Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

Long-term mental wellbeing of adolescents and young adults diagnosed with venous thromboembolism: results from a multistage mixed methods study.

Essentials Long-term mental wellbeing of adolescents and young adults with venous thromboembolism is unclear. This multistage mixed methods study was based on Danish nationwide registry data and interviews. Mental wellbeing is negatively impacted in the long-term and uncertainty of recurrence is pivotal. The perceived health threat is more important than disease severity for long-term mental wellbeing. SUMMARY: Background Critical and chronic illness in youth can lead to impaired mental wellbeing. Venous thromboembolism (VTE) is a potentially traumatic and life-threatening condition. Nonetheless, the long-term mental wellbeing of adolescents and young adults (AYAS) with VTE is unclear. Objectives To investigate the long-term mental wellbeing of AYAS (aged 13-33 years) diagnosed with VTE. Methods We performed a multistage mixed method study based on data from the Danish nationwide health registries, and semistructured interviews with 12 AYAS diagnosed with VTE. An integrated mixed methods interpretation of the findings was conducted through narrative weaving and joint displays. Results The integrated mixed methods interpretation showed that the mental wellbeing of AYAS with VTE had a chronic perspective, with a persistently higher risk of psychotropic drug purchase among AYAS with a first-time diagnosis of VTE than among sex-matched and age-matched population controls and AYAS with a first-time diagnosis of insulin-dependent diabetes mellitus. Impaired mental wellbeing was largely connected to a fear of recurrence and concomitant uncertainty. Therefore, it was important for the long-term mental wellbeing to navigate uncertainty. The perceived health threat played a more profound role in long-term mental wellbeing than disease severity, as the potential life threat was the pivot which pointed back to the initial VTE and forward to the perception of future health threat and the potential risk of dying of a recurrent event. Conclusion Our findings show that the long-term mental wellbeing of AYAS diagnosed with VTE is negatively affected, and highlights these patients' need for adequate support.

Edoxaban versus placebo, aspirin, or aspirin plus clopidogrel for stroke prevention in atrial fibrillation. An indirect comparison analysis.

As non-valvular atrial fibrillation (AF) brings a risk of stroke, oral anticoagulants (OAC) are recommended. In 'real world' clinical practice, many patients (who may be, or perceived to be, intolerant of OACs) are either untreated or are treated with anti-platelet agents. We hypothesised that edoxaban has a better net clinical benefit (NCB, balancing the reduction in stroke risk vs increased risk of haemorrhage) than no treatment or anti-platelet agents. We performed a network meta-analysis of published data from 24 studies of 203,394 AF patients to indirectly compare edoxaban with aspirin alone, aspirin plus clopidogrel, and placebo. Edoxaban 30 mg once daily significantly reduced the risk of all stroke, ischaemic stroke and mortality compared to placebo and aspirin. Compared to aspirin plus clopidogrel, there was a lower risk of intra-cranial haemorrhage (ICH). Edoxaban 60 mg once-daily had a reduced risk of any stroke and systemic embolism compared to placebo, aspirin, and aspirin plus clopidogrel. Mortality rates for both edoxaban doses were estimated to be lower compared to any anti-platelet, and significantly lower compared to placebo. With overall reduced risk of ischemic stroke and ICH, both edoxaban doses bring a NCB of mean (SD) 1.68 (0.15) saved events per 100 patients per year compared to anti-platelet drugs in a clinical trial population. The NCB was demonstrated to be lower, at 0.77 (0.12) events saved (p< 0.01) when modeled to data from a 'real world' cohort of AF patients. In conclusion, edoxaban is likely to provide even better protection from stroke and ICH than placebo, aspirin alone, or aspirin plus clopidogrel in both clinical trial populations and unselected community populations. Both edoxaban doses would also bring a positive NCB compared to anti-platelet drugs or placebo/non-treatment based on 'real world' data.

Dabigatran adherence in atrial fibrillation patients during the first year after diagnosis: a nationwide cohort study.

