Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH 44106-7284, USA.
Thromb Res. 2010 Mar;125(3):210-5. doi: 10.1016/j.thromres.2009.11.028.
Factor XII (FXII) is a coagulation protein that is essential for surface-activated blood coagulation tests but whose deficiency is not associated with bleeding. For over forty years, investigators in hemostasis have not considered FXII important because its deficiency is not associated with bleeding. It is because there is a dichotomy between abnormal laboratory assay findings due to FXII deficiency and clinical hemostasis that investigators sought explanations for physiologic hemostasis independent of FXII. FXII is a multidomain protein that contains two fibronectin binding consensual sequences, two epidermal growth factor regions, a kringle region, a proline-rich domain, and a catalytic domain that when proteolyzed turns into a plasma serine protease. Recent investigations with FXII deleted mice that are protected from thrombosis indicate that it contributes to the extent of developing thrombus in the intravascular compartment. These findings suggest that it has a role in thrombus formation without influencing hemostasis. Last, FXII has been newly appreciated to be a growth factor that may influence tissue injury repair and angiogenesis. These combined studies suggest that FXII may become a pharmacologic target to reduce arterial thrombosis risk and promote cell repair after injury, without influencing hemostasis.
凝血因子 XII（FXII）是一种凝血蛋白，对于表面激活的血液凝血试验至关重要，但缺乏 FXII 并不会导致出血。四十多年来，止血领域的研究人员一直认为 FXII 不重要，因为其缺乏与出血无关。正是由于 FXII 缺乏导致的实验室检测异常结果与临床止血之间存在二分法，研究人员才寻求独立于 FXII 的生理止血的解释。FXII 是一种多功能蛋白，包含两个纤维连接蛋白结合共识序列、两个表皮生长因子区域、一个 Kunitz 结构域、一个富含脯氨酸的结构域和一个催化结构域，该结构域经蛋白水解后转化为血浆丝氨酸蛋白酶。最近对具有抗血栓形成保护作用的 FXII 缺失小鼠的研究表明，它有助于血管腔内血栓形成的程度。这些发现表明，它在不影响止血的情况下在血栓形成中发挥作用。最后，FXII 被新认为是一种生长因子，可能影响组织损伤修复和血管生成。这些综合研究表明，FXII 可能成为一种药物靶点，以降低动脉血栓形成的风险，并促进损伤后的细胞修复，而不影响止血。
