<b>BACKGROUND: </b>There is currently little evidence defining the clinical importance of detecting and treating isolated distal DVT (IDDVT). International guidelines vary regarding diagnostic and therapeutic advice. The potential benefits of anticoagulation are unquantified. We sought to evaluate the feasibility of a randomized controlled study within a modern framework and provide a primary outcome point estimate.<b>METHODS: </b>In this open-label, external pilot randomized controlled trial, consecutive, symptomatic, ambulatory patients with IDDVT were approached for inclusion. Participants were allocated to receive either therapeutic anticoagulation or conservative management. Patients underwent blinded color-duplex imaging at 7 and 21 days and follow-up at 3 months. Principal feasibility outcomes included recruitment rate and attrition. The principal clinical outcome was a composite including proximal propagation, pulmonary embolism, death attributable to VTE disease, or major bleeding. Analysis was by intention to treat.<b>RESULTS: </b>In total, 93 patients with IDDVT were screened, and 70 of those eligible (88.6%) were recruited. All patients but one were followed-up by direct contact after 90 days. Allocation crossover occurred in 15 patients (21.4%). The principal clinical outcome occurred in four of 35 of those conservatively treated (11.4%) and zero of 35 in the anticoagulated group (absolute risk reduction, 11.4%; 95% CI, -1.5 to 26.7, P = .11, number needed to treat of nine). There were no major bleeding episodes.<b>CONCLUSIONS: </b>We have established the feasibility of definitive study regarding the value of therapeutic anticoagulation in IDDVT and provide an approximate point estimate for serious complications with a contemporary conservative strategy.<b>Trial Registry: </b>Current Controlled Trials; No.: ISRCTN75175695; URL: www.controlled-trials.com.
BACKGROUND: Isolated distal deep vein thrombosis (IDDVT) is frequently found in symptomatic outpatients, but its long term outcome is still uncertain.
AIMS: To assess IDDVT long term outcome and the impact of IDDVT characteristics on outcome.
METHODS: In a prospective, single center study we enrolled symptomatic outpatients in whom IDDVT was detected by whole-leg compression ultrasonography. Patients with provoked IDDVT were treated with low molecular weight heparins (LMWH) for 30 days while those with unprovoked IDDVT received with vitamin K antagonists (VKA) for three months. The primary end-point was the rate of the composite of pulmonary embolism (PE), proximal deep vein thrombosis (DVT), and IDDVT recurrence/extension during 24 month follow-up.
RESULTS: 90 patients (age 61 ± 18, male 48.9%) were enrolled. Risk factors for thrombosis were reduced mobility (34.4%), obesity (25.3%), surgery (15.6%), and previous DVT (15.6%) and cancer in 8 patients (8.9%). Eighty-eight patients were treated (56 with LMWH and 32 with VKA). During follow-up (median 24 ± 2 months), 17 events were recorded, which included 3 PE (two in cancer patients), 4 proximal DVTs (one in cancer patient) and 10 IDDVT. Male sex (HR 4.73 CI95%: 1.55-14.5; p=0.006) and cancer (HR 5.47 CI95%: 1.76-17.6; p=0.003) were associated with a higher risk of complications, whereas IDDVT anatomical characteristics, anticoagulant therapy type, and provoked IDDVT were not.
CONCLUSIONS: The risk of recurrent venous thromboembolism after IDDVT may be relevant in male patients or in patients with active cancer. Larger studies are needed to address this issue.
AIM: No study of strong methodology could be found to resolve the controversy of optimal treatment of distal deep venous thrombosis (DDVT). Some inconclusive evidence exists on two approaches to care: anticoagulants and compression therapy or compression therapy and Duplex scanning monitoring. Different studies report propagation to popliteal vein in 8% of patients without anticoagulant treatment, while a complete thrombus resolution within 4 weeks occurred in 20% of patients. We report data of a study conducted in patients affected by DDVT and treated with nadroparin administered once daily in association with compression therapy.
