Hedner Ulla, Ezban Mirella
Department of Medicine, University of Lund, Sweden.
Annu Rev Med. 2008;59:29-41. doi: 10.1146/annurev.med.59.061606.095605.
For hemophilia patients with inhibitors against FVIII or FIX, the development of recombinant factor VIIa (rFVIIa) raises the possibility of a therapeutic alternative whose availability and convenience of treatment are comparable to those of FVIII or FIX. In support of this new concept for the treatment of bleeding episodes, pharmacological doses of FVIIa have been shown to induce hemostasis. Pharmacological doses of rFVIIa enhance thrombin generation on thrombin-activated platelets, thereby facilitating the formation of strong, well-structured fibrin plugs resistant to premature proteolysis. Modified rFVIIa molecules with a stronger hemostatic potential have been produced. Inhibition of the FVII-TF-dependent pathway (TFPI and rFVIIai) has been tried in attempts to prevent thrombosis, with promising results in animal models so far not confirmed in clinical trials.
对于体内产生针对FVIII或FIX抑制物的血友病患者而言，重组凝血因子VIIa（rFVIIa）的出现为他们带来了一种治疗选择，其可用性和治疗便利性与FVIII或FIX相当。为支持这一针对出血发作的治疗新概念，药理剂量的FVIIa已被证明可诱导止血。药理剂量的rFVIIa可增强凝血酶激活血小板上的凝血酶生成，从而促进形成强大、结构良好且能抵抗过早蛋白水解的纤维蛋白凝块。已制备出具有更强止血潜力的改良型rFVIIa分子。为预防血栓形成，人们尝试抑制FVII-TF依赖性途径（TFPI和rFVIIai），目前在动物模型中取得了有前景的结果，但尚未在临床试验中得到证实。