BACKGROUND: There is a perception among physicians that lack of routine monitoring with non-vitamin K antagonist oral anticoagulants (NOACs) may lead to poor adherence to medication. We studied adherence during the first year of usage in a cohort of patients with newly diagnosed non-valvular atrial fibrillation (AF) started on the NOAC, dabigatran etexilate. METHODS AND RESULTS: Nationwide Danish patient and prescription purchase registries were used to identify newly diagnosed AF patients taking dabigatran, comorbidities, and refill patterns under a twice-daily, one pill regimen. Adherence was characterized among remaining users (N = 2960) after 1 year using the proportion of days covered (PDC), gap rates and restart rates. The overall 1-year PDC was 83.9%, with 76.8% of patients having a 1-year PDC in excess of 80%. Patients with a CHA2 DS2 -VASc score ≥ 2 were more adherent to medication regimes than patients with a CHA2 DS2 -VASc score of 1 (PDC ratio, 1.12; 95% confidence interval [CI], 1.08-1.17) and generally patients with higher morbidity showed more adherence. Patients with prior bleeding were not less adherent to medication regimes than patients with no prior bleeding (PDC ratio, 1.02; 95% CI, 0.98-1.06). The overall gap rate was 1.4 gaps per year. There were no clear tendencies in gap rates among subgroups, although patients with higher morbidity tended to have slightly more, but shorter, gap periods. CONCLUSIONS: More than 75% of patients were showed > 80% adherence to medication regimes during the first year. Patients with higher morbidity, including patients with a higher risk of stroke or bleeding, exhibited better adherence. This improvement may be attributable to more regular contact with the healthcare system.

Preoperative plasma D-dimer predicts 1-year survival in colorectal cancer patients with absence of venous thromboembolism (VTE): a prospective clinical cohort study.

BACKGROUND: Fibrin formation is required for tumor angiogenesis, metastasis and invasion. Cancer discovered at the same time as or shortly after venous thromboembolism (VTE) tends to be advanced, and the prognosis poor. Previous studies have demonstrated that plasma D-dimer - a degradation product of cross-linked fibrin - correlates with tumor stage and prognosis in patients with colorectal cancer. However, it remains unclear whether D-dimer is of prognostic significance in colorectal cancer patients with absence of VTE. OBJECTIVE: To examine whether the preoperative plasma D-dimer level predicts 1-year survival in pre- and postoperative VTE-negative colorectal cancer patients admitted for surgery. METHODS: We measured preoperative D-dimer levels in 157 patients, and computed Kaplan-Meier survival curves according to the levels of D-dimer. Cox proportional-hazard regression analysis was used to compute hazard ratio as a measure of 1-year mortality rate ratio, controlling for potential confounding factors. The Aalborg Hospital's standard cut-off level of 0.3 mg L(-1) was used to distinguish negative and positive D-dimer results. RESULTS: The overall 1-year survival rate was 87.3% (95% confidence interval (CI), 81.0-91.6%), with 78.1% survival (95% CI, 65.9-86.4%) in the positive D-dimer group compared with 93.6% survival (95% CI, 86.2-97.1%) in the negative D-dimer group. The adjusted hazard ratio of death in the positive D-dimer group compared with the negative D-dimer group was 3.6 (95% CI, 1.3-9.9). CONCLUSION: A positive preoperative D-dimer is associated with a poor prognosis in colorectal cancer patients with absence of VTE.

Precision and accuracy of point-of-care testing coagulometers used for self-testing and self-management of oral anticoagulation therapy.

BACKGROUND: Oral anticoagulation therapy is monitored by the use of the International Normalized Ratio (INR). Patients who perform self-testing or self-management use a point-of-care testing (POCT) coagulometer (INR monitor) to estimate their INRs. A precondition for a correct dosage of coumarins is a correct INR estimation, and the method and apparatus used for providing the INR measurements are crucial in this context. Several studies have been published regarding the precision and accuracy of these POCT coagulometers, and have led to diverse conclusions. It is difficult and challenging to perform an overview of the literature, owing to the vast amount of papers, with differences in design, statistical analysis, etc. OBJECTIVES: The aim of this systematic review was to analyze the current literature, especially regarding the precision and accuracy of the POCT coagulometers, to provide recommendations for clinical use and quality control, and to point out areas for future research. METHODS: We included a total of 22 studies, of which four were characterized as high-quality studies. RESULTS: The precision of the POCT coagulometers was generally adequate for clinical use. Their performance in terms of accuracy has to be viewed in the context of the inherent inaccuracies of INR measurements. CONCLUSIONS: The accuracy of POCT coagulometers seems, in this respect, to be generally acceptable, and they can be used in a clinical setting.

