Giuseppe Camporese

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.

An unexpectedly high rate of pulmonary embolism in patients with superficial thrombophlebitis of the thigh

PURPOSE The rate of objectively proven pulmonary embolism in patients with thrombophlebitis of the greater saphenous vein was studied. METHODS Consecutive ambulant patients with thrombophlebitis of the greater saphenous vein, involving the above-knee segment, underwent a complete venous echo color Doppler examination of the lower limbs, perfusion lung scanning, and chest radiography. A high probability of pulmonary embolism was defined as the presence of two or more large segmental defects, one large and two or more moderate perfusion defects, or four or more moderate perfusion defects, with no corresponding abnormality found by means of chest radiography. RESULTS Of the 21 patients included in the study, findings compatible with a high probability of pulmonary embolism were detected in seven patients (33.3%; 95% CI, 14.6 to 57. 0), although clinical symptoms of pulmonary embolism were present only in one patient. No association was found between the presence of thrombosis at the saphenofemoral junction and the risk for pulmonary embolism. CONCLUSION The rate of pulmonary embolism in patients with thrombophlebitis of the greater saphenous vein is unexpectedly high. This risk is similarly high in patients with thrombosis at the saphenofemoral junction and in patients without thrombosis at the saphenofemoral junction. Our results are consistent with those of other recent investigations and suggest that superficial thrombophlebitis of the thigh is not as benign a disease entity as previously described.

Low-Molecular-Weight Heparin versus Compression Stockings for Thromboprophylaxis after Knee Arthroscopy: A Randomized Trial

BACKGROUND Knee arthroscopy, the most common orthopedic operation worldwide, carries a definite risk for deep venous thrombosis; however, postsurgical thromboprophylaxis is not routinely recommended. OBJECTIVE To evaluate whether low-molecular-weight heparin (LMWH) better prevents deep venous thrombosis and does not cause more complications than graduated compression stockings in adults having knee arthroscopy. DESIGN Assessor-blind, randomized, controlled trial. SETTING The Department of Knee Surgery, Abano Terme Clinic, Abano Terme (knee surgery, random assignment, and bleeding event survey), and the Unit of Angiology, University Hospital of Padua, Padua (efficacy outcomes evaluation, follow-up, data management, and analysis), Italy. PATIENTS 1761 consecutive patients undergoing knee arthroscopy between March 2002 and January 2006. INTERVENTION Patients were randomly assigned to wear full-length graduated compression stocking for 7 days (660 patients) or to receive a once-daily subcutaneous injection of LMWH (nadroparin, 3800 anti-Xa IU) for 7 days (657 patients) or 14 days (444 patients). The data and safety monitoring board prematurely stopped the 14-day heparin group after the second interim analysis. MEASUREMENTS Combined incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality (primary efficacy end point) and combined incidence of major and clinically relevant bleeding events (primary safety end point). All patients had bilateral whole-leg ultrasonography at the end of the allocated prophylactic regimen or earlier if indicated. All patients with normal findings were followed for 3 months, and none was lost to follow-up. RESULTS The 3-month cumulative incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality was 3.2% (21 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, 2.3 percentage points [95% CI, 0.7 to 4.0 percentage points]; P = 0.005), and 0.9% (4 of 444 patients) in the prematurely stopped 14-day LMWH group. The cumulative incidence of major or clinically relevant bleeding events was 0.3% (2 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, -0.6 percentage point [CI, -1.5 to 0.2 percentage points]), and 0.5% (2 of 444 patients) in the 14-day LMWH group. LIMITATIONS The study was not double-blind or double-dummy. Almost half of the events making up the composite outcome measure were distal deep venous thromboses. Stockings were used instead of placebo because of local prophylaxis policies. CONCLUSION In patients undergoing knee arthroscopy, prophylactic LMWH for 1 week reduced a composite end point of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality more than did graduated compression stockings.