METHODS: One hundred and ten patients with DDVT of the gastrocnemius or tibial veins, assessed by Duplex scanning, were enrolled in 8 clinical centres of the Lazio Region. At baseline, patient demographics, medical history (including risk factors for DDVT), circumferences of both calves and ankles, and a VAS-pain scale were recorded. At 7 and 28 days from baseline, patients were re-assessed by Duplex scanning, calves and ankles circumferences and VAS-pain were measured, and the patients were asked about possible side effects.
RESULTS: At the end of the study period, no propagation to the popliteal vein was observed, and no side effects were reported. Overall, the calf circumference in the affected leg significantly decreased from baseline (38.1 cm) to week 1 (37.1 cm), and to week 4 (35.7 cm). Also the VAS-pain scores significantly decreased during the study - the observed means were 58.4, 30.7, and 12.7 at the three visits, respectively. The percentage of partial recanalization of tibial DVT at 7 days was lower than gastrocnemius DVT (31.6% vs. 59.8%) whereas the percentage of total recanalization at 28 days was comparable (52.6% vs. 59.8%). Complete recanalization occurred in 56.4% of all patients.
CONCLUSION: Our study suggests that anticoagulant treatment, associated with compression therapy, is safe and causes clinical improvement (as assessed by calf measurements) and pain relief. Overall complete resolution (56.4%) is significantly higher than in untreated patients (20%). Such results, together with the already reported higher satisfaction of patients for the once-daily administration regimen, should be considered as a viable option for the treatment of DDVT.
BACKGROUND: The clinical significance of isolated calf vein thrombosis (ICVT) remains controversial. Several studies have shown that the majority of ICVT do not propagate above the knee while other studies have suggested ICVT propagation and recommend full anticoagulation. The purpose of this study was to determine the progression of ICVT, identify risk factors for clot propagation, and to evaluate further thrombotic events associated with it.
METHODS: This study consisted of 156 patients and a total of 180 limbs. All patients included had ICVT involving either the tibial, peroneal, gastrocnemius, or the soleal vein. After initial diagnosis, all patients were started on prophylactic dose of low molecular weight heparin (LMWH) or unfractionated heparin, unless already anticoagulated. All limbs were monitored using duplex ultrasonography scans at intervals of 2 to 3 days, 1 to 3 months, and 6 to 8 months from the initial time of diagnosis. Outcomes examined included lysis of clot, propagation to a proximal vein, and pulmonary emboli.
RESULTS: ICVT was detected in 180 limbs of 156 patients. No significant difference was noted in the gender of the patients or limb preference. Twenty-four patents had both limbs involved. The mean age was 77 years old and the mean follow-up was 5.1 months. The soleal vein was most commonly involved. The second most common vein involved was peroneal, followed by posterior tibial and then gastrocnemius. The least commonly involved vein was the anterior tibial with only one positive result on each side. Fifteen of 180 limbs (9%) had complete resolution of the thrombus within 72 hours. Of these, six were anticoagulated to a therapeutic level. All patients had a follow-up duplex scan within 1 to 3 months' time, and none had recurrence. At the 1 to 3-month follow-up, 11 of 180 patients (7%) had propagation to a proximal vein; all of whom were in a high-risk group to develop a deep vein thrombosis (DVT), either after an orthopedic procedure, stroke, or malignancy. Nine of 156 patients developed a pulmonary emboli also diagnosed within the 1 to 3-months' time period. At the 6 to 8-month follow-up, there was no further propagation of any additional limbs and no further incidences of pulmonary emboli.
CONCLUSION: ICVT can be safely observed in asymptomatic patients without therapeutic anticoagulation. In our study, patients who have had orthopedic procedures, those with malignancy, and those that were immobile seemed to have a higher incidence of clot propagation. In this group, we recommend full anticoagulation until the patient is ambulatory or the follow-up duplex scan is negative. Our data also suggest that a follow-up duplex scan is not beneficial when performed within 72 hours or after 3 months.
BACKGROUND: Half of all lower limb deep vein thromboses (DVT) are distal DVT that are equally distributed between muscular calf vein thromboses (MCVT) and deep calf vein thromboses (DCVT). Despite their high prevalence, MCVT and DCVT have never been compared so far, which prevents possible modulation of distal DVT management according to the kind of distal DVT (MCVT or DCVT).