Impact of vascular disease in predicting stroke and death in patients with atrial fibrillation: the Danish Diet, Cancer and Health cohort study.

BACKGROUND: The presence of vascular disease (peripheral artery disease [PAD] and/or myocardial infarction [MI]) may impact on the risk of stroke and death among patients with incident atrial fibrillation (AF). To test this hypothesis, we analyzed data from a large Danish prospective cohort, the Danish Diet, Cancer and Health (DCH) study, to assess the risk of stroke or death among those who developed AF according to concomitant presence of vascular disease. METHODS: A prospective cohort study of 57, 053 persons (27, 178 men and 29, 876 women, respectively), aged between 50 and 64 years. The risk of stroke or death for patients with vascular disease was assessed amongst 3315 patients with incident AF (mean age, 67.1years; 2130 men, 1185 women) using Cox proportional hazard models, after a median follow-up of 4.8 years. RESULTS: Of the subjects with AF, 417 (12.6%) had 'vascular disease' (PAD and/or prior MI). The risk of the primary endpoint (stroke or death) was significantly higher in patients with vascular disease at 1-year follow-up (crude hazard ratio [HR] 2.51 [1.91-3.29]), with corresponding crude HRs for PAD and MI being 3.51 (2.40-5.13), and 1.99 (1.46-2.72), respectively. For the secondary endpoints of death or stroke individually, these risk estimates were similar (crude HR 2.48 [1.89-3.26] and 1.77 [1.18-2.66], respectively). After adjustment for risk factors within the CHADS(2) score, the adjusted HR for the primary endpoint (stroke or death) in patients with vascular disease was 1.91 (1.44-2.54), which was also significant for death (1.97 [1.48-2.62]). CONCLUSION: Vascular disease (prior MI and PAD) is an independent risk factor for the primary endpoint of 'stroke or death' in patients with AF, even after adjustment for the CHADS(2) risk score, although this is driven by the impact on mortality. This reaffirms that patients with vascular disease represent a 'high-risk' population, which necessitates proactive management of all cardiovascular risk factors and effective thromboprophylaxis (i.e. oral anticoagulation), which has been shown to significantly reduce the risk of stroke and death in AF.

International Normalized Ratio (INR), coagulation factor activities and calibrated automated thrombin generation - influence of 24 h storage at ambient temperature.

International Normalized Ratio (INR) measurements are used to monitor oral anticoagulation therapy with coumarins. Single coagulation factor activities and calibrated automated thrombin (CAT) generation are considered as more advanced methods for evaluating overall haemostatic capacity. The aims were to assess the variability of INR, coagulation factor activities, and CAT, during 24 h of storage of blood samples at ambient temperature. A total of 24 patients on stable coumarin treatment were followed prospectively for 6 weeks. INR was analyzed at 0, 6 and 24 h after blood sampling and 1-stage clotting activity of coagulation factors II, VII, IX, and X as well as CAT generation was recorded after 0 and 24 h respectively. Statistical analyses included Bland-Altman plot, 95% limits of agreement, and a variability test using a mixed effect model. The level of INR remained statistically unchanged from 0 to 6 and 24 h of storage. Coagulation factor activities and CAT revealed no significant difference induced by 24 h of storage, although the limits of agreement were wide. Patients' individual INR, coagulation factor activities, and CAT generation were not significantly influenced by 24 h storage of blood samples, but for the CAT generation analyses a trend toward time dependency was detected.

Molecular and immunohistochemical studies on epidermal responses in Atlantic salmon Salmo salar L. induced by Gyrodactylus salaris Malmberg, 1957.

