凝血因子 VII 的生化、分子和临床方面及其在止血和血栓形成中的作用。,Haematologica

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凝血因子 VII 的生化、分子和临床方面及其在止血和血栓形成中的作用。
Haematologica ( IF 8.2 ) Pub Date : 2021-01-07 , DOI: 10.3324/haematol.2020.248542
Francesco Bernardi ₁ , Guglielmo Mariani ₂

Affiliation

活化的因子 VII (FVIIa) 是第一种凝血蛋白酶，只有在与暴露于血液的组织因子 (TF) 复合后才表现出其生理促凝血潜力。对 FVIIa-TF 复合物和 F7 基因的深入了解有助于了解与低或高 FVII 活性 (FVIIc) 相关的 Janus 临床发现。先天性 FVII 缺乏症是隐性遗传出血性疾病中最常见的一种，是由 F7 基因的异质突变引起的。完全 FVII 缺乏会导致围产期死亡。在 FVIIc 水平明显适度差异的患者中观察到范围广泛的出血症状，从危及生命的颅内出血到轻度黏膜出血。尽管临床相关的 FVIIc 阈值水平仍不确定，但已设计出有效的管理，包括预防，大大提高了患者的生活质量。TF 在患病动脉中的暴露促进了对 FVII 在心血管疾病中作用的研究。FVIIc 水平被发现是心血管死亡的预测因子，并且与 F7 基因变异显着相关。这些基因型-表型关系是人类研究最广泛的关系之一。全基因组分析将关联扩展到与 F7 一起解释 > 50% FVII 水平血浆变异的众多位点。然而，F7 变异预测血栓形成的能力并未在众多人群研究中得到一致证实。

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Biochemical, molecular and clinical aspects of coagulation factor VII and its role in hemostasis and thrombosis.

Activated factor VII (FVIIa), the first protease of clotting, expresses its physiological procoagulant potential only after complexing with tissue factor (TF) exposed to blood. Deep knowledge of the FVIIa-TF complex and F7 gene helps to understand the Janus-faced clinical findings associated to low or elevated FVII activity (FVIIc). Congenital FVII deficiency, the most frequent among the recessively inherited bleeding disorders, is caused by heterogeneous mutations in the F7 gene. Complete FVII deficiency causes perinatal lethality. A wide range of bleeding symptoms, from life-threatening intracranial hemorrhage to mild mucosal bleeding, is observed in patients with apparently modest differences in FVIIc levels. Though clinically relevant FVIIc threshold levels are still uncertain, effective management, including prophylaxis, has been devised, substantially improving the quality of life of patients. The exposure of TF in diseased arteries fostered investigation on the role of FVII in cardiovascular disease. FVIIc levels were found to be predictors of cardiovascular death and to be markedly associated to F7 gene variation. These genotype-phenotype relationships are among the most extensively investigated in humans. Genome-wide analyses extended association to numerous loci that, together with F7, explain >50% of FVII level plasma variance. However, the ability of F7 variation to predict thrombosis was not consistently evidenced in the numerous population studies. Main aims of this review are to highlight i) the biological and clinical information that distinguishes FVII deficiency from the other clotting disorders and ii) the impact exerted by genetically predicted FVII level variation on bleeding as well as on the thrombotic states.

更新日期：2021-01-09

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