Systematic Review and Meta-Analysis of the Pooled Rate of Post-Thrombotic Syndrome After Isolated Distal Deep Venous Thrombosis.

OBJECTIVE: To identify the rate of post-thrombotic syndrome (PTS) after isolated distal deep venous thrombosis (IDDVT) by performing a meta-analysis of the rate of PTS across randomised and observational studies. DATA SOURCES: MEDLINE, Embase, the Cochrane Controlled Trials Register, Clinicaltrials.gov, European Union Clinical Trials, International Standard Randomised Controlled Trial Number, and the Australian and New-Zealand Trials Registries. REVIEW METHODS: This review followed PRISMA guidelines using a registered protocol (CRD42021282136). Databases were searched up to December 2021 and prospective studies reporting the development of post-thrombotic syndrome were included; these were pooled with the meta-analysis. RESULTS: The results showed a post-thrombotic rate of 17% (95% CI 11 - 26%) (seven studies, 217 cases, 1 105 participants). Heterogeneity was high (I2 = 89%). On meta-regression, the rate of post-thrombotic syndrome was not correlated with the length of follow up (p = .71). Three studies (302 participants) reported the severity of post-thrombotic syndrome: 78% were mild (Villalta score 5 - 9); 11% were moderate (Villalta score 10 - 14), and 11% were severe (Villalta score ≥ 15). CONCLUSION: The risk of post-thrombotic syndrome after IDDVT was one in five and the risk of severe clinical manifestations, including ulceration, was one in 50. There was significant clinical, methodological, and statistical heterogeneity between studies and a substantial risk of bias from pooled studies. Randomised trials to support interventions for prevention of post-thrombotic syndrome are urgently needed.

Characterization of intramuscular calf vein thrombosis on routine knee MRI.

OBJECTIVE: Literature regarding intramuscular calf vein thrombosis (IMCVT) or infrapopliteal deep vein thrombosis (DVT) evaluation by magnetic resonance imaging (MRI) is limited, particularly with regard to routine unenhanced knee examinations. We attempt to correlate routine unenhanced MRI findings with ultrasound evaluations of the lower extremity deep venous system. MATERIALS AND METHODS: The radiology information system was searched, yielding a total of 67 patients who had undergone both routine knee MRI and duplex ultrasound examinations within 14 days. The MRI examination findings recorded were the presence and pattern of edema, segmental vein dilation, intraluminal signal on fluid-sensitive sequences, and abnormal hyperintense signal on axial T1-weighted sequences. The presence and extent of thrombus more centrally (i.e., intramuscular calf vein thrombosis with or without extension into the popliteal vein) was reassessed on ultrasound. RESULTS: When comparing patients with positive (n = 13) and negative (n = 54) ultrasound, there were significant differences in each of these parameters: perivascular edema, intramuscular edema, focal vein dilation, and abnormal fluid-sensitive signal. In the subset of patients with popliteal extension of the intramuscular calf vein thrombosis compared with those without any deep vein thrombosis, there was a statistically significant increase in peripopliteal edema, abnormal fluid-sensitive signal, and abnormal hyperintense T1 signal. CONCLUSION: Imaging findings on routine unenhanced MRI have a high rate of concordance with duplex ultrasound performed through the calf in the detection of intramuscular calf vein thrombosis.

Treatment of Isolated Below the Knee Deep Vein Thrombosis.

The natural history of isolated distal deep-vein thrombosis (IDDVT) is still uncertain, as well as the real clinical risks associated with the disease and the need for its diagnosis and treatment. While more and more IDDVTs are diagnosed in everyday clinical practice, their appropriate therapeutic management is, unfortunately, far from straightforward, and different recommendations on how patients with diagnosed IDDVT should be treated are present between expert professionals and even among international guidelines. The present article aims at briefly reviewing the issue of IDDVT therapy in general, particularly focusing on the different approaches to the treatment of the disease that have been suggested by recent guidelines, those that are currently adopted in clinical practice, and necessary future directions.

Management of isolated calf vein thrombosis in cancer patients.

