142: Cerebral Thrombosis After Intravenous Immunoglobulin Therapy of Immune Thrombocytopenia

Intravenous Immunogloblin (IVIG) is frequently used in the treatment of immune-mediated disorders such as immune thrombocytopenia, inflammatory diseases, and as replacement therapy in immune deficiencies. It is prepared from plasma pooled from thousands of healthy donors and has been used since 1952. It is generally considered safe and secure with acceptable adverse events including headaches, fever, myalgia, urticaria, and nausea. However, rare serious adverse events (SAE) can occur. Over the last decade, IVIG use has dramatically increased across the world. Following one case of IVIG-SAE, we reviewed incidence of such SAE through reports of Quebec Hemovigilance System (QHS). A 16-year-old female presented for severe thrombocytopenia. Given her age and menorrhagia, we choose to give platelet-enhancing agents. She had recurrent episodes of severe thrombocytopenia. First IVIG infusion was followed by severe aseptic meningitis. Given new episode of thrombocytopenia, she received fractionated IVIG infusion which again resulted in normalisation of platelet count, but was complicated within 10 days by hemiparesis and seizures, associated with sinus vein thrombosis. She eventually had a good outcome without minimal sequelae. Through QHS, we found four other reports of thrombotic events possibly related to IVIG therapy, all being adults. Based upon most recent estimates, this corresponded to 0.6% to 1.6% of all reported IVIG-related SAE in QHS. Over a five year period (2005 to 2010), there have been 112 CNS-related events including headaches or aseptic meningitis. The incidence of all reported events further ranged between 1:6683 and 1:9580 events per gram of IVIG given. Since the first report of IVIG-associated thrombosis in 1986, more than one hundred cases have been reported, with only six paediatric cases. Patient's predispositions, such as advanced age, previous thrombotic events, and hypercoagulable state were found to be associated with higher risk of thrombosis. Rapid infusion, high dosage and concentration, have also been implicated. The thrombotic effects of IVIG may be due to contamination with activated coagulation factor XI, arterial vasospasm or increased blood viscosity. ITP has itself been paradoxically recognized as a possible prothrombotic condition. The presence of large platelets with enhanced endothelial adherence, as well as complement activation may partly explain such enhanced thrombotic propensity. Clinicians should have a high suspicion for intracranial complications, including thrombosis, in patients receiving IVIG and history of recurrent headache. IVIG related complications should be thoroughly investigated and properly reported, in order to improve hemovigilance system and study of such rare serious adverse events.

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