Development of a Predictive Model for Pulmonary Embolism in Gastrointestinal Cancer Patients with Isolated Distal Deep Vein Thrombosis.

Insufficient data exist about the clinical presentation, short-term, and long-term outcomes of patients with isolated distal deep vein thrombosis (IDDVT), that is, thrombosis in infrapopliteal veins without proximal extension or pulmonary embolism (PE). To determine the clinical characteristics, short-term, and 1-year outcomes in patients with IDDVT and to compare the outcomes in unadjusted and multivariable adjusted analyses with patients who had proximal DVT. This was a multicenter, international cohort study in participating sites of the Registro Informatizado Enfermedad Tromboembólica (RIETE) registry conducted from March 1, 2001, through February 28, 2021. Patients included in this study had IDDVT. Patients with proximal DVT were identified for comparison. Patients were excluded if they had a history of asymptomatic DVT, upper-extremity DVT, coexisting PE, or COVID-19 infection. Primary outcomes were 90-day and 1-year mortality, 1-year major bleeding, and 1-year venous thromboembolism (VTE) deterioration, which was defined as subsequent development of proximal DVT or PE. A total of 33 897 patients were identified with isolated DVT (without concomitant PE); 5938 (17.5%) had IDDVT (mean [SD] age, 61 [17] years; 2975 male patients [50.1%]), and 27 959 (82.5%) had proximal DVT (mean [SD] age, 65 [18] years; 14 315 male patients [51.2%]). Compared with individuals with proximal DVT, those with IDDVT had a lower comorbidity burden but were more likely to have had recent surgery or to have received hormonal therapy. Patients with IDDVT had lower risk of 90-day mortality compared with those with proximal DVT (odds ratio [OR], 0.47; 95% CI, 0.40-0.55). Findings were similar in 1-year unadjusted analyses (hazard ratio [HR], 0.52; 95% CI, 0.46-0.59) and adjusted analyses (HR, 0.72; 95% CI, 0.64-0.82). Patients with IDDVT had a lower 1-year hazard of VTE deterioration (HR, 0.83; 95% CI, 0.69-0.99). In 1-year adjusted analyses of patients without an adverse event within the first 3 months, IDDVT was associated with lower risk of VTE deterioration (adjusted HR, 0.48; 95% CI, 0.24-0.97). By 1-year follow-up, symptoms or signs of postthrombotic syndrome were less common in patients with IDDVT (47.6% vs 60.5%). Results of this cohort study suggest that patients with IDDVT had a less ominous prognosis compared with patients with proximal DVT. Such differences were likely multifactorial, including the differences in demographics, risk factors, comorbidities, particularly for all-cause mortality, and a potential association of thrombus location with VTE deterioration and postthrombotic syndrome. Randomized clinical trials are needed to assess the optimal long-term management of IDDVT.

Background: Isolated distal deep vein thrombosis (IDDVT) is a common form of venous thromboembolism (VTE). Limited data exist about the clinical characteristics, initial treatment, and short-term outcomes of these patients. Methods: Using the data from the RIETE registry (05/2001-02/2019), we identified patients with IDDVT without pulmonary embolism (PE). We determined the clinical presentation, initial treatment, and 30-day and 90-day outcomes. We compared the findings with patients with proximal DVT without PE. Results: We identified 5,359 patients with IDDVT (mean age 61±17 years, 50% women). The most prevalent comorbidities were hypertension (39%), anemia (28%), prior VTE (14%), active cancer (12%), heart failure (6.7%), and diabetes (6.6%). Recent surgery was reported in 16%. Most participants received anticoagulation (99%), most commonly with low-molecular-weight heparin (88%). No patient received thrombolytics and use of vena cava filters was rare (0.4%). At 30 days, 59 patients (1.1% [99% CI, 0.8%-1.5%]) died, including only 3 from PE (0.1% [99% CI, 0.01%-0.2%]), 44 (0.8% [99% CI, 0.5%-1.2%]) had nonfatal VTE recurrence, and 31 (0.6% [99% CI, 0.4%-0.9%]) had major bleeding. At 90 days, 2.9% (99% CI, 2.4%-3.6%) died (no additional death from PE), 1.5% (99% CI, 1.1%-2.0%) had nonfatal VTE recurrence, and 0.9% (99% CI, 0.6%-1.3%) had major bleeding. When compared with 25,420 individuals with proximal DVT without PE, those with IDDVT had lower co-morbidity burden including diabetes, heart failure, and cancer, but were more likely to have had recent surgery (P<0.001 for all). Patients with IDDVT also had lower odds of 30-day and 90-day death and major bleeding in bivariate and multivariable analyses (Figure). Conclusions: In a large multinational study, IDDVT occurred in patients with low comorbidity burden. Most patients with IDDVT received anticoagulation. Fatal PE was rare, and patients had a more benign prognosis compared with those with proximal DVT.

