Proximal Deep Vein Thrombosis Research Articles

Fibrin monomer complex on postoperative day 1 is correlated with the volume of deep vein thrombosis after knee surgery

PurposePatients undergoing knee surgery are at high risk for deep vein thrombosis (DVT), which is infrequent but potentially life-threatening. It has not been identified how to efficiently detect high-risk DVT while minimizing bleeding complications from anticoagulation. We hypothesized that the degree of activation of thrombotic markers may correlate with the size of the thrombus. Therefore, we investigated the correlation between thrombotic markers and DVT thrombus volume in patients after knee surgery.MethodsThis retrospective study involved 29 patients who underwent around knee osteotomy or total / unicompartmental knee arthroplasty from 2018 to 2020. Fibrin monomer complex (FMC) at 1, and 7 days after surgery, and D-dimer at 4, and 7 days after surgery were investigated. In addition, the volume of DVT was estimated with ultrasonography at the 7 days after surgery. Body mass index, surgical time, and total volume of blood loss were also evaluated. Factors related to thrombus volume were examined statistically.ResultsNine patients (31.0%) exhibited asymptomatic distal DVT, whereas 1 patient (3.4%) experienced asymptomatic proximal DVT. No patients had pulmonary embolism. Statistical analysis showed that only FMC concentration on postoperative day 1 was significantly correlated with thrombus volume (p < 0.001, 95% confidence interval 0.41 to 0.839, r = 0.679).ConclusionsThe FMC concentration was a useful early indicator of deep vein thrombosis after knee surgery. Monitoring the FMC concentration could enable selective identification of patients with a high thrombus volume, which is associated with a high risk for pulmonary embolism.

Catheter directed thrombolysis for deep vein thrombosis in 2022: Rationale, evidence base and future directions

IntroductionCatheter directed thrombolysis (CDT) has evolved as a treatment modality for patients diagnosed with proximal and caval deep vein thrombosis (DVT) and has shown to be superior in certain subset of patient population despite conflicting evidence as seen in the large 4 randomized controlled trials. Rationale for CDT in acute DVT patientsDVT adversely affects the quality of life and adds significantly to the treatment and hospitalization costs. CDT and pharmaco-mechanical catheter directed thrombolysis (PCDT) has been shown to accelerate symptom resolution, decrease symptom severity and decrease recurrence rates with successful procedures in certain patients. Randomized clinical trials (RCTs)Four RCTs have evaluated the use of CDT and PCDT in acute proximal DVT patients suggesting clinical benefit compared to anticoagulation alone. These trials suggested using CDT for proximal DVT patients with a lower bleeding risk as CDT may decrease PTS. Successful CDT treatment showed improvement in moderate to severe symptoms of post thrombotic syndrome (PTS). However, these studies have limitations including the use of non-standard techniques, different equipment and different endpoints. Future directions and conclusionOur goal is to highlight the factors which can potentially improve CDT outcomes in proximal DVT patients. Based on studies, patients with proximal DVT and a low bleeding risk may benefit from early CDT by decreased symptom severity of PTS, however, improvement in procedural technique, equipment and procedural success rates is necessary. With appropriate patient selection, and objective endpoints, we can further establish the benefit of CDT and PCDT in acute DVT patients.

Characteristics and Treatment Strategy of Isolated Calf Deep Venous Thrombosis after Fractures: A Review of Recent Literature.

Isolated calf deep venous thrombosis (ICDVT) includes thrombosis located at the far end of the popliteal vein, such as the anterior tibial vein, posterior tibial vein, fibular vein, and intramuscular vein of the soleus and gastrocnemius. This type of thrombosis has the highest incidence, accounting for approximately half of all deep vein thrombosis (DVT) cases; however, there is no consistent recommendation for ICDVT treatment across countries, and there is also no optimal management strategy. In recent years, increasing evidence has shown that ICDVT can develop into proximal DVT, even causing pulmonary embolism (PE). Therefore, some experts suggest anticoagulant therapy for this type of DVT, while others hold an opposing attitude. Therefore, the treatment strategy for this type of DVT has become a hot and difficult research topic. The purpose of this review is to summarize the characteristics of ICDVT and the effects of different treatment strategies by analyzing recent and important classical works in the literature in an attempt to provide recommendations for the treatment of this most common type of DVT in orthopaedic clinics.

