Symptomatic Deep Vein Thrombosis Research Articles

MM-450: Anti-Thrombotic Therapy for Ambulatory Patients with Multiple Myeloma Receiving Immunomodulatory Agents: A Systematic Review

Context Multiple myeloma (MM) is a malignant plasma cell disorder characterized by clonal plasma cells and is associated with an increased risk of thromboembolism, especially in people receiving immunomodulatory agents, including lenalidomide, pomalidomide, and thalidomide. Objective 1) To systematically review the evidence for the relative efficacy and safety of anticoagulants in MM patients; and (2) to maintain this review as a living systematic review. Design Comprehensive literature search that included (1) major electronic searches (February 2021) of the following databases: CENTRAL, MEDLINE, and Embase; (2) conference proceedings; (3) reference lists of included studies; and (4) ongoing studies in trial registries. As part of the living systematic review approach, we are running continual searches on a monthly basis. Setting Randomized controlled trials (RCTs). Participants Ambulatory people with MM receiving immunomodulatory agents who otherwise have no standard therapeutic or prophylactic indication for anticoagulation. Interventions Any of: Aspirin (ASA), vitamin K antagonist (VKA), low-molecular-weight heparin (LMWH), or direct oral anticoagulants (DOAC). Main Outcomes Measures All-cause mortality, symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and minor bleeding. Results Of 1004 identified citations, we included nine articles reporting four RCTs that enrolled 813 participants. ASA versus VKA: One RCT compared ASA to VKA at six months and at two years follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to VKA on studied outcomes. ASA versus LMWH: Two RCTs compared ASA to LMWH at six months and at two years follow-up. The pooled data failed to confirm or exclude a beneficial or detrimental effect of ASA relative to LMWH on studied outcomes. VKA versus LMWH: One RCT compared VKA to LMWH at six months and at two years follow-up. The data did not confirm or exclude a beneficial or detrimental effect of VKA relative to LMWH on studied outcomes. ASA versus DOAC: One RCT compared ASA to DOAC at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to DOAC on studied outcomes. Conclusions People with MM considering anti-thrombotic agents should balance the possible benefits of reduced thromboembolic complications with the possible harms and burden of anticoagulants.

Effectiveness and Tolerability of Fondaparinux vs Enoxaparin in a Population of Indian Patients with Symptomatic Deep Vein Thrombosis: A Retrospective Real-World Study.

BackgroundFondaparinux is the first approved anticoagulant drug among factor Xa inhibitors, with proven effectiveness and safety in preventing deep vein thrombosis. However, limited data are available supporting the benefit-risk profile of fondaparinux vs enoxaparin in a real-world group of Indian patients with deep vein thrombosis.ObjectiveTo compare the effectiveness and tolerability of fondaparinux vs enoxaparin in patients with symptomatic deep vein thrombosis in a long-term real-world setting.MethodsData from the electronic medical records of adult patients diagnosed with deep vein thrombosis prescribed fondaparinux (n = 503) or enoxaparin (n = 508) as monotherapy were analyzed. Effectiveness was analyzed in terms of recurrence, duration, and type of deep vein thrombosis event, and tolerability as bleeding events at initial hospitalization and follow-up visits up to 3 months duration. Appropriate statistical methods were used to determine the significance (p < 0.05) between the two groups.ResultsThe deep vein thrombosis recurrence in the fondaparinux group was non-inferior (2.78%) when compared with enoxaparin (3.76%), with a mean duration of 47 and 48 days, respectively. The number of events and mean duration of events (in days) were not significant (p > 0.05). Major bleeding events were higher in the enoxaparin group at 3.17% than the fondaparinux group at 2.19%, and the difference was not statistically significant (p > 0.05).ConclusionsThe weight-based, once-daily subcutaneous fondaparinux dose showed non-inferior effectiveness and a comparable tolerability profile when compared with the twice-daily enoxaparin dose for the management of symptomatic deep vein thrombosis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00273-4.