Clinical Outcomes of Isolated Distal Deep Vein Thrombosis Associated with Cancer: The Cleveland Clinic Experience

Isolated distal deep vein thrombosis (IDDVT) is presumed to be more benign than proximal DVT (PDVT) or pulmonary embolism (PE), suggesting a need for different management approaches. This subgroup analysis of the RE-COVERY DVT/PE global, observational study investigated patient characteristics, hospitalization details, and anticoagulant therapy in patients with IDDVT in real-world settings in 34 countries enrolled from January 2016 to May 2017. Data were analyzed descriptively according to the type and location of the index venous thromboembolism (VTE): IDDVT, PDVT ± distal DVT (DDVT), and PE ± DVT. Of the 6,095 eligible patients, 323 with DVT located outside the lower limb and no PE were excluded. Of the remaining 5,772 patients, 17.6% had IDDVT, 39.9% had PDVT ± DDVT, and 42.5% had PE ± DVT. IDDVT patients were younger and had fewer risk factors for VTE than the other groups. Other comorbidities were less frequent in the IDDVT group, except for varicose veins, superficial thrombophlebitis, and venous insufficiency. IDDVT patients were less likely to be diagnosed in an emergency department (22.3 vs. 29.7% for PDVT ± DDVT and 45.4% for PE ± DVT) or hospitalized for VTE (29.2 vs. 48.5% for PDVT ± DDVT and 75.0% for PE ± DVT). At hospital discharge or 14 days after diagnosis (whichever was later), non-vitamin K antagonist oral anticoagulants were the most commonly used anticoagulants (55.6% for IDDVT, 54.7% for PDVT ± DDVT, and 52.8% for PE ± DVT). Although differences in patient characteristics, risk factors, and clinical management were identified, anticoagulant treatment of IDDVT was almost equal to that of PDVT or PE. Prospective studies should investigate whether, in a global perspective, this is an appropriate use of anticoagulants.