Catheter-Directed Thrombolysis for Postpartum Deep Venous Thrombosis.

Venous thromboembolism is a major concern during pregnancy as well as in the postpartum period. In acute proximal deep venous thrombosis, endovascular recanalization with locally administered thrombolytic agents has evolved as therapeutic alternative to anticoagulation alone. However, data on the bleeding risk of thrombolysis in the postpartum period is limited. We addressed the key clinical question of safety outcomes of catheter-directed thrombolysis (CDT) in the peri- and postpartum period. Therefore, we performed a non-exhaustive literature review and illustrated the delicate management of a patient with postpartum acute iliofemoral thrombosis treated with CDT and endovascular revascularization with thrombectomy, balloon angioplasty and stenting.

Anticoagulation as secondary prevention of massive lung thromboses in hospitalized patients with COVID-19

Anticoagulation as secondary prevention of massive lung thromboses in hospitalized patients with COVID-19

Incidence, timing, location, risk factors, and nomogram of lower extremity deep venous thrombosis after acutecarbon monoxide poisoning.

Data on lower extremity deep venous thrombosis (DVT) following acute carbon monoxide (CO) poisoning are lacking. This study aimed to identify the incidence rate, timing, locations, risk factors, and nomogram of lower extremity DVT after acute CO poisoning. A total of 203 patients with acute CO poisoning from October 2019 to April 2021 were included in this retrospective study. Multivariate logistic regression analysis was performed to identify the independent risk factors associated with lower extremity DVT. Nomogram was drawn and area under the curve (AUC) was calculated to predict lower extremity DVT. Overall, 14.3% (29/203) had lower extremity DVT, with incidence rates of 2.5% (5/203) for proximal DVT and 11.8% (24/203) for distal DVT. The lower extremity DVTs involved intermuscular vein in 28 patients, popliteal vein in 5 patients, and posterior tibial vein in 3 patients. The mean time from end of exposure to diagnosis of lower extremity DVT was 1.24days. Among 29 lower extremity DVT cases, 6 (23.1%) DVT cases had thrombolysis. Multivariate logistic regression analysis revealed that long coma duration (P < 0.001) and high D-dimer levels (P < 0.001) were significantly associated with lower extremity DVT. The discrimination of nomogram was good with AUC of 0.93 (95% CI, 0.89-0.98). Clinicians should be aware of and concerned with lower extremity DVT after acute CO poisoning, especially in patientswith long coma duration and high D-dimer levels.

Early Detection and Management of Venous Thrombosis in Skull Base Surgery: Role of Routine Doppler Ultrasound Monitoring.

Venous thromboembolism (VTE), encompassing deep venous thrombosis (DVT) and pulmonary embolism (PE), causes postoperative morbidity and mortality in neurosurgical patients. The use of pharmacological prophylaxis for DVT prevention in the immediate postoperative period carries increased risk of intracranial hemorrhage, especially after skull base surgeries. To investigate the impact of routine Doppler ultrasound monitoring in prevention and tiered management of VTE after skull base surgery. We retrospectively analyzed a large cohort of consecutive adult patients who were prospectively and uniformly managed with routine monitoring by Doppler ultrasound for DVT after resection of a skull base tumor. A total of 389 patients who underwent 459 surgeries for intracranial tumor resection were analyzed. Skull base meningioma was the most common pathology. Forty-four (9.59%) postoperative VTEs were detected: 9 (1.96%) with PE with or without DVT and 35 (7.63%) with DVT alone. Four cases of subsegmental PE were diagnosed without evidence of lower extremity DVT, possibly in the setting of peripherally inserted central catheters maintenance. One patient had a preoperative proximal DVT and underwent a prophylactic inferior vena cava filter but expired from PE after discharge. Prior history of VTE (risk ratio [RR] 5.13; 95% CI 2.76-7.18; P < .01), anesthesia duration (RR 1.14; 95% CI 1.03-1.27; P = .02), and blood transfusion (RR 1.95; 95% CI 1.01-3.37; P = .04) were associated with VTE development on multivariate analysis. Routine postoperative venous ultrasound monitoring detects asymptomatic DVT guiding management. This is an alternative strategy to prescribing pharmacological VTE prophylaxis immediately after lengthy surgeries for intracranial tumors. Peripherally inserted central catheters were associated with subsegmental PE.

