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Misleading hepatitis B test results due to intravenous immunoglobulin administration: implications for a clinical trial of rituximab in immune thrombocytopenia

Authors

  • Donald M. Arnold,

    1. From the Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario; Canadian Blood Services, Hamilton, Ontario; St Joseph's Healthcare, Hamilton, Ontario; the Departments of Oncology, Medicine, and Community Health and Epidemiology, NCIC Clinical Trials Group, Queen's University, Kingston, Ontario; Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario; and Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
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  • Mark A. Crowther,

    1. From the Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario; Canadian Blood Services, Hamilton, Ontario; St Joseph's Healthcare, Hamilton, Ontario; the Departments of Oncology, Medicine, and Community Health and Epidemiology, NCIC Clinical Trials Group, Queen's University, Kingston, Ontario; Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario; and Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
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  • Ralph M. Meyer,

    1. From the Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario; Canadian Blood Services, Hamilton, Ontario; St Joseph's Healthcare, Hamilton, Ontario; the Departments of Oncology, Medicine, and Community Health and Epidemiology, NCIC Clinical Trials Group, Queen's University, Kingston, Ontario; Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario; and Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
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  • Julie Carruthers,

    1. From the Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario; Canadian Blood Services, Hamilton, Ontario; St Joseph's Healthcare, Hamilton, Ontario; the Departments of Oncology, Medicine, and Community Health and Epidemiology, NCIC Clinical Trials Group, Queen's University, Kingston, Ontario; Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario; and Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
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  • Julie DiTomasso,

    1. From the Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario; Canadian Blood Services, Hamilton, Ontario; St Joseph's Healthcare, Hamilton, Ontario; the Departments of Oncology, Medicine, and Community Health and Epidemiology, NCIC Clinical Trials Group, Queen's University, Kingston, Ontario; Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario; and Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
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  • Nancy M. Heddle,

    1. From the Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario; Canadian Blood Services, Hamilton, Ontario; St Joseph's Healthcare, Hamilton, Ontario; the Departments of Oncology, Medicine, and Community Health and Epidemiology, NCIC Clinical Trials Group, Queen's University, Kingston, Ontario; Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario; and Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
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  • Anne McLeod,

    1. From the Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario; Canadian Blood Services, Hamilton, Ontario; St Joseph's Healthcare, Hamilton, Ontario; the Departments of Oncology, Medicine, and Community Health and Epidemiology, NCIC Clinical Trials Group, Queen's University, Kingston, Ontario; Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario; and Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
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  • John G. Kelton

    1. From the Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario; Canadian Blood Services, Hamilton, Ontario; St Joseph's Healthcare, Hamilton, Ontario; the Departments of Oncology, Medicine, and Community Health and Epidemiology, NCIC Clinical Trials Group, Queen's University, Kingston, Ontario; Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario; and Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
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  • This research was presented as an abstract at the American Society of Hematology meeting in December 2009.

Donald M. Arnold, MD, MSc, FRCP(C), HSC 3V-48, 1200 Main Street West, Hamilton, Ontario, Canada; e-mail: arnold@mcmaster.ca.

Abstract

BACKGROUND: Rituximab may cause reactivation of hepatitis B virus (HBV) even in patients with remote HBV infection. Thus, the presence of hepatitis B core antibodies (anti-HBc) was an exclusion criterion for a randomized trial of rituximab for patients with immune thrombocytopenia. A high seroprevalence of anti-HBc observed among patients screened for the trial prompted this substudy to investigate for an association between anti-HBc seropositivity and exposure to intravenous immunoglobulin (IVIG).

STUDY DESIGN AND METHODS: This was a retrospective case-control study that was a substudy of a randomized controlled trial.

RESULTS: Of 24 trial participants screened at one center, 11 (45.8%) were anti-HBc positive and of those, 10 (90.0%) had received IVIG in the preceding 4 weeks. Of 13 seronegative patients screened, five (38.5%) had received IVIG (odds ratio, 16; 95% confidence interval, 1.5-166.1). Seven (70%) of 10 seropositive participants subsequently reverted to negative upon repeat testing. Serial testing before and after IVIG (n = 2) demonstrated transient anti-HBc that lasted for up to 11 weeks after the last dose of IVIG. Samples from three of five different IVIG products were found to contain anti-HBc.

CONCLUSIONS: Passive transfer of anti-HBc from certain IVIG products may lead to misinterpretation of hepatitis test results with implications for treatment and clinical trial eligibility. To avoid misleading test results, anti-HBc should be measured before or 3 months after IVIG administration; alternatively an IVIG product known to be free of anti-HBc should be used.

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