Raffaela Anastasio

Serial 2-Point Ultrasonography Plus D-Dimer vs Whole-Leg Color-Coded Doppler Ultrasonography for Diagnosing Suspected Symptomatic Deep Vein Thrombosis: A Randomized Controlled Trial

CONTEXT Patients with suspected deep vein thrombosis (DVT) of the lower extremities are usually investigated with ultrasonography either by the proximal veins (2-point ultrasonography) or the entire deep vein system (whole-leg ultrasonography). The latter approach is thought to be better based on its ability to detect isolated calf vein thrombosis; however, it requires skilled operators and is mainly available only during working hours. No randomized comparisons are yet available evaluating the relative values of these 2 strategies. OBJECTIVE To assess if the 2 diagnostic strategies are equivalent for the management of symptomatic outpatients with suspected DVT of the lower extremities. DESIGN, SETTING, AND PATIENTS A prospective, randomized, multicenter study of consecutive symptomatic outpatients (n = 2465) with a first episode of suspected DVT of the lower extremities who were randomized to undergo 2-point or whole-leg ultrasonography. Data were taken from ultrasound laboratories of 14 Italian universities or civic hospitals between January 1, 2003, and December 21, 2006. Patients with normal ultrasound findings were followed up for 3 months, with study completion on March 20, 2007. MAIN OUTCOME MEASURE Objectively confirmed 3-month incidence of symptomatic venous thromboembolism in patients with an initially normal diagnostic workup. RESULTS Of 2465 eligible patients, 345 met 1 or more exclusion criteria and 22 refused to participate; therefore, 2098 patients were randomized to either 2-point (n = 1045) or whole-leg (n = 1053) ultrasonography. Symptomatic venous thromboembolism occurred in 7 of 801 patients (incidence, 0.9%; 95% confidence interval [CI], 0.3%-1.8%) in the 2-point strategy group and in 9 of 763 patients (incidence, 1.2%; 95% CI, 0.5%-2.2%) in the whole-leg strategy group. This met the established equivalence criterion (observed difference, 0.3%;95% CI, -1.4% to 0.8%). CONCLUSION The 2 diagnostic strategies are equivalent when used for the management of symptomatic outpatients with suspected DVT of the lower extremities. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00353093.

Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis : the Duration of Anticoagulation based on Compression UltraSonography (DACUS) study

Residual vein thrombosis (RVT) indicates a prothrombotic state and is useful for evaluating the optimal duration of oral anticoagulant treatment (OAT). Patients with a first episode of deep vein thrombosis, treated with OAT for 3 months, were managed according to RVT findings. Those with RVT were randomized to either stop or continue anticoagulants for 9 additional months, whereas in those without RVT, OAT was stopped. Outcomes were recurrent venous thromboembolism and/or major bleeding. Residual thrombosis was detected in 180 (69.8%) of 258 patients; recurrent events occurred in 27.2% of those who discontinued (25/92; 15.2% person-years) and 19.3% of those who continued OAT (17/88; 10.1% person-years). The relative adjusted hazard ratio (HR) was 1.58 (95% confidence interval [CI], 0.85-2.93; P = .145). Of the 78 (30.2%) patients without RVT, only 1 (1.3%; 0.63% person-years) had a recurrence. The adjusted HR of patients with RVT versus those without was 24.9 (95% CI, 3.4-183.6; P = .002). One major bleeding event (1.1%; 0.53% person-years) occurred in patients who stopped and 2 occurred (2.3%; 1.1% person-years) in those who continued OAT. Absence of RVT identifies a group of patients at very low risk for recurrent thrombosis who can safely stop OAT. This trial was registered at http://www.ClinicalTrials.gov as no. NCT00438230.