Real world prescribing practices of apixaban or rivaroxaban lead-in doses for the treatment of venous thromboembolism in hospitalized patients.

The oral factor Xa inhibitors (OFXAi) apixaban and rivaroxaban are increasingly utilized for the treatment of venous thromboembolism (VTE) with recommended initial higher dose 7- and 21-day lead-in regimens, respectively. In patients receiving initial parenteral anticoagulation, it remains unknown if the full recommended higher dose OFXAi lead-in regimens are warranted, or if days can be subtracted. We aimed to describe when clinicians may deviate from recommended lead-in durations and evaluate clinical outcomes in these scenarios. This is a retrospective, observational study of patients 18years or older who were treated with rivaroxaban or apixaban for acute pulmonary embolism (PE) or symptomatic proximal deep vein thrombosis (DVT) that received parenteral anticoagulation for at least 24h before transitioning to the OFXAi. Among our cohort of 171 patients with acute VTE who received parenteral anticoagulation for a median of 48h, 134 (78%) were prescribed a full OFXAi lead-in and 37 (22%) were prescribed a reduced lead-in. Patients in the reduced lead-in group were older with more cardiac comorbidities and antiplatelet use. There were four recurrent thromboembolic events within 3months, two in the reduced lead-in group and two in the full lead-in group (5% vs. 2%, p = 0.206). Bleeding within 3months occurred in 9 (5%) patients, with 6 events occurring in the reduced lead-in group and 3 events in the full lead-in group (16% vs. 2%, p = 0.004). Prescribing patterns of OFXAi lead-in therapy duration are variable in patients receiving initial parenteral anticoagulation. Larger cohorts are needed to better define the safety and efficacy of lead-in reduction.

Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial

BackgroundHospitalized patients with COVID‐19 suffered initially from high rates of venous thromboembolism (VTE), with possible associations between therapeutic anticoagulation and better clinical outcomes in observational studies. ObjectiveTo test whether therapeutic anticoagulation improves clinical outcomes in severe COVID‐19. Patients/MethodsIn this multicenter, open‐label, randomized controlled trial, we recruited acutely ill medical COVID‐19 patients with D‐dimer >1000 ng/ml or critically ill COVID‐19 patients in four Swiss hospitals, from April 2020 until June 2021, with a 30‐day follow‐up. Participants were randomized to in‐hospital therapeutic anticoagulation versus low‐dose anticoagulation in acutely ill participants/intermediate‐dose anticoagulation in critically ill participants, with enoxaparin or unfractionated heparins. The primary outcome was a centrally adjudicated composite of 30‐day all‐cause mortality, VTE, arterial thrombosis, and disseminated intravascular coagulopathy (DIC), with screening for proximal deep vein thrombosis. ResultsAmong 159 participants, 55.3% were critically ill and 94.3% received corticosteroids. Before study inclusion, pulmonary embolism had been excluded in 71.7%. The primary outcome occurred in 4/79 participants randomized to therapeutic anticoagulation and 4/80 to low/intermediate anticoagulation (5.4% vs. 5.0%; risk difference +0.4%; adjusted hazard ratio 0.76, 95% confidence interval 0.18–3.21), including three deaths in each group. All primary outcomes and major bleeding (n = 3) occurred in critically ill participants. There was no asymptomatic proximal deep vein thrombosis and no difference in major bleeding. ConclusionsAmong patients with severe COVID‐19 treated with corticosteroids and with exclusion of pulmonary embolism at hospital admission for most, risks of mortality, thrombotic outcomes, and DIC were low at 30 days. The lack of benefit of therapeutic anticoagulation was too imprecise for definite conclusions.

