Toss H, Ernofsson M, Wallentin L, Seigbahn A
Department of Cardiology, University Hospital, Uppsala, Sweden.
J Thromb Thrombolysis. 1998;5(1):3-7. doi: 10.1023/A:1008870612206.
Resistance to activated protein C (APC resistance) is the single most important hemostatic defect associated with venous thromboembolic disease. However, little is. Known about this defect in arterial disease. The aim of this study was thus to investigate the frequency and prognostic importance of APC resistance and its influence on the coagulation system in one type of arterial thrombosis. In this study, 323 patients admitted to hospital because of unstable coronary artery disease, that is, unstable angina pectoris or non-Q-wave myocardial infarction, were investigated and compared with a reference group of apparently healthy individuals. The patients participated in a prospective, multicenter, randomized, and placebo-controlled investigation evaluating the protective value of low molecular weight heparin (dalteparin) in unstable coronary artery disease. The APC ratio was assayed using a modified activated partial thromboplastin time reaction method to measure the response to activated protein C. APC resistance was defined as an APC ratio </=2.2. Signs of thrombin activation were measured by prothrombin fragment 1+2 levels. The 7.2% (23/318) occurrence of APC resistance found in patients did not differ from the 5.8% (4/69) level in the reference population (P = 0.16). A significant elevation of the prothrombin fragment 1+2 median level of 2.5 nM (interquartile range, 1.9-3.2 nM) was found in the patients with APC resistance compared with 1.7 nM (interquartile range, 1.2-2.4nM) in the group with a normal APC ratio (P < 0.01). During the 150-day follow-up period, there was no increased risk of cardiac events in patients with APC resistance. Although accompanied by signs of increased thrombin formation, APC resistance doesnot seem to be an important risk factor for the development of instability in coronary artery disease.
对活化蛋白C的抵抗（APC抵抗）是与静脉血栓栓塞性疾病相关的最重要的单一止血缺陷。然而，对于动脉疾病中的这种缺陷知之甚少。因此，本研究的目的是调查APC抵抗的频率及其对一种动脉血栓形成类型的预后重要性，以及它对凝血系统的影响。在本研究中，对323例因不稳定冠状动脉疾病（即不稳定型心绞痛或非Q波心肌梗死）入院的患者进行了调查，并与一组明显健康的个体组成的对照组进行了比较。这些患者参与了一项前瞻性、多中心、随机、安慰剂对照的研究，评估低分子量肝素（达肝素）对不稳定冠状动脉疾病的保护作用。使用改良的活化部分凝血活酶时间反应方法测定APC比值，以测量对活化蛋白C的反应。APC抵抗定义为APC比值≤2.2。通过凝血酶原片段1+2水平测量凝血酶激活的迹象。患者中发现的APC抵抗发生率为7.2%（23/318），与对照组人群中的5.8%（4/69）水平无差异（P = 0.16）。与APC比值正常组的1.7 nM（四分位间距，1.2 - 2.4 nM）相比，APC抵抗患者的凝血酶原片段1+2中位水平显著升高至2.5 nM（四分位间距，1.9 - 3.2 nM）（P < 0.01）。在150天的随访期内，APC抵抗患者发生心脏事件的风险没有增加。尽管伴有凝血酶形成增加的迹象，但APC抵抗似乎不是冠状动脉疾病不稳定发展的重要危险因素。
