Six‐week low‐molecular‐weight heparin versus 12‐week warfarin for calf deep vein thrombosis: A randomized, prospective, open‐label study

Current guidelines suggest a 3-month anticoagulant treatment course for isolated distal deep vein thrombosis (IDDVT), but shorter durations of treatment are frequently prescribed in clinical practice. We investigated whether a 6-week treatment with low-molecular-weight heparin (LMWH) at intermediate dosage can be an effective and safe alternative to vitamin K antagonists (VKA) in patients with IDDVT (non-inferiority trial). In a multicenter, open-label, randomized trial, 260 outpatients with symptomatic IDDVT were randomly assigned to receive either LMWH followed by VKA for 12 weeks or LMWH 1 mg/kg subcutaneously twice a day for 2 weeks followed by 1 mg/kg subcutaneously once a day for 4 weeks. The follow-up was 6 months and the primary endpoint was the composite measure of recurrent venous thromboembolism (VTE) defined as: recurrence or extension of IDDVT, proximal DVT, and pulmonary embolism (PE). The study was stopped prematurely due to slow recruiting rates. The primary efficacy outcome occurred in 14 patients receiving LMWH (10.8%) and in five patients receiving VKA (3.8%); risk difference was 0.069 (95% CI: 0.006-0.132), hazard ratio 2.8 (95% CI: 1.04-7.55). There was one PE in the VKA group and one proximal DVT in the LMWH group. IDDVT recurrence was 10.0% in the LMWH group versus 3.1% in the VKA group (p = .024). Two patients had clinically relevant bleedings (1.6%) in the LMWH group versus one (0.8%) in VKA group (p = .56). In conclusion, VKA for 12 weeks seems superior to LMWH for 6 weeks in reducing the risk of VTE recurrences in our cohort of outpatients with IDDVT.We investigated whether a 6-week treatment with low-molecular-weight heparin at intermediate dosage can be an effective and safe alternative to vitamin K antagonists in patients with isolated distal deep vein thrombosis. imag

Edoxaban in Atrial Fibrillation and Venous Thromboembolism\u2014Ten Key Questions and Answers: A Practical Guide

Edoxaban is the fourth non-vitamin K antagonist oral anticoagulant now available for clinical use in the prevention of stroke/systemic embolism in atrial fibrillation (AF) and in the treatment of venous thromboembolism (VTE), after the completion of large-scale randomized comparative clinical trials with the vitamin K antagonist warfarin. Edoxaban has some peculiar pharmacological properties and outcome data. Here a group of experts in AF and VTE answers a set of questions on its practical use, trying to define the profile of patients that would be most appropriate for its use

Incidence of a first thromboembolic event in carriers of isolated lupus anticoagulant

Among the so called antiphospholipid (aPL) antibodies Lupus Anticoagulant (LAC) is considered the strongest risk factor for thromboembolic events. In individuals without a previous thromboembolic event (carriers), LAC is a risk factor when associated with the presence of anticardiolipin (aCL) and a\u3b22-Glycoprotein I (a\u3b22GPI) antibodies. On the other hand, data on carriers of isolated LAC positivity are sparse and inconclusive. The aim of this study was to prospectively determine the incidence of thrombosis in a cohort of carriers of isolated LAC positivity. One-hundred seventy-nine carriers of LAC confirmed twelve weeks apart and in a reference laboratory were studied. During a total follow up of 552 person-years, there were seven thromboembolic events (1.3% person-y). All the seven patients had at least one adjunctive major risk factor for thrombosis. The cumulative incidence of thromboembolic eventswas 3.1% (95% CI 0.6-5.6) after 2 years, and 5.9% (95% CI 1.2- 10.6) after 5 and 10 years. On a multivariate regression analysis considering age, sex, autoimmune disease, risk factors for arterial and venous thrombosis, use of aspirin, only age was found to be an independent predictor of thromboembolic events (HR=1.1, 95% CI 1.0-1.2, p= 0.02). These data might be relevant in clinical practice and underline the importance of differentiating LAC carriers in terms of isolated positivity or positivity associated with the presence of antibodies to aCL and \u3b22-glycoprotein I

Safety and feasibility of a diagnostic algorithm combining clinical probability, D-dimer and ultrasonography in suspected upper extremity deep vein thrombosis::A prospective management study