To analyze risk factors for the occurrence and progression of isolated distal deep vein thrombosis (IDDVT) of lower limbs, and to explore the predictive value of dynamic changes of coagulation index D-dimer on the occurrence and progression of IDDVT in acute brain injury (ABI) patients during perioperative period. A retrospective case-control study was conducted. Perioperative ABI patients admitted to department of neurocritical care unit (NCCU) of the First Affiliated Hospital of University of Science and Technology of China from September 2019 to May 2020 were enrolled. Patients' baseline characteristics, disease characteristics, treatment approaches, outcomes and coagulation function index at 1, 2-4, 5-7 and > 7 days post operation were analyzed between patients with IDDVT and patients with progressive IDDVT. Risk factors for IDDVT occurrence and progression were identified by multivariate Logistic regression. Receiver operating characteristic curve (ROC curve) were drawn to assess the predictive value of coagulation indexes for IDDVT occurrence and progression. A total of 164 ABI patients were enrolled. Most of the patients were elderly [age was 60 (51, 69) years], male [99 cases (60.4%)], and severe cases [Glasgow coma score (GCS) at admission was 6 (5, 8)]. The rates of IDDVT occurrence and progression were 61.6% (101 cases) and 16.8% (17 cases), respectively, the rate of proximal deep venous thrombosis (DVT) was 12.8% (21 cases). Compared with the IDDVT group (101 patients), patients without IDDVT group were younger (years: 55±13 vs. 62±13), length of intensive care unit (ICU) stay were shorter (days: 12±6 vs. 15±7), body mass index (BMI) and GCS at admission were higher [59 patients, BMI (kg/m2): 23±5 vs. 19±8, GCS scores: 7±2 vs. 6±2], the differences were statistically significant (all P < 0.05). Compared with patients with IDDVT progression group, male patients were fewer [61.9% (52/84) vs. 88.2% (15/17)], the proportion of transfusion of red blood cell and anticoagulant therapy were lower [8.3% (7/84) vs. 29.4% (5/17) and 47.6% (40/84) vs. 94.1% (16/17)], the proportion of cerebral herniation was higher [42.9% (38/84) vs. 11.8% (2/17)] in patients without IDDVT progressive group. All of the differences were statistically significant (all P < 0.05). D-dimer were increased in two groups of whether IDDVT occurrence or not over time. D-dimer peaked on 5-7 days after surgery in IDDVT occurrence group, and then decreased. D-dimer peaked at > 7 days after surgery in patients without IDDVT. With time, D-dimer were increased in groups of whether IDDVT progression or not, both peaked at 5-7 days postoperation, and then decreased. Compared with non-IDDVTgroup, D-dimer was significantly increased in IDDVT group from 2-4 days after surgery [mg/L: 4.1 (2.3, 8.0) vs. 2.4 (1.7, 3.4), P < 0.05], and lasted until 5-7 days [mg/L: 5.5 (3.3, 11.4) vs. 3.9 (2.6, 5.8), P < 0.05]. Compared with IDDVT group, D-dimer was significantly increased in IDDVT progressive group from 2-4 days [mg/L: 11.2 (4.7, 20.0) vs. 3.7 (2.1, 6.8), P < 0.05], and lasted until 7 days [mg/L: 11.0 (3.0, 18.9) vs. 4.1 (2.6, 6.5), P < 0.05]. Multivariate Logistic regression analysis showed that age > 60 years [odds ratio (OR) = 3.43, 95% confidence interval (95%CI) was 1.69-6.96, P = 0.001], GCS score at admission > 8 (OR = 0.35, 95%CI was 0.17-0.76, P = 0.008), length of ICU stay > 13 days (OR = 2.25, 95%CI was 1.08-4.70, P = 0.031) were risk factors for IDDVT. Gender (OR = 0.19, 95%CI was 0.02-0.71, P = 0.019), transfusion of red blood cell (OR = 6.50, 95%CI was 1.33-31.94, P = 0.021), cerebral herniation (OR = 0.18, 95%CI was 0.37-0.90, P = 0.036) were risk factors for IDDVT profression. ROC curve analysis showed that age and D-dimer at 5-7 days were predicators of IDDVT [the area under curve ROC (AUC) were 0.68 and 0.72, 95%CI were 0.60-0.75 and 0.64-0.80, both P value were 0.000 1]. When the cut-off value of age was 60 years old and the D-dimer was 5.4 mg/L, the sensitivity were 60.6% and 54.4%, specificity were 71.2% and 80.9%, respectively, positive predictive value were 78.7%, 84.5%, negative predictive value were 51.2%, 48.1%, respectively. The elevation of D-dimer to 3.9 times at days 5-7 compared with day 1 of NCCU stay was a predicator of IDDVT progression (AUC = 0.81, 95%CI was 0.71-0.88, P = 0.000 1). The sensitivity, specificity, positive predictive value and negative predictive value were 76.5%, 74.6%, 41.9% and 93.0%, respectively. IDDVT occurrence and progressiveare common in severe ABI patients during perioperative period. The dynamic change of D-dimer, especially at days 5-7, is a valuable predictor of IDDVT progressionin ABI patients, which is helpful for guiding implementation of deep vein ultrasound of lower limb.

The Safety and Efficacy of Anticoagulation for the Management of Isolated Distal Deep Vein Thrombosis in Patients with Cancer

Survival and recurrent venous thromboembolism in patients with first proximal or isolated distal deep vein thrombosis and no pulmonary embolism

Comparison of clinical outcomes among patients with proximal versus isolated distal deep vein thrombosis: A systematic review and meta-analysis.

Management of isolated distal deep vein thrombosis (IDDVT) remains controversial. We summarize recent studies regarding the natural history of IDDVT as well as pertinent therapeutic trials. We also provide our management approach. IDDVT is more commonly associated with transient risk factors and less often associated with permanent, unmodifiable risk factors than proximal DVT. IDDVT has a significantly lower risk of proximal extension and recurrence than proximal DVT. Cancer-associated IDDVT has a similar natural history to cancer-associated proximal DVT, with substantially less favourable outcomes than noncancer-associated IDDVT. Anticoagulant treatment reduces the risk of proximal extension and recurrence in IDDVT at the cost of increased bleeding risk. Intermediate dosing of anticoagulation may be effective for treating noncancer-associated IDDVT in patients without prior DVT. IDDVT with a transient risk factor can be treated for 6 weeks in patients without a prior DVT. Unprovoked IDDVT in patients without malignancy can be treated for 3 months. Outpatients without malignancy or a prior DVT can be left untreated and undergo surveillance compression ultrasound in one week to detect proximal extension, but few patients opt for this in practice. Cancer-associated IDDVT should be treated analogously to cancer-associated proximal DVT.

Clinical outcomes of isolated distal deep vein thrombosis versus proximal venous thromboembolism in cancer patients: The Cleveland Clinic experience

Thrombus Size Matters: A Risk Assessment Model for Predicting Pulmonary Embolism in Isolated Distal Deep Vein Thrombosis.

