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Interference of thrombin in immunological assays for hirudin specific antibodies.

Publication ,  Journal Article
Hamilton, RG; Levy, JH; Marder, VJ; Sane, DC
Published in: J Immunol Methods
July 31, 2012

Recombinant hirudins (desirudin, lepirudin) are direct thrombin inhibitors administered as anticoagulants for heparin-induced thrombocytopenia (HIT) and venous thromboembolism (VTE) prophylaxis. Although these small polypeptides are widely used, concern exists over reports of antigenicity. In the largest study of r-hirudin immunogenicity to-date, we evaluated the prevalence, quantity and specificity of IgG immune responses to desirudin (15 mg SC q12h for as long as clinically required) in 245 surgical and medically-ill subjects enrolled in DESIRABLE, a multicenter, open-label, clinical trial of hospitalized patients requiring VTE prophylaxis. Sera obtained before and 30 days after desirudin administration were analyzed for IgG anti-desirudin by immunoenzymetric assay using immobilized desirudin to bind desirudin-reactive antibody and peroxidase conjugated monoclonal-anti-human IgG Fc to detect bound IgG antibody. Of 245 study subjects, 19 (7.7%) were antibody "responders" (>2-fold increase in IgG antibody levels with >50% inhibition by desirudin 30 days post-treatment). There were no differences between responders and non-responders in incidence of clinical outcomes or bleeding-related adverse events. Forty-six patients had detectable desirudin-reactive IgG antibody prior to treatment, with no significant increase in antibody levels after exposure and no increase in clinical events. The origin of pre-existing hirudin-reactive IgG antibody requires further investigation involving suspected anti-thrombin-thrombin interactions. These results indicate a low potential for immunogenicity, with <8% of patients developing IgG antibodies after desirudin administration for VTE prophylaxis. In contrast to reports on lepirudin, production of anti-hirudin antibodies to desirudin has no apparent effect on clinical events.

Duke Scholars

Published In

J Immunol Methods

DOI

EISSN

1872-7905

Publication Date

July 31, 2012

Volume

381

Issue

1-2

Start / End Page

50 / 58

Location

Netherlands

Related Subject Headings

  • Venous Thromboembolism
  • Time Factors
  • Thrombocytopenia
  • Thrombin
  • Reproducibility of Results
  • Recombinant Proteins
  • Middle Aged
  • Male
  • Immunology
  • Immunoglobulin G
 

Citation

APA
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ICMJE
MLA
NLM
Hamilton, R. G., Levy, J. H., Marder, V. J., & Sane, D. C. (2012). Interference of thrombin in immunological assays for hirudin specific antibodies. J Immunol Methods, 381(1–2), 50–58. https://doi.org/10.1016/j.jim.2012.04.008
Hamilton, Robert G., Jerrold H. Levy, Victor J. Marder, and David C. Sane. “Interference of thrombin in immunological assays for hirudin specific antibodies.J Immunol Methods 381, no. 1–2 (July 31, 2012): 50–58. https://doi.org/10.1016/j.jim.2012.04.008.
Hamilton RG, Levy JH, Marder VJ, Sane DC. Interference of thrombin in immunological assays for hirudin specific antibodies. J Immunol Methods. 2012 Jul 31;381(1–2):50–8.
Hamilton, Robert G., et al. “Interference of thrombin in immunological assays for hirudin specific antibodies.J Immunol Methods, vol. 381, no. 1–2, July 2012, pp. 50–58. Pubmed, doi:10.1016/j.jim.2012.04.008.
Hamilton RG, Levy JH, Marder VJ, Sane DC. Interference of thrombin in immunological assays for hirudin specific antibodies. J Immunol Methods. 2012 Jul 31;381(1–2):50–58.
Journal cover image

Published In

J Immunol Methods

DOI

EISSN

1872-7905

Publication Date

July 31, 2012

Volume

381

Issue

1-2

Start / End Page

50 / 58

Location

Netherlands

Related Subject Headings

  • Venous Thromboembolism
  • Time Factors
  • Thrombocytopenia
  • Thrombin
  • Reproducibility of Results
  • Recombinant Proteins
  • Middle Aged
  • Male
  • Immunology
  • Immunoglobulin G