Background: Traditionally, the focus of the diagnosis of venous thromboembolism (VTE) is on deep vein thrombosis (DVT) of the leg and pulmonary embolism. Until recently, upper extremity DVT (UEDVT) was regarded as an uncommon presentation of VTE; however, the more widespread use of central venous catheters has caused a significant increase in its incidence. Therefore, effective and safe diagnostic strategies are needed. Aims: This diagnostic management study assessed the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. Methods: In- and outpatients with suspected UEDVT were recruited from January 2010 until July 2012 in 16 hospitals in Europe and the United States, after approval of the protocol by the institutional review boards. Main exclusion criteria were previous UEDVT and the use of therapeutic doses of anticoagulants. Informed consent was obtained from all participants. The algorithm consisted of the sequential application of the Constans' clinical decision score1 (score), Ddimer testing and compression ultrasonography. Patients were first categorized as UEDVT likely or unlikely by the score. In patients with an unlikely score and a normal D-dimer, UEDVT was considered excluded and no further testing was done. All other patients underwent ultrasonography, which first assessed the presence of UEDVT and then superficial vein thrombosis (SVT). The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a diagnostic work-up excluding both UEDVT and SVT. To confirm an acceptable failure rate of excluding UEDVT (upper 95% confidence interval below 3%), approximately 400 patients needed to be included. Results: The study population comprised of 406 consecutive patients with suspected UEDVT. The algorithm was feasible and could be completed in 96%. Of the 406 patients, 203 had an unlikely probability score and D-dimer was measured, except in three cases. In 87 patients (22%) an unlikely score was combined with a normal D-dimer, and therefore UEDVT was excluded. All these patients had an uneventful 3 month follow up. The remaining 113 patients with an unlikely and 203 patients with a likely probability score underwent ultrasonography. Ultrasonography was repeated if indicated according to protocol; seven times (1.7%) because of an indeterminate ultrasonography result and in 45 of the 51 patients (13%) with the combination of a likely score, abnormal D-dimer and normal ultrasonography. To summarize, of the 406 included patients, 103 patients had UEDVT (25%), 55 had SVT (14%) and in 249 patients the algorithm excluded UEDVT and SVT. Of these, one patient developed UEDVT during follow-up, hence, an overall failure rate of 0.40% (95% CI: 0.0-2.2%). Summary/Conclusions: A new diagnostic algorithm which combines a clinical decision score, D-dimer and ultrasonography can safely and effectively exclude venous thrombosis of the upper extremity. This approach is attractive as it is simple, quick and non-invasive, and very similar to the well established algorithm for suspected DVT of the leg which could facilitate its implementation in clinical practice

The influence of factor V Leiden and G20210A prothrombin mutation on the presence of residual vein obstruction after idiopathic deep-vein thrombosis of the lower limbs

none9It was our aim to assess whether factor V Leiden (FVL) and G20210A prothrombin (FII) mutation are associated with the presence of residual vein obstruction (RVO) after a standard course of anticoagulation for a first episode of idiopathic proximal deep-vein thrombosis (DVT) of the lower limbs, with or without symptomatic pulmonary embolism (PE). Patients were enrolled in two prospective multicentre studies: PROLONG and PROLONG II. RVO was detected by compression ultrasonography according to the method of Prandoni on the day of anticoagulation withdrawal. Patients were also screened for FVL and FII mutation. The presence of FVL and/or FII mutation was determined in 872/963 (90.5%) patients, in 753 of whom RVO was assessed. FVL was significantly less frequent among subjects with isolated PE (7/176:4%) than among patients with either DVT and PE (15/133:11.3%; p=0.0018) or isolated DVT (89/563:15.8%; p<0.0001), confirming the FVL paradox. The rate of FII mutation was similar among patients with isolated PE (11/176:6.2%) and patients with either DVT and PE (12/133:9%) or isolated DVT (52/563:9.2%). FVL and FII mutation were not significantly associated with RVO at the multivariate analysis in all patients, although data suggest that FVL and FII mutation may have a differential effect on RVO in the subgroups of patients with DVT and DVT plus PE patients. Male sex and isolated DVT were significantly associated with RVO in all patients. In conclusion, male sex and isolated DVT are associated with RVO, while FVL and FII mutations are not significantly associated with RVO in this study.noneB. Cosmi;C. Legnani;V. Pengo;A. Ghirarduzzi;S. Testa;D. Poli;D. Prisco;A. Tripodi;G. PalaretiB., Cosmi; C., Legnani; Pengo, Vittorio; A., Ghirarduzzi; S., Testa; D., Poli; D., Prisco; A., Tripodi; G., Palaret