Congenital absence of inferior vena cava

Sir—In their report, M Ruggeri and colleagues (Feb 10, p 441) point out the clinical relevance of the congenital absence of the inferior vena cava (IVC) in young patients (<30 years) as a potential independent risk factor for deep vein thrombosis (DVT). In the past 23 months, we have assessed 21 young patients with objectively documented acute venous thromboembolism (15 with isolated DVT, four with isolated pulmonary embolism, and two with DVT and pulmonary embolism). As part of a diagnostic screening in the emergency room, in case of non-compressibility of the common femoral vein, we apply an ultrasonographic investigation of the legs from distal veins to the inferior vena cava (IVC). Because of this approach, aplasia or agenesia of the IVC have been suspected and subsequently confirmed by computed tomography in two cases (9·5% [95% CI 2·7–21·7]). The table shows the clinical characteristics of the patients. Patient 1 had an evident compensatory enlargement of the vena azygos. This patient was referred to us because of signs and symptoms of acute DVT with respiratory failure; perfusion-ventilation lung scanning confirmed the presence of pulmonary embolism. Patient 2 was a young woman who developed bilateral leg swelling in absence of evident risk factors. In these two cases, the mutation for factor V Leiden (G1691A) was diagnosed. The prevalence of the acute IVC in our young population is apparently higher than that reported by Ruggeri and colleagues. Although our approach required computed tomography, only in the case of suspected IVC alterations, this approach seems to be effective for detecting at least an equal number of acute IVC than that detected by routine computed tomography. In conclusion, acute IVC seems to be a not so rare a finding in young patients with confirmed acute venous thormboembolism. Potential advantages of ultrasonography over computed tomography for detecting acute IVC and the weight of congenital thrombophilia in these patients should be investigated in larger series.

Gastrointestinal bleeding due to angiodysplasia in patients with type 1 von Willebrand disease: report on association and management

The presence of gastrointestinal angiodysplasia (GI-A) can represent an urgent haematological problem as it produces serious bleeding, which is usually untreatable. It has been recognized that G-IA frequently occurs in patients with type 2–3 and acquired von Willebrand disease (VWD) but the strength of this association is unclear. One hypothesis relays on the lack of high molecular weight (HMW) molecules of von Willebrand factor (VWF) in the plasma [1]. Other findings suggest a potential role being played by the 3916T mutation of the esone 28 coding factor vW (domain A1) [2]. Angiodysplastic lesions can be found along the entire length of the GI tract, from the tongue to the colon. Although there are several diagnostic methods such as endoscopy, push enteroscopy, helical computed tomography (CT), mesenteric angiography and, more recently, video capsule endoscopy [3] available, the identification of angiodysplasia remains extremely difficult to document and most of the patients remain undiagnosed. Thereby, most patients are treated solely medically with several and mainly ineffective approaches [3]. Most previous publications on VWD and angiodysplasia have been reports of the association itself and there is little published data on the management and follow-up of affected patients. In addition, no such association has yet been documented in patients with type 1 VWD. We report our experiences in the management and follow-up of three patients suffering from angiodysplasia and type 1 VWD, according to the current classification [4]. Their baseline phenotypic characteristics are outlined in Table 1; investigation and management of individual patients are summarized in Table 2. The first patient was a 49-year-old female with inherited type 1 VWD but no serious bleeding tendency. She presented with melena and irondeficiency anaemia. Activity of both von Willebrand factor antigen (VWF:Ag) and von Willebrand factor Ristocetin co-factor activity (VWF:RCo) was reduced to <20%. GI endoscopy and colonoscopy proved normal at the time of her first hospital admission. The patient was treated with blood replacement, tranexamic acid and desmopressin (DDAVP) infusion, but these latter two approaches did not effectively reduce the bleeding. We therefore initiated VWF/factor VIII (FVIII) concentrate (Haemate P , CSL Behring) at the therapeutic dosage, 40–50 IU kg every day and then every two days for 4 weeks following hospital discharge. She did not display any bleeding symptoms for the next 5 months, when she then experienced a new incident of melena and serious anaemia (haemoglobin <7.0 g dL). Mesenteric angiography and capsular endoscopy were thus performed: the latter procedure revealed two small angiodysplastic lesions in the ileum, clinically insignificant. We therefore initiated medical therapy with oestrogen and Haemate P 30 IU kg every alternate day for 8 weeks. However, the patient experienced an adverse event to oestrogen therapy and serious bleeding when the VWF concentrate was withdrawn. Symptoms of anaemia continued for the next 22 months; GI bleeding was always reduced during prophylaxis with Haemate P but commenced again whenever this was suspended. At that time, we repeated GI Correspondence: Sergio Siragusa, MD, Haematology and Thrombosis/Haemostasis Unit, Department of Oncology, University Hospital of Palermo, Via del Vespro 127, I-90127 Palermo, Italy. Tel./fax: + 39 091 6554574; e-mail: sergio.siragusa@unipa.it