Deep Vein Thrombosis : An Unusual Presentation in COVID-19 Patients-Our Experience and Comparison with Non COVID-19 Deep Vein Thrombosis Cases

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was found in Wuhan China which caused the acute respiratory illness and became the pandemic as declared by World Health Organization on March 11, 2020. Viral inclusion bodies have been identified in endothelial cells in a variety of organs. Deep Vein Thrombosis(DVT) is one atypical presentation which is thought to be triggered by endothelial dysfunction and exacerbated by hypoxia in patients with COVID-19.&#x0D; Methods: It was a single center retrospective study in Kathmandu University Dhulikhel Hospital. All the data were taken between January, 2020 till May, 2021 who were presented in OPD or inpatient department with symptoms of DVT and required admission. Presence or absence or concomitant COVID-19 was tested by RT-PCR test.&#x0D; Result: There were a total of 52 patients admitted as DVT, among which 26(50%) were male and 26(50%) were female. Twenty patients (38.5%) were COVID-19 positive and 32 (61.5%) were COVID-19 negative. Mean age for among those patients was 50.50±4.8 years, average hospital stay was 6.4±0.6 days, after anticoagulation therapy target INR was reached in 3.8±0.17 days and CVI was present in 14(70%) for COVID positive with DVT. Similarly, mean age was 46.80±3.3 years, average hospital stay was 4.6±0.3 days, after anticoagulation therapy target INR was reached in 3.3±0.21 days and CVI was present in 18(56.65%) with COVID negative with DVT.&#x0D; Conclusion: COVID-19 is still the mysterious virus and exact mechanism of this disease is still a debate which may need many years to solve. Sometimes DVT can be the only presentation of this disease

Application of manual aspiration thrombectomy in the treatment of deep vein thrombosis in cancer patients: Descriptive retrospective cohort study.

ObjectivesTo determine the outcomes and feasibility of endovascular treatment, mainly based on manual aspiration thrombectomy (MAT) with adjunctive percutaneous balloon angioplasty with or without stent deployment, for treatment of symptomatic ilio-femoral deep vein thrombosis (IFDVT) in cancer patients.Materials and methodsIn this retrospective cohort study, 135 consecutive patients (56 men; mean age, 63 years; 149 limbs) with acute (n = 113; 83.7%) and subacute to chronic (n = 22; 16.3%) symptomatic IFDVT underwent MAT-based endovascular treatment. Among them, adjunctive balloon angioplasty and stent placement was performed in 94 patients. Technical and clinical success regarding stage and cause of DVT was assessed.ResultsTechnical success (complete thrombus removal without residual thrombus or stenosis) was achieved in 89.6%, and subjective symptom improvement was stated by 71.5% of treated patients. The primary patency rates were 88.1%, 81.6%, 76.0%, 74.1% and 69.1% at 1, 3, 6, 12, and 30 months, respectively. Recurrent IFDVT occurred in 19.3% (26/135) of patients, 0.79 cases per patients-years of follow up. According to the analysis by causes of IFDVT, recurrence rate was 19.3% (11/57), 21.2% (12/57), and 14.3% (3/21) in unknown, compression/invasion of the vein by cancerous mass, and May-Thurner syndrome groups, respectively (p = 0.798). No procedure-related complication developed.ConclusionsEndovascular treatment based on MAT is a feasible treatment option with favorable outcomes and minimal risk of complication in cancer patients with symptomatic IFDVT.

Rivaroxaban for the Treatment of Symptomatic Isolated Distal Deep Vein Thrombosis – RIDTS Study

Background: The optimal management of patients with isolated distal deep vein thrombosis (IDDVT) is uncertain. Observational studies report similar therapeutic strategies as for patients with proximal DVT or pulmonary embolism (PE), but shorter treatment duration. We compared two different durations of treatment with rivaroxaban in patients with symptomatic IDDVT. Methods: In a randomized, double-blind, placebo-controlled trial, patients with symptomatic IDDVT received 6 weeks of rivaroxaban at standard doses and were assigned to rivaroxaban 20 mg once daily or placebo for additional 6 weeks. Randomization was done using a computer-generated randomization list and was stratified by study center. Primary efficacy outcome was a composite of recurrent IDDVT, proximal DVT, symptomatic or fatal PE. Primary safety outcome was ISTH-defined major bleeding. We here report the results of the 6-month follow-up. Findings: Of the 402 randomized patients, 200 received rivaroxaban and 202 placebo. IDDVT was unprovoked in 41.0% and 42.6% of patients, respectively. The primary efficacy outcome occurred in 5 patients (2.5%) on rivaroxaban and 21 (10.4%) treated with placebo (p=0.001). Recurrent IDDVT occurred in 3 (1.5%) and 16 (7.9%)(p=0.002); proximal DVT or PE in 2 (1.0%) and 5 (2.5%) (p=0.45), respectively. There were 3 (0.7%) major bleeding events prior to randomization, none after randomization. Interpretation: Rivaroxaban administered for 3 months effectively and safely reduces recurrent venous thrombosis as compared to 6 weeks of treatment during a 6-month follow up. The incidence of proximal DVT and PE was low and similar between the two groups. Clinical Trial Registration Details: EudraCT Number: 2016-000958-36. Clinical Trial Gov identifier: NCT02722447. Funding Information: Unrestricted grant from Bayer Italy. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the local institutional review boards or ethics committees of all participating centers and was performed in accordance with the declaration of Helsinki (52nd WMA General Assembly, Edinburgh, Scotland, October 2000) as well as with the International Conference on Harmonisation (ICH) guidelines on Good Clinical Practise (GCP).

