Transfusion Medicine
|
ORIGINAL ARTICLE
Intravenous immunoglobulin-induced haemolysis: a case report and review of the literature M. J. Desborough,1,2 J. Miller,3 S. J. Thorpe,4 M. F. Murphy1,2,5 & S. A. Misbah3 1
NHS Blood and Transplant, John Radcliffe Hospital, Oxford, UK, 2 Department of Haematology, John Radcliffe Hospital, Oxford, UK, of Clinical Immunology, John Radcliffe Hospital, Oxford, UK, 4 Biotherapeutics Group, National Institute for Biological Standards and Control, Potters Bar, UK, and 5 Department of Transfusion Medicine, University of Oxford, Oxford, UK 3 Department
Received 2 June 2013; accepted for publication 25 September 2013
SUMMARY Objectives: To review the incidence and clinical features of intravenous immunoglobulin (IVIg)-induced haemolysis. Background: Haemolysis can be a severe complication of IVIg administration. It is due to the passive transfer of blood group antibodies and may result in significant anaemia and renal failure. Methods: We report a case of severe IVIg-induced haemolysis; review the data reported to vigilance groups (The Medicines and Healthcare Products Regulatory Agency, European Union Drug Regulatory Authorities, Food and Drug Administration and the Canada Vigilance Centre) between January 1998 and May 2012; and systematically review IVIg-induced haemolysis case reports (between January 1948 and January 2013). Results: Nine hundred-twenty five cases of IVIg-induced haemolysis were identified from a review of cases reported to vigilance groups; 62 case reports were included in the systematic review. The majority of these were due to administration of doses of at least 2 g kg−1 of IVIg (97%). IVIg-induced haemolysis was reported most commonly for patients with blood group A (65%) or AB (26%). One case report noted that in two patients with IVIg-induced haemolysis both received IVIg from the same batch. Conclusion: We make the following recommendations for the management of suspected cases of IVIg-induced haemolysis: 1 Stop IVIg infusion and perform tests for haemolysis. 2 Check titres of anti-blood group antibodies in IVIg.
Correspondence: Dr. Michael J. Desborough, NHS Blood and Transplant, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK. Tel.: +07736843592; fax: +01865387957; e-mail: [email protected]
© 2013 The Authors Transfusion Medicine © 2013 British Blood Transfusion Society
3 Provide supportive management for patient with fluid and/or red blood cell transfusions if necessary. 4 Consider quarantine of the IVIg batch if found to be high titre for anti-A/B. 5 Report reaction to regulatory/vigilance body. Key words: haemolysis, haemovigilance, intravenous immunoglobulin. Intravenous immunoglobulin (IVIg) infusions are used for a wide range of indications. They are used either prophylactically (in low doses to treat primary or secondary immunoglobulin deficiencies) or for immunomodulatory treatment in higher doses to treat a range of autoimmune and inflammatory conditions including haematological and neurological disorders (Dalakas, 2004). IVIg is created from the pooled plasma of 5000–15 000 donors and has a multitude of effects on the immune system including modulation of the expression and function of Fc receptors, interference with the activation of complement and the cytokine network and provision of anti-idiotypic antibodies (Kazatchkine & Kaveri, 2001). IVIg contains predominantly IgG with trace amounts of IgA and IgM, cytokines and soluble CD4 and CD8 receptors (Blasczyk et al., 1993; Lam et al., 1993). A fraction of the IgG content of therapeutic immunoglobulin is blood group antibodies, e.g. anti-A, anti-B or anti-D (Case et al., 1972). IVIg is clinically effective and generally well tolerated. Irrespective of dose, a small proportion of patients (
|
ORIGINAL ARTICLE
Intravenous immunoglobulin-induced haemolysis: a case report and review of the literature M. J. Desborough,1,2 J. Miller,3 S. J. Thorpe,4 M. F. Murphy1,2,5 & S. A. Misbah3 1
NHS Blood and Transplant, John Radcliffe Hospital, Oxford, UK, 2 Department of Haematology, John Radcliffe Hospital, Oxford, UK, of Clinical Immunology, John Radcliffe Hospital, Oxford, UK, 4 Biotherapeutics Group, National Institute for Biological Standards and Control, Potters Bar, UK, and 5 Department of Transfusion Medicine, University of Oxford, Oxford, UK 3 Department
Received 2 June 2013; accepted for publication 25 September 2013
SUMMARY Objectives: To review the incidence and clinical features of intravenous immunoglobulin (IVIg)-induced haemolysis. Background: Haemolysis can be a severe complication of IVIg administration. It is due to the passive transfer of blood group antibodies and may result in significant anaemia and renal failure. Methods: We report a case of severe IVIg-induced haemolysis; review the data reported to vigilance groups (The Medicines and Healthcare Products Regulatory Agency, European Union Drug Regulatory Authorities, Food and Drug Administration and the Canada Vigilance Centre) between January 1998 and May 2012; and systematically review IVIg-induced haemolysis case reports (between January 1948 and January 2013). Results: Nine hundred-twenty five cases of IVIg-induced haemolysis were identified from a review of cases reported to vigilance groups; 62 case reports were included in the systematic review. The majority of these were due to administration of doses of at least 2 g kg−1 of IVIg (97%). IVIg-induced haemolysis was reported most commonly for patients with blood group A (65%) or AB (26%). One case report noted that in two patients with IVIg-induced haemolysis both received IVIg from the same batch. Conclusion: We make the following recommendations for the management of suspected cases of IVIg-induced haemolysis: 1 Stop IVIg infusion and perform tests for haemolysis. 2 Check titres of anti-blood group antibodies in IVIg.
Correspondence: Dr. Michael J. Desborough, NHS Blood and Transplant, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK. Tel.: +07736843592; fax: +01865387957; e-mail: [email protected]
© 2013 The Authors Transfusion Medicine © 2013 British Blood Transfusion Society
3 Provide supportive management for patient with fluid and/or red blood cell transfusions if necessary. 4 Consider quarantine of the IVIg batch if found to be high titre for anti-A/B. 5 Report reaction to regulatory/vigilance body. Key words: haemolysis, haemovigilance, intravenous immunoglobulin. Intravenous immunoglobulin (IVIg) infusions are used for a wide range of indications. They are used either prophylactically (in low doses to treat primary or secondary immunoglobulin deficiencies) or for immunomodulatory treatment in higher doses to treat a range of autoimmune and inflammatory conditions including haematological and neurological disorders (Dalakas, 2004). IVIg is created from the pooled plasma of 5000–15 000 donors and has a multitude of effects on the immune system including modulation of the expression and function of Fc receptors, interference with the activation of complement and the cytokine network and provision of anti-idiotypic antibodies (Kazatchkine & Kaveri, 2001). IVIg contains predominantly IgG with trace amounts of IgA and IgM, cytokines and soluble CD4 and CD8 receptors (Blasczyk et al., 1993; Lam et al., 1993). A fraction of the IgG content of therapeutic immunoglobulin is blood group antibodies, e.g. anti-A, anti-B or anti-D (Case et al., 1972). IVIg is clinically effective and generally well tolerated. Irrespective of dose, a small proportion of patients (
