BACKGROUND: 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; 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: 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: To determine the long-term incidence, risk factors, and associated morbidity and mortality of recurrent deep vein thrombosis (DVT).
SUMMARY BACKGROUND DATA: Few studies have examined the long-term natural history and impact of recurrent DVT.
METHODS: We conducted a prospective observational study that followed 153 consecutive patients with an acute first episode of DVT. Clinical examination and ultrasound were performed serially for at least 5 years. Location and extent of the initial DVT, recurrence, pulmonary embolism, cause of mortality, signs and symptoms of post thrombotic syndrome (PTS), and the risk factors were recorded.
RESULTS: The incidence of recurrence at 5 years was 26.1%. Patients with both proximal and distal DVT had a higher recurrence rate than proximal (17/48 35% vs. 12/49, 24%, P = 0.27) or calf alone (11/56, 20%, P = 0.08). Unprovoked DVT and age >65 years were associated with higher recurrence rates (P < 0.001; relative risk [RR]: 2.9, 95% confidence interval [CI]: 1.5-5.7) and (P = 0.025; RR: 1.5, 95% CI: 1-2.3), respectively. Thrombophilia was not associated with increased risk of recurrence (P = 0.21). Patients with DVT due to surgery or trauma had a lower recurrence (P < 0.001). Ipsilateral recurrence was associated with increased severity of PTS (P < 0.001; RR: 1.6, 95% CI: 1.4-2.2). PE occurred 47 times, 12 (25%) of which were fatal events.
CONCLUSIONS: Factors associated with a higher rate of recurrence included unprovoked DVT and age >65. Elevated thrombus burden had a trend towards higher risk. Patients with surgery and trauma had low recurrence rates. Ipsilateral recurrence was strongly associated with PTS. PE occurred frequently and was a common cause of death.
AIM: The optimal treatment of isolated distal deep vein thrombosis (ID-DVT) is still controversial. A complete anticoagulation as soon as the diagnosis is made is recommended by some authors. Alternatively, other authors suggest to perform serial ultrasonography assessments to detect the possible extension of DVT towards proximal veins. Only in this case the treatment should be initiated. Furthermore, the optimal duration of treatment is far from established. The Treatment of Isolated Calf Thrombosis (TICT) study was set up to assess the efficacy and safety of a particular treatment regimen of ID-DVT based on low molecular weight heparins (LMWH).
METHODS: The drug treatment consisted of a twice-daily subcutaneous administration of a full dose of weight-adjusted LMWH for one week, followed by a half dose of LMWH administered once-daily for another three weeks. At the end of the four-week period of treatment, a colour-coded Doppler ultrasonography (CCDU) assessment was scheduled and after three months a follow-up visit was performed. If a patient was unable to attend the visit, he was contacted by a phone-call to assess if any adverse events occurred. The study enrolled 192 outpatients with ID-DVT confirmed by CCDU. Twenty-one out of 192 patients (10.9%) were excluded for violation of protocol. Thus 171 (39.9% men, mean age of 60.45 years ) were eligible and were included in the study. Sixty-one patients (36.6%) presented an unprovoked ID-DVT.
RESULTS: Events during the period of treatment (4 weeks). Ten out of 171 patients (5.8%) had complications: five patients showed an extension proximal to the knee (2.9%) all with an unprovoked ID-DVT; two showed an extension of thrombus within the distal veins. Three patients (1.7%) suffered from minor bleeding; there was no major bleeding. Further events during three months of observation occurred. Five patients had thrombus recurrences: four patients showed a proximal DVT (3 with a previous unprovoked ID-DVT, 1 with a previous ID-DVT secondary to a traumatic leg fracture, with persistent difficulty of deambulation); one, with a previous secondary thrombosis, showed a ID-DVT.
CONCLUSIONS: In our study only 2.9% of patients with ID-DVT showed a progression of thrombosis to proximal deep veins; the majority of thrombus progression, during the treatment period, was observed in patients with unprovoked ID-DVT. Our results support the usefulness of a prolonged treatment in unprovoked ID-DVT.
The aim of this study was to evaluate different durations of treatment in patients with calf venous thrombosis (CVT) involving 1 or more deep veins. The authors studied 2 groups of patients with postsurgical CVT diagnosed by echo-color Doppler. The first group consisted of 68 patients with CVT involving a single vein, and the second group consisted of 124 patients with CVT involving 2 or more veins. Immediately after diagnosis, all patients were treated with nadroparin calcium and sodium warfarin. Heparin treatment was withdrawn after 5-6 days of treatment, when the international normalized ratio (INR) was stabilized between 2 and 3. Each group was divided into 2 subgroups receiving anticoagulation treatment for 6 or 12 weeks, respectively. The endpoint was proximal extension of the thrombotic lesion, defined as the extension of the thrombus to the popliteal and/or femoral vein. In patients with single-vessel CVT there was no significant difference between the 2 subgroups, whereas in patients with CVT involving 2 or more vessels, a statistically significant difference was observed, the number of cases showing proximal extension of the thrombus being higher among patients treated for 6 weeks. Twelve weeks of anticoagulation treatment is better than 6 weeks only in patients with postsurgical CVT involving 2 or more veins.
BACKGROUND: Venous thromboembolic disease remains a difficult problem in the trauma patient population. The purpose of this study was to delineate the incidence and natural history of below-knee deep venous thrombosis (BKDVT) in high-risk trauma patients.
METHODS: Patients were stratified into risk categories (low, high, or very high) for deep venous thrombosis on the basis of an institutional practice management guideline and known risk factors. All at-risk patients received either sequential compression devices (SCDs) or subcutaneous heparin (SQH) compounds, and high-risk patients also underwent weekly surveillance by duplex scanning. Very-high-risk patients had prophylactic inferior vena cava (IVC) filter placement. This prospective, observational study examines the duplex results on all high-risk patients. Data regarding method of prophylaxis, the incidence of proximal propagation on serial duplex examinations, and changes in management (anticoagulation or IVC filter placement) were collected on the high-risk patients who developed a BKDVT.
RESULTS: Between March 1997 and June 2001, 601 patients were stratified into the high-risk category and underwent a total of 1,109 duplex examinations. Eighty-five patients (14.1%) had 113 BKDVTs. These patients underwent a total of 212 duplex examinations; all patients developed their BKDVTs within 34 days. Weekly incidence was 40 (47.1%), 25 (29.4%), 15 (17.6%), 1 (1.2%), and 4 (4.7%) for weeks 1 through 5, respectively. SCDs, SQH compounds, and SCDs with SQH compounds were used on 73, 3, and 9 patients, respectively. In 4 of 85 (4.7%) patients, the BKDVT propagated proximally to an above-knee location in 4 to 8 days. Two of these patients were anticoagulated, and two underwent placement of an IVC filter. One patient (1.2%) with a BKDVT that had not propagated on duplex study developed a pulmonary embolus.
CONCLUSION: Patients identified as high-risk by our practice management guideline had a 14.1% incidence of a BKDVT; 94.1% were diagnosed within the first 3 weeks of hospitalization. Proximal propagation occurred in 4.7% and led to changes in management. Serial duplex examination of the BKDVT alone, rather than systemic anticoagulation or IVC filter placement, appears to be a reasonable treatment alternative.
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.