Various strains of Atlantic salmon exhibit different levels of susceptibility to infections with the ectoparasitic monogenean Gyrodactylus salaris. The basic mechanisms involved in this differential ability to respond to this monogenean were elucidated using controlled and duplicated challenge experiments. Highly susceptible East Atlantic salmon allowed parasite populations to reach up to 3000 parasites per host within 6 weeks, whereas less susceptible Baltic salmon never reached larger parasite burdens than 122 parasites per host during the same period. The present study, comprising immunohistochemistry and gene expression analyses, showed that highly susceptible salmon erected a response mainly associated with an increased expression of interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma), IL-10 and infiltration of CD3-positive cells in the epidermis of infected fins. Less susceptible salmon showed no initial response in fins but 3-6 weeks post-infection a number of other genes (encoding the immune-regulating cytokine IL-10, cell marker MHC II and the pathogen-binding protein serum amyloid A) were found to be up-regulated. No proliferation of epithelial cells was seen in the skin of less susceptible salmon, and IL-10 may play a role in this regard. It can be hypothesized that resistant salmon regulate the parasite population by restricting nutrients (sloughed epithelial cells and associated material) and thereby starve the parasites. In association with this 'scorched-earth strategy', the production of pathogen-binding effector molecules such as serum amyloid A (SAA) (or others still not detected) may contribute to the resistance status of the fish during the later infection phases.

High preoperative prevalence of deep venous thrombosis in patients with colorectal cancer.

BACKGROUND: Deep venous thrombosis (DVT) is a major complication of cancer and a predictor of reduced survival. The postoperative prevalence of DVT in colorectal cancer surgery is high, but the preoperative prevalence is unknown. The aim of this observational study was to estimate the preoperative prevalence of DVT in patients with colorectal cancer. METHODS: Some 193 consecutive patients with newly diagnosed colorectal cancer admitted for intended curative surgery were examined with compression ultrasonography for DVT before surgery. RESULTS: DVT was detected in 15 (7.8 per cent) of the 193 patients, with a prevalence of 16 per cent in women (12 of 76) versus 2.6 per cent in men (three of 117 (adjusted odds ratio (OR) 5.8 (95 per cent confidence interval (c.i.) 1.4 to 23.2)). The risk of DVT was strongly correlated with increasing American Society of Anesthesiologists (ASA) risk score: adjusted OR 6.8 (95 per cent c.i. 1.6 to 28.7 for ASA group III or IV versus ASA group I or II). Pulmonary embolism was detected in two patients (1.0 per cent). CONCLUSION: A high preoperative prevalence of DVT was observed in patients with colorectal cancer, especially among women and patients in ASA groups III and IV.

ABO blood groups and risk of venous thromboembolism during pregnancy and the puerperium. A population-based, nested case-control study.

OBJECTIVES: To examine possible associations of ABO blood types with the risk of venous thromboembolism (VTE) in pregnancy and the puerperium. PATIENTS AND METHODS: We conducted a nested case-control study within a cohort of 71,729 women who gave birth to 126,783 children in the North Jutland County, Denmark, from 1980 to 2001. We identified 129 cases with VTE in pregnancy (n = 61) or the puerperium (n = 68), and 258 controls with no VTE. We collected information on ABO blood groups and possible maternal confounding factors and estimated the relative risk [odds ratio (OR)]. RESULTS: Women with an A or AB blood group had elevated risk estimates of VTE in pregnancy or the puerperium compared with women with a O blood group [adjusted ORs 2.4, 95% confidence interval (CI) 1.3, 4.3, and 2.0, 95% CI 0.7, 5.8, respectively]. No increased risk estimate was found for group B (adjusted OR 1.2, 95% CI 0.5, 3.0). The increased risk estimates of VTE for blood groups A and AB appeared present in both pregnancy (adjusted ORs of 3.9, 95% CI 1.5, 9.7, and 2.2, 95% CI 0.4, 12.5) and in the puerperium (adjusted ORs of 2.4, 95% CI 1.0, 4.9 and 2.7, 95% CI 0.8, 9.3). Furthermore, blood groups A and AB appeared to be associated with increased risk estimates for both DVT and pulmonary embolism. CONCLUSION: Keeping the modest statistical precision of our study in mind, blood groups A and AB may be associated with increased risk estimates for VTE in pregnancy and the puerperium.

Validity of D-dimer tests in the diagnosis of deep vein thrombosis: a prospective comparative study of three quantitative assays.