Dural Tear Does not Increase the Rate of Venous Thromboembolic Disease in Patients Undergoing Elective Lumbar Decompression with Instrumented Fusion

Evaluate if dural tears (DTs) are an indirect risk factor for venous thromboembolic disease through increased recumbency in patients undergoing elective lumbar decompression and instrumented fusion. This was a retrospective cohort study of consecutive patients undergoing elective lumbar decompression and instrumented fusion at a single institution between 2016 and 2019. Patients were divided into cohorts: those who sustained a dural tear and those who did not. The cohorts were compared using Student's t-test or Wilcoxon Rank Sum for continuous variables and Fisher exact or chi-squared test for nominal variables. Six-hundred and eleven patients met inclusion criteria, among which 144 patients (23.6%) sustained a DT.The DT cohort tended to be older (63.6 vs. 60.6 years, P=0.0052) and have more comorbidities (Charlson Comorbidity Index 2.75 vs. 2.35, P= 0.0056). There was no significant difference in the rate of symptomatic deep vein thrombosis (2.1% vs. 2.6%, P= 1.0) or pulmonary embolus (1.4% vs. 1.50%, P= 1.0). Intraoperatively, DT was associated with increased blood loss (754 mL vs. 512 mL, P < 0.0001), operative time (224 vs. 195 minutes, P < 0.0001), and rate of transfusion (19.4% vs. 9.4%, P= 0.0018). Postoperatively, DT was associated with increased time to ambulation (2.6 vs. 1.4 days, P < 0.0001), length of stay (5.8 vs. 4.0 days, P < 0.0001), and rate of discharge to rehab (38.9 vs. 25.3%, P= 0.0021). While DTs during elective lumbar decompression and instrumentation led to later ambulation and longer hospital stays, the increased recumbency did not significantly increase the rate of symptomatic venous thromboembolic disease.

Management and Outcomes of Patients with Isolated Superficial Vein Thrombosis under Real Life Conditions (INSIGHTS-SVT)

Management and outcomes of superficial vein thrombosis (SVT) are highly variable and not well described. Therefore, the INvestigating SIGnificant Health TrendS in the management of SVT (INSIGHTS-SVT) study collected prospective data under real life conditions. Prospective observational study of objectively confirmed acute isolated SVT. The primary outcome was a composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), and extension or recurrence of SVT at three months. The primary safety outcome was clinically relevant bleeding. A total of 1 150 patients were included (mean age 60.2 ± 14.7 years; 64.9% women; mean BMI 29.4 ± 6.3 kg/m2). SVT was below the knee in 54.5%, above the knee in 26.7%, above and below the knee in 18.8%. At baseline, 93.6% received pharmacological treatment (65.7% fondaparinux, 23.2% heparins, 4.3% direct oral anticoagulants [DOACs], 14.5% analgesics), 77.0% compression treatment, and 1.9% surgery; 6.4% did not receive any anticoagulation. The primary outcome occurred in 5.8%; 4.7% had recurrent or extended SVT, 1.7% DVT, and 0.8% PE. Clinically relevant non-major bleeding occurred in 1.2% and major bleeding in 0.3%. Complete clinical recovery of SVT was reported in 708 patients (62.4%). Primary outcome adjusted by propensity score and for treatment duration was lower with fondaparinux compared with low molecular weight heparin (4.4% vs. 9.6%; hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.3 - 0.9; p= .017). On multivariable analysis, associated factors for primary outcome included another SVT prior to the present SVT event (HR 2.3), age per year (HR 0.97), duration of drug treatment per week (HR 0.92), and thrombus length (HR 1.03). At three month follow up, patients with isolated SVT are at risk of thromboembolic complications (mainly recurrent or extended SVT), despite anticoagulation. In this real life study, about one third had received either heparins, oral anticoagulants, or no anticoagulation.

Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism: Results of the Select-D™ Pilot Trial

Introduction: Venous thromboembolism (VTE) in cancer patients is an important and increasingly frequent clinical challenge. In the UK, dalteparin is a licensed low molecular weight heparin (LMWH), administered subcutaneously, for the extended treatment and prevention of recurrence of acute VTE in cancer patients, considered standard treatment prior to the trial starting. Rivaroxaban is a highly selective direct Factor Xa inhibitor with oral bioavailability; a direct oral anticoagulant (DOAC). Data comparing LMWH and DOACs in cancer patients with VTE are limited.Methods: Select-d is a prospective, randomised, open label, multicentre pilot trial comparing dalteparin (200 IU/kg daily, month 1 and 150 IU/kg, months 2-6); and rivaroxaban (15mg twice daily for 3 weeks then 20mg once daily, for 6 months in total) for cancer patients with VTE [symptomatic or incidental pulmonary embolism (iPE) or symptomatic lower extremity proximal deep vein thrombosis (DVT)]. After 6 months of trial treatment, DVT patients who were residual vein thrombosis (RVT) positive by compression ultrasound and patients with PE at presentation, could be randomised to placebo or rivaroxaban for a further 6 months. The original sample size of 530 patients was large to provide sufficient numbers in the second randomisation (150 in each arm) to assess the duration of anticoagulation. The trial sample size was reduced when the second randomisation closed due to a high attrition rate. The revised sample size of 200 patients in each arm provides estimates of the primary outcome (VTE recurrence) to within +/- 4.5% (i.e. width of 95% confidence interval (CI) of 9%), assuming VTE recurrence rates of 10% at 6 months. Secondary outcomes included major bleeds and clinically relevant non-major bleeds (CRNMB) [including overt bleeds resulting in unscheduled contact with a physician or interruption or discontinuation of study drug], acceptability, survival and health economics.Results: 406 patients were recruited between October 2013 and December 2016 from 58 sites across the UK; 203 patients randomised to each arm. Patients had a median age of 67 years (range 22-87); 214 (53%) were males; 386 (95%) from white ethnic origin. Patients presented with either early or locally advanced disease (n=156; 38%), metastatic disease (n=240; 59%), or haematological malignancies (n=10; 3%). Over half of the patients had iPE (n=214; 53%); 47% (n=192) had symptomatic PE or DVT. 280 (69%) patients were receiving anticancer treatment at the time of their VTE; the majority receiving chemotherapy (n=232; 83%) or targeted therapy (n=41; 15%).The VTE recurrence rate at 6 months was 11% (95% CI 7-17%) for patients on dalteparin and 4% (95% CI 2-9%) for patients on rivaroxaban. Major bleeds were similar across trial arms [6 bleeds from 6 patients (3%; 95% CI 1-6%) on the dalteparin arm; 9 bleeds from 8 patients (4%; 95% CI 2-8%) on the rivaroxaban arm]. There were more CRNMBs on the rivaroxaban arm; 5 bleeds from 5 patients (2%; 95% CI 1-6%) on dalteparin compared with 28 bleeds from 27 patients (13%; 95% CI 9-19%) on rivaroxaban. In total, 11 patients (5%; 95% CI 3-9%) on the dalteparin arm had bleeds categorised as either major bleeds or CRNMBs compared to 34 patients (17%; 95% CI 12-22%) on the rivaroxaban arm.208 (54%) patients completed 6 months of trial treatment [100 (52%) patients on dalteparin; 108 (55%) on rivaroxaban]. Overall survival at 6 months was 70% (95% CI 63-76%) on dalteparin and 74% (95% CI 68-80%) on rivaroxaban. The second randomisation only recruited 92 of the required 300 patients; 82 were PEs (61 iPE and 21 symptomatic) and 10 were DVTs. Patients did not continue to the second randomisation due to: death or withdrawal (50%); being RVT negative (12%); failing the other eligibility criteria (24%) or declining randomisation (14%).Conclusion: Select-d is a large pilot randomised trial for the treatment of VTE, investigating a DOAC versus a LMWH in patients with cancer. Treating with rivaroxaban resulted in a very low VTE recurrence rate at 6 months with a similar number of major bleeds reported across trial arms but more CRNMBs were seen with rivaroxaban. A large phase III trial will confirm the use of rivaroxaban for the treatment of VTE in cancer patients. DisclosuresYoung:Leo Pharma: Honoraria; Bayer: Honoraria, Research Funding; Helsinn: Honoraria. Kakkar:Bayer: Honoraria, Research Funding; Janssen: Honoraria; Sanofi: Honoraria; Daiichi Sankyo: Honoraria.