Combined pharmacomechanical thrombectomy with selective catheter-directed thrombolysis in patients with acute proximal deep vein thrombosis.

Background The aim of this study was to evaluate the characteristics and the outcomes of combined percutaneous pharmacomechanical thrombectomy with selective catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis. Methods Between March 2018 and February 2020, a total of 37 patients (21 males, 16 females; mean age: 55±13.8 years; range, 21 to 79 years) with symptomatic acute iliofemoral vein thrombosis who underwent combined percutaneous pharmacomechanical thrombectomy and catheter-directed thrombolysis were retrospectively analyzed. All patients received a three-step therapy: (i) insertion of a temporary inferior vena cava filter, (ii) percutaneous pharmacomechanical thrombectomy via rotational mechanical thrombectomy device with an adjuvant 0.15 mg/kg recombinant tissue-type plasminogen activator alteplase, and (iii) catheter-directed thrombolysis with continuous 1 mg/h tissue-type plasminogen activator alteplase. Data including demographic characteristics of the patients, bleeding complications, technical success, and adjuvant angioplasty rates were analyzed. The Kaplan-Meier analysis was used to evaluate freedom from re-thrombosis at 3, 6, and 12 months of follow-up was calculated. Results The majority of the patients had left-sided (n=22, 59.4%) proximal deep vein thrombosis. Successful insertion of the inferior vena cava filter was achieved in 97.2% (n=36) of patients. The technical success rate was 89.1% (n=33). Adjuvant venous angioplasty was performed in four patients (10.8%) and no venous stents were used. No major bleeding was occurred, while minor bleeding was observed mostly in the form of hematuria (n=12, 32.4%). No mortality was observed. The 3, 6, and 12-month freedom from re-thrombosis rates were 96.3%, 92.6%, and 86.0%, respectively. Conclusion Combined percutaneous pharmacomechanical thrombectomy and catheter-directed thrombolysis seems to be an effective and safe treatment of the iliofemoral acute deep vein thrombosis with acceptable minor bleeding complications post-interventionally.

Increased Prevalence of Elevated D-Dimer Levels in Patients on Direct Oral Anticoagulants: Results of a Large Retrospective Study.

Elevated D-dimer levels during anticoagulant therapy with vitamin K antagonists (VKA) are associated with an increased risk of thrombosis. It has been hypothesized that elevated D-dimer levels in patients receiving direct oral anticoagulants (DOACs) also indicate an increased risk of thrombosis recurrence, but data on the distribution of D-dimer levels in patients with VTE on DOACs are sparse. In the present study we retrospectively analyzed D-dimer levels in patients taking DOACs after first or recurrent venous thrombosis (n = 1,716, 1,126 thereof rivaroxaban, 481 apixaban, 62 edoxaban, and 47 dabigatran). Patients on VKA (n = 402) served as control group. Thrombotic events in the study population were categorized into distal deep venous thrombosis (DVT, n = 552 patients), distal DVT with pulmonary embolism (PE, n = 166), proximal DVT (n = 685), proximal DVT with PE (n = 462), PE without DVT (n = 522), DVT of the upper extremity (n = 78), cerebral venous sinus thrombosis (CVST, n = 48), and other venous thrombosis (n = 74). In VKA users a median D-dimer level of 0.20 mg/l was observed. In patients on DOACs D-dimer levels were significantly higher, with 0.26 mg/l for rivaroxaban, 0.31 mg/l for apixaban (P < 10−16 each), 0.24 mg/l for edoxaban (P = 2 × 10−5), and 0.25 mg/l for dabigatran (P = 4 × 10−4). These differences in comparison to patients on VKA treatment could not be explained by the patients' age, sex, body mass index, and type of thrombosis as these characteristics did not differ significantly between cohorts. Moreover, the prevalence of D-dimer levels above age-adjusted cut-offs [≥0.50 mg/l in ≤50-year-old patients, ≥(age × 0.01) mg/l in >50-year-old patients] was higher in patients on rivaroxaban (13.9%, RR 1.74, 95% CI 1.21–2.50), apixaban (17.0%, RR 2.14, 95% CI 1.45–3.15) and dabigatran (23.4%, RR 2.94, 95% CI 1.59–5.44) than in patients on VKA (8.0%). In patients on edoxaban D-dimer levels above the reference range were observed in 14.5%, but no statistical significance was reached in comparison to the VKA cohort. In conclusion, the obtained data suggest, that the type of oral anticoagulant should be considered in the clinical assessment of D-dimer levels in thrombosis patients. Further studies are warranted to evaluate a potential association between elevated D-dimer levels and thrombosis risk in patients on DOACs.

