Oral anticoagulant treatment with coumarin derivatives does not influence plasma homocysteine concentration.

BACKGROUND: High circulating levels of homocysteine are a risk factor for arterial and venous thrombosis. This association has been established in numerous case-control studies. In some of these studies, patients were treated with anticoagulants at the time of venapuncture. It is not clear whether homocysteine concentrations are influenced by anticoagulants. If anticoagulation does, indeed, have an effect on homocysteine levels, it might underestimate or overestimate the possible association of homocysteine levels and vascular disease. METHODS: In this study we used two different groups to investigate the effect of coumarin derivatives on homocysteine concentrations. Homocysteine levels were measured in 40 patients who were on the waiting list for orthopedic surgery and who were expected to receive prophylactic anticoagulant therapy after the operation. Measurements were taken before the operation, as well as during and after coumarin therapy. Homocysteine concentrations were also measured in a second study group consisting of 12 healthy volunteers who were treated with oral anticoagulants. RESULTS: Mean homocysteine concentrations increased by 6% (95% CI 2-10%) during the treatment with coumarin derivatives. This corresponds to a 1 mumol/L increase in homocysteine concentration. After the anticoagulant treatment period, the concentrations decreased again. We determined that this slight increase does not influence the interpretation of epidemiological studies. We also observed no significant effect of anticoagulants on homocysteine concentration after 13 weeks of treatment of healthy volunteers (decrease of 3.6%, or approximately 0.6 micromol/L; 95% CI -17.5-8.5%). CONCLUSION: We conclude that anticoagulation does not influence homocysteine concentrations to any significant degree.

Exclusion of venous thromboembolism: evaluation of D-Dimer PLUS for the quantitative determination of D-dimer.

The objective of this study was to evaluate if D-Dimer PLUS (Dade Behring, USA), a rapid fully automated assay, could be used as an initial screening test in the diagnosis of venous thromboembolism (VTE). Samples from 274 consecutive symptomatic patients with suspected pulmonary embolism (n=229; 79% outpatients, 21% inpatients), deep venous thrombosis (n=37; 84% outpatients, 16% inpatients) or suspected for both complications (n=8) were tested with this D-dimer assay with a Sysmex CA-1500 Coagulation Analyzer. Clinical probability for pulmonary embolism (PE) or deep venous thrombosis (DVT) was staged according to a pretest risk score proposed by Wells. Final diagnosis of PE and/or DVT was established by spiral-computed tomography of the pulmonary arteries or compression ultrasonography, respectively. PE was diagnosed in 13.5% of the patients, whereas DVT was confirmed in 17.7% of the patients. The optimal cut-off value for exclusion of venous thromboembolism was 130 mug/l, and sensitivity, specificity and negative predictive value (NPV) were 95.0% (95% CI: 92.4-97.6), 30.4% (95% CI: 25.0-35.8) and 97.2% (95% CI: 95.2-99.2), respectively. In fact, two patient with PE were missed using D-Dimer PLUS; both cases were outpatients. In conclusion, this assay appears to be safe when implemented in an algorithm based on clinical assessment, D-dimer concentration, and radiological diagnostic techniques to stratify the risk for PE or DVT. However, higher sensitivities and negative predictive values were claimed in the scarce published reports for the D-Dimer PLUS assay than found in this study.

In vivo recovery and safety of human factor VIII product AAFACT in patients with haemophilia A.

AAFACT, a monoclonal purified, solvent/detergent treated human plasma-derived coagulation factor VIII concentrate obtained from plasma of voluntary, non-remunerated blood donors, is manufactured and marketed in the Netherlands by Sanquin Plasma Products since 1995. In a postmarketing surveillance study, 70 previously treated haemophilia A patients were included (73% severe, 14% moderate and 13% mild haemophilia A). Most of these patients were followed during 4 years for the appearance of adverse events, possible transmissions of blood-borne viruses and the occurrence of antibodies against FVIII. The efficacy of treatment was determined in each patient by the in vivo recovery of FVIII. During this study, only six adverse events, possibly related to the use of AAFACT, were reported. None of these were indicated as serious. Transmissions of HIV, HAV, HBV and HCV in the seronegative patients have not been observed. In none of the patients, inhibitors to FVIII were detected. The in vivo recovery of FVIII during this study was not different from the in vivo recovery observed in eight patients during the preregistration study. There was a correlation of in vivo recovery with age and body weight. From these results, we conclude that the clinical usage of this human plasma-derived FVIII product is efficient and safe.