Goldenberg N A, Hathaway W E, Jacobson L, McFarland K, Manco-Johnson M J
Section of Hematology, Oncology, and Bone Marrow Transplantation, Department of Pediatrics, University of Colorado at Denver, Denver, USA.
Haemophilia. 2006 Nov;12(6):605-14. doi: 10.1111/j.1365-2516.2006.01345.x.
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.
本研究的目的是评估最近开发的凝血形成与溶解（CloFAL）整体检测法在体外和体内对因子VIII（FVIII）缺乏症的分析敏感性，以确定该整体检测法是否受FVIII抑制剂影响，并与FVIII活性比较，使用CloFAL检测法研究A型血友病患者对FVIII替代治疗的凝血反应。在成人和儿童中，FVIII缺乏的受试者与健康受试者相比，CloFAL检测法的凝血指数（CI）显著降低（成人中位CI分别为2%和94%；儿童中位CI分别为3%和63%；每组P<0.001），并且在所有个体中与基于活化部分凝血活酶时间的FVIII活性显著相关（r = 0.78；P<0.001）。CloFAL检测法对FVIII活性缺乏具有分析敏感性，并且也受血管性血友病因子存在的影响。没有FVIII抑制性抗体的重度A型血友病患者，尽管CI均一降低至0 - 1%，但在CloFAL检测法波形中显示出相当大的异质性。在重度A型血友病患者的FVIII输注半衰期研究中，CloFAL检测法显示输注后30分钟凝血性显著升高，在随后的48小时内凝血性逐渐降至基线。在每种情况下，由CloFAL检测法CI确定的对FVIII输注的凝血反应曲线在质量上不同于通过FVIII活性测量的曲线。这些发现表明，在A型血友病的治疗监测中，CloFAL检测法可能作为FVIII活性测量的辅助检测方法有用。
