Management of Mixed Warm/Cold Autoimmune Hemolytic Anemia: A Case Report and Review of Current Literature

Abstract

Background. Mixed warm/cold autoimmune hemolytic anemia (AIHA) is a rare diagnostic entity with limited therapeutic options. Previous literature has described the diagnostic difficulty in this pathology and the limited response rates to corticosteroids. Furthermore, there is limited evidence regarding the use of rituximab in this condition. Methods. Alongside our case report, we conducted a scoping review of case reports/case series describing mixed AIHA, their treatment, and clinical outcomes since 2000. Inclusion criteria included a confirmed diagnosis of mixed AIHA (confirmed warm antibodies and cold agglutinins based on DAT). Case Summary/Results. We present a case of mixed AIHA in an 83-year-old female presenting with extensive, bilateral pulmonary embolisms and left renal vein thrombosis. The patient underwent extensive workup with no identifiable provoking etiology. Initial treatment involved prednisone therapy was transitioned to rituximab upon diagnosis of mixed AIHA. The patient demonstrated a mixed response with stable hemoglobin and transfusion independence; however, with persistently elevated hemolytic indices following completion of rituximab treatment. Our literature review identified 16 articles; two were excluded for unavailable clinical details. The most commonly associated conditions included autoimmune conditions (n = 5, 26%) and lymphoproliferative disorders (n = 3, 12%). The most common treatment involved corticosteroids; seven studies involved the use of rituximab. Conclusion. Mixed AIHA represents a complex diagnosis and optimal management is not well established. Consistent with our case, recent literature suggests a promising response to rituximab and a limited response to steroid treatment. Given the limited literature, additional studies are required to elucidate optimal management of this unique pathology.

Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management

“…Mixed AHIA or combined cold and warm AIHA is characterized by the simultaneous presence of an IgG warm autoantibody and a cold-reactive IgM antibody with a low titer but a broad temperature range in the blood circulation, reacting up to 37 • C [2,3,39,[87][88][89][90][91][92][93]. The syndrome is marked by significant hemolysis, resulting from both intravascular and extravascular hemolysis.…”

“…The illness may be severe but shows a favorable response to steroid therapy [39]. However, mixed AIHA often follows a chronic trajectory with intermittent periods of deterioration [2,3,89,91]. The condition accounts for 5-8% of all AIHA; of these, 50% of cases are idiopathic while 25-42% of cases are associated with systemic lupus erythematosus (SLE) [3,4].…”

“…Treatment usually involves glucocorticoids with patients having a good and rapid response [39]. However, again, rituximab and/or complement inhibitors may be considered [60,91]; see treatments under wAIHA and CAD above.…”

Autoimmune Hemolytic Anemias

“…Treatment usually involves glucocorticoids with patients having a good and rapid response [39]. However, again, rituximab and/or complement inhibitors may be considered [60,91]; see treatments under wAIHA and CAD above.…”