The Effects of Rivaroxaban Exposure and Clinical Risk Factors on Efficacy and Safety Outcomes in the Prevention of Venous Thromboembolism after Elective Hip or Knee Replacement Surgery

Introduction: The oral factor Xa inhibitor rivaroxaban has previously demonstrated a predictable pharmacokinetic (PK) and pharmacodynamic profile, and has been developed for fixed dose administration without routine coagulation or therapeutic drug monitoring (TDM). The objectives of this study were to investigate the relationship between rivaroxaban exposure and efficacy/safety outcomes, and to evaluate the relative influence of relevant clinical risk factors in patients receiving rivaroxaban for venous thromboembolism prevention (VTE-P) after elective total hip replacement (THR) or total knee replacement (TKR) surgery to assess whether TDM might further improve the benefit-risk profile of rivaroxaban in this population.Methods: An exposure-response analysis was conducted using data from patients receiving rivaroxaban (10 mg once daily [OD] for ≤35 days after THR or ≤14 days after TKR) in the phase 3 REgulation of Coagulation in ORthopedic Surgery to prevent DVT and PE (RECORD) trials (efficacy population, n = 4246; safety population, n = 6097). Due to a lack of measured PK data in the phase 3 trials, individual rivaroxaban exposure metrics (area under the plasma concentration-time curve, maximum concentration and trough concentration [Ctrough]) were estimated using an integrated population PK model based on clinical risk factors, regimen and (where available) PT measurements. Exposure estimates were improved by applying an adjustment function based on the linear relationship between PK and prothrombin time measurements (measured centrally using a rivaroxaban-sensitive thromboplastin reagent) obtained in the phase 2/3 rivaroxaban studies. The composite efficacy outcome was total VTE (any objectively-documented asymptomatic or symptomatic deep vein thrombosis [proximal and/or distal], non-fatal pulmonary embolism and death). Safety endpoints were major bleeding, and a composite of major and non-major clinically relevant (NMCR) bleeding occurring (1) ≤3 days after surgery (days 1-4) and (2) >3 days after surgery (after day 4). The relationships between exposure/clinical risk factors and outcomes in terms of event rates were evaluated using logistic regression models.Results: The model-estimated rivaroxaban exposures are summarized in the Table. In the final model, age and creatinine clearance were included as forced variables for all endpoints. Exposure was not found to be a significant predictor of total VTE, major bleeding (days 1-4 and after day 4), or of the composite safety endpoint of major and NMCR bleeding during days 1-4. For major and NMCR bleeding after day 4, a statistically significant exposure-response relationship was observed, with Ctrough displaying the strongest association. The odds ratios (ORs) associated with Ctrough in the 5th and 95th percentiles versus the median were 0.82 (95% confidence interval [CI]: 0.77-0.87) and 1.68 (95% CI: 1.21-2.33), respectively. The relationship was shallow, with a predicted absolute increase in major and NMCR bleeding of ~1% at the 5th percentile of Ctrough to 2% at the 95th percentile (Figure). No clinical risk factors were predictors of total VTE or of major bleeding (days 1-4 and after day 4), or of major and NMCR bleeding after day 4. Male versus female sex (OR: 3.05; 95% CI: 1.92-4.93) and geographical region (OR: 1.63; 95% CI: 0.98-2.70, for the USA/Canada vs Western Europe) were significant predictors (p < 0.00001 and p <0.001, respectively) of major and NMCR bleeding during days 1-4.Conclusions: An exposure-response relationship for total VTE and major bleeding events was not observed in patients enrolled in the RECORD trials despite significant reductions in VTE with rivaroxaban versus the comparator enoxaparin, indicating a favorable benefit-risk ratio over the range of rivaroxaban concentrations observed with the 10 mg OD fixed dose. Exposure, and particularly Ctrough, was the predominant predictor of major and NMCR bleeding after day 4. These data are consistent with rivaroxaban phase 2 VTE-P studies, in which no significant dose-response relationship was observed for total VTE, but post-operative bleeding events increased dose dependently over the ranges of rivaroxaban doses of 5-40 mg OD and 2.5-30 mg twice daily. Based on these findings it is unlikely that TDM would further improve the benefit-risk profile of rivaroxaban for VTE prevention after THR and TKR. [Display omitted] DisclosuresBerkowitz:Bayer US: Employment. Fox:Bayer HealthCare Pharmaceuticals: Consultancy, Honoraria; AstraZeneca: Research Funding; Janssen Biotech, Inc.: Consultancy, Honoraria. Schmidt:Bayer HealthCare Pharmaceuticals: Consultancy. Weitz:Bayer HealthCare Pharmaceuticals: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Portola Pharmaceuticals: Consultancy, Honoraria; Daiichi-Sankyo: Consultancy, Honoraria; Pfizer, Inc.: Consultancy, Honoraria; Janssen Biotech, Inc.: Consultancy, Honoraria; Ionis Pharmaceuticals: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Novartis Pharmaceuticals: Consultancy, Honoraria; Merck & Co., Inc.: Consultancy, Honoraria. Garmann:Bayer AG: Employment. Kubitza:Bayer AG: Employment. Mueck:Bayer AG: Employment. Peters:Janssen Research & Development: Employment. Reinecke:Bayer AB: Employment; Bayer AG: Employment. Solms:Bayer AG: Employment. Spiro:Bayer US: Employment. Yan:Janssen Research & Development: Employment. Zhang:Janssen Research & Development: Employment. Willmann:Bayer AG: Employment.