OBJECTIVES: To assess the diagnostic reliability of a new quantitative D-dimer assay (VIDAS New) and an established quick test (Nycocard D-dimer assay) in the diagnosis of deep vein thrombosis (DVT) compared with ultrasonography. A third assay (Auto Dimer) became available during sample collection and has been included in the final assessment. The diagnostic performance of the Auto Dimer assay was evaluated on three different coagulation analysers. DESIGN: A clinical prospective study of patients admitted to hospital for evaluation of DVT. Setting. The admission ward at Aalborg Hospital. Subjects. A total of 113 outpatients with suspected DVT. Main outcome measures. Compression ultrasonography was used as the reference method for a diagnosis of DVT and compared with different D-dimer assays. The results were expressed as sensitivity, specificity, positive predictive value and negative predictive value (NPV). RESULTS: Deep vein thrombosis was established in 49 patients (43%). Two D-dimer assays (VIDAS New and Auto Dimer) showed sensitivities of 90 and 88%, specificities of 42 and 44%, and NPV's of 85 and 83%, respectively. The Nycocard D-dimer assay showed a sensitivity of 63%, specificity of 67% and NPV of 71%. CONCLUSIONS: The diagnostic performance of VIDAS New and the Auto Dimer D-dimer assays is almost identical, but this study suggests that neither of the D-dimer assays is suitable as the only screening method for DVT, in a situation with a high pretest probability of DVT. This call for a differential strategy that distinguishes between cases of low and high clinical probability using either a D-dimer test or ultrasonography. Abbreviations DVT, deep venous thrombosis, NPV, negative predictive value, PPV, positive predictive value

[Evidence-based use of clinical biochemistry]. / Evidensbaseret anvendelse af klinisk biokemi.

Evidence-based use of clinical biochemistry integrates into clinical decision-making the best research evidence with the clinical expertise of the physician and the expectations and concerns of the patient. The best research evidence for the clinical use of a biochemical test should be appraised in close collaboration between clinicians and specialists in clinical biochemistry, as familiarity with both the clinical problem and the analytical performance of the test is necessary. At present, it is difficult to ensure an evidence-based use of biochemical tests. More and methodologically better studies of the clinical value of biochemical tests are needed, and methods should be developed that make it possible to assess the results of such studies by systematic reviews and meta-analyses. Clinical biochemistry is an interdisciplinary specialty, and papers on the clinical value of biochemical tests are published in a vast number of journals of different clinical specialties as well as those of clinical biochemistry. It is thus almost impossible to keep abreast of the subject. The establishment of a system for literature surveillance focusing on methodologically sound studies of the clinical value of biochemical tests would be advantageous. Lastly, training and education on how to find and assess the existing evidence for the clinical use of biochemical tests are needed.

Revascularisation of fresh compared with demineralised bone grafts in rats.

Revascularisation of bone grafts is influenced by both the anatomical origin and the pre-implantation processing of the graft. We investigated the revascularisation by entrapment of 141Ce (cerium)-labelled microspheres in large, fresh and demineralised syngeneic grafts of predominantly cancellous (iliac bone) or cortical (tibial diaphysis) bone three weeks after heterotopic implantation in rats. The mean (SD) 141Ce deposition index (counts per minute (cpm) of mg recovered implant/cpm of mg host iliac bone) was higher in fresh iliac bone grafts, 0.98 (0.46) compared to that of demineralised iliac bone, 0.32 (0.20), p < 0.001, and fresh tibial bone grafts, 0.51 (0.27), p = 0.007. We found no significant difference in the mean 141Ce deposition index between fresh tibial bone grafts and demineralised tibial bone grafts, 0.35 (0.42), p = 0.4, or between demineralised tibial grafts and demineralised iliac bone grafts, p = 0.8. The results suggest that whereas fresh cancellous grafts are revascularised more completely than fresh cortical grafts, there is no difference in the revascularisation of demineralised cancellous and cortical grafts. In addition, fresh cancellous bone is revascularised more completely than demineralised cancellous bone, whereas there is no difference between fresh and demineralised cortical bone.

The relationship between revascularisation and osteogenesis in fresh or demineralised bone grafts.

