Objective To investigate the efficacy of using a rapid plasma d-dimer test as an adjunct to compression ultrasound for diagnosing clinically suspected deep vein thrombosis. Design d-dimer concentrations were determined in all patients with a normal ultrasonogram at presentation. Repeat ultrasonography was performed 1 week later only in patients with abnormal d-dimer test results. Main outcome measure Patients with normal ultrasonograms were not treated with anticoagulants and were followed for 3 months for thromboembolic complications. Setting University research and affiliated centres. Subjects 946 patients with clinically suspected deep vein thrombosis. Results Ultrasonograms were abnormal at presentation in 260 (27.5%) patients. Of the remaining 686 patients tested for d-dimer, 88 (12.8%) had abnormal concentrations. During follow up venous thromboembolic complications occurred in one of the 598 patients who were not treated with anticoagulants and who had an initial normal ultrasonogram and d-dimer concentration, whereas thromboembolic complications occurred in two of the 83 untreated patients who had abnormal d-dimer concentrations but a normal repeat ultrasonogram. The cumulative incidence of venous thromboembolic complications during follow up was 0.4% (95% confidence interval 0% to 0.9%). The rapid plasma d-dimer test used as an adjunct to compression ultrasonography resulted in a reduction in the mean number of repeat ultrasound examinations and additional hospital visits from 0.7 to 0.1 per patient. Conclusions Testing for d-dimer as an adjunct to a normal baseline ultrasound examination decreased the number of subsequent ultrasound examinations considerably without any increased risk of venous thromboembolic complications in patients not receiving anticoagulants. The use of ultrasound and testing for d-dimer enabled treatment decisions to be made at the time of presentation in most patients.

Summary The factors associated with persistent instability of oral anticoagulant treatment (OAT) were investigated in a case‐control study. The most unstable patients from 35 Italian anticoagulation clinics were matched with stable controls, for gender, age and OAT indication. Socio‐demographic data, medical history, dietary and life habits, cytochrome P450 CYP2C9 variants, blood cell count, liver and renal functions were investigated. An ‘Abbreviated Mental Test’ (AMT) and a questionnaire to assess patient compliance to, and comprehension of, OAT indications and mechanisms were administered. An International Normalized Ratio (INR) above 4·5 was more frequently found in cases (n = 77) than controls (n = 80) (12·3% vs. 0·4%; P < 0·0001). The odds ratio for instability was significantly higher for: people who worked versus pensioners, acenocoumarol versus warfarin, and an insufficient score in the AMT and/or in the questionnaire. Cytochrome P450 CYP2C9 variants *1/*3 or *2/*3 or *3/*3 were more frequent among cases than controls (29·9% vs.15·0%; P = 0·042). No differences were observed as regards the other variables. In conclusion, we found that high intra‐individual variability in OAT control was multifactorial, but poor OAT comprehension was prevalent.

Background-Bridging therapy with low-molecular-weight heparin is usually recommended in patients who must stop oral anticoagulants before surgical or invasive procedures. To date, there is no universally accepted bridging regimen tailored to the patient's thromboembolic risk. This prospective inception cohort management study was designed to assess the efficacy and safety of an individualized bridging protocol applied to outpatients. Methods and Results-Oral anticoagulants were stopped 5 days before the procedure. Low-molecular-weight heparin was started 3 to 4 days before surgery and continued for 6 days after surgery at 70 anti-factor Xa U/kg twice daily in high-thromboembolic-risk patients and prophylactic once-daily doses in moderate-to low-risk patients. Oral anticoagulation was resumed the day after the procedure with a boost dose of 50% for 2 days and maintenance doses afterward. The patients were followed up for 30 days. Of the 1262 patients included in the study (only 15% had mechanical valves), 295 (23.4%) were high-thromboembolic-risk patients and 967 (76.6%) were moderate-to low-risk patients. In the intention-to-treat analysis, there were 5 thromboembolic events (0.4%; 95% confidence interval, 0.1 to 0.9), all in high-thromboembolic-risk patients. There were 15 major (1.2%; 95% confidence interval, 0.7 to 2.0) and 53 minor (4.2%; 95% confidence interval, 3.2 to 5.5) bleeding episodes. Major bleeding was associated with twice-daily low-molecular-weight heparin administration (high-risk patients) but not with the bleeding risk of the procedure. Conclusions-This management bridging protocol, tailored to patients' thromboembolic risk, appears to be feasible, effective, and safe for many patients, but safety in patients with mechanical prosthetic valves has not been conclusively established.

SummaryThe occurrence of a “rebound hypercoagulable state” in patients after discontinuation of oral anticoagulants is still a matter of debate and no definite recommendation can be made on the best procedure for anticoagulant withdrawal. The present study investigated the changes in the levels of markers of activated blood coagulation in 32 patients (pts) in whom warfarin treatment (for venous thromboembolic disease) was randomly withdrawn abruptly (n = 17, group A) or gradually (n = 15, group B: ⅔ of initial dose the 1st week, ⅓ the 2nd weeks and nothing from the 3rd week on). Blood was sampled at baseline, once a week for the first three weeks and after 2 months. At the 1st week group A had significantly higher F1+2 and TAT values (p <0.001); at the 2nd week F1 + 2 levels remained higher (p <0.05) though INR values were not different from those of group B. After baseline, higher than normal F1+2 levels were recorded in 32/66 (48%) controls in group A vs 15/60 (25%) in group B (p <0.01); at the 2nd week, 10/17 (59%) patients in group A vs 1/15 (7%) in group B still had higher than normal F1+2 levels (p <0.01 ). The values of areas under curve (AUC) and maximum concentrations of all variables were not statistically different in the two groups; however, very high levels were observed in a few cases of group A. Thrombotic events (one DVT recurrence and one thrombophlebitis in a varicose vein) occurred in 2 pts of group A, both with high F1+2 and TAT AUC values. In conclusion, the present study shows that withdrawal of oral anticoagulants elicits low grade transient clotting activation, which is more intense and longer lasting after abrupt discontinuation. In single cases, however, such activation is particularly intense. It is possible that these cases are at greater risk of thrombotic complications.

Our data showed a strong interaction between oral contraceptive use and the presence of either R506Q or G20210A mutations. In non-oral contraceptive users the risk of venous thromboembolism was significantly increased in carriers of R506Q but not in those with the G20210A mutation.