Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months.

BACKGROUND: The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear. AIM: To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis. METHODS: In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry. RESULTS: Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes. CONCLUSION: The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.

Evaluation of low PAI-1 activity as a risk factor for hemorrhagic diathesis.

BACKGROUND: Prospective studies of the epidemiology and clinical significance of low plasminogen activator inhibitor type 1 (PAI-1) activity are lacking. OBJECTIVE: To evaluate the prevalence of low PAI-1 activity in patients with a bleeding tendency in comparison with a normal population. METHODS: In 586 consecutive patients, referred because of bleeding symptoms, we added analyses of PAI-1 activity and tissue plasminogen activator complex with PAI-1 (t-PA-PAI-1) to the routine investigation, consisting of platelet count, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, von Willebrand factor activity, and antigen. Controls were 100 blood donors and 100 age- and sex-matched healthy individuals. The latter were also evaluated regarding the previous bleeding episodes. The bleeding history was classified as clinically significant or not, and the criteria were fulfilled in 75% of the patients and 18% of the healthy controls. RESULTS: The routine laboratory investigation of the patients was negative in 57%. Low PAI-1 activity, defined as <1.0 U mL(-1), was found in 23% of the patients and in 13% and 10% of the blood donors and healthy controls, respectively (odds ratio and 95% CI, 2.04; 1.11-3.77 and 2.75; 1.39-5.42, respectively). The difference remained statistically significant after the adjustment for body mass index, use of estrogens, sex and age (odds ratio for patients vs. healthy controls 3.23; 95% CI, 1.22-8.56, P = 0.019). The distribution of the 4G/5G genotypes in the patients was not different from that of two control populations. No specific symptom predicted for low PAI-1, which did not aggravate the clinical picture in association with the other hemostatic defects. Low tPA-PAI-1 was not associated with the increased bleeding tendency. CONCLUSION: Low PAI-1 activity is common in patients with a bleeding diathesis, but it is a risk factor of minor clinical importance and not associated with specific bleeding manifestations.

A randomized study of alpha-interferon plus ribavirin for 6 months or 12 months for the treatment of chronic hepatitis C in patients with bleeding disorders.

Little is known about the optimal treatment in patients with chronic hepatitis C virus (HCV) who were infected by pooled plasma products. The aim of our study was to compare the efficacy of 6 and 12 months of combination therapy with interferon alpha-2b and ribavirin in patients with bleeding disorders and chronic HCV. In a randomized open study, 61 patients with haemophilia or von Willebrand disease received treatment with a combination of interferon alpha-2b and ribavirin at standard dosage for 6 or 12 months. Follow-up was done with analysis of HCV RNA after an additional 6 months. The prevalence of HCV genotype 1 was 67%. Overall, sustained viral response was achieved in 41%; 13 of 30 patients (43%) treated for 6 months vs. 12 of 31 patients (39%) treated for 12 months. The rate of sustained response was 22% in those with HCV genotype 1 and 80% in other genotypes (100% in genotype 2), with no difference between the treatment durations. The number of early discontinuations due to side-effects was 3 and 9, respectively. The study was stopped prematurely due to introduction of a more effective regimen, and the numbers are not sufficient to state equality. We conclude that the efficacy and safety of combination therapy against chronic hepatitis C in patients infected by pooled plasma products is similar to that observed in other populations. Six months of therapy seems sufficient in the case of HCV genotype 2. For other genotypes, the decision regarding duration of therapy has to be based on the tolerance of the individual patient together with experiences from other studies.

Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of Anticoagulation Trial.

BACKGROUND: The length of time after an episode of venous thromboembolism during which the risk of newly diagnosed cancer is increased is not known, and whether vitamin K antagonists have an antineoplastic effect is controversial. METHODS: In a prospective, randomized study of the duration of oral anticoagulation (six weeks or six months) after a first episode of venous thromboembolism, patients were questioned annually about any newly diagnosed cancer. After a mean follow-up of 8.1 years, we used the Swedish Cancer Registry to identify all diagnoses of cancer and causes of death in the study population. The observed numbers of cases of cancer were compared with expected numbers based on national incidence rates, and the standardized incidence ratios were calculated. RESULTS: A first cancer was diagnosed in 111 of 854 patients (13.0 percent) during follow-up. The standardized incidence ratio for newly diagnosed cancer was 3.4 (95 percent confidence interval, 2.2 to 4.6) during the first year after the thromboembolic event and remained between 1.3 and 2.2 for the following five years. Cancer was diagnosed in 66 of 419 patients (15.8 percent) who were treated for six weeks with oral anticoagulants, as compared with 45 of 435 patients (10.3 percent) who were treated for six months (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.4). The difference was mainly due to the occurrence of new urogenital cancers, of which there were 28 cases in the six-week group (6.7 percent) and 12 cases in the six-month group (2.8 percent) (odds ratio, 2.5; 95 percent confidence interval, 1.3 to 5.0). The difference in the incidence of cancer between the treatment groups became evident only after two years of follow-up, and it remained significant after adjustment for sex, age, and whether the thromboembolism was idiopathic or nonidiopathic. Older age at the time of the venous thrombosis and an idiopathic thromboembolism were also independent risk factors for a diagnosis of cancer. No difference in the incidence of cancer-related deaths was detected. CONCLUSIONS: The risk of newly diagnosed cancer after a first episode of venous thromboembolism is elevated during at least the following two years. Subsequently, the risk seems to be lower among patients treated with oral anticoagulants for six months than among those treated for six weeks.

