Investigation of Intragam® P Haemolysis Adverse Events

Aim  To understand the underlying cause of a cluster of haemolysis-type adverse event (AE) reports received by CSL/ARCBS in patients receiving Intragam® P. Method  The cluster of AE reports were analysed with respect to patient factors (clinical indication, dose, blood group, concomitant medications and blood products, bone marrow reserve), product factors (batch results, production records) and changes in clinical practice (administration protocols, infusion kits). All Intragam P haemolysis related AEs from clinical trials and post-marketing exposure were reviewed, as well as international literature on this subject. Result Sixteen haemolysis type cases were reported to ARCBS/CSL over a 3 month period, ranging from abnormal laboratory test results (positive Coombs test) to clinical symptoms requiring transfusion. Ten of these reports were received in 4 days from 2 Victorian hospitals following the detection of 2 cases, which precipitated a retrospective review that identified additional similar cases. All patients received high dose (doses exceeding 400–600 mg/kg given every 3–4 weeks either in frequency or quantity) and all but one (where evidence suggested an underlying disorder) were of blood group A or AB. Eight patients were recipients of bone marrow transplants. No product or batch related factors or processes likely to have contributed to the haemolysis type AEs were identified. Anti-A and Anti-B titres of all Intragam P batches were investigated and confirmed to be within regulatory approved release specifications and pharmacopoeial limits. Conclusion  Haemolysis type adverse events are a recognised consequence of IVIG administration and are widely discussed in the literature. This investigation has confirmed the association of high dose IVIG in recipients of blood group A or AB and increased risk of haemolysis type adverse events. It also highlighted the possibility of accentuating any consequent anaemia in patients with diminished bone marrow reserve (eg post bone marrow transplant patients). Pre-infusion ABO blood groups should be determined in patients receiving high dose IVIG and their haemoglobin levels monitored in the days following therapy.