To evaluate the risk factors of isolated distal deep vein thrombosis (IDDVT) in the lower limbs by using a combination of Doppler ultrasound and thrombus molecular markers. A prospective cohort study was used. We selected 145 patients with deep vein thrombosis of the lower limbs. They were divided into the IDDVT group and the non-IDDVT group. We compared the differences in Doppler ultrasound and biochemical indexes between the two groups. The independent influencing factors of IDDVT were analyzed using logistic regression, and we plotted the receiver operating characteristic (ROC) curve. We compared 47 IDDVT cases diagnosed by DSA with 47 non-IDDVT cases selected at random. The diameter of the common femoral vein (CFV) of the affected side, deep femoral vein, and the great saphenous vein, thickness of subcutaneous tissue, and serum D-dimer (D-D) and thrombin-antithrombin III complexes (TAT) were significantly higher in the IDDVT group than the non-IDDVT group (P < .05). Logistic regression analysis showed that CFV diameter, subcutaneous tissue thickening, D-D, and TAT were all independent risk factors for IDDVT (P < .05). The combined predictor had higher predictive sensitivity, specificity, and Youden's index (93.6, 87.2, and 0.808, respectively) than using thrombus molecular markers alone or Doppler ultrasound alone. D-D and TAT, the thrombosis molecular markers, CFV diameter, and thickening of subcutaneous tissue, as well as the Doppler ultrasound, all have their own independent effects on IDDVT. When Thrombosis molecular markers and Doppler ultrasound are used in combination, they can predict which patients are at high risk of IDDVT and help doctors in making clinical decisions pertaining to prevention and treatment.

Current guidelines suggest a 3-month anticoagulant treatment course for isolated distal deep vein thrombosis (IDDVT), but shorter durations of treatment are frequently prescribed in clinical practice. We investigated whether a 6-week treatment with low-molecular-weight heparin (LMWH) at intermediate dosage can be an effective and safe alternative to vitamin K antagonists (VKA) in patients with IDDVT (non-inferiority trial). In a multicenter, open-label, randomized trial, 260 outpatients with symptomatic IDDVT were randomly assigned to receive either LMWH followed by VKA for 12 weeks or LMWH 1 mg/kg subcutaneously twice a day for 2 weeks followed by 1 mg/kg subcutaneously once a day for 4 weeks. The follow-up was 6 months and the primary endpoint was the composite measure of recurrent venous thromboembolism (VTE) defined as: recurrence or extension of IDDVT, proximal DVT, and pulmonary embolism (PE). The study was stopped prematurely due to slow recruiting rates. The primary efficacy outcome occurred in 14 patients receiving LMWH (10.8%) and in five patients receiving VKA (3.8%); risk difference was 0.069 (95% CI: 0.006-0.132), hazard ratio 2.8 (95% CI: 1.04-7.55). There was one PE in the VKA group and one proximal DVT in the LMWH group. IDDVT recurrence was 10.0% in the LMWH group versus 3.1% in the VKA group (p = .024). Two patients had clinically relevant bleedings (1.6%) in the LMWH group versus one (0.8%) in VKA group (p = .56). In conclusion, VKA for 12 weeks seems superior to LMWH for 6 weeks in reducing the risk of VTE recurrences in our cohort of outpatients with IDDVT.

Isolated distal deep vein thrombosis (IDDVT) represents a common manifestation of venous thromboembolism (VTE), accounting for up to 50% of cases involving lower-extremity deep vein thrombosis (DVT). In contrast to proximal DVT, IDDVT exhibits a higher association with transient risk factors and less frequently occurs spontaneously. IDDVT generally entails a substantially lower risk of proximal extension, pulmonary embolism, post-thrombotic syndrome, and recurrence compared to proximal DVT. Nevertheless, specific patient subgroups, including those with active cancer, prior VTE, unprovoked IDDVT, and involvement of more than one vein, demonstrate a noteworthy recurrence risk. Unlike proximal DVT, the optimal therapeutic management of IDDVT remains uncertain. In clinical practice, the predominant approach for managing IDDVT involves anticoagulation rather than ultrasound imaging surveillance, due to a significant reduction in the risk of proximal extension and recurrence. Conversely, serial imaging is typically preferred for individuals without risk factors for extension or at high risk for bleeding. Finally, anticoagulant duration relies on the different risk of VTE recurrence within the specific patient subgroups considered. This review offers an updated overview of the epidemiology, risk factors, and natural history of IDDVT, emphasizing therapeutic management in accordance with current guideline recommendations and the latest evidence, trying to provide a way out of this dark forest.

Clinical outcomes of cancer-associated isolated distal deep vein thrombosis: a comparison between asymptomatic and symptomatic thrombosis-findings from the ONCO DVT Study.