Department for Coagulation Disorders, Lund University, Skåne University Hospital, Malmö, Sweden.
Br J Haematol. 2010 Nov;151(4):381-6. doi: 10.1111/j.1365-2141.2010.08378.x. Epub 2010 Oct 1.
The by-passing agents, recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (APCC), are important tools in the treatment of patients with haemophilia A and high-responding inhibitory antibodies. It has been observed clinically that in some patients undergoing immune tolerance induction the bleeding frequency decreases, hypothetically caused by a transient haemostatic effect of infused FVIII not measurable ex vivo. We evaluated how by-passing agents and factor VIII (FVIII) affect thrombin generation (TG) in vitro using plasma from 11 patients with severe haemophilia A and high titre inhibitors. Samples were spiked with combinations of APCC, rFVIIa and five different FVIII products. Combination of APCC and FVIII showed a synergistic effect in eliciting TG (P<0·005) for four FVIII products. When rFVIIa and FVIII were combined the interaction between the preparations was found to be additive. APCC and rFVIIa were then combined without FVIII, resulting in an additive effect on thrombin production. Each product separately increased TG above baseline. In conclusion, the amount of thrombin formed in vitro by adding a by-passing agent, was higher in the presence of FVIII. Our findings support the use of FVIII in by-passing therapy to optimize the haemostatic effect.
旁路制剂，重组活化因子 VII（rFVIIa）和活化的凝血酶原复合物浓缩物（APCC），是治疗 A 型血友病和高反应性抑制性抗体患者的重要工具。临床上观察到，在一些接受免疫耐受诱导的患者中，出血频率降低，推测是由于输注的 FVIII 产生了体外不可测量的短暂止血作用。我们评估了旁路制剂和因子 VIII（FVIII）如何在体外使用来自 11 名患有严重 A 型血友病和高滴度抑制剂的患者的血浆来影响血栓生成（TG）。样品中添加了 APCC、rFVIIa 和五种不同的 FVIII 产品的组合。对于四种 FVIII 产品，APCC 和 FVIII 的组合表现出协同作用，可引发 TG（P<0·005）。当 rFVIIa 和 FVIII 组合时，制剂之间的相互作用是相加的。然后不添加 FVIII 而将 APCC 和 rFVIIa 组合，导致对凝血酶生成的相加作用。每个产品单独增加了 TG 超过基线。总之，在添加旁路制剂的情况下，体外形成的血栓酶量在存在 FVIII 的情况下更高。我们的发现支持在旁路治疗中使用 FVIII 来优化止血作用。
