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Summary Background Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications. We studied the frequency of bleeding complications in outpatients treated routinely in anticoagulation clinics. Methods In a prospective cohort from thirty-four Italian anticoagulation clinics, 2745 consecutive patients were studied from the start of their oral anticoagulation (warfarin in 64%, acenocourmarol in the rest). The target anticoagulation-intensity was low (international normalised ratio [INR] ≤2·8) in 71% of the patients and high (> 2·8) in the remainder. We recorded demographic details and the main indication for treatment and, every 3·4 months, INR and outcome events. Such events included all complications (bleeding, thrombosis, other), although only bleeding events are reported here, and deaths. We divided bleeding into major and minor categories. Findings 43% of the patients were women. Nearly three-fifths of the patients were aged 60·79; 8% were over 80. The main indication for treatment was venous thrombolism (33%), followed by non-ischaemic heart disease (17%). Mean follow-up was 267 days. Over 2011 patient-years of follow-up, 153 bleeding complications occurred (7·6 per 100 patient-years). 5 were fatal (all cerebral haemorrhages, 0·25 per 100 patient-years), 23 were major (1·1), and 125 were minor (6·2). The rate of events was similar between sexes, coumarin type, size of enrolling centre, and target INR. The rate was higher in older patients: 10·5 per 100 patient-years in those aged 70 or over, 6·0 In those aged under 70 (relative risk 1·75, 95% CI 1·29–2·39, p vs 6·0 per 100 patient-years) (1·80, 12–2·7, p vs 6·3, 1·75, 1·27–2·44, p 4 5, 7·91, 5·44–11·5, p Interpretation We saw fewer bleeding events than those recorded in other observational and experimental studies. Oral anticoagulation has become safer in recent years, especially if monitored in anticoagulation clinics. Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing.

Thirty-seven patients affected by polycythaemia rubra vera (PRV) and with at least one additional thrombotic risk factor (overt vascular disease, diabetes mellitus, treated hypertension, smoking habit

This study was carried out in order to evaluate changes in pulmonary vascular reactivity and in hemorheology induced by pentoxifylline infusion (100 mg) at rest and during standardized exercise in patients with chronic cor pulmonale secondary to chronic obstructive pulmonary disease. The administration of pentoxifylline at rest was associated with reduction in mean pulmonary artery pressure (p less than 0.01), pulmonary vascular resistance (p less than 0.01) and right ventricular stroke work index (p less than 0.02). Standard exercise performed after pentoxifylline infusion was also associated with significant reduction in mean pulmonary artery pressure and pulmonary vascular resistance. Rheologic tests showed less evident changes. Our data suggest that pentoxifylline significantly improves pulmonary hemodynamics at rest and partly reverses its changes, after exercise, in patients with chronic obstructive pulmonary disease.

The aim of this study was to investigate the blood coagulation changes in three patients with homocystinuria, in baseline condition and during therapy. At baseline, antithrombin III activity and factor VII levels were reduced in all three patients; antithrombin III protein and protein C antigen were also slightly lowered in one patient, and factor X in another. beta-Thromboglobulin, a measure of platelet activation, was increased in one case. During pyridoxine treatment, antithrombin III activity was rapidly restored to normal; factor VII increased and beta-thromboglobulin decreased. These data suggest that, in addition to platelet activation, abnormalities of blood clotting, and particularly reduction of antithrombin III, may play a role in the thrombotic tendency associated with homocystinuria. The nature of these clotting alterations is still uncertain, but their improvement during active metabolic treatment suggests that the defect in amino acid transsulfuration of homocystinuria may directly affect synthesis or activity of some liver-dependent clotting factors.

Hemorheologic parameters were measured in cerebrovascular patients with a history of stroke or recurrent ischemic attacks in a quiescent phase of the disease. All patients were submitted to aortic arch angiography and then classified according to the presence or absence of detectable arterial lesions. In comparison with a group of control subjects, cerebrovascular patients had significantly elevated levels of blood and plasma viscosity, fibrinogen, factors VIII:C and VIIIR:Ag and lowered values of erythrocyte filtration. Blood viscosity was increased and erythrocyte filtration reduced only in male patients. Elderly patients had higher blood viscosity and fibrinogen levels, and those with a history of stroke also showed the highest hematocrit and plasma viscosity values. Patients with a stroke history compared with those affected by remittent ischemic attacks, and patients with positive in comparison with those with negative angiograms were characterized only by higher fibrinogen (and sometimes factor VIII) levels, but not by other differences in hemorheologic values. It is concluded that changes in hemorheologic values consistent with hyperviscosity are a feature of cerebrovascular patients also in the quiescent phase of the disease and not only as a result of acute ischemic attacks. These changes are however most frequent in males and in elderly subjects, while they seem to be almost evenly distributed in patients with or without evidence of arterial disease.

SummaryThe paper reports on rate and type of thrombotic events occurring during the observational, prospective, inception-cohort, multicenter ISCOAT study. 2,745 unselected, daily practice patients, consecutively referring to 34 Italian anticoagulation clinics to monitor the oral anticoagulant treatment, were included in the study from beginning of their first anticoagulant course. During a total follow-up of 2,011 patient-years of treatment 70 thrombotic events (3.5 per 100 patient years) were recorded in 67 patients: 20 fatal (1%), 39 major (1.9%) and 11 minor (0.6%). 34/70 events occurred within the first 90 days of treatment (relative risk - at multivariate analysis - of 90 = 20.6, C.I. 12.7-33.5; p 70 y (1.62, C.I. 1.0-2.61; p 2 = 1.88, C.1.1.16-3.07; p The recorded rate of thrombotic events was lower than that reported in the few available studies. A greater risk should be expected during the first 90 days of treatment, when anticoagulation levels are 70 years and in those with cerebrovascular/peripheral arterial disease.