The risk of ipsilateral versus contralateral recurrent deep vein thrombosis in the leg. The DURAC Trial Study Group.

OBJECTIVES: To investigate the risk of ipsilateral versus contralateral recurrent deep vein thrombosis in the leg. DESIGN: An open prospective long term follow-up multicentre trial. Patients were followed by frequent outpatient visits at each centre during the first 12 months after inclusion and thereafter annually. SETTING: Sixteen hospitals in central Sweden. SUBJECTS: A total of 790 consecutive patients with objectively verified first episode of acute deep vein thrombosis and without diagnosed malignant disease were recruited from a randomized study comparing 6 weeks with 6 months of oral antivitamin K therapy as secondary thromboprophylaxis. MAIN OUTCOME MEASURES: Deep vein thrombosis in the contralateral leg was confirmed by venography or ultrasound. With regard to the ipsilateral leg, venography was required. RESULTS: A recurrent episode of venous thromboembolism was documented in 192 patients after a mean (+/-SD) period of 31(+/-29) months. In 26 additional patients with ipsilateral symptoms the diagnostic critera were not fulfilled. One hundred and eleven patients have deceased and 69 patients withdrew from the study. The 392 patients without recurrent episodes were followed for a median of 96 months with 90% for at least 48 months. An objectively verified recurrent contralateral and ipsilateral deep vein thrombosis occurred in 95 and 54 cases, respectively, and in 41 patients pulmonary embolism was documented. In two patients thromboses with unusual locations were registered. The risk of contralateral versus ipsilateral recurrence was significantly increased with a risk ratio of 1.6 (95% confidence interval 1.4-1.9) in a time to event model. In a multivariate analysis none of the investigated variables were significantly associated with the side of recurrent thrombosis. CONCLUSIONS: The risk of a recurrent deep vein thrombosis is increased in the contralateral leg. This brings into question the importance of an impaired venous flow for recurrent episodes of thrombosis.

Pulmonary embolism: a follow-up study of the relation between the degree of right ventricle overload and the extent of perfusion defects.

OBJECTIVES: To describe the course of changes in perfusion lung scintigraphy (LS) after acute pulmonary embolism (PE) and test the hypothesis that patients with persistent pulmonary hypertension (PH)/right ventricle (RV) dysfunction after acute PE can be differentiated from those without through larger perfusion defects (PDf) on LS. Design. Prospective, one-year follow-up study with repeated LS and echocardiography-Doppler investigations. SETTING: Single centre, University Hospital. SUBJECTS: Patients with clinical suspicion of acute PE with a diagnosis confirmed by LS and/or pulmonary angiography and able to undergo repeated investigations. Of the 78 patients included, a six-week follow-up was completed in 67 and a one-year follow-up in 64. MAIN OUTCOME MEASURES: Time course of PDf in relation to time course of pulmonary artery systolic pressure (PAsP) and RV function. RESULTS: Initially, PDf decreased exponentially, until the beginning of a stable phase, which was achieved within 54 days for 90% of the patients and within 148 days for all. The temporal relation for the regress of PDf and decrease in PAsP was loose. Patients with persistent PDf suffered PH/RV dysfunction more often than those without. However, the variability in the degree of haemodynamic changes for a given extent of PDf was large. CONCLUSIONS: After acute PE, LS is of use for the identification of the group of patients that may have persistent PH/RV dysfunction. However. since the identification of individual patients is uncertain, LS cannot replace echocardiography-Doppler in the identification of persistent PH/RV dysfunction after acute PE.

The risk of recurrent venous thromboembolism in carriers and non-carriers of the G1691A allele in the coagulation factor V gene and the G20210A allele in the prothrombin gene. DURAC Trial Study Group. Duration of Anticoagulation.

