Intravenous immune globulin and thromboembolic adverse events: A systematic review and meta‐analysis of RCTs

Abstract

1Prior case reports and observational studies indicate that intravenous immune globulin (IVIg) products may cause thromboembolic events (TEEs), leading the FDA to require a boxed warning in 2013. The effect of IVIg treatment on the risk of serious TEEs (acute myocardial infarction, ischemic stroke, or venous thromboembolism) was assessed using adverse event data reported in randomized controlled trials (RCTs) of IVIg. RCTs of IVIg in adult patients from 1995 to 2015 were identified from Pubmed, Embase, ClinicalTrials.Gov, and two large prior reviews of IVIg's therapeutic applications. Trials at high risk of detection or reporting bias for serious adverse events were excluded. 31 RCTs with a total of 4,129 participants (2,318 IVIg-treated, 1,811 control) were eligible for quantitative synthesis. No evidence was found of increased TEE risk among IVIg-treated patients compared with control patients (odds ratio 5 1.10, 95% CI: 0.44, 2.88; risk difference 5 0.0%, 95% CI: 20.7%, 0.7%, I2 5 0%). No significant increase in risk was found when arterial and venous TEEs were analyzed as separate endpoints. Trial publications provided little specific information concerning the methods used to ascertain potential adverse events. Care should be taken in extrapolating the results to patients with higher baseline risks of TEE.

Cerebral venous thrombosis after intravenous immunoglobulin therapy in immune thrombocytopenic purpura

“…[ 8 ] However, a recent meta-analysis of IVIg and thromboembolic events suggest that the absolute risk of combined arterial and venous thrombosis with IVIg therapy is low. [ 9 ] However, the study noted higher number of venous thrombosis than arterial thrombosis among IVIg-treated patients. Moreover, the study had underrepresentation of ITP and other autoimmune hematologic conditions and hence cannot be generalized.…”

Effectiveness of immunoglobulin prophylaxis in reducing clinical complications of hematopoietic stem cell transplantation: a systematic review and meta‐analysis

“…Meta‐analysis of three studies revealed an increased rate of VOD in recipients receiving IVIG. Thromboembolic events have been reported to be associated with IVIG presumably due to a hypercoagulable state, although a recent meta‐analysis did not confirm such an association . Thrombotic events are usually associated with high doses and rapid administration of IVIG .…”

Original research: Second IVIg course in Guillain-Barré syndrome with poor prognosis: the non-randomised ISID study

“…First, approximately 80% of GBS patients treated with one IVIg course recover relatively well 5. Second, serious side effects may occur, including anaphylaxis, acute kidney injury, thromboembolic events or haemolytic anaemia 9 10. Third, IVIg is an expensive and relatively scarce blood product.…”