Impaired spontaneous thrombolytic activity in elderly and in habitual smokers, as measured by a new global thrombosis test Hideo Ikarugi a,b , Tsutomu Yamashita b , Rumiko Aoki b , Hiromitsu Ishii c , Kenichi Kanki a and Junichiro Yamamoto b We used a new test (the Go ¨ ro ¨ g Thrombosis Test) for assessing the effect of aging, smoking and exercise habits on the overall thrombotic status including platelet reactivity and spontaneous thrombolytic activity of 30 healthy young males (mean, 21.1 6 0.4 years) and 34 elderly males (64.5 6 1.1 years). The occlusion time (OT) and the lysis time (LT) were measured from a single native blood sample. The OT is an index of platelet activation and subsequent occlusive thrombus formation by high shear stress, while the LT is an index of the resumption of blood flow due to thrombolysis. The LTs in the elderly group were significantly longer than in the young group (P < 0.001). The LTs of elderly smokers were significantly longer than those of non-smokers (P < 0.001). Exercise did not affect the LT significantly. Platelet reactivity to shear stress (OT) was not affected either by aging, smoking or exercise habits. Suppressed spontaneous thrombolytic activity in elderly males and smokers could be a mechanism of acute thrombotic events in these people. Blood Coagul Fibrinolysis 14:781–784 & 2003 Lippincott Williams & Wilkins. Blood Coagulation and Fibrinolysis 2003, 14:781–784 Keywords: tests, thrombolysis, thrombosis, aging, smoking a Laboratory of Health and Sport Sciences, Kobe University of Commerce, Kobe, b Laboratory of Physiology, Faculty of Nutrition, and High Technology Research Centre, Kobe Gakuin University, Kobe, and c Medical Corportation Jinkeikai, Ishii Hospital, Akashi, Japan. Sponsorship: This work was partly supported by a grant from the Science Research Promotion Fund of the Japanese Private School Promotion Foundation. Correspondence and requests for reprints to H. Ikarugi, Laboratory of Health and Sport Sciences, Kobe University of Commerce, 8-2-1 Gakuen-Nishimachi, Nishi-ku, Kobe, 651-2197 Japan. Tel: +81 78 794 7094; fax: +81 78 794 6166; e-mail: ikarugi@kobeuc.ac.jp Received 17 December 2002 Revised 12 April 2003 Accepted 12 June 2003 Introduction Prevention of atherothrombotic life-style-related dis- eases such as myocardial infarction and stroke is an important social task in many developed countries. There is an urgent need for a simple and physiologi- cally relevant test, which can be used both for risk assessment in epidemiological studies and in clinical practice. Platelet activation and spontaneous thrombo- lytic activity of blood are the two major determinants of the outcome of an acute thrombotic event [1,2]. Plate- lets, activated by shear forces at the site of a stenosis or fissure of an atherosclerotic plaque play a pivotal role in arterial thrombus formation [1,2]. Compared with numerous, although physiologically relevant, platelet agonists, such as adenosine diphosphate, collagen, thromboxane and epinephrine, the decisive role of shear stress in initiating coronary occlusion is now indisputable. However, there is no commercially avail- able platelet function test that allows the assessment of platelet activation and aggregation by shear stress as sole stimulus. Furthermore, as opposed to anti- coagulation and dilution of the native blood, the most physiological way of studying platelets is in the natural environment, in the unadulterated native blood [3]. Only testing native blood allows the assessment of thrombin generation, perhaps the most important deter- minant of thrombus formation. However, all currently available platelet function tests are carried out from anticoagulated blood. Spontaneous lysis of a fibrin- stabilized thrombus is the main physiological protection against tissue damage, the consequence of lasting vascular occlusion [4,5]. It has recently been shown that spontaneous thrombolysis is also controlled by throm- bin [6,7]. Development of a clinically useful in-vitro thrombolysis test was hampered by the early observa- tion that clot lysis happens only in vivo but not in vitro [8]. For this reason, testing of whole blood was replaced by purified plasma proteins such as fibrinogen or euglobulin. However, these elaborate techniques are not suitable for routine clinical use. Furthermore, these fibrinolysis assays do not take into account that an arterial, platelet-rich thrombus is much more resistant to lysis than a venous thrombus or blood clot. This is because aggregated platelets release plasminogen acti- vator inhibitors in the vicinity of thrombus [9]. In a recent publication we provided evidence for the specificity and sensitivity of a new global in-vitro test of platelet function and spontaneous thrombolysis [10]. The aim of the present study was to use this Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Short communication 781 0957–5235 & 2003 Lippincott Williams & Wilkins DOI: 10.1097/01.mbc.0000061369.39736.38