Risk factors for inhibitor formation in haemophilia: A prevalent case-control study

M. V. Ragni, O. Ojeifo, J. Feng, J. Yan, K. A. Hill, S. S. Sommer, M. N. Trucco, D. J. Brambilla, Doreen Brettler, Pat Forand, Peg Geary, Bruce Ewenstein, Carol Sweeney, Louis Aledort, Stephanie Seremetis, Joan McCarthy, Donna DiMichelel, Ilene Goldberg, Lloyd Barron, Arnette HamsGilbert White, Brenda Nielsen, Aime Grimsley, Joan Cox-Gill, Andrea Boyd, David Green, Lisa Boggio, Sandy Harris, Keith Hoots, Madeline Cantini, George Buchanan, Cynthia Rutherford, Patricia Dunnagan, William Haire, Elizabeth Hanlon, Thomas Kisler, Stabler Sally, Sheryl Giambartolomei, Gowthami Arepally, Marsha Shhwartz, Joseph Addiego, Alison Matsunaga, Beth Chase, Laurence Wolff, Gregory Thomas, Robina Ingram

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Inhibitor formation is a major complication of haemophilia treatment. In a prevalent case-control study, we evaluated blood product exposure, genotype and HLA type on haemophilia A inhibitor formation. Product exposure was extracted from medical records. Genotype was determined on stored DNA samples by detection of virtually all mutations-SSCP (DOVAM-S) and subcycling PCR. HLA typing was performed by PCR amplification and exonuclease-released fluorescence. Cases experienced higher intensity factor, 455 vs. 200U per exposure, P 0.100. Genotype was not associated with race. Time to immune tolerance was shorter for titres 0.50. Inhibitor formation is associated with high intensity product exposure, CNS bleeding, African-American race and low frequency of missense mutations. The ideal time to initiate prophylaxis to reduce CNS bleeding and inhibitor formation will require prospective studies.

Original languageEnglish (US)
Pages (from-to)1074-1082
Number of pages9
JournalHaemophilia
Volume15
Issue number5
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Hemophilia A
Case-Control Studies
Genotype
Hemorrhage
Single-Stranded Conformational Polymorphism
Histocompatibility Testing
Polymerase Chain Reaction
Immune Tolerance
Exonucleases
Missense Mutation
African Americans
Medical Records
Fluorescence
Prospective Studies
Mutation
DNA
Therapeutics

Keywords

  • Central nervous system bleeding
  • Factor VIII
  • Haemophilia
  • Inhibitor

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

Ragni, M. V., Ojeifo, O., Feng, J., Yan, J., Hill, K. A., Sommer, S. S., ... Ingram, R. (2009). Risk factors for inhibitor formation in haemophilia: A prevalent case-control study. Haemophilia, 15(5), 1074-1082. https://doi.org/10.1111/j.1365-2516.2009.02058.x

Risk factors for inhibitor formation in haemophilia : A prevalent case-control study. / Ragni, M. V.; Ojeifo, O.; Feng, J.; Yan, J.; Hill, K. A.; Sommer, S. S.; Trucco, M. N.; Brambilla, D. J.; Brettler, Doreen; Forand, Pat; Geary, Peg; Ewenstein, Bruce; Sweeney, Carol; Aledort, Louis; Seremetis, Stephanie; McCarthy, Joan; DiMichelel, Donna; Goldberg, Ilene; Barron, Lloyd; Hams, Arnette; White, Gilbert; Nielsen, Brenda; Grimsley, Aime; Cox-Gill, Joan; Boyd, Andrea; Green, David; Boggio, Lisa; Harris, Sandy; Hoots, Keith; Cantini, Madeline; Buchanan, George; Rutherford, Cynthia; Dunnagan, Patricia; Haire, William; Hanlon, Elizabeth; Kisler, Thomas; Sally, Stabler; Giambartolomei, Sheryl; Arepally, Gowthami; Shhwartz, Marsha; Addiego, Joseph; Matsunaga, Alison; Chase, Beth; Wolff, Laurence; Thomas, Gregory; Ingram, Robina.

In: Haemophilia, Vol. 15, No. 5, 2009, p. 1074-1082.

Research output: Contribution to journalArticle

Ragni, MV, Ojeifo, O, Feng, J, Yan, J, Hill, KA, Sommer, SS, Trucco, MN, Brambilla, DJ, Brettler, D, Forand, P, Geary, P, Ewenstein, B, Sweeney, C, Aledort, L, Seremetis, S, McCarthy, J, DiMichelel, D, Goldberg, I, Barron, L, Hams, A, White, G, Nielsen, B, Grimsley, A, Cox-Gill, J, Boyd, A, Green, D, Boggio, L, Harris, S, Hoots, K, Cantini, M, Buchanan, G, Rutherford, C, Dunnagan, P, Haire, W, Hanlon, E, Kisler, T, Sally, S, Giambartolomei, S, Arepally, G, Shhwartz, M, Addiego, J, Matsunaga, A, Chase, B, Wolff, L, Thomas, G & Ingram, R 2009, 'Risk factors for inhibitor formation in haemophilia: A prevalent case-control study', Haemophilia, vol. 15, no. 5, pp. 1074-1082. https://doi.org/10.1111/j.1365-2516.2009.02058.x
Ragni, M. V. ; Ojeifo, O. ; Feng, J. ; Yan, J. ; Hill, K. A. ; Sommer, S. S. ; Trucco, M. N. ; Brambilla, D. J. ; Brettler, Doreen ; Forand, Pat ; Geary, Peg ; Ewenstein, Bruce ; Sweeney, Carol ; Aledort, Louis ; Seremetis, Stephanie ; McCarthy, Joan ; DiMichelel, Donna ; Goldberg, Ilene ; Barron, Lloyd ; Hams, Arnette ; White, Gilbert ; Nielsen, Brenda ; Grimsley, Aime ; Cox-Gill, Joan ; Boyd, Andrea ; Green, David ; Boggio, Lisa ; Harris, Sandy ; Hoots, Keith ; Cantini, Madeline ; Buchanan, George ; Rutherford, Cynthia ; Dunnagan, Patricia ; Haire, William ; Hanlon, Elizabeth ; Kisler, Thomas ; Sally, Stabler ; Giambartolomei, Sheryl ; Arepally, Gowthami ; Shhwartz, Marsha ; Addiego, Joseph ; Matsunaga, Alison ; Chase, Beth ; Wolff, Laurence ; Thomas, Gregory ; Ingram, Robina. / Risk factors for inhibitor formation in haemophilia : A prevalent case-control study. In: Haemophilia. 2009 ; Vol. 15, No. 5. pp. 1074-1082.
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