Ariëns R A, Alberio G, Moia M, Mannucci P M
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Ospedale Maggiore IRCCS and University of Milan, Italy.
Thromb Haemost. 1999 Feb;81(2):203-7.
An association between deficiency of tissue factor pathway inhibitor (TFPI) and thrombosis has not been clearly demonstrated in humans, but previous studies have focused on the measurement of plasma TFPI, which is only a small part of the total body TFPI. The major fraction of this natural anticoagulant can be measured in plasma after release by heparin injection. To investigate if deficiency of heparin-releasable TFPI is associated with thrombosis. we measured TFPI activity in plasma before and 10 min after intravenous injection of 7500 IU unfractionated heparin in 64 young patients with venous thrombosis, 49 young patients with arterial thrombosis and 38 healthy individuals. Post-heparin TFPI activity levels were significantly lower in the group of patients with venous thrombosis than in controls (mean+/-SD: 230%+/-39 vs 260%+/-34, p = 0.0002), whereas there was no difference for patients with arterial thrombosis. Defining the normal range as the mean+/-2 SD of TFPI activity in controls, twelve patients had low post-heparin TFPI activity levels, seven with venous and five with arterial thrombosis. Low levels of TFPI activity were confirmed by immunoassay in six of the seven patients with venous thrombosis and two of the five patients with arterial thrombosis, and were present also in at least one first degree relative of six patients, suggesting that the defect might be inheritable. However, the causative role of low heparin-releasable TFPI remains uncertain, because co-segregation of the defect with thrombotic symptoms could not be demonstrated in the small number of families studied.
组织因子途径抑制物（TFPI）缺乏与血栓形成之间的关联在人类中尚未得到明确证实，但以往的研究主要集中在血浆TFPI的测量上，而血浆TFPI只是全身TFPI的一小部分。这种天然抗凝剂的主要部分可在注射肝素后从血浆中释放出来进行测量。为了研究肝素可释放的TFPI缺乏是否与血栓形成有关，我们对64例年轻静脉血栓患者、49例年轻动脉血栓患者和38名健康个体静脉注射7500 IU普通肝素前及注射后10分钟测定了血浆中的TFPI活性。静脉血栓患者组肝素注射后TFPI活性水平显著低于对照组（均值±标准差：230%±39 vs 260%±34，p = 0.0002），而动脉血栓患者组则无差异。将正常范围定义为对照组TFPI活性均值±2个标准差，12例患者肝素注射后TFPI活性水平较低，其中7例为静脉血栓患者，5例为动脉血栓患者。7例静脉血栓患者中有6例、5例动脉血栓患者中有2例通过免疫测定证实TFPI活性水平较低，并且在6例患者的至少一位一级亲属中也存在这种情况，提示该缺陷可能具有遗传性。然而，肝素可释放的TFPI水平低的致病作用仍不确定，因为在少数研究的家族中未能证实该缺陷与血栓症状的共分离现象。