The results concerning the risk of recurrent venous thromboembolism (VTE) in carriers of the G1691A mutation in the coagulation factor V gene are not consistent and this risk in carriers of the G20210A polymorphism in the prothrombin gene has hitherto not been reported. We followed 534 patients for 48 months after their first episode of objectively documented VTE. The prevalence of the G1691A allele in 467 (87.5%) of the patients and in 207 controls was 25.3% and 8.2%, respectively, in heterozygote form and 2.4% and 0.5%, respectively, in homozygote form. The adjusted odds ratio (OR) for the first VTE was 4.4 (95% CI 2.6-7.8). The risk of recurrent VTE in heterozygotes was not statistically different from non-carriers (17.8% vs 17.6%), with 85% power to detect a hazard ratio of 2.35. Homozygotes had a significantly increased risk (p = 0.036) of recurrent VTE. The prevalence of the G20210A allele in 456 patients and 207 controls was 6.1% and 1.4%, respectively. The adjusted OR was 4.6 (95% CI 1.6-19.3) for the first VTE in 28 carriers of this polymorphism. The risk of recurrent VTE for these was not statistically different from non-carriers with an OR of 0.9 (95% CI 0.2-2.9).

Pulmonary embolism: one-year follow-up with echocardiography doppler and five-year survival analysis.

BACKGROUND: The long-term prognosis for patients with pulmonary embolism (PE) is dependent on the underlying disease, degree of pulmonary hypertension (PH), and degree of right ventricular (RV) dysfunction. A precise description of the time course of pulmonary artery pressure (PAsP)/RV function is therefore of importance for the early identification of persistent PH/RV dysfunction in patients treated for acute PE. Other objectives were to identify variables associated with persistent PH/RV dysfunction and to analyze the 5-year survival rate for patients alive 1 month after inclusion. METHODS AND RESULTS: Echocardiography Doppler was performed in 78 patients with acute PE at the time of diagnosis and repeatedly during the next year. A 5-year survival analysis was made. The PAsP decreased exponentially until the beginning of a stable phase, which was 50 mm Hg at the time of diagnosis of acute PE was associated with persistent PH after 1 year. The 5-year mortality rate was associated with underlying disease. Only patients with persistent PH in the stable phase required pulmonary thromboendarterectomy within 5 years. CONCLUSIONS: An echocardiography Doppler investigation performed 6 weeks after diagnosis of acute PE can identify patients with persistent PH/RV dysfunction and may be of value in planning the follow-up and care of these patients.

Can all patients with deep vein thrombosis receive low-molecular-weight heparin in an outpatient setting?

Studies have shown subcutaneous low- molecular-weight heparin (LMWH) to be at least as safe and efficacious as intravenous unfractionated heparin (UFH) for the treatment of venous thromboembolism (VTE). Furthermore, unlike UFH, LMWH is administered on a once- or twice-daily basis without monitoring in uncomplicated cases. Consequently, it has been suggested that the large majority of patients with VTE could be treated on an outpatient basis. Exceptions include patients with an increased risk of haemorrhage, pregnant women, children and those with renal insufficiency. Outpatient management would offer economic advantages and be more convenient for both the patient and the hospital staff.

Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate.

To test the hypothesis that right ventricular (RV) systolic dysfunction at the time of diagnosis of pulmonary embolism (PE) is a predictor of mortality rate, 126 consecutive patients with PE were examined with echocardiography Doppler (ED) on the day of diagnosis. RV function was assessed by evaluation of wall motion on a four-point scale. The material was divided into two groups: group A (n = 56) with normal or slightly reduced RV function and group B (n = 70) with moderately or severely reduced RV function. The overall mortality rate was 7.9% in the hospital and 15.1% within 1 year. Four deaths occurred in group A and 15 in group B (p = 0.04). All in-hospital deaths (n = 10) occurred in group B (p = 0.002). The variables associated with mortality rate were RV dysfunction and cancer (in-hospital, p = 0.002 and 0.004; 1 year, p = 0.04 and < 0.001, respectively). Nine (7.1%) deaths (all in-hospital) were caused by PE. Five of these patients had advanced-stage cancer. The in-hospital mortality rate in patients without cancer was 4%, all from PE and all in group B. In conclusion, RV dysfunction when diagnosis of PE is established is associated with mortality rate. A strategy for risk stratification of patients with PE with ED may be of clinical usefulness.

A 6-month venographic follow-up in 164 patients with acute deep vein thrombosis.

