Agren A, Wiman B, Stiller V, Lindmarker P, Sten-Linder M, Carlsson A, Holmström M, Odeberg J, Schulman S
Department of Hematology, Coagulation Unit, King Gustaf V Research Institute, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
J Thromb Haemost. 2006 Jan;4(1):201-8. doi: 10.1111/j.1538-7836.2005.01709.x.
Prospective studies of the epidemiology and clinical significance of low plasminogen activator inhibitor type 1 (PAI-1) activity are lacking.
To evaluate the prevalence of low PAI-1 activity in patients with a bleeding tendency in comparison with a normal population.
In 586 consecutive patients, referred because of bleeding symptoms, we added analyses of PAI-1 activity and tissue plasminogen activator complex with PAI-1 (t-PA-PAI-1) to the routine investigation, consisting of platelet count, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, von Willebrand factor activity, and antigen. Controls were 100 blood donors and 100 age- and sex-matched healthy individuals. The latter were also evaluated regarding the previous bleeding episodes. The bleeding history was classified as clinically significant or not, and the criteria were fulfilled in 75% of the patients and 18% of the healthy controls.
The routine laboratory investigation of the patients was negative in 57%. Low PAI-1 activity, defined as <1.0 U mL(-1), was found in 23% of the patients and in 13% and 10% of the blood donors and healthy controls, respectively (odds ratio and 95% CI, 2.04; 1.11-3.77 and 2.75; 1.39-5.42, respectively). The difference remained statistically significant after the adjustment for body mass index, use of estrogens, sex and age (odds ratio for patients vs. healthy controls 3.23; 95% CI, 1.22-8.56, P = 0.019). The distribution of the 4G/5G genotypes in the patients was not different from that of two control populations. No specific symptom predicted for low PAI-1, which did not aggravate the clinical picture in association with the other hemostatic defects. Low tPA-PAI-1 was not associated with the increased bleeding tendency.
Low PAI-1 activity is common in patients with a bleeding diathesis, but it is a risk factor of minor clinical importance and not associated with specific bleeding manifestations.
目前缺乏关于低纤溶酶原激活物抑制剂1型（PAI - 1）活性的流行病学及临床意义的前瞻性研究。
与正常人群相比，评估有出血倾向患者中低PAI - 1活性的患病率。
在586例因出血症状前来就诊的连续患者中，我们在常规检查（包括血小板计数、出血时间、凝血酶原时间、活化部分凝血活酶时间、纤维蛋白原、因子VIII、血管性血友病因子活性及抗原）基础上，增加了PAI - 1活性及组织纤溶酶原激活物与PAI - 1复合物（t - PA - PAI - 1）的分析。对照组为100名献血者及100名年龄和性别匹配的健康个体。对后者也评估了既往出血发作情况。出血史被分类为具有临床意义或无临床意义，75%的患者及18%的健康对照符合标准。
57%的患者常规实验室检查结果为阴性。PAI - 1活性低于1.0 U mL⁻¹被定义为低PAI - 1活性，分别在23%的患者、13%的献血者及10%的健康对照中发现（优势比及95%可信区间分别为2.04；1.11 - 3.77及2.75；1.39 - 5.42）。在对体重指数、雌激素使用情况、性别及年龄进行校正后，差异仍具有统计学意义（患者与健康对照的优势比为3.23；95%可信区间，1.22 - 8.56，P = 0.019）。患者中4G/5G基因型的分布与两个对照组的分布无差异。没有特定症状可预测低PAI - 1，低PAI - 1与其他止血缺陷相关时并未加重临床症状。低tPA - PAI - 1与出血倾向增加无关。
低PAI - 1活性在有出血素质的患者中很常见，但它是临床重要性较小的危险因素，且与特定出血表现无关。