METHODS: Using data from the French, multicenter, prospective observational OPTimisation de l'Interrogatoire dans l'évaluation du risque throMbo-Embolique Veineux (OPTIMEV) study, we compared the clinical presentation and risk factors of 268 symptomatic isolated DCVT and 457 symptomatic isolated MCVT and the 3-month outcomes of the 222 DCVT and 390 MCVT that were followed-up.
RESULTS: During the entire follow-up, 86.5% of DCVT patients and 76.7% of MCVT patients were treated with anticoagulant drugs (P = .003). MCVT was significantly more associated with localized pain than DCVT (30.4% vs 22.4%, P = .02) and less associated with swelling (47.9% vs 62.7%, P < .001). MCVT and DCVT patients exhibited the same risk factors profile, except that recent surgery was slightly more associated with DCVT (odds ratio, 1.70%; confidence interval, 1.06-2.75), and had equivalent comorbidities as evaluated by the Charlson index. At 3 months, no statistically significant difference was noted between MCVT and DCVT in death (3.8% vs 4.1%), venous thromboembolism recurrence (1.5% vs 1.4%), and major bleeding (0% vs 0.5%).
CONCLUSION: Isolated symptomatic MCVT and DCVT exhibit different clinical symptoms at presentation but affect the same patient population. Under anticoagulant treatment and in the short-term, isolated distal DVT constitutes a homogeneous entity. Therapeutic trials are needed to determine a consensual mode of care of MCVT and DCVT.
BACKGROUND: Treatment of isolated calf muscle vein thrombosis (ICMVT) is controversial. There are no data from prospective, controlled studies. Objective of this article was to compare the efficacy and safety of a short-term course of anticoagulation with compression therapy alone.
METHODS: We prospectively randomized patients with symptomatic, sonographically proven ICMVT in the soleal and/or gastrocnemial muscle veins in two treatment arms. The first received low-molecular-weight heparin for 10 days at therapeutic dosage (nadroparin 180 anti-activated factor X units once daily) and compression therapy for three months, and the second received compression therapy alone. Primary efficacy endpoint of the study was sonographically proven progression of ICMVT into the deep veins and clinical pulmonary embolism (PE) as confirmed by objective testing. Secondary efficacy and primary safety endpoints were major bleeding, death not due to PE, and complete sonographically proven recanalization of the muscle vein. We assessed transient and permanent risk factors for venous thromboembolism.
RESULTS: One-hundred seven patients were finally ruled eligible for evaluation: 89% outpatients, 11% hospitalized patients. In the heparin group (n=54) progression to deep vein thrombosis (DVT) occurred in two patients (3.7%), in the group compression therapy alone (n=53) progression to DVT occurred in two patients (n.s.). No clinical PE and no death occurred. Thrombus recanalization after 3 months was not statistically significant different between the two study groups. No major bleeding occurred.
CONCLUSION: The data do not show superiority of a short-term regimen of low-molecular-weight heparin and compression therapy in comparison with compression therapy alone in patients with ICMVT in a rather low-risk population.
OBJECTIVE: The ideal treatment for hospitalized patients with isolated gastrocnemius and/or soleal venous thrombosis is unclear. Recommendations range from watchful waiting to full-dose anticoagulation. This study examines the effectiveness of practice patterns at a single institution as measured by progression of thrombus.
METHODS: All consecutive inpatients with a duplex scan diagnosis of isolated gastrocnemius and/or soleal vein clot (no other thrombotic segments were identified) and where two consecutive duplex studies (Intersocietal Commission for the Accreditation of Vascular Laboratories laboratory) were available for review were included. Two study groups were identified. TX group included patients who received anticoagulation treatment (heparin [fractionated or unfractionated], heparin substitutes, or warfarin) and the NoTX group included those who did not receive anticoagulant. Demographic, risk factors, comorbidities, length of hospital and intensive care unit stay, ambulatory status, and underlying hypercoagulable states were recorded. Thrombus progression rate in the two groups was compared using the χ2 test. A multivariate logistic regression model was used to examine the effect of anticoagulation treatment as well as the above demographic and clinical factors on the risk of progression.