Endovenous laser treatment of the small saphenous vein

PURPOSE Endovenous laser treatment is a minimally invasive technique for ablation of the incompetent great (GSV) and small saphenous vein (SSV). Compared with the GSV, fewer data are available on SSV laser ablation and are not validated. This multicenter prospective study evaluated the feasibility, safety, and efficacy of endovenous laser ablation to treat SSVs. METHODS Between January 2003 and January 2007, 204 patients (229 limbs) with CVD and incompetent SSVs (evaluated by the CEAP classification) who were eligible for surgery underwent consecutive laser ablation procedures. Many required additional treatment for varicose tributaries and perforator veins with phlebectomy and foam sclerotherapy, Energy was delivered to the vein wall by a 600-microm optical fiber using 810-nm or 980-nm diode laser. Ablations were performed with duplex ultrasound (DU) guidance and tumescent anesthesia. Follow-up was with clinical examination and DU imaging. RESULTS DU imaging showed immediate occlusion of the SSV with no thrombosis in the proximal veins. No complications occurred intraoperatively. All patients had postoperative ecchymosis, but it was minimal. Three patients had distal thrombotic complications. Superficial phlebitis after complementary surgery occurred in three cases. Complete occlusion with absence of flow </=2 months of follow-up was detected in 226 SSV (98.7%). It occurred 22 in patients with large SSV diameter. Recanalization was found in one patient at 12 months and in two patients at 24 months. Seven limbs had reflux in previously treated areas, treated segments, and segments in continuity with them. Three underwent an intervention to correct symptomatic reflux. The other four had no symptoms. After 1 year, eight limbs developed reflux in new locations and four underwent treatment. Symptoms resolved in most patients soon after the operation. The mean follow-up was 16 months (range, 2-39 months). After 8 to 12 months postprocedurally, the laser-treated veins were fibrotic and almost indistinguishable on DU imaging from the surrounding tissues. In five patients (2.25%) postoperative paresthesia occurred >2 to 3 days postoperatively and persisted in the follow-up. No paresthesia occurred in our last series whenever a larger amount of tumescent cold saline was infused around the vein. CONCLUSION Endovenous laser ablation of the SSV has excellent early and midterm results. The prevalence of thrombosis and paresthesia is very low. Symptom relief is very good.

The incidence of venous thromboembolism following gynecologic laparoscopy: a multicenter, prospective cohort study

Background: Information on the incidence of venous thromboembolism (VTE) following laparoscopic procedures is inadequate and there is currently no solid evidence to guide the use of thromboprophylaxis in this setting. Gynecologic laparoscopy is a common procedure, and is frequently performed in low‐risk patients. To our knowledge, there are no clinical studies specifically designed to assess the incidence of VTE in this setting. Methods: In a prospective cohort study, consecutive patients undergoing gynecologic laparoscopy underwent compression ultrasonography (CUS) and clinical assessment to evaluate the incidence of clinically relevant VTE. CUS was performed 7 ± 1 and 14 ± 1 days postoperatively. A subsequent telephone contact was scheduled at 30 and 90 days. No patient received pharmacologic or mechanical prophylaxis. Patients with malignancy or previous VTE were excluded from the study. Results: We enrolled 266 consecutive patients; mean age was 36.3 years, range: 18–72. The most common indications for laparoscopy were ovarian cysts in 25.6% of patients, endometriosis in 21.0% of patients, unexplained adnexal masses in 12.4% of patients, and infertility in 7.5% of patients. The mean duration of the procedure was 60.5 min (range: 10–300 min). In particular, in 55.6% of patients the duration exceeded 45 min. There were neither episodes of CUS detected DVT (0/247; 0%, 95% CI 0–1.51%) or clinically relevant VTE after follow‐up (0/256; 0%, 95% CI 0–1.48%). No patient died of fatal pulmonary embolism (0/266; 0%, 95% CI 0–1.42%). Conclusions: Gynecologic laparoscopy in non‐cancer patients is a low‐risk procedure for postoperative VTE.

A randomized double‐blind study of low‐molecular‐weight heparin (parnaparin) for superficial vein thrombosis: STEFLUX (Superficial ThromboEmbolism and Fluxum)

Summary.  Background:  Optimal doses and duration of low‐molecular‐weight heparin (LMWH) for the treatment of superficial vein thrombosis (SVT) are still uncertain.

Incidence and risk factors for venous thromboembolism after laparoscopic surgery for colorectal cancer

Background Limited data are currently available concerning the risk for venous thromboembolism (VTE) after laparoscopic surgery for cancer. Methods Consecutive patients who had laparoscopic surgery for colorectal cancer were included in a prospective multicenter study. Compression ultrasonography of the lower limbs was performed at 8+/-2 days after surgery. The primary study outcome was symptomatic objectively confirmed or ultrasonography-detected VTE at day 8+/-2 after surgery. Results 305 patients were included in the study, mean age 67+/-11 years, 54% males. All included patients received prophylaxis with low molecular weight heparin from the day of surgery to the day of ultrasonography. VTE was diagnosed in 54 patients (17.7%), in all of them as deep vein thrombosis of the lower limbs. Obesity and age ≥70 years were independent predictors for VTE at day 8+/-2. Conclusions The risk of VTE after laparoscopic surgery for colorectal cancer is substantial despite antithrombotic prophylaxis and is more common in obese and old patients.

