Two automatic coagulometers--ACL 810 (Instrumentation Laboratory), a laser-nephelometric centrifugal analyzer, and KoaguLab 40 A (Ortho Diagnostics), an optical automatic coagulometer--were compared with the manual tilt-tube method for the performance of prothrombin time (PT). Seven ISI- (International Sensitivity Index) calibrated commercial thromboplastin reagents were used for duplicate determinations in 30 normal subjects, 30 patients with liver disease, and 30 patients receiving stabilized oral anticoagulation. Clotting times were longer with the manual method than with ACL 810 and, to a lesser extent, with KoaguLab 40 A. Average imprecision of duplicate determinations (CV) was less than 1% with ACL 810; KoaguLab 40 A and the manual method had similarly higher imprecisions (2.8% and 2.7%). Differences in origin and slope of the regression curves of clotting times obtained with the coagulometers over the tilt-tube method were observed with all the reagents tested. Transformation of clotting times to PT ratios did not eliminate the bias resulting from the different clot-detection methods. A higher percentage of patients with liver disease had abnormal PT ratios when their plasma was tested with the coagulometers than with the manual method. Transformation of PT ratios to International Normalized Ratios effectively eliminated the bias resulting from the different thromboplastin reagents but had no effect on the bias resulting from the different clot-detection methods. A significant proportion of patients appeared excessively anticoagulated (INR greater than 4.5) with the coagulometers but not with the manual method. These results highlight the need for standardization of both instrumentations and reagents to improve monitoring of oral anticoagulant treatment.

Summary:Habitual smoking is one of the best established risk factors for cardiovascular disease. The pathogenesis of smoke-induced damage is not so well clarified, but it probably includes-among some other aspects-an activation of the hemostatic system. Recently it has been shown that smoking a single cigarette can significantly decrease the coronary blood flow in coronary patients as well as in normal subjects. We tested the hypothesis that the acute effects of smoke are mediated by the hemostatic system. Seven healthy male volunteers, aged 20-40 years (mean 32f6 years), entered the study. All were habitual smokers, but had abstained from smoking in the 12 hours preceding the test. After lying in absolute rest for about 30 minutes, each subject smoked a cigarette containing 1.2 mg of nicotine. Immediately before and after smoking, blood was drawn by clear venipuncture for the evaluation of the following hemostatic variables: collageninduced platelet aggregation by the method of Born; thromboxane B2 (TxB,) production by platelets stimulated with collagen, radioimmunoassay (RIA); plasma beta thromboglobulin (TG) (RIA); plasma fibrinopeptide A (FPA) (RIA); plasma fibrinolytic activity in the euglobulin fraction (NEF) (fibrin plate method). The following results, respectively before and after smoking, were observed: collagen-induced platelet aggregation 55 f 3 v s . diameter 8.8 f0.7 vs. 9.1 f0.7 mm. None of these variables was significantly changed after smoking. We conclude that acute smoking does not induce a prothrombotic state.

Platelet function (as production of thromboxane B2 by platelets stimulated with collagen, and plasma beta-thromboglobulin) and thrombin activity (as plasma fibrinopeptide A) were investigated in eight young (mean age 27 +/- 3 SE years) male patients in which type 1 diabetes mellitus had been diagnosed 2 to 6 months previously. They were all in excellent stable metabolic control (mean HbA1c 5.6 +/- 0.4 SE %) and free from any complications. The haemostatic variables were assessed at rest and after cycloergometric exercise to exhaustion. When compared to age- and sex-matched healthy controls, patients showed higher beta-thromboglobulin, fibrinopeptide A and thromboxane B2 at rest. After exercise, plasma beta-TG increased only in the controls. Platelet and thrombin activation are present in the very early stages of type 1 diabetes mellitus, in the absence of any complications.

Platelet function and thrombin activity were investigated in 12 hospitalized patients (7 men and 5 women, mean age 53 years) who had had transient cerebral ischemic attacks in the previous 2-12 weeks. Each patient was given an extensive clinical and instrumental evaluation, including Doppler sonography of the cervical and lower limb vessels, cerebral angiography, and head computed tomography scan, after which relevant atherosclerotic disease was excluded. The controls consisted of 12 subjects hospitalized for nonvascular neurologic problems and matched for age, sex, and risk factors to the transient ischemic attack patients. Collagen-induced platelet thromboxane B 2 production, plasma /3-thromboglobulin, and fibrinopeptide A were significantly higher in the patients than the controls. Platelet aggregabllity by collagen was the same in the 2 groups. Platelet hyperfunction and enhanced thrombin activity are present in patients some weeks after the acute episode, suggesting that the hemostatic system has a primary pathogenetic role. (Stroke 1987; 18:892-895)

The prothrombin time (PT) is the most widely used assay to monitor oral anticoagulation (OA). Although it has been established that both thromboplastin and instrumentation significantly affect the results, major standardization attempts have been devoted to the calibration of reagents rather than of instruments. To provide safe laboratory monitoring of OA, an International Sen sitivity Index (ISI) for thromboplastin has been introduced. We have compared two automatic coagulometers, the ACL (Instrumentation Laboratory), a laser-nephelometer centrifugal analyzer which measures the intensity of the light scattered by a plasma sample before, during and after clot formation and the KOAGULAB 40A (Ortho Diagnostics), an optical automatic coagulometer, with the till tube technique for the performance ofPT. Five calibrated commercial thromboplastins have been used for replicate determinations in 30 normals, 30 liver disease patients and 30 patients on stabilized OA. The overall observed imprecision (C.V.) was 1.1% for ACL, 2.9% for the KOAGULAB 40A and 3.0% for the till tube technique. The F test for the two-way interaction of ratios was statistically significant (p< O.OOl) for the large majority of reagent/technique combinations in normals and in liver disease patients. Internatio nal normalized ratios were also significantly different (p< O.OOl) in most instances in patients on OA. Inadequate anticoagulation (INR<2.0)was observed in 18% of patients with the ACL , in 31% with the KOAGULAB 40A and in 33% with the till tube technique. Excessive anticoagulation (INR> 4.5) was observed in 19% of the patients with the ACL, in 7% with KOAGULAB 40A and in 3% with the till tube tech nique. These data highlight the need for standardization of both instrumentations and reagents to improve monitoring of OA.