Role of anticoagulants in therapy and prevention of recurrent venous thromboembolism in patients with cancer: a meta-analysis of randomized trials with apixaban

Background Venous thromboembolic complications (VTEC) are a major non-oncological cause of death of patients with malignant neoplasm (MNP). This determines the high significance of antithrombotic therapy for the treatment and secondary prevention of VTEC in this population. During recent years, low-molecular weight heparins (LMWH) have been a "gold standard" for the treatment of cancer-associated venous thrombosis (CAVT). In the recent decade, direct oral anticoagulants (DOACs) have become extensively used for the treatment and prevention of VTEC relapse in non-oncological patients and also for primary prevention of VTEC following orthopedic surgery. Taking into account the oral route of administration, the predictable and convenient pharmacokinetic profile, and the absence of need for coagulation monitoring, it seems possible to use DOACs for the treatment and secondary prevention of VTEС in oncological patients. A meta-analysis of 4 randomized clinical trials (RCTs) showed a higher efficacy of DOACs compared to LMWHs, however, with a greater risk of bleedings in CAVT. In two of four studies using apixaban (more than 40% of weight in meta-analysis), no increase in bleedings was noted.Aim The aim of this study was to perform a systematic search for comparative clinical studies with apixaban and to perform a meta-analysis to answer the question on clinical efficacy and safety of apixaban in the treatment and secondary prevention of recurrent VTEC in patients with CAVT.Material and methods The systematic search was performed in three reference databases, Medline (PubMed), Cochrane Library (CENTRAL), and eLibrary. The search was aimed at publications containing results of RCTs using apixaban for the treatment and prevention of VTEC in patients with MNP. A totality of 678 titles was found; 15 articles were selected for detailed studying, and 4 RCTs were included into the final analysis. The meta-analysis was performed according to the criteria of PRISMA guidelines. Relative risk (RR) was used as a measure of the effect. The meta-analysis was performed by the Mantel-Haenszel method using the R software. Statistical heterogeneity was evaluated with the Cochran criterion (I2); heterogeneity was considered significant at I2 ≥50 %, which was a reason for performing a random-effects meta-analysis. For this meta-analysis, the primary outcome measure was new VTECs (symptomatic or detected proximal deep vein thrombosis and/or symptomatic, detected or fatal pulmonary thromboembolism plus symptomatic upper extremity thromboses, celiac veinous thromboses, and cerebral veinous thromboses if they were included into the efficacy endpoint of the primary studies). The primary safety measure was major bleeding according to ISTH criteria. Other variables included major and clinically significant minor bleedings as well as overall death rate.Results During the systematic search, 4 RCTs were selected. The meta-analysis of the treatment and secondary prevention of VTEC in patients with MNP showed that apixaban was more effective than the active control (88% of LMWHs) in prevention of VTEC relapse. The RR was 0.59; 95 % confidence interval (CI): 0.40-0.86 in the absence of statistically significant differences from the control in the risk of major bleedings (statistically non-significant decrease by 21%), the sum of major and clinically significant minor bleedings, and overall death rate.Conclusion According to the results of the meta-analysis, the DOAC apixaban may be a drug of choice for the treatment and prevention of VTEC relapse in patients with MNO.