Longitudinal Haemostatic Biomarker Trajectories Predict Cancer-Associated Venous Thromboembolism

Background: Venous thromboembolism is an important complication of cancer. Elevated biomarkers of hypercoagulability, such as D-Dimer and Prothrombin Fragment 1.2 (F1.2), are associated with an increased risk of cancer-associated VTE. However, the evolution of these biomarkers during the course of disease is incompletely understood. Moreover, it is unclear whether potential longitudinal changes in these biomarkers over time harbor additional prognostic information on VTE risk in the oncologic setting.Aim: To define the role of longitudinal haemostatic biomarker trajectories for personalized prediction of VTE risk in patients with cancer.Methods: In this prospective cohort study, 164 patients with active malignancy were enrolled at cancer diagnosis or at progression after complete or partial remission (median age: 62 years [51-69; female sex: n=79 (48%); tumor sites: lung n=58 (35%), brain n=48 (29%), pancreas n=33 (20%), colon n=22 (13%), stomach n=3 (2%); metastatic disease: n=72 (44%)). D-Dimer (median: 0.8 µg/mL [25th-75th percentile: 0.4-2.0]), F1.2 (227 pmol/L [166-332]), and others (to be presented at the meeting) were measured at study inclusion, as well as during 637 follow-up visits each 1 month apart, for a planned number of 7 total visits (median number of visits: 5 [4-7]). Primary endpoint of the study was a composite of symptomatic, objectively-confirmed, and independently-adjudicated deep vein thrombosis and/or pulmonary embolism (VTE) during the observation period of 250 days. Joint models of longitudinal and time-to-event data were implemented to study how the haemostatic biomarker trajectories associate with the risk of cancer-associated VTE.Results: The primary endpoint of VTE occurred in 18 patients, corresponding to a 250-day VTE risk of 12.1% (95% confidence interval (CI): 7.8-18.5). Graphical inspection of biomarker trajectories with a moving average suggested that levels of D-Dimer (Figure 1, Panel A) and F1.2 (Figure 1, Panel B) increased before the occurrence of VTE. Indeed, in linear mixed modeling, D-Dimer increased by 0.19 µg/mL/month (0.05-0.32, p=0.007) in patients who eventually developed VTE, but remained constant in patients who did not develop VTE (change per month=0.01 µg/mL, -0.09-0.9, p=0.97). Similarly, F1.2 increased by 9.8 pmol/L/month (0.2-19.5, p=0.045) in patients who developed VTE, while the corresponding increase in patients who did not develop VTE was smaller and not statistically significant (3.3 pmol/L/month, -1.2-7.9, p=0.155). In joint modeling, a doubling of the D-Dimer trajectory was associated with a 2.8-fold increase in the risk of VTE (Hazard ratio (HR)=2.79, 95%CI: 1.66-4.69, p<0.0001). A corresponding increase in F1.2 was associated with a 2.6-fold increase in VTE risk (HR=2.61, 1.02-6.74, p=0.046), respectively. While patients with metastatic cancer had higher levels of both D-Dimer (1.2 vs. 0.6 µg/mL, p<0.0001) and F1.2 (249 vs. 219 pmol/L, p=0.0003) than non-metastatic patients, the prognostic associations between the biomarker trajectories and VTE risk was highly comparable between these two patient groups (p for interaction=0.48, HR for D-Dimer trajectory in non-metastatic patients=3.16 (1.65-6.06, p=0.001), HR for D-Dimer trajectory in metastatic patients=2.51 (1.38-4.56, p=0.003); results for F1.2 not shown).Conclusions: D-Dimer and F1.2 increase before the onset of cancer-associated VTE, but remain relatively constant over time in patients with cancer who do not develop VTE. So-called joint models can successfully link these biomarker trajectories to the prospective risk of VTE. These findings apply similarly to patients with metastatic and non-metastatic cancers. We conclude that the assessment of haemostatic biomarker trajectories in patients with cancer is a novel concept that could substantially advance the personalized assessment of VTE risk in the oncologic setting. [Display omitted] DisclosuresPabinger:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sobi: Consultancy, Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Failure of the Ottawa Score to Predict the Risk of Recurrent Venous Thromboembolism in Cancer Patients: The Prospective PREDICARE Cohort Study.

