The incidence of both bleeding and thromboembolic events increases sharply with advanced age. Because higher thromboembolic risk with age often makes it unfeasible to withhold oral anticoagulation from elderly patients, future studies should focus on ways to lower the bleeding risk.

Summary. Surgery in anticoagulated patients is problematic. Coumarin therapy is often discontinued or reversed to reduce the perioperative bleeding risk. Meanwhile, the thromboembolic risk is enhanced. We sought to determine the frequency of bleeding and thromboembolism in anticoagulated patients undergoing routine surgery and to investigate the role of patient characteristics and the level of anticoagulation. We studied patients who attended the Leiden Anticoagulation Clinic for treatment relating to mechanical heart valve prostheses, atrial fibrillation or myocardial infarction and underwent surgery at the Leiden University Medical Centre between 1994 and 1998. Outcome events were bleeding and thromboembolism in the perioperative period. Seventy-two complications occurred in 603 interventions, yielding an overall frequency of 11AE9% [95% confidence interval (CI): 9AE3-14AE9], 9AE5% (n ¼ 57) for haemorrhage and 2AE5% (n ¼ 15) for thromboembolism.Younger patients tended to have more complications [odds ratio (OR) for >65 years of age: 0AE5, 95% CI 0AE3-1AE0] as did patients with atrial fibrillation (OR for atrial fibrillation versus mechanical heart valve prostheses: 1AE8, 95% CI 0AE8-4AE2). High postoperative levels of anticoagulation were associated with a slightly increased risk of complications [OR international normalized ratio (INR) > 3 vs. INR < 2: 1AE3, 95% CI 0AE6-3AE0]. We conclude that routine surgery in anticoagulated patients yields a high perioperative bleeding and thromboembolic risk. While neither patient characteristics nor the level of anticoagulation appeared to play a major role in the occurrence of complications, the risk was clearly associated to the type of surgery, with the highest risk in thoracic surgery.

Aim-To evaluate possible long term side effects of high doses of sex steroids in the management of constitutionally tall stature, with special attention to hypothalamic-gonadal function.Methods-Sixty four tall adult men and 180 tall adult women, who received supraphysiological doses of sex hormones during puberty, were interviewed in a standardised way at a mean follow up period of 10 years after cessation of treatment. Sixty one untreated tall adult men and 94 untreated tall adult women served as controls. Results-The majority of the subjects were satisfied with their decision regarding hormone treatment. Seventy seven per cent of the women and 78% of the men reported one or more side effects during treatment. Most side effects were mild. In women, only 3% stopped treatment because of an adverse event; in men, the reported side effects never stopped treatment. The frequency of reported side effects in women was higher during treatment with high doses of oestrogens than during oral contraceptive use, indicating a dose dependent relationship. Amenorrhoea of longer than six months after cessation of therapy was found in 5%. Menstrual cycle characteristics of previously treated women were comparable with controls. Malignancy was not reported. Information about a total of 127 pregnancies was obtained and revealed no distinct differences in details and outcome between previously treated women and men, and controls. Conclusions-At a mean follow up of 10 years there is no evidence that pharmacological doses of sex hormones have a long term effect on reproductive function. However, this period is still too short to draw definite conclusions. (Arch Dis Child 1995; 73: 311-315)

Article abstract-Background: The use of oral anticoagulant therapy for the prevention of arterial thromboembolism in patients who have had ischemic stroke is controversial. Coumarins may increase the bleeding risk in patients with cerebral ischemia of arterial origin. Objectives: 1) To calculate incidence rates of bleeding and thromboembolic events in patients with noncardiac cerebral ischemia who were treated routinely in an anticoagulation clinic. 2) To assess which factors contribute to the occurrence of events. 3) To determine the optimal intensity of oral anticoagulant therapy in these patients. Methode: The authors studied all patients treated for noncardiac cerebral ischemia at the Leiden anticoagulation clinic between 1993 and 1998. Outcome events were major hemorrhage, major arterial thromboembolism, and death. Results: The authors observed 356 patients for 644 patient-years. The incidence of major hemorrhage was 3.9 per 100 patient-years (95% CI, 2.5 to 5.7) and that of thromboembolism was 3.0 per 100 patient-years (95% CI, 1.8 to 4.6). The incidence of hemorrhage varied with the duration of treatment (relative risk [RR] of the first versus the second half-year, 3.8; 95% CI, 1.9 to 7.6), age (RR for age >65 years, 3.7; 95% CI, 1.1 to 12.3), and the intensity of oral anticoagulation (RR, 1.8 for each 0.5 international normalized ratio [INR] unit increase; 95% CI, 1.5 to 2.3). The optimal intensity of oral anticoagulant therapy was 2.5 to 3.5 INR; the best target value was 3.0 INR. Conclusion. The risk of hemorrhage with anticoagulant therapy is high in patients with ischemic stroke of arterial origin but is mainly confined to early use and elderly patients. NEUROLOGY 2001;57· 1993-1999 Patients with atrial fibrillation 1 or myocardial infarction 2 4 benefit from treatment with coumarins; however, treatment introduces a moderate annual bleeding risk of 2% to 3%. A study of coumarins in patients with atrial fibrillation and recent nondisabling cerebral ischemia showed a 65% reduction of recurrent strokes with an accompanying annual bleeding risk of less than 3% percent. 5 These results suggest that oral anticoagulation may prevent stroke in a wider ränge of indications.To investigate whether coumarins also could improve the outcome for patients with stroke of noncardiac origin, the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) was designed. SPIRIT was an open, multicenter clinical trial in which patients with cerebral ischemia of presumed arterial origin were randomized between low-dose aspirin (30 mg daily) and full-dose anticoagulation (international normalized ratio [INR], 3.0 to 4.5). 6 The trial was prematurely terminated after the first interim analysis revealed an excessive rate of bleeding complications (7% per year) in patients randomized to oral anticoagulation. Subsequent analyses revealed differences between patients that might help to explain the observed risks; high INR levels äs well äs the presence of leukoaraiosis appeared to be related to the bleeding risk in particular. 6 7 ...