Winckers Kristien, Thomassen Stella, Ten Cate Hugo, Hackeng Tilman M
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
Department of Internal Medicine, CARIM, Maastricht University Medical Centre, Maastricht, the Netherlands.
PLoS One. 2017 Feb 3;12(2):e0168273. doi: 10.1371/journal.pone.0168273. eCollection 2017.
Only 10% of plasma TFPIα (TFPI) exists in the full length form, the rest circulates as a C-terminally truncated form. However, blood platelets exclusively contain full length TFPI, which is released at the site of injury upon platelet activation, and which could play an important local regulatory role in thrombin generation and prevention of thrombosis.
The anticoagulant activities of full length and truncated TFPI were investigated using thrombin generation assays. Blood samples were obtained from 30 healthy volunteers (10 male subjects, 10 female subjects, and 10 females using oral contraceptives). Platelet TFPI was released in platelet rich plasma and in platelet isolates using convulxin or thrombin, and measured by free TFPI ELISA and thrombin generation assays.
Full length TFPI and platelet TFPI were much more potent inhibitors of thrombin generation than truncated TFPI, which was virtually inactive. Although mean plasma TFPI antigen levels decreased from men (0.30 nM) to women (0.20 nM) to women using oral contraceptives (0.11 nM), no relevant differences were found in platelet TFPI among those subgroups.
Platelets release similar amounts of TFPI regardless of plasma TFPI concentrations and is unaffected by sex or oral contraceptive use. We speculate that platelet TFPI is important to prevent systemic coagulation and thrombosis and restrict thrombus formation to the site of the growing platelet plug. The stable contribution of platelet TFPI to the anticoagulant potential in plasma is likely to become particularly relevant under conditions of low plasma TFPI levels in combination of oral contraceptives use.
血浆中只有10%的组织因子途径抑制物α（TFPI）以全长形式存在，其余以C端截短形式循环。然而，血小板仅含有全长TFPI，其在血小板活化时于损伤部位释放，并且可能在凝血酶生成及预防血栓形成中发挥重要的局部调节作用。
使用凝血酶生成试验研究全长和截短型TFPI的抗凝活性。从30名健康志愿者（10名男性受试者、10名女性受试者以及10名使用口服避孕药的女性）获取血样。使用convulxin或凝血酶在富血小板血浆和血小板分离物中释放血小板TFPI，并通过游离TFPI ELISA和凝血酶生成试验进行测量。
全长TFPI和血小板TFPI对凝血酶生成的抑制作用比截短型TFPI强得多，截短型TFPI实际上无活性。尽管血浆TFPI抗原平均水平从男性（0.30 nM）降至女性（0.20 nM）再降至使用口服避孕药的女性（0.11 nM），但在这些亚组的血小板TFPI中未发现相关差异。
无论血浆TFPI浓度如何，血小板释放的TFPI量相似，且不受性别或口服避孕药使用的影响。我们推测血小板TFPI对于预防全身凝血和血栓形成以及将血栓形成限制在不断增长的血小板栓子部位很重要。在血浆TFPI水平低且使用口服避孕药的情况下，血小板TFPI对血浆抗凝潜力的稳定贡献可能会变得尤为重要。