Recurrent venous thromboembolism (VTE) despite curative anticoagulation is frequent in patients with cancer. Identifying patients with a high risk of recurrence could have therapeutic implications. A prospective study was designed to validate the Ottawa risk score of recurrent VTE in cancer patients. In a prospective multicenter observational cohort, adult cancer patients with a recent diagnosis of symptomatic or incidental lower limb deep vein thrombosis or pulmonary embolism (PE) were treated with tinzaparin for 6 months. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment. All clinical events were centrally reviewed and adjudicated. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. A C-statistic value of > 0.70 was needed to validate the Ottawa score. A total of 409 patients were included and analyzed on an intention-to-treat basis. Median age was 68 years, 60.4% of patients had PE, and VTE was symptomatic in 271 patients (66.3%). The main primary sites were lung (31.3%), lower digestive tract (14.4%), and breast (13.9%) cancers. The Ottawa score was high (≥ 1) in 58% of patients. The 6-month cumulative incidence of recurrent VTE was 7.3% (95% confidence interval [CI]: 4.9-11.1) overall, and 5.0% (95% CI: 2.3-10.8) versus 9.1% (95%CI: 6.1-13.6) in the Ottawa low versus high risk groups, respectively. The C-statistic value was 0.60 (95% CI: 0.55-0.65). In this prospective cohort of patients with cancer receiving tinzaparin for VTE, the Ottawa score failed to accurately predict recurrent VTE.

Challenges in the diagnostic approach of suspected pulmonary embolism in COVID-19 patients

ABSTRACT Accumulating studies on COVID-19 patients report high incidences of thrombotic complications, but guidance on the best diagnostic approach for suspected pulmonary embolism (PE) in COVID-19 patients is lacking. Diagnosing PE in these patients is challenging as signs and symptoms of PE and COVID-19 show wide overlap, D-dimer levels are often elevated in the absence of thrombosis and computed tomography pulmonary angiography (CTPA) may be unfeasible in the case of severe renal impairment and/or hemodynamic instability. This narrative review discusses available literature and guidelines on current diagnostic algorithms for suspected PE in special patient populations, in particular COVID-19. A special focus is on reviewing the literature aimed at identifying symptoms with a high suspicion for PE and on the diagnostic performance of diagnostic algorithms for suspected PE in the setting of COVID-19. Based on available literature, the index of suspicion for PE should be high in the case of unexplained abrupt worsening of respiratory status, typical symptoms of deep-vein thrombosis and/or acute unexplained right ventricular dysfunction. Despite the lack of prospective diagnostic management studies, we propose to adhere to current diagnostic algorithms applying assessment of pretest probability and D-dimer testing as available evidence suggests that these might be considered safe. Preferably, algorithms using adjusted D-dimer thresholds are recommended as it likely improves the yield of the clinical decision rule/D-dimer combination.

Clinical Outcomes of a Pharmacomechanical Catheter-Directed Venous Thrombolysis Strategy that Included Rheolytic Thrombectomy in a Multicenter Randomized Trial

PurposeTo describe the clinical outcomes of a pharmacomechanical catheter-directed venous thrombolysis (PCDT) strategy that included AngioJet rheolytic thrombectomy. MethodsIn the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis multicenter randomized trial, physicians at 33 sites designated AngioJet as their preferred device for PCDT. In these sites, 364 patients with acute proximal lower-extremity deep vein thrombosis (DVT) were randomized to a strategy of PCDT that incorporated either AngioJet along with anticoagulation or anticoagulation alone. Relief from presenting DVT symptoms was evaluated over 30 days of follow-up. Postthrombotic syndrome (PTS), quality of life (QOL), recurrent venous thromboembolism (VTE), and safety were evaluated over 24 months of follow-up. ResultsWithin 30 days, AngioJet-PCDT led to a greater improvement in leg swelling (mean difference calf circumference 0.55 cm, P = .009), venous QOL (mean difference 6.5 Venous Insufficiency Epidemiologic and Economic Study [VEINES]-QOL points, P = .0073), and venous symptoms (mean difference 5.6 VEINES-symptoms points, P = .0134) than control, with differences most apparent in iliofemoral DVT. AngioJet-PCDT reduced PTS at 6 months (24% with AngioJet-PCDT vs 40% with control, P = .003) but did not influence PTS or QOL between 12 and 24 months. Major bleeding, pulmonary embolism, renal failure, and bradycardia were infrequent with AngioJet-PCDT (<2% each), but 24-month VTE recurrence may have been more frequent (13.9% with AngioJet-PCDT vs 6.8% with control, P = .03) ConclusionsIn patients with acute proximal DVT, a treatment strategy that included first-line AngioJet-PCDT was reasonably safe and led to an improved symptom status and venous QOL at 1 month and reduced PTS at 6 months compared with anticoagulation alone. However, AngioJet-PCDT did not influence PTS or the QOL beyond 6 months and may have increased recurrent VTE.