Thrombotic burden, D-dimer levels and complete compression ultrasound for diagnosis of acute symptomatic deep vein thrombosis of the lower limbs

BackgroundDiagnostic algorithms for deep vein thrombosis (DVT) include D-dimer for its high negative predictive value, thus reducing the need for imaging. Small thrombi may be associated with low D-dimer levels, increasing false negatives. AimTo assess the sensitivity and thus the false negative rates of standard and age-adjusted D-dimer cut offs for isolated distal DVT (IDDVT) in outpatients. Materials and methodsWe enrolled consecutive outpatients with suspected DVT of the lower limbs referring to our vascular emergency department from 2009 to 2018. Patients underwent D-dimer testing (STA, Stago, cut-off: 500 μg/L), pretest clinical probability (PTP) evaluation and complete compression ultrasonography. Follow-up was 3 months. ResultsAmong 3948 patients (M:1554–39%, median age 69), 486 proximal DVTs (12.3%) and 348 IDDVTs (8.8%) were diagnosed. Median D-dimer was higher in proximal than IDDVT (3960 vs 1400 μgr/L; p = 0.001). The false negative rate of the standard D-dimer cut-off was 2% (95%CI: 0.8–3.2%) for proximal DVT and 14.7% (95% CI: 11–81%) for IDDVT. The false negative rate of the age-adjusted cut-off was 4.9% (3–7%) for proximal DVT and 19.5% (95% CI: 15.4–24.7%) for IDDVT. Conclusions: Small calf thrombi are associated with low D-dimer levels, and age-adjusted D-dimer may be below the cut-off more frequently in subjects with IDDVT than standard cut-off D-dimer, although such D-dimer levels might exclude IDDVT that require treatment.

Utility of hereditary thrombophilia testing among patients with lower extremity deep vein thrombosis

ObjectiveDespite a growing consensus that testing for hereditary thrombophilia (HT) is not recommended in the setting of venous thromboembolism (VTE), such testing is still often requested. We evaluated the effects of HT on the risk of recurrent VTE for patients with lower extremity deep vein thrombosis (DVT). MethodsWe conducted a multihospital retrospective study of 867 patients with first-time proximal lower extremity DVT who had undergone testing for HT. Patients with and without HT were compared regarding their VTE recurrence risk via Kaplan-Meier and multivariable analysis. ResultsHT was present in 166 patients (19%). The baseline characteristics were similar between the patients with HT and without HT. No significant difference was found in the recurrence rates between the two groups (HT, 17%; no HT, 15%; P = .345). A Kaplan-Meier survival analysis revealed no significant differences in VTE-free survival between the patients with and without HT (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.77-1.84; P = .421). On multivariable analysis, the presence of HT was not associated with recurrent VTE. A higher body mass index (HR, 1.06; 95% CI, 1.03-1.10; P = .004) and unprovoked DVT (HR, 2.48; 95% CI, 1.69-3.66; P < .001) were risk factors for recurrence. ConclusionsHT had no significant impact on the recurrence risk for patients with first-time lower extremity DVT. HT test results would, thus, not be expected to change clinical management and should therefore not be requested routinely for patients with DVT.

Determinants of Quality of Life in Patients with Post-Thrombotic Syndrome

Chronic post-thrombotic syndrome (PTS) may develop in up to 50% of patients after deep vein thrombosis (DVT), and may reduce patients' quality of life (QoL). We aimed to evaluate the association of PTS severity with QoL in patients with proximal DVT submitted for medical treatment and also to identify modifiable and non-modifiable risk factors related to PTS. Patients with iliac or femoropopliteal DVT observed in Vascular Surgery consultation in our institution from 1year period with unilateral DVT were selected. Patients with total vein recanalization were excluded. Villalta scale was applied to assess PTS degree and VEINES-QoL/Sym questionnaire was used as a disease-specific QoL measure. Correlation between PTS degree and VEINES-QoL/Sym score and predictors of PTS were determined. Fifty-six patients were accepted to enter the study. From those, 66.1% were female, 64.3% (n=36) had iliac and 35.7% (n=20) femoropopliteal DVT. PTS was present in 52.8% of iliac and 65.0% of femoropopliteal DVT patients observed for consultation (P=0.41). There was a significant correlation with PTS degree and both VEINES-QoL and VEINES-Sym scores (P<0.01). Major depression (odds ratio OR=5.63, P=0.04) and regular wear of compressing stockings (OR=4.69, P=0.04) were the only independent factors associated with PTS. Patients with depression had lower QoL scores, while patients with PTS who wear compression stockings had similar QoL scores compared to patients without PTS. Ultrasound alterations (OR=3.28, P=0.17), age, gender, iliac DVT, multiple DVT and time after DVT (P>0.20) were not associated with PTS syndrome. VEINES-QoL/Sym had moderate inverse correlation with PTS degree. Depression was associated with both PTS and lower QoL scores. Patients with PTS criteria compliant to wearing compressing stockings had similar QoL scores to patients without PTS.