The treatment of isolated calf vein thrombosis remains widely debated. This study highlights the characteristics of isolated calf vein thrombosis in cancer patients and compares to isolated calf vein thrombosis in patients without history of cancer. Between July 2013 and April 2014, a retrospective chart review of consecutive patients with isolated calf vein thrombosis was performed recording patient risk factors, ultrasound characteristics of the thrombus, treatment modalities, long-term recurrence of venous-thromboembolism, incidence of bleeding, and mortality. Of 131 patients with isolated calf vein thrombosis, 53 (40.1%) had history of cancer. Isolated calf vein thrombosis occurred at an older age in cancer patients (66.7 vs 58.5 years, p = 0.004). The anatomical characteristics of isolated calf vein thrombosis on ultrasound were comparable in both groups. Isolated calf vein thrombosis in cancer patients was less likely to be treated with anticoagulation (60.4% vs 80.8%, p = 0.018). However, a trend towards higher incidence of bleeding after initiation of anticoagulation for isolated calf vein thrombosis in cancer patients (11.3% vs 6.4%, p = 0.351) was noted. Mortality in cancer patients was higher (37.7% vs 9.00%, p < 0.001) but was unrelated to isolated calf vein thrombosis or its treatment. In conclusion, the risks of bleeding seem to exceed the benefits of anticoagulation in approximately 50% of cancer patients with isolated calf vein thrombosis. The management of isolated calf vein thrombosis does not seem to impact the survival of cancer patients.

Management and outcomes of axial isolated distal deep vein thrombosis at North Shore Hospital, New Zealand: a retrospective audit.

BACKGROUND: It is standard of care to treat proximal vein deep vein thrombosis (DVT) for a minimum of 3 months. Conversely, management of isolated distal DVT (IDDVT) is controversial, with options including observation and repeat ultrasound scan within 1 week to detect and anticoagulate those with proximal propagation, or anticoagulation for periods of up to 3 months. AIM: The aim was to assess the rates of proximal propagation and venous thromboembolism (VTE) recurrence within 3 months of diagnosis of IDDVT, and to examine how the duration of treatment might influence this. METHODS: Study patients were identified by retrospective audit of data from the North Shore Hospital VTE database. All patients presenting with established axial vein distal DVT from July 2007 to June 2012 were included. A 6-week treatment duration cut-off was used to separate the treatment arms (<6 weeks vs 6 weeks vs >6 weeks), and Fisher's exact or Pearson's Chi-squared tests were used to assess between-group comparisons. RESULTS: Five hundred and seven patients were included in the study, mean age 59.7 years; 53% female. There were three cases of proximal propagation, all occurring in those receiving <6 weeks treatment. There were six VTE recurrences, three in the <6 week and three in the ≥6 week treatment groups respectively. Malignancy was the only significant predictor of VTE recurrence (P = 0.001). CONCLUSION: A 6-week duration of anticoagulation appears to be an effective and safe treatment for isolated axial distal DVT, with low rates of VTE recurrence and proximal propagation.

Comparison of clinical outcomes among patients with isolated axial vs muscular calf vein thrombosis: A systematic review and meta-analysis.

OBJECTIVE: Thrombi in the axial calf veins have quite different anatomical and physiological characteristics from that in the muscular calf veins, but their treatment was usually addressed in the same manner. We performed a meta-analysis of randomized and cohort studies to compare clinical outcomes among patients with isolated axial vs muscular calf deep vein thrombosis (DVT). METHODS: Recurrent venous thromboembolism (VTE) was selected as the primary outcome. Resolution, proximal propagation of calf DVT, pulmonary embolism (PE), major bleeds, and clinically relevant non-major bleeds were separately analyzed as secondary outcomes. Data were pooled and compared with risk ratio (RR) and 95% confidence interval (CI). RESULTS: Thirteen studies, consisting of 4889 patients, met the inclusion criteria and were included for analysis. A greater rate of recurrent VTE (FE model: RR, 1.23; 95% CI, 1.00-1.53; I2 = 29%), resolution (FE model: RR, 1.32; 95% CI, 1.01-1.72; I2 = 31%), proximal propagation (FE model: RR, 1.63; 95% CI, 1.10-2.41; I2 = 40%), and PE (FE model: RR, 2.79; 95% CI, 1.31-5.95; I2 = 0%) in the axial group compared with the muscular group. There was no difference in the pooled estimates for major bleeds (FE model: RR, 1.09; 95% CI, 0.61-1.95; I2 = 0%), and clinically relevant non-major bleeds (FE model: RR, 1.80; 95% CI, 0.93-3.48) in the axial and muscular arms. CONCLUSIONS: Patients with calf DVT limited to muscular veins might have a lower rate of recurrent VTE, resolution, proximal propagation, and PE vs those with axial calf vein involvement and exhibited similar safety outcomes.