Incidence and risk factors for symptomatic venous thromboembolism following anterior cruciate ligament reconstruction.

To determine the incidence of symptomatic venous thromboembolism (VTE) following anterior cruciate ligament (ACL) reconstruction using a large national database and to identify corresponding independent risk factors. The Humana administrative claims database was reviewed for patients undergoing ACL reconstruction from 2007 to 2017. Patient demographics, medical comorbidities, as well as concurrent procedures were recorded. Postoperative incidence of VTE was measured by identifying symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) at 30 days, 90 days, and 1 year postoperatively. Univariate analysis and binary logistic regression were performed to determine independent risk factors for VTE following surgery. A total of 11,977 patients were included in the study. The incidence of VTE was 1.01% (n = 120) and 1.22% (n = 146) at 30 and 90 days, respectively. Analysis of VTE events within the first postoperative year revealed that 69.6% and 84.3% of VTEs occurred within 30 and 90 days of surgery, respectively. Logistic regression identified age ≥ 45 (odds ratio [OR] = 1.88; 95% confidence interval [CI] 1.32-2.68; p < 0.001), inpatient surgery (OR = 2.07; 95% CI 1.01-4.24; p = 0.045), COPD (OR = 1.51; 95% CI 1.02-2.24; p = 0.041), and tobacco use (OR = 1.75; 95% CI 1.17-2.62; p = 0.007), as well as concurrent PCL reconstruction (OR = 3.85; 95% CI 1.71-8.67; p = 0.001), meniscal transplant (OR = 17.68; 95% CI 3.63-85.97; p < 0.001) or osteochondral allograft (OR = 15.73; 95% CI 1.79-138.43; p = 0.013) as independent risk factors for VTE after ACL reconstruction. The incidence of symptomatic postoperative VTE is low following ACL reconstruction, with the majority of cases occurring within 90 days of surgery. Risk factors include age ≥ 45, inpatient surgery, COPD, tobacco use and concurrent PCL reconstruction, meniscal transplant or osteochondral allograft. III.

Incidence of venous thromboembolism in patients with non-hematological cancer admitted for COVID-19 at a third-level hospital in Madrid.

An increased risk of venous thromboembolism (VTE) in hospitalized patients with COVID-19 has been reported. We aimed to describe the incidence rate of VTE on patients with non-hematological cancer who required hospitalization due to COVID-19 at our center. In this prospective study, non-hematological cancer patients hospitalized for confirmed COVID-19 at our institution from 1st March to 30th April 2020, were evaluated daily for VTE complications during their hospital stay, and after discharge until 30th June 2020. Furthermore, Doppler ultrasound of lower limbs was routinely performed in asymptomatic patients based on D-dimer levels and current active cancer therapy. The primary outcome of this study was the cumulative incidence of VTE. Secondary outcomes were the cumulative incidence of bleeding and mortality. A total of 58 hospitalized non-hematological cancer patients and confirmed COVID-19 were identified. Median follow-up since initial symptoms of COVID-19 was 91 days (IQR 19–104). Pulmonary embolism was diagnosed in three (5%) patients. Symptomatic catheter-related deep vein thrombosis (DVT) was observed in one patient. Doppler ultrasound of lower limbs was done in 11 asymptomatic patients, showing distal DVT in two of them (18%). The cumulative incidence of VTE on day 14 after admission was 10%, without new VTE events after hospital discharge and up to 90 days follow-up. No bleeding complication was observed. Seventeen patients (29%) died in the first 14 days after COVID-19 diagnosis. Four patients died after discharge due to malignancy progression. The cumulative incidence of VTE in non-hematological cancer patients under active treatment was 10% at day 14 after admission, with no further new events in the following 12 weeks.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11239-021-02448-w.

Compression stockings for preventing deep vein thrombosis in airline passengers.

Air travel might increase the risk of deep vein thrombosis (DVT). It has been suggested that wearing compression stockings might reduce this risk. This is an update of the review first published in 2006. To assess the effects of wearing compression stockings versus not wearing them for preventing DVT in people travelling on flights lasting at least four hours. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 April 2020. We also checked the bibliographies of relevant studies and reviews identified by the search to check for any additional trials. Randomised trials of compression stockings versus no stockings in passengers on flights lasting at least four hours