UNLABELLED: A total of 164 patients were recruited from a randomized trial comparing a low molecular weight heparin, dalteparin, given subcutaneously once daily with a continuous intravenous infusion of unfractionated heparin in the initial treatment of acute deep vein thrombosis. The primary objective of this follow-up study was to investigate whether there were any differences between the two treatment groups with respect to Marder score changes 6 months after the initial diagnosis using repeated venography. The secondary objectives were to analyse whether certain haemostatic and acute phase parameters or patient characteristics influenced the venographic outcome. RESULTS: Complete lysis of the thrombus was observed in 38.4% of the patients and a partial lysis in another 54.3% assessed by venography 6 months after the acute event. Extension of the thrombus was seen in 7.3% of the patients. There were no significant differences in the change in mean Marder score before treatment and at the 6 month follow-up between the two treatment groups, irrespective of thrombus localisation. In a regression model, male gender, low levels of orosomucoid and increased levels of d-dimer in plasma on day 5 were independently associated (p <0.05) with an enhanced absolute resolution of the thrombus at 6 months. No differences in symptoms and signs in the thrombotic leg at follow-up, comparing the treatment given, or thrombus extension at diagnosis and 6 months later, were demonstrated. CONCLUSION: Dalteparin given once daily subcutaneously was as effective as continuous intravenous infusion of unfractionated heparin in the initial treatment of deep vein thrombosis assessed by Marder score evaluation 6 months after the acute event.

The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The Duration of Anticoagulation Trial Study Group.

BACKGROUND: A consensus has not been reached about the optimal duration of oral anticoagulant therapy after a second episode of venous thromboembolism. METHODS: In a multicenter trial, we compared six months of oral anticoagulant therapy with anticoagulant therapy continued indefinitely in patients who had had a second episode of venous thromboembolism. Of 227 patients enrolled, 111 were randomly assigned to six months of anticoagulation and 116 were assigned to receive anticoagulant therapy indefinitely; for both groups, the target international normalized ratio was 2.0 to 2.85. The initial episodes of deep-vein thrombosis (n = 193) and pulmonary embolism (n = 34), as well as recurrent episodes, were all objectively confirmed. RESULTS: After four years of follow-up, there were 26 recurrences of venous thromboembolism that fulfilled the diagnostic criteria, 23 in the group assigned to six months of therapy (20.7 percent) and 3 in the group assigned to continuing therapy (2.6 percent). The relative risk of recurrence in the group assigned to six months of therapy, as compared with the group assigned to therapy of indefinite duration, was 8.0 (95 percent confidence interval, 2.5 to 25.9). There were 13 major hemorrhages, 3 in the six-month group, (2.7 percent) and 10 in the infinite-treatment group (8.6 percent). The relative risk of major hemorrhage in the six-month group, as compared with the infinite-treatment group was 0.3 (95 percent confidence interval, 0.1 to 1.1). There was no difference in mortality between the two groups. CONCLUSIONS: Prophylactic oral anticoagulation that was continued for an indefinite period after a second episode of venous thromboembolism was associated with a much lower rate of recurrence during four years of follow-up than treatment for six months. However, there was a trend toward a higher risk of major hemorrhage when anticoagulation was continued indefinitely.

Use of low molecular weight heparin (dalteparin), once daily, for the treatment of deep vein thrombosis. A feasibility and health economic study in an outpatient setting. Swedish Venous Thrombosis Dalteparin Trial Group.

OBJECTIVES: To test the safety and feasibility of treating deep vein thrombosis (DVT) in an outpatient setting, using the low molecular weight heparin dalteparin, to calculate the potential and actual cost reductions achievable as a result of such a treatment regimen. DESIGN: An open, nonrandomized, multicentre trial. SETTING: Fourteen hospitals in central Sweden. SUBJECTS: Ambulant patients, aged 18 years or older. with symptomatic DVT in the leg, diagnosed using phlebography or ultrasound (Duplex-Doppler). INTERVENTIONS: Dalteparin (Fragmin) at a fixed dose of 200 i.u. kg-1 body weight, was administered once daily subcutaneously for at least 4 consecutive days. Treatment with warfarin was initiated from the first day of dalteparin administration. Outpatient treatment was encouraged whenever possible Financial calculations were performed independently at two hospitals, giving an average cost for all actions. OUTCOME MEASURES: Increasing severity of symptoms (or thromboembolic recurrences during the 3-months follow-up period), pulmonary embolism (PE), bleeding events, and death during the initial phase and follow-up period. RESULTS: Of 434 patients, 35% and 64% were treated in hospital within 24 and 72 h, respectively, and thereafter as outpatients. The overall frequency of serious complications was 0.92% (exact 95% confidence interval, 0.25-2.35%) during the initial phase and one patient suffered a PE and three patients had a recurrent DVT during the follow-up period. A cost reduction of 2705529 Swedish crowns (34.5%) was achieved in this study compared with traditional in-patient treatment. CONCLUSIONS: Dalteparin, administered subcutaneously, once daily, for the initial treatment of DVT yields large cost reductions and is well tolerated and effective in an outpatient setting.