Development of Risk Prediction Model for Muscular Calf Vein Thrombosis with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: This study aims to establish a risk prediction model for muscular calf vein thrombosis (MCVT) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: The research sample consisted of 248 patients with AECOPD and all of them underwent vascular ultrasounds of both lower limbs in this retrospective study. Univariate analysis and multivariate logistic regression analysis were conducted on factors with significant group differences to screen for the independent risk factors of MCVT. A nomogram to predict the risk of MCVT was constructed and validated with bootstrap resampling. Results: According to the exclusion criteria, 240 patients were included for analysis, divided into the MCVT group (n = 81) and the non-MCVT group (n = 159). Multivariate logistic regression analyses showed that hypertension, elevated MPV, reduced albumin (ALB), elevated D-dimer and bed rest ≥3 days were independent risk factors for MCVT in AECOPD. A nomogram model for predicting AECOPD with MCVT was established based on them. The area under the curve (AUC) of receiver operating characteristic (ROC) curve for the prediction model and the simplified Wells score was 0.784 (95% CI: 0.722-0.847) and 0.659 (95% CI: 0.583-0.735), respectively. The cut-off value and Youden index of prediction model were 0.248 and 0.454, respectively. At the same time, the sensitivity, specificity, positive predictive value, and negative predictive value of the prediction model were 85.9%, 59.5%, 84.6%, and 77.4%, respectively. The sensitivity and specificity of the simplified Wells score were 67.9% and 56.3%, respectively. Validation by the use of bootstrap resampling revealed optimal discrimination and calibration, and the decision analysis curve (DAC) suggested that this prediction model involved high clinical practicability. Conclusion: We developed a nomogram that can predict the risk of MCVT for AECOPD patients. This model has the potential to assist clinicians in making treatment recommendations and formulating corresponding prevention measures.

Two Weeks of Low Molecular Weight Heparin for Isolated Symptomatic Distal Vein Thrombosis (TWISTER study).

BACKGROUND: Treatment of low-risk patients with isolated symptomatic distal deep vein thrombi (IDDVT) is uncertain. OBJECTIVE: assess whether two weeks of therapeutic anticoagulation is efficacious/safe for IDDVT. PRIMARY OUTCOME: symptomatic three-month venous thromboembolism (VTE) incidence in the two-week anticoagulation group. Secondary outcomes included post-thrombotic syndrome (PTS) and bleeding. METHODS: Prospective multicentre cohort study. Consecutive low-risk IDDVT patients enrolled within 72 h of diagnosis and treated with therapeutic dose enoxaparin or rivaroxaban. At two weeks, patients had repeat complete whole leg compression ultrasound (CUS)/clinical review. If resolution of leg symptoms AND no radiological evidence of thrombus extension, anticoagulation was stopped. If ongoing symptoms and/or radiographic extension within distal veins, anticoagulation was continued for four more weeks. Patients with extension into the popliteal vein on two-week ultrasound were treated off-study. Patients were reviewed at three and six months. FINDINGS/INTERPRETATION: 241 eligible patients received ≥2 weeks anticoagulation. 167/241 (69%) were assigned to the 2-week anticoagulation group; 71/241 (30%) to the six-week anticoagulation group; 3/241 patients (1%) had extension into the popliteal vein on two-week CUS. Two patients in the two-week anticoagulation group had symptomatic IDDVT recurrence in ≤3 months; VTE recurrence 2/156; 1.3%(95% CI 0.05-4.85%). 69% of patients had complete resolution of symptoms within two weeks. Six-month PTS rates were 8/184, 4.4%(95% CI 2.1-8.5%). No major bleeding was reported. Our findings suggest it's safe/efficacious to stop therapeutic anticoagulation at two weeks in low-risk IDDVT patients with resolution of symptoms/no extension on ultrasound. This could replace 6-12 weeks of anticoagulation for ambulatory, low-risk IDDVT patients. TRIAL REGISTRATION: ClinicalTrials.govNCT01252420.

Postoperative complications after lower extremity arterial bypass increase the risk of new deep venous thrombosis.