Analysis of an algorithm incorporating limited and whole-leg assessment of the deep venous system in symptomatic outpatients with suspected deep-vein thrombosis (PALLADIO): A prospective, multicentre, cohort study

BACKGROUND Compression ultrasonography is the mainstay of diagnosis of deep-vein thrombosis (DVT) of the legs. Compression ultrasonography can be extended to the entire deep venous system (whole-leg) or restricted to the proximal veins only (limited), and the two approaches are clinically equivalent. We aimed to assess the diagnostic value of an algorithm combining whole-leg and limited compression ultrasonography. METHODS We did a prospective, multicentre, cohort study at eight centres in five countries. Consecutive outpatients aged 18 years or older with suspected DVT underwent D-dimer measurement and pretest clinical probability assessment. DVT was ruled out without further testing if pretest probability was unlikely and D-dimer was negative (group 1). Patients in whom either pretest probability was likely or who were positive for D-dimer underwent limited compression ultrasonography only (group 2). Finally, patients in whom pretest probability was likely and who had a positive measurement for D-dimer underwent extended whole-leg compression ultrasonography (group 3). All patients in whom DVT was ruled out were followed up for 3 months. The primary outcome was the incidence of objectively recorded venous thromboembolism. The primary analysis included all patients managed according to the study protocol. This study is registered with ClinicalTrials.gov, number NCT01412242. The final results are reported here. FINDINGS Between March 1, 2011, and July 31, 2014, 1348 consecutive outpatients were referred for this study, of whom 1162 were eligible to participate. After pretest probability assessment and D-dimer testing, 351 were in group 1, 401 in group 2, and 410 in group 3. Limited compression ultrasonography was positive in 12 (3%) patients in group 2 and extended whole-leg compression ultrasonography was positive in 200 (49%) patients in group 3. 82 (39%) of all DVT diagnosed at baseline were isolated distal thromboses. 26 protocol violations were reported. Thus, 351 patients from group 1, 371 patients in group 2, and 202 patients in group 3 who had been excluded for DVT by the algorithm were included in the primary analysis at 3 months. One, four, and three DVTs were reported, respectively. Thus, the 3-month incidence of venous thromboembolism in untreated patients after a negative diagnostic strategy was 0·87% (95% CI 0·44-1·70). INTERPRETATION An algorithm combining limited and whole-leg compression ultrasonography could be a reliable, safe, and convenient method for diagnostic management of outpatients with clinically suspected DVT. FUNDING None.

Risk factors for recurrent events in subjects with superficial vein thrombosis in the randomized clinical trial SteFlux (Superficial Thromboembolism Fluxum)

BACKGROUND/AIMS To evaluate risk factors for recurrent events in patients enrolled in the SteFlux (Superficial Thromboembolism Fluxum) clinical trial which compared different doses and duration of low molecular weight heparin (parnaparin) for superficial vein thrombosis (SVT). MATERIALS AND METHODS Outpatients with acute SVT of at least 4 cm in length of the internal or external saphenous veins or their collaterals were randomized in a double blind fashion to receive either parnaparin 8500 UI aXa od for ten days followed by placebo for 20 days or 8500 UI aXa od for ten days followed by 6400 UI aXa od for 20 days or 4250 UI aXa od for 30 days. Outcomes were the composite of symptomatic and asymptomatic deep vein thrombosis, pulmonary embolism and SVT recurrence or extension in the first 30+/-3 days with a 60+/-3 day follow-up. RESULTS 98 outcomes (14.7%) were recorded during 93 days among 664 patients (M/F: 246/418, mean age 65). After correction for treatment, outcomes during 33 days were associated with previous venous thromboembolism (VTE) and/or SVT and/or family history of VTE (odds ratio-OR: 2.5; 95% confidence interval - CI: 1.4-4.8; p=0.003). After stopping LMWH treatment, only the absence of varicose veins (OR: 2.5; 95% CI 1.3-5.0; p=0.004) and previous VTE and/or SVT and/or family history of VTE (OR: 1.9; 95% CI:1.0-3.7; p=0.048) were significantly associated with outcomes. CONCLUSIONS SVT patients with these factors may deserve a higher intensity and/or longer anticoagulant treatment.

Benign outcome of objectively proven spontaneous recanalization of internal carotid artery occlusion.

OBJECTIVE Spontaneous recanalization of intracranial internal carotid artery (ICA) occlusion is frequent in embolic strokes. Spontaneous recanalization of the extracranial portion of the ICA occlusion of atherosclerotic or embolic origin is only anecdotally reported, and data are lacking about its incidence, natural history, and outcome in long-term follow-up. METHODS Consecutive patients with ICA occlusion were prospectively identified and followed-up to detect the incidence of a spontaneous recanalization. Patients with objectively confirmed recanalization were prospectively followed-up to observe their natural history and the onset of new cerebrovascular events. ICA occlusion and spontaneous recanalization were diagnosed by means of color-coded Doppler ultrasound imaging or selective contrast angiography, or both. All patients were evaluated and treated for atherosclerotic risk factors. RESULTS Spontaneous recanalization occurred in 16 of 696 patients (2.3%; 95% confidence interval, 1.3%-3.7%) with ICA occlusion after a mean interval of 38 months from the diagnosis of occlusion. Spontaneous recanalization was detected with color-coded Doppler ultrasound imaging and with selective contrast angiography, with a complete agreement of diagnostic findings. Two patients presented with symptomatic spontaneous recanalization. All patients with spontaneous recanalization were asymptomatic after a mean follow-up of 66.2 months. CONCLUSIONS Spontaneous recanalization of previously occluded extracranial ICAs is more frequent than anticipated. Once it occurs, spontaneous recanalization seems to have a benign long-term course.