Pediatric AIHA is a rare hematological disorder that may be severely life-threatening, requiring systems support, and aggressive and rapid management [15].

Unfortunately, the presence of autoantibodies in the serum of some pediatric patients fails to achieve a good response even with intravenous pulse steroids to induce remission and to get well-matched PRBCs for transfusion. Previous research on adult patients showed that the use of PE therapy may be effective at treating AIHA. This is achieved through removing autoimmune antibodies from the intravascular space [3]. However, pediatric data on the use of PE in AIHA patients is almost lacking due to the rarity of these cases.

Warm antibody AIHA (w-AIHA) is the most common AIHA type in the pediatric population, and it is classified as a category II recommendation for PE according to the latest American Society of Aphaeresis (ASFA) guidelines. However, cold agglutinin disease (CAS) and paroxysmal cold hemoglobinuria (PCH) are responsible for the less frequent, more resistant forms of the disease with the optimal role of apheresis therapy is not well established and decisions in those patients need to be individualized (ASFA Category III). In addition, a small subset of cases is recognized as mixed AIHA, with serological work-up revealing findings of both AIHA types [9, 15].

In our study, we have addressed 19 severe pediatric cases of AIHA with impending or actual hemodynamic instability and impending cardiovascular collapse from severe anemia. All patients showed initial failure of response to high doses of steroids (pulse IV methylprednisolone on 30 mg/kg/dose). All patients received PE sessions to be able to transfuse even the least mismatched PRBCs available for the patient (up to 4 + incompatible).

Most of our patients (57.9%) had associated immunological disorders, and this is well reported with cases of w-AIHA. While 40% of w-AIHA in children is idiopathic, underlying disorders leading to secondary w-AIHA most commonly include immunodeficiencies, autoimmune diseases, and infections (mostly viral) [15]. Less frequent causes include malignancies, and previous history of transfusions or transplantation [5].

Three of our patients (15.8%) had Evans syndrome, which accounts for up to 30% of all AIHA in children and is characterized by the presence of at least two immune cytopenias [11, 15]. Children with anemia and thrombocytopenia have remission later than the other children [10].

Forty-two percent of patients had received IVIG, either as an initial line of management with steroids pre-PICU admission with an unsuccessful response or as an adjuvant immunotherapy for patients with incomplete response after PE. This could help to emphasize the role of PE as an initial line of management in those AIHA pediatric patients with impending system collapse without wasting time with other treatment lines, especially when IVIG is not available and or costly.

Although mismatched PRBCs transfusion may be fatal with reported incidences between 5.5% and 30% [8]; no transfusion reactions related to PRBCs transfusion were observed in our study group, even with the use of the least mismatched PRBCs available (up to 4 + incompatible) during the PE sessions.

Relapse was defined as recurrence of anemia, along with hemolysis (i.e., reticulocyte count > 120,000/mm; haptoglobin < 10 mg/dL, indirect bilirubin > 1 mg/dL, lactate dehydrogenase twice normal limits), after having reached a complete response [6]. In our patients, 5 (28%) cases showed recurrence of the hemolytic manifestations months later with further need for PE sessions to control their acute manifestations.

Previously documented 5–eightfold risk of increased mortality in cases with Hb less than 6 g/dL at presentation, multi-treatment, acute kidney injury, Evans’ syndrome, and infections [2]. A case series of 13 very severe relapsed/refractory primary AIHA reported a mortality of 57%, despite treatment including Packed red cell transfusions, pulse steroids, IVIG, rituximab, and plasma-exchange [4]. More recently, 30% mortality was shown in a series of 44 AIHA patients admitted to intensive care unit for severe anemia [7]. In our study, there were two mortalities. One patient with primary AIHA developed several ICU complications, sepsis and died after 88 days of ICU stay. The other had SCID with secondary AIHA and died of severe infection complicating his immunodeficiency.

The retrospective nature of the study, the rarity of this disorder in the pediatric population and the lack of control group was a limiting factor for formulating a standard approach for management of severe acute pediatric AIHA refractory to first line management. However, to the best of our knowledge, we are the first to describe the role and outcome of PE in the acute management of a cohort of pediatric patients with AIHA requiring transfusion and refractory to high doses of corticosteroids rather than single case based reports.