New perspectives for prevention of the post-thrombotic syndrome

While on conventional anticoagulation, up to 50% of patients with one or more episodes of proximal deep vein thrombosis (DVT) can develop post-thrombotic (PTS) manifestations. The potential strategies for PTS prevention are the treatment of acute DVT with catheter-directed thrombolysis (CDT), the use of elastic compression stockings (ECS) and that of the direct oral anticoagulants (DOAC) in place of vitamin K antagonists (VKA) for the initial and long-term treatment of DVT. Based on the results of three randomized clinical trials, CDT cannot be recommended on a routine basis because of its invasiveness, the associated risk of major bleedings and the uncertainty about its efficacy. According to the results of a placebo-controlled randomized clinical trial, ECS are no longer recommended for PTS prevention on a routine basis. However, based on the results of a recent subanalysis of a prospective cohort study, patients with residual vein thrombosis and/or popliteal valve reflux at three months are likely to benefit from ECS for at least six months. Finally, following the demonstration that the inadequacy of VKA therapy plays a key role in the PTS development, several retrospective and prospective studies have shown that the use of DOACs for the initial and long-term treatment of DVT in place of VKAs reduces the risk of PTS by approximately 50%. In conclusion, the availability of DOACs and the potential of ECS in selected patients with proximal DVT are expected to play a key role for decreasing the rate and the severity of PTS in the forthcoming years.

Defining the role of risk stratification and duplex ultrasound in the diagnosis of acute lower extremity deep vein thrombosis

ObjectiveRisk stratification using the plasma D-dimer level and Wells score has been proposed as a safe strategy to rule out acute lower extremity deep vein thrombosis (DVT) and limit the use of duplex ultrasound (DUS) for low-risk patients. A widely used diagnostic protocol defining the role of pretest probability and D-dimer testing in lieu of DUS has not been reported. Our aim was to define the risk of DVT in a standard population of emergency department patients who had presented with acute lower extremity symptoms and determine the role of DUS for these patients. MethodsOutpatients presenting to the emergency department with symptoms concerning for lower extremity DVT were prospectively enrolled. All the patients underwent whole leg DUS and clinical and laboratory assessments for DVT using the Wells criteria and plasma D-dimer testing. The patients were stratified into three groups according to the combination of their Wells score and plasma D-dimer level. The prevalence of DVT and the statistical performance of the combined Wells score and plasma D-dimer were compared. ResultsA total of 3087 patients were enrolled. Most of the patients had had a negative plasma D-dimer level and Wells score (n = 2290 patients). A total of 222 patients had had a positive plasma D-dimer level and Wells score. The overall prevalence of acute DVT in the present study was 7.3%. Of the 2290 patients with a negative Wells score and negative plasma D-dimer level, 4 had had a diagnosis of DVT (negative predictive value, 99.8%). In contrast, DVT was present in 181 of 222 patients (81.5%) with a positive Wells score and plasma D-dimer level (positive predictive value, 81.5%). The plasma D-dimer level also correlated with the DVT location, and the D-dimer levels were highest for the patients with proximal DVT. ConclusionsThe combination of a negative Wells score and negative plasma D-dimer level can safely exclude the presence of DVT. Patients with a negative Wells score and negative plasma D-dimer level are unlikely to benefit from DUS. In contrast, patients with a positive D-dimer level and positive Wells score will benefit from whole leg DUS to rule out the presence of high-risk DVT.