RESULTS: A total of 141 patients were included in the study, 76 of whom (54%) received anticoagulation. Forty-three patients (30%) had progression of their venous thrombosis: 33% (25/76) in the TX group and 28% (18/65) in the NoTX group (P=.50, by χ2 test). Results from multivariate logistic regression showed that treatment had no significant impact on outcome (Odds ratio=1.28, 95% confidence interval: 0.55-3.01; P=.57]. Patients with end-stage renal disease (6%), or stroke (13%) had significantly higher risk of progression (P<.05). None of the other clinical or demographic factors were significantly associated with the risk of progression.
CONCLUSION: The results speak to the lack of efficacy of anticoagulation in the management of gastrocnemius and/or soleal vein thrombosis in the hospitalized patient. When measured by thrombus progression, treating these patients without anticoagulation appears to be equally efficacious as subjecting patients to anticoagulant therapy. A prospective, randomized clinical trial will be an important step in fully addressing this clinical dilemma.
The natural history of calf deep-vein thrombosis (DVT) is still uncertain and it is debated whether it warrants to be diagnosed and treated. We aimed to investigate the complication rate of untreated isolated calf DVT (ICDVT). Symptomatic outpatients were prospectively managed with serial compression ultrasonography (SCUS). Those without proximal DVT and with likely pre-test clinical probability (PCP) or altered D-dimer received immediate subsequent complete examination of calf deep veins (CCUS) by a different operator. The result of CCUS was kept blind both to the managing doctor and the patient and disclosed after three months. Primary outcome was the rate of venous thromboembolism at three months. We examined 431 subjects (196 males; median age 68.0 years) in whom five outcomes were recorded (1.2%; 95% confidence intervals [CI]: 0.4-2.7). If CCUS results had been available, outcomes would have been recorded in 3/424 patients (0.7%; 95% CI: 0.2-2.1) with two events in subjects negative at both serial and complete CUS. ICDVT was diagnosed in 65 subjects (15.3%; 95% CI: 12-19); of whom 59 remained uneventful (one was lost to follow-up). A significant higher rate of outcomes was recorded in subjects with than without ICDVT (5/64; 7.8%; 95% CI: 3-17 vs. 3/351; 0.8%; 95% CI: 0-2; p=0.003). However, after excluding two events picked at serial CUS in subjects with ICDVT, the difference became barely significant (3/64; 4.7%; 95% CI: 1-13; p=0.049). Thrombotic evolution of untreated ICDVT in high-risk subjects may be relevant. Larger studies are needed to address this issue.
There is currently little evidence defining the clinical importance of detecting and treating isolated distal DVT (IDDVT). International guidelines vary regarding diagnostic and therapeutic advice. The potential benefits of anticoagulation are unquantified. We sought to evaluate the feasibility of a randomized controlled study within a modern framework and provide a primary outcome point estimate.
METHODS:
In this open-label, external pilot randomized controlled trial, consecutive, symptomatic, ambulatory patients with IDDVT were approached for inclusion. Participants were allocated to receive either therapeutic anticoagulation or conservative management. Patients underwent blinded color-duplex imaging at 7 and 21 days and follow-up at 3 months. Principal feasibility outcomes included recruitment rate and attrition. The principal clinical outcome was a composite including proximal propagation, pulmonary embolism, death attributable to VTE disease, or major bleeding. Analysis was by intention to treat.
RESULTS:
In total, 93 patients with IDDVT were screened, and 70 of those eligible (88.6%) were recruited. All patients but one were followed-up by direct contact after 90 days. Allocation crossover occurred in 15 patients (21.4%). The principal clinical outcome occurred in four of 35 of those conservatively treated (11.4%) and zero of 35 in the anticoagulated group (absolute risk reduction, 11.4%; 95% CI, -1.5 to 26.7, P = .11, number needed to treat of nine). There were no major bleeding episodes.
CONCLUSIONS:
We have established the feasibility of definitive study regarding the value of therapeutic anticoagulation in IDDVT and provide an approximate point estimate for serious complications with a contemporary conservative strategy.Trial Registry: Current Controlled Trials; No.: ISRCTN75175695;