Background Deep venous thrombosis after any surgical operations is considered a preventable complication. Lower extremity bypass surgery is a commonly performed operation to improve blood flow to lower extremities in patients with severe peripheral arterial disease. Despite advances in endovascular surgery, lower extremity arterial bypass remains the gold standard treatment for severe, symptomatic peripheral arterial disease. The purpose of this study is to identify the clinical risk factors associated with development of deep venous thrombosis after lower extremity bypass surgery. Methods The American College of Surgeons' NSQIP database was utilized and all lower extremity bypass procedures performed in 2013 were examined. Patient and procedural characteristics were evaluated. Univariate and multivariate logistic regression analysis was used to determine independent risk factors for the development of postoperative deep venous thrombosis. Results A total of 2646 patients (65% males and 35% females) underwent lower extremity open revascularization during the year 2013. The following factors were found to be significantly associated with postoperative deep venous thrombosis: transfusion >4 units of packed red blood cells (odds ratio (OR) = 5.21, confidence interval (CI) = 1.29-22.81, p = 0.03), postoperative urinary tract infection (OR = 12.59, CI = 4.12-38.48, p < 0.01), length of hospital stay >28 days (OR = 9.30, CI = 2.79-30.92, p < 0.01), bleeding (OR = 2.93, CI = 1.27-6.73, p = 0.01), deep wound infection (OR = 3.21, CI = 1.37-7.56, p < 0.01), and unplanned reoperation (OR = 4.57, CI = 2.03-10.26, p < 0.01). Of these, multivariable analysis identified the factors independently associated with development of deep venous thrombosis after lower extremity bypass surgery to be unplanned reoperation (OR = 3.57, CI = 1.54-8.30, p < 0.01), reintubation (OR = 8.93, CI = 2.66-29.97, p < 0.01), and urinary tract infection (OR = 7.64, CI = 2.27-25.73, p < 0.01). Presence of all three factors was associated with a 54% incidence of deep venous thrombosis. Conclusions Development of deep venous thrombosis after lower extremity bypass is a serious but infrequent complication. Patients who require unplanned return to the operating room, reintubation, or develop a postoperative urinary tract are at high risk for developing postoperative deep venous thrombosis. Increased monitoring of these patients and ensuring adequate deep venous thrombosis prophylaxis for such patients is suggested.

Anticoagulation in patients with isolated distal deep vein thrombosis: a meta-analysis.

Essentials The optimal management of isolated distal deep vein thrombosis (IDDVT) is undefined. This meta-analysis aimed to assess the clinical benefit of anticoagulation for IDDVT. Anticoagulation reduced the rate of pulmonary embolism without increasing major bleeding risk. Recurrent thromboembolism was less common with more than 6 weeks vs. 6 weeks of anticoagulation. SUMMARY: Background The optimal management of patients with isolated distal deep vein thrombosis (IDDVT), concerning both the need for anticoagulation and its duration, is undefined. Objectives We performed a meta-analysis of randomized and cohort studies in patients with IDDVT to assess the clinical benefit of: (i) anticoagulation versus no anticoagulation; and (ii) anticoagulant treatment for 6 weeks versus for > 6 weeks. Methods The primary outcome of this analysis was recurrent venous thromboembolism (proximal propagation, recurrence of deep vein thrombosis, and pulmonary embolism). Data were pooled and compared by the use of odds ratio (OR) and 95% confidence interval (CI). Results A reduction in the rate of recurrent venous thromboembolism was observed in patients who received anticoagulation relative to those who did not receive anticoagulation (either therapeutic or prophylactic) (20 studies, 2936 patients; OR 0.50, 95% CI 0.31-0.79), without an increase in the risk of major bleeding (OR 0.64, 95% CI 0.15-2.73). The rate of pulmonary embolism was lower in anticoagulant-treated patients than in controls (15 studies, 1997 patients; OR 0.48, 95% CI 0.25-0.91). A lower rate of recurrent venous thromboembolism was observed in patients who received > 6 weeks of anticoagulant therapy than in those who received 6 weeks of anticoagulant therapy (four studies, 1136 patients; OR 0.39, 95% CI 0.17-0.90). Conclusions In patients with IDDVT, anticoagulation (both therapeutic and prophylactic) reduces the rate of recurrent venous thromboembolism and the incidence of pulmonary embolism as compared with no anticoagulation, without an increased risk of major bleeding. Anticoagulation for > 6 weeks should be preferred over shorter durations.

Clinical thromboembolic detterrent stockings application: are thromboembolic detterrent stockings in practice matching manufacturers application guidelines.

BACKGROUND: Thromboembolic detterrent (TED) stockings have been shown to be effective in the reduction of thromboembolic events in post operative patients. These manufactured stockings create graduated compression from ankle to calf. AIM: To assess whether the manufacturers' recommendations for application were being met in a District general hospital setting and whether this achieved the desired gradient of compression. METHODS: We carried out pressure measurements on 100 legs in post-operative patients and recorded reasons for poorly fitting stockings. Pressure measurements were taken at standard positions around calf and ankle using a pre-calibrated subbandage pressure measuring device. RESULTS: About 20% of stockings were worn incorrectly by patients. Median pressure applied at the ankle was 13 mmHg (range, 6.5-18.5) compared to the manufacturers' intended compression of 18 mmHg. Only 14% of the stockings showed an acceptable gradation of reduced pressure between ankle and calf. About 23% of the stockings exerted a positive pressure at calf level compared to the ankle. CONCLUSION: Most TED stockings do not produce a standardised Siegel profile pressure gradient decrease from ankle to calf. This may be due in part to fluid changes after surgery in combination with the large variation in size of lower limbs. Our District general hospital utilises three of the six sizes of TED stocking, and remeasurement was not taking place every 24 h as per guidance. This as the result show not only negates the benefit of TED stockings but may also exert harm in terms of venous thromboembolism risk. This finding adds further weight to the argument of whether TED stockings may not be having the desired prophylactic effect and may even be resulting in harm in select cases.

