凝血因子Ⅷ缺乏症研究进展

doi:10.16150/j.1671-2870.2025.05.010

摘要/Abstract

摘要：

凝血因子Ⅷ（factor Ⅷ，FⅧ）缺乏症是一种罕见的出血性疾病，可表现为自发性或延迟性危及生命的出血。FⅧ由2个催化亚基（FⅧ-A₂）和2个载体亚基（FⅧ-B₂）组成，除了在止血中发挥重要的作用外，还具有多种功能，包括血管生成、维持妊娠、伤口愈合和骨代谢等。FⅧ缺乏根据病因的不同分为遗传性和获得性两类，遗传性FⅧ缺乏症全球发病率为0.05/10万。大多数遗传性FⅧ缺乏患者通常表现为FⅧ-A缺乏。获得性FⅧ缺乏症通常由过度消耗和合成减少等因素引起，比遗传性更为常见。在极少数情况下，获得性FⅧ缺乏症患者可能会产生针对FⅧ亚基的抑制物，这可能是特发性的，也可能与合并症（如恶性肿瘤或自身免疫性疾病有关）。诊断FⅧ缺乏症的一线检测方法是FⅧ活性定量检测。对于遗传性FⅧ缺乏症患者，需要通过酶联免疫吸附试验测定其FⅧ缺乏的类型，并检测相关分子遗传突变。若考虑获得性FⅧ缺乏症，还需要通过免疫试验检测抑制物。FⅧ缺乏症治疗主要包括FⅧ替代治疗和（或）免疫抑制治疗。FⅧ替代选择已经从传统的新鲜冷冻血浆、旧血浆、全血和低温沉淀，发展到血浆衍生和重组FⅧ浓缩物。虽然FⅧ缺乏症的治疗靶点和阈值目前尚未明确，但对严重的FⅧ缺乏症患者进行及时诊断和适当管理，可以显著降低其发病率和死亡率。

关键词: 凝血因子Ⅷ缺乏, 获得性凝血因子Ⅷ缺乏, 凝血因子Ⅷ抑制物, 凝血障碍

Abstract:

Coagulation factor Ⅷ (FⅧ) deficiency is a rare bleeding disorder that can manifest as spontaneous or delayed life-threatening hemorrhage. FⅧ is composed of two catalytic subunits (FⅧ-A₂) and two carrier (FⅧ-B₂) subunits that have several functions in addition to its important role in hemostasis, including angiogenesis, maintenance of pregnancy, wound healing, and bone metabolism. FⅧ deficiencies can be classified as congenital or acquired according to etio-logy. The global incidence of congenital FⅧ deficiency is 0.05 per 100 000. Most patients with congenital FⅧ deficiency typically present with FⅧ-A deficiency. Acquired FⅧ deficiency, which typically arises from factors such as hyperconsumption and decreased synthesis, is more common than the congenital form. In rare instances, patients with acquired FⅧ deficiency may develop inhibitors targeting FⅧ subunits. The occurrence can be idiopathic or associated with comorbidities, such as malignancies or autoimmune disorders. A quantitative functional FⅧ activity assay is the first-line screening test for diagnosing FⅧ deficiency. For congenital FⅧ deficiency, enzyme-linked immunosorbent assays (ELISA) are required to determine the type of deficiency and to detect associated molecular genetic mutations. If acquired FⅧ deficiency is suspected, immunological tests are also required to detect inhibitors. Treatment primarily includes FⅧ replacement therapy and/or immunosuppressive therapy. Therapeutic options for FⅧ replacement have evolved from traditional fresh frozen plasma (FFP), old plasma, whole blood, and cryoprecipitate to plasma-derived and recombinant FⅧ concentrates. Although treatment targets and thresholds for FⅧ deficiency have not been clearly established, timely diagnosis and appropriate management of patients with severe FⅧ deficiency can significantly reduce the morbidity and mortality rates.

Key words: Coagulation factor Ⅷ deficiency, Acquired coagulation factor Ⅷ deficiency, Coagulation factor Ⅷ inhibitor, Coagulation disorder

中图分类号:

R554
R446

谢靓哲, 戴菁, 武文漫, 王学锋. 凝血因子Ⅷ缺乏症研究进展[J]. 诊断学理论与实践, 2025, 24(05): 542-547.

XIE Liangzhe, DAI Jing, WU Wenman, WANG Xuefeng. Research advances in coagulation factor Ⅷ deficiency[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(05): 542-547.

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分类	病理生理学	相关疾病	诊断	治疗
自身免疫性	自身抗体介导的抑制或快速清除	自身免疫性疾病：系统性红斑狼疮、类风湿性关节炎恶性肿瘤：实体瘤、血液系统疾病药物：异烟肼等意义未明的单克隆免疫球蛋白血症等	临床表现：严重出血实验室检查：FⅧ活性<10%，Bethesda试验（中和抗体），结合试验（非中和抗体）	止血治疗：大剂量FⅧ、抗纤溶
非自身免疫性	过度消耗或合成减少	手术、弥散性血管内凝血、炎症性肠病、过敏性紫癜、脓毒血症、血栓形成、肺栓塞、卒中等肝病、白血病药物：丙戊酸钠、托珠单抗等	临床表现：出血不严重实验室检查：FⅧ活性20%~70%，其他凝血因子可能缺乏	+抗体消除：免疫抑制剂、血浆置换