Bone formation generally depends on adequate blood flow. Failure of bone grafts has been attributed to delayed revascularisation of the graft. We compared the relationship between revascularisation and osteogenesis, evaluated as entrapment of (141)Ce-labelled microspheres and uptake of (85)Sr, respectively, in fresh or demineralised syngeneic bone grafts 3 weeks after heterotopic implantation in rats. Whereas a moderately high linear correlation between (85)Sr and (141)Ce radioactivity was found both in the (intact) host iliac bone (r = 0.75, p = 0.0001) and implanted fresh syngeneic grafts (r = 0.50, p = 0.001), no correlation could be demonstrated in demineralised grafts (r = 0.09, p = 0.6). The results may indicate differences in the mechanisms of vascularisation and osteogenesis in the grafts used fresh or after demineralization but are, at present, difficult to fully explain.

Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis.

Sudden infant death syndrome or "cot death" has until the late eighties been a significant cause of death in children between the ages of 1 month and 1 year. Approximately two per 1000 children born alive dies of sudden infant death syndrome each year in Western Europe, North America, and Australia. The vulnerability of the infant brain stem to ischemia has been suggested to be a conceivable cause of sudden infant death syndrome. This is compatible with a hypothesis that genetic risk factors for cerebral thrombosis could cause microinfarction in the brain stem during the first month of life, affecting vital centers or their blood supply. The presence of three common point mutations seen in families with thrombophilia (1691G-->A in the coagulation factor V gene, 677C-->T in the methylenetetrahydrofolate reductase gene, and the 20210G-->A mutation in the prothrombin gene) could increase the risk for thrombosis in the child. This prompted us to investigate these genetic markers of thromboembolic disease in 121 cases of sudden infant death syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudden infant death syndrome. The frequency of homozygous 1691G-->A mutation in SIDS cases was higher than expected (odds ratio: 7.3, 95% confidence interval, 1.2-45.8). The allele frequencies (theta;) in cases of sudden infant death syndrome of the 1691G-->A, 677C-->T, and 20210G-->A alleles was 2.6% (1.0-5.5), 32.6% (26.8-38.9), and 0.9% (0.1-3.4), respectively. None of the allele frequencies found in the background population (3.4% for the 1691G-->A allele, 29% for the 677C-->T allele, and 1% for the 20210G-->A allele) differed significantly from that in cases of sudden infant death syndrome. In 5,251,027 inhabitants in Denmark, the incidence of venous thromboembolism was 0.9 per 1000 per year in the background population, and less than one-thousandth of these were children. Consequently it is not likely that venous thrombosis is a major cause of sudden infant death syndrome. On the other hand, this does not exclude other known or unknown risk factors for thrombosis as possible etiological factors for sudden infant death syndrome. It is likely that we must continuously employ the exclusion principle on possible etiological causes in genetic material from a large group of victims of sudden infant death syndrome if the phenomenon of sudden infant death syndrome is to be ascribed to a specific hereditary disorder.

Evaluation of a simple dosage scheme for transition from phenprocoumon to warfarin in oral anticoagulation.

Phenprocoumon, whose elimination half-time is 144 hours, has been the traditional oral anticoagulant of choice in Europe. However, today's most widely used drug is warfarin, whose elimination half-time is 40 hours. This study aims to evaluate a method for safe transition from phenprocoumon to warfarin, which is sometimes required. Hence, the large difference in their elimination rates may on occasion lead to serious overdosage upon transition from one drug to the other. According to average equipotent doses, a stepwise increase in warfarin dose was calculated based on the elimination half-times of the two drugs. The dosage scheme was subsequently tested in a pilot study including 35 patients. The conversion scheme was then adjusted based on the results from the pilot study. The new scheme was tested in 69 patients. The transition factor was 2.3, which implies that equipotency was achieved when the warfarin dose was 2.3 times larger than the phenprocoumon dose (in mg). This scheme proved optimal for 75% of the patients. However, the dose had to be adjusted individually in the remaining 25% of the patients to a level corresponding to the measured international normalised ratios. No patients experienced haemorrhages or thromboembolic complications during the period of changeover. In conclusion, the proposed scheme for changing medication from phenprocoumon to warfarin is safe and convenient.