Influence of factor VIII on overall coagulability and fibrinolytic potential of haemophilic plasma as measured by global assay: monitoring in haemophilia A

Authors

  • N. A. GOLDENBERG,

    1. Section of Hematology, Oncology, and Bone Marrow Transplantation, Department of Pediatrics, University of Colorado at Denver and Health Sciences Center/The Children's Hospital, Denver
    2. Mountain States Regional Hemophilia and Thrombosis Center, Aurora, CO, USA
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  • W. E. HATHAWAY,

    1. Section of Hematology, Oncology, and Bone Marrow Transplantation, Department of Pediatrics, University of Colorado at Denver and Health Sciences Center/The Children's Hospital, Denver
    2. Mountain States Regional Hemophilia and Thrombosis Center, Aurora, CO, USA
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  • L. JACOBSON,

    1. Mountain States Regional Hemophilia and Thrombosis Center, Aurora, CO, USA
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  • K. MCFARLAND,

    1. Mountain States Regional Hemophilia and Thrombosis Center, Aurora, CO, USA
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  • M. J. MANCO-JOHNSON

    1. Section of Hematology, Oncology, and Bone Marrow Transplantation, Department of Pediatrics, University of Colorado at Denver and Health Sciences Center/The Children's Hospital, Denver
    2. Mountain States Regional Hemophilia and Thrombosis Center, Aurora, CO, USA
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Neil A. Goldenberg, MD, Assistant Professor of Internal Medicine and Pediatrics UCDHSC and The Children's Hospital, Denver Associate Director, Mountain States Regional Hemophilia and Thrombosis Center, PO Box 6507, Aurora, CO 80045, USA.
Tel.: +1 303 724 0365; fax: +1 303 724 0947;
e-mail: neil.goldenberg@uchsc.edu

Abstract

Summary.  The objectives of the present study were to evaluate the analytical sensitivity of the recently developed Clot Formation and Lysis (CloFAL) global assay for factor VIII (FVIII) deficiency, both in vitro and ex vivo, to determine whether this global assay is influenced by FVIII inhibitors, and to investigate the coagulative response to FVIII replacement in haemophilia A patients using the CloFAL assay in comparison with FVIII activity. Among adults and children alike, the CloFAL assay coagulation index (CI) was significantly decreased in FVIII-deficient vs. healthy subjects (adults median CI: 2% vs. 94% respectively; children median CI: 3% vs. 63%; P < 0.001 for each), and correlated significantly with activated partial thromboplastin time-based FVIII activity across all individuals (r = 0.78; P < 0.001). The CloFAL assay was analytically sensitive to deficient FVIII activity and also influenced by the presence of von Willebrand factor. Severe haemophilia A patients without inhibitory antibodies to FVIII showed considerable heterogeneity in CloFAL assay waveforms, despite a uniformly diminished CI of 0–1%. During FVIII infusion half-life studies in patients with severe haemophilia A, the CloFAL assay demonstrated a marked rise in coagulability 30 min following infusion, with progressive decrease in coagulability towards baseline over the ensuing 48-h period. In each case, the profile of coagulative response to FVIII infusion as determined by CloFAL assay CI differed qualitatively from that measured by FVIII activity. These findings indicate that the CloFAL assay may be useful as an adjunctive test to FVIII activity measurements in the therapeutic monitoring of haemophilia A.

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