We thank Walgaard et al. for their comments on our recent article [1] and agree with their assertion that clinical trials, like SID-GBS, [2] are necessary to assess benefits and risks of SID in GBS, including potentially life threatening side effects such as hemolytic anemia (HA).
Differences between our patients and the SID-GBS cohort include different IVIG brands/products possibly containing different amounts of anti-A and -B antibodies and a potentially different repertoire of comorbidities and host susceptibilities. [1-3] The timelines of IVIG infusion are comparable in both groups (<2 weeks) and unlikely to be related to increased incidence of HA. High dosage >2 gm/kg and non-O blood groups are considered risks for the development of HA with IVIG therapy. [1,3-5] Individual patient factors, such as an inflammatory state reflected by elevated ESR and/or CRP, have been hypothesized to increase the risk of HA with IVIG administration. [5] Moreover, HA appears more prevalent with liquid compared to lyophilized IVIG preparations possibly due to higher titers of anti-A and anti-B antibodies in liquid formulations which vary within IVIG lots and formulations. [3,4] It has also been proposed that liquid IVIG preparations with longer shelf lives are more prone to IgG aggregation, contributing to hemolysis. [3] There are no FDA mandated industry standards for labeling or permissible amounts of these antibodies in IVIG formulations. [3]
Clinical trials like SID-GBS will establish whether or not SID is efficacious in patients with severe GBS. [2] Irrespective of SID -GBS results, concerted efforts should be made by industry and regulators, with guidance of clinicians, to minimize the presence of anti-A and -B autoantibodies in IVIG formulations to reduce the probability of HA, particularly in non-O blood group patients receiving IVIG.
1. Nguyen TP, Biliciler S, Wahed A, Sheikh K. Occurrence of hemolytic anemia in patients with GBS treated with high-dose IVIg. Neurol Neuroimmunol Neuroinflammation 2014;1:e50
2. Walgaard C. Second IVIg Dose in Guillain-Barre syndrome patients with poor prognosis. In: Netherlands Trial Register [online]. Available at: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2224
3. Padmore R. Hemolysis upon intravenous immunoglobulin transfusion. Transfusion and apheresis science. Transfus Apher Sci 2012;46:93-96.
4. Kahwaji J et al. Acute hemolysis after high-dose intravenous immunoglobulin therapy in highly HLA sensitized patients. Clin J Am Soc Nephrol 2009;4:1993-1997.
5. Daw Z et al. Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin:a case series analysis. Transfusion 2008;48:1598-1601.
For disclosures, please contact the editorial office at [email protected].
We thank Walgaard et al. for their comments on our recent article [1] and agree with their assertion that clinical trials, like SID-GBS, [2] are necessary to assess benefits and risks of SID in GBS, including potentially life threatening side effects such as hemolytic anemia (HA).
Differences between our patients and the SID-GBS cohort include different IVIG brands/products possibly containing different amounts of anti-A and -B antibodies and a potentially different repertoire of comorbidities and host susceptibilities. [1-3] The timelines of IVIG infusion are comparable in both groups (<2 weeks) and unlikely to be related to increased incidence of HA. High dosage >2 gm/kg and non-O blood groups are considered risks for the development of HA with IVIG therapy. [1,3-5] Individual patient factors, such as an inflammatory state reflected by elevated ESR and/or CRP, have been hypothesized to increase the risk of HA with IVIG administration. [5] Moreover, HA appears more prevalent with liquid compared to lyophilized IVIG preparations possibly due to higher titers of anti-A and anti-B antibodies in liquid formulations which vary within IVIG lots and formulations. [3,4] It has also been proposed that liquid IVIG preparations with longer shelf lives are more prone to IgG aggregation, contributing to hemolysis. [3] There are no FDA mandated industry standards for labeling or permissible amounts of these antibodies in IVIG formulations. [3]
Clinical trials like SID-GBS will establish whether or not SID is efficacious in patients with severe GBS. [2] Irrespective of SID -GBS results, concerted efforts should be made by industry and regulators, with guidance of clinicians, to minimize the presence of anti-A and -B autoantibodies in IVIG formulations to reduce the probability of HA, particularly in non-O blood group patients receiving IVIG.
1. Nguyen TP, Biliciler S, Wahed A, Sheikh K. Occurrence of hemolytic anemia in patients with GBS treated with high-dose IVIg. Neurol Neuroimmunol Neuroinflammation 2014;1:e50
2. Walgaard C. Second IVIg Dose in Guillain-Barre syndrome patients with poor prognosis. In: Netherlands Trial Register [online]. Available at: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2224
3. Padmore R. Hemolysis upon intravenous immunoglobulin transfusion. Transfusion and apheresis science. Transfus Apher Sci 2012;46:93-96.
4. Kahwaji J et al. Acute hemolysis after high-dose intravenous immunoglobulin therapy in highly HLA sensitized patients. Clin J Am Soc Nephrol 2009;4:1993-1997.
5. Daw Z et al. Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin:a case series analysis. Transfusion 2008;48:1598-1601.
For disclosures, please contact the editorial office at [email protected].