Incidence and Outcomes Associated with 6,841 Isolated Distal Deep Vein Thromboses in Patients with 13 Common Cancers.

The epidemiology of isolated distal deep venous thrombosis (iDDVT) among cancer patients is not well described, particularly the incidence of recurrent venous thromboembolism (rVTE) and effect on mortality by cancer type. The cumulative incidence (CI) of iDDVT was determined for patients with 13 common cancers between 2005 and 2017 using the California Cancer Registry linked to the California Patient Discharge and Emergency Department Utilization datasets. The CI of rVTE was calculated and association of incident cancer-associated thrombosis (CT) location with rVTE was determined using Cox proportional hazards regression models. The association of incident CT location with overall and cancer-specific mortality was determined using Cox models, stratified by cancer site, and adjusted for individual characteristics. Among 942,109 cancer patients, CT occurred in 62,003 (6.6%): of these, 6,841 (11.0%) were iDDVT. Compared with more proximal sites of CT, iDDVT was associated with similar risk for rVTE. IDDVT was associated with increased mortality across all cancer types when compared with patients without CT (hazard ratio: 1.56-4.60). The effect of iDDVT on mortality was similar to that of proximal DVT (pDVT) for most cancers except lung, colorectal, bladder, uterine, brain, and myeloma, where iDDVT was associated with a lesser association with mortality. iDDVT represented 11% of CT. The risk of rVTE after iDDVT was similar to other sites of CT and rVTE occurred in more proximal locations after an incident iDDVT. IDDVT was associated with increased mortality and this effect was similar to that of pulmonary embolism or pDVT for most cancer types.

Romiplostim for chemotherapy‐induced thrombocytopenia: Efficacy and safety of extended use

BackgroundChemotherapy‐induced thrombocytopenia (CIT) is common during treatment with antineoplastic therapies and may adversely impact chemotherapy dose intensity. There is no approved therapy for CIT. In our recent phase II randomized study, romiplostim led to correction of platelet counts in 85% of treated patients and allowed resumption of chemotherapy, with low rates of recurrent CIT in the first two cycles or 8 weeks of chemotherapy. However, there is a lack of long‐term data on the efficacy and safety of romiplostim in CIT. ObjectivesTo analyze efficacy and safety of romiplostim in the patients in the phase 2 study, who received romiplostim for ≥1 year. Patients/MethodsTwenty‐one patients remained on romiplostim for ≥1 year. We analyzed the effect of romiplostim on platelet counts, absolute neutrophil counts, and hemoglobin, as well as impact on ongoing chemotherapy. We also tracked venous or arterial thrombotic events. ResultsDuring the study period, romiplostim was effective in preventing reduction of chemotherapy dose intensity due to CIT. Fourteen of the 20 (70%) analyzable patients experienced no episode of CIT, 4 subjects experienced a single chemotherapy dose delay due CIT, and 2 patients required a chemotherapy dose reduction. Platelet counts were preserved throughout the duration of the extension analysis. One patient experienced a proximal deep vein thrombosis, and one patient experienced multiple tumor‐related ischemic events. ConclusionsLong‐term use of romiplostim for treatment of CIT was effective and safe, with no evidence of resistance or increased risk of thrombosis.

Prevalence and Clinical Characteristics of Proximal Deep Venous Thrombosis After a High-Density Coronavirus Disease 2019 Cluster in a Japanese Psychiatric Hospital.

The prevalence of deep venous thrombosis (DVT) among hospitalized psychiatric patients after coronavirus disease 2019 (COVID-19) infection remains unclear.Methods and Results:We retrospectively investigated the prevalence of proximal DVT after COVID-19 infection among 50 hospitalized patients in a Japanese psychiatric hospital that in which a COVID-19 cluster developed between August and September 2020. The prevalence of proximal DVT was 10.0%. Patients with proximal DVT had a lower body weight and higher maximum D-dimer levels and International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE scores. After COVID-19 infection, hospitalized psychiatric patients are at high risk of DVT and should be carefully followed up.