Sheffield Haemophilia and Thrombosis Centre, University of Sheffield, Sheffield, UK.
Br J Haematol. 2011 Sep;154(5):618-25. doi: 10.1111/j.1365-2141.2011.08688.x. Epub 2011 Jul 14.
Haemophilia A is caused by a reduction in clotting factor VIII (FVIII). FVIII coagulant activity (FVIII:C) can be measured by three methods; the one-stage activated partial thromboplastin time-based clotting assay, the two-stage Xa generation-based clotting assay and the chromogenic Xa generation-based assay. The FVIII:C of most patients with haemophilia A are concordant regardless of the assay method employed. Up to a third of patients show assay discrepancy, usually with the two-stage and chromogenic assays being much lower than the one-stage assay. Very rarely, patients have been reported with lower one-stage compared to two-stage and chromogenic assays, but here we report that the mutation p.Tyr365Cys accounts for most of these patients and, at least in the UK, is not rare. We have identified this mutation in 23 different families. Affected male index individuals had a lower mean one-stage FVIII:C of 27 iu/dl compared to two-stage FVIII:C mean of 77 iu/dl. Affected individuals had minimal or absent bleeding symptoms and when these were present they were usually in patients with another co-inherited bleeding disorder. Affected individuals often had surgery without the need to correct the one-stage FVIII:C.
血友病 A 是由凝血因子 VIII（FVIII）减少引起的。FVIII 凝血活度（FVIII:C）可以通过三种方法测量；基于一期活化部分凝血活酶时间的凝固测定法、基于二期 Xa 生成的凝固测定法和基于显色 Xa 生成的测定法。大多数血友病 A 患者的 FVIII:C 无论采用哪种检测方法都一致。多达三分之一的患者显示出检测差异，通常是二期和显色测定法明显低于一期测定法。非常罕见的情况下，也有报道称患者的一期测定值低于二期和显色测定值，但这里我们报告说，突变 p.Tyr365Cys 是这些患者的主要原因，至少在英国，这种突变并不罕见。我们在 23 个不同的家族中发现了这种突变。受影响的男性指数个体的一期 FVIII:C 平均为 27 iu/dl，低于二期 FVIII:C 的平均 77 iu/dl。受影响的个体几乎没有或没有出血症状，当这些症状出现时，通常是在另一个同时遗传的出血性疾病患者中。受影响的个体经常进行手术，而无需纠正一期 FVIII:C。