A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group.

BACKGROUND: The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still a matter of debate. METHODS: We performed a multicenter trial comparing six weeks of oral anticoagulant treatment with six months of such therapy in patients who had a first episode of venous thromboembolism. Anticoagulant therapy consisted of warfarin or dicumarol. Of the 902 patients enrolled, 5 were later excluded because they had congenital protein C deficiency; 443 were randomly assigned to receive six weeks of oral anticoagulant therapy with a targeted international normalized ratio (INR) of 2.0 to 2.85, and 454 were randomly assigned to receive six months of such therapy. The initial diagnoses were confirmed by means of venography in cases of deep-vein thromboses (n = 790) and with perfusion-ventilation scanning or angiography in cases of pulmonary embolism (n = 107); recurrences were confirmed in the same way. RESULTS: After two years of follow-up, there had been 123 recurrences of venous thromboembolism that met the diagnostic criteria, 80 in the six-week group (18.1 percent; 95 percent confidence interval, 14.5 to 21.6) and 43 in the six-month group (9.5 percent; 95 percent confidence interval, 6.8 to 12.2). The odds ratio for recurrence in the six-week group was 2.1 (95 percent confidence interval, 1.4 to 3.1). There was no difference in mortality or the rate of major hemorrhage between the six-week and six-month groups. CONCLUSIONS: Six months of prophylactic oral anticoagulation after a first episode of venous thromboembolism led to a lower recurrence rate than did treatment lasting for six weeks. The difference between the two groups occurred between 6 weeks and 6 months after the start of treatment, and the rates of recurrence remained nearly parallel for 1 1/2 years thereafter.

Influence of changes in lifestyle on fibrinolytic parameters and recurrence rate in patients with venous thromboembolism.

A prospective, non-randomized, interventional study was carried out to evaluate the effect of changes in lifestyle on abnormal fibrinolytic parameters, and the influence of those, in turn, on the risk of recurrence among patients with venous thromboembolism. Patients with elevated plasminogen activator inhibitor 1 (PAI-1) levels or decreased release of tissue plasminogen activator (t-PA) antigen were given information and advice about improved diet, increased physical activity, weight loss and/or cessation of smoking. Totally 144 patients (119 with elevated PAI-1 and 25 with deficient t-PA release) were followed with repeated analyses of the fibrinolytic parameters for a median of 8 months after the initial advice, and 65% of the patients managed to execute at least one change in their lifestyle. The reduction of PAI-1 activity after one, two and three changes in lifestyle were -2.4, -10.0 and -14.0 AU/ml (-10, -30 and -48% of baseline activity), respectively. Those who accomplished two or three changes in their lifestyle had a greater chance of normalizing the PAI-1 level than those with no or only one change (P = 0.009). The effects of improved diet, weight loss and increased physical activity on the PAI-1 level were of a similar magnitude, -7.0 to -10.4 AU/ml (24-32% reduction). The effect on t-PA release was more difficult to evaluate due to the limited number of those patients. After a follow-up of 6 years (mean) after the first visit the patients were inquired about recurrent events, with a response rate of 86%.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis.

Two hundred and four consecutive patients with venographically confirmed deep vein thrombosis (DVT) were randomised either to a low molecular weight heparin, Fragmin, administered subcutaneously (s.c.) once daily as a fixed dose of 200 IU anti-factor Xa/kg or to continuous intravenous infusion of unfractionated heparin (UFH). The UFH dose was adjusted to maintain the activated partial thromboplastin time between 1.5 and 3.0 times the upper limit of the reference value at each centre. Fragmin or UFH was given for a minimum of 5 days until anticoagulation with warfarin, given from day 1, was established (i.e. an Internation Normalised Ratio, of 2.0-3.0). A second venogram was obtained after Fragmin or UFH treatment. There were no significant differences in the change in mean Marder score before and after treatment between the two treatment groups, irrespective of thrombus localisation. No major bleeding events, symptomatic pulmonary embolism, symptomatic thrombosis progression or death occurred during hospitalisation. Eight documented venous thromboembolic events occurred before the follow-up visit 6 months after randomisation: 5 in patients treated with Fragmin and 3 in those treated with UFH. Six of these events occurred after cessation of warfarin treatment. In conclusion Fragmin given s.c. once daily in a fixed dose adjusted for body weight, is no less effective or safe than a continuous infusion of UFH in the initial treatment of acute DVT.