic events were associated with Hb levels £6 g/dL at onset, intravascular hemolysis, and previous splenectomy. Predictors of a fatal outcome were severe infections, particularly in splenectomized cases, acute renal failure, Evans syndrome, and multitreatment (4 or more lines). The identification of severe and potentially fatal AIHA in a largely heterogeneous disease requires particular experienced attention by clinicians. (Blood. 2014;

Autoimmune Hemolytic Anemia Confers an Independent Risk Factor for Thrombosis: Retrospective Cohort Study Using the “STRIDE” Database

“…Additionally, we acknowledge that our patients' initial clinical presentation of AIHA may not correspond to their date of diagnosis in STRIDE, which can be typical for tertiary referral centers like Stanford. This may explain why we found that AIHA patients Austin Publishing Group Submit your Manuscript | www.austinpublishinggroup.com with thrombosis did not have more severe laboratory evidence of haemolysis at the time of their diagnosis at Stanford than those without thrombosis, in contrast to prior studies [19]. Being a tertiary center, Stanford's patient population is also likely to have more severe disease.…”

“…Prior studies have shown that thrombosis is correlated with low hemoglobin at the time of AIHA onset and laboratory evidence of haemolysis [19,20]. We did not find these to be the case for our AIHA cohort.…”

“…Our results confirm that AIHA patients have a higher incidence of thrombosis (29%) than non-AIHA patients (19%). This thrombosis incidence in AIHA patients is on the higher end of present estimates that include 11% [19], 20% [20], and 27% [29]. This may be due to the enrichment for more medically complex patients at Stanford Hospital and Clinics.…”

“…Haemolysis is generally thought to cause thromboembolism due to the abnormal exposure of phosphatidylserine following red cell destruction, which promotes coagulation [18]. In support, work by Barcellini, et al [11] and Lecouffe-Desprets, et al have suggested that thrombosis in AIHA is associated with more severe anemia at the time of AIHA onset and at the time of the thrombotic event [19,20]. However, these studies excluded patients with secondary causes of AIHAi.e., lymphoproliferative disorders, infections, and autoimmune disorders-which comprise the majority of AIHA cases as mentioned above.…”

“…Prior studies have been smaller in size or descriptive [5,26,27], done in the context of specific hyper coagulable states [28,29], or with a design that excluded secondary AIHA patients or lacked anon-AIHA cohort matched for relevant AIHA risk factors [14][15][16][17]19,20].…”