No consensus exists for use of anticoagulation for calf vein thrombosis.

The ideal treatment of calf vein thrombosis (CVT) remains undefined. We assessed practice patterns at a single institution for CVT. Physicians were sent an online survey with 8 multiple choice questions about management of CVT. A total of 99 physicians of varying specialties participated in the survey. A total of 48.5% anticoagulate patients with CVT and 51.5% do not. Of those who anticoagulate, 62.3% use low molecular weight heparin and 11% use IV heparin. Treatment duration is 3 months for 58% and 6 months for 30% of responders. Of those who do not anticoagulate, 71.2% reassess for clot propagation or resolution with a duplex exam. IVC filters are used by 46% when there is a contraindication to anticoagulation and 13.7% when clot propagation is noted on follow-up scan. These results suggest that there is no consensus treatment of CVT. There is a higher than expected rate of IVC filters placed for CVT.

Early treatment outcome of isolated calf vein thrombosis after total knee arthroplasty.

PURPOSE: In contrast to proximal deep vein thrombosis (DVT), the treatment of isolated calf vein thrombosis (ICVT) remains controversial. This study aimed to investigate early treatment outcomes of ICVT after total knee arthroplasty (TKA). METHODS: Medical records of 313 patients who underwent TKA from October 2007 to December 2009 were retrospectively reviewed. A DVT-computed tomography (CT) was performed 7 days after surgery. ICVT was identified in 76 limbs of 73 patients. Of them, follow-up DVT-CT was available in 39 limbs of 37 patients. The patients with ICVTs were categorized into two groups: oral anticoagulation group (group I, 17 patients with 18 limbs) and conservative treatment group (group II, 20 patients with 21 limbs). Group I received an oral vitamin K antagonist for 3 to 6 months following low molecular weight heparin. Change of thrombus extent and development of pulmonary embolism (PE) was assessed in follow-up DVT-CT. RESULTS: Mean age was 68 years and 95% were female. Of 39 limbs with ICVT, 16 (41%) involved major lower leg veins (posterior tibial vein or peroneal vein), 13 (33%) involved muscular veins (soleal vein or gastrocnemius vein) and 10 (26%) involved both. During 1 to 6 months, follow-up DVT-CT revealed complete thrombus resolution in all limbs and there was no proximal propagation of thrombus or PE in both groups. CONCLUSION: There is no evidence of DVT propagation or newly developed PE in the conservative treatment group. This result suggests that anticoagulation therapy for ICVT patients without PE after TKA may not be mandatory.

Early treatment outcome of isolated calf vein thrombosis after total knee arthroplasty / 대한외과학회지

PURPOSE: In contrast to proximal deep vein thrombosis (DVT), the treatment of isolated calf vein thrombosis (ICVT) remains controversial. This study aimed to investigate early treatment outcomes of ICVT after total knee arthroplasty (TKA). METHODS: Medical records of 313 patients who underwent TKA from October 2007 to December 2009 were retrospectively reviewed. A DVT-computed tomography (CT) was performed 7 days after surgery. ICVT was identified in 76 limbs of 73 patients. Of them, follow-up DVT-CT was available in 39 limbs of 37 patients. The patients with ICVTs were categorized into two groups: oral anticoagulation group (group I, 17 patients with 18 limbs) and conservative treatment group (group II, 20 patients with 21 limbs). Group I received an oral vitamin K antagonist for 3 to 6 months following low molecular weight heparin. Change of thrombus extent and development of pulmonary embolism (PE) was assessed in follow-up DVT-CT. RESULTS: Mean age was 68 years and 95% were female. Of 39 limbs with ICVT, 16 (41%) involved major lower leg veins (posterior tibial vein or peroneal vein), 13 (33%) involved muscular veins (soleal vein or gastrocnemius vein) and 10 (26%) involved both. During 1 to 6 months, follow-up DVT-CT revealed complete thrombus resolution in all limbs and there was no proximal propagation of thrombus or PE in both groups. CONCLUSION: There is no evidence of DVT propagation or newly developed PE in the conservative treatment group. This result suggests that anticoagulation therapy for ICVT patients without PE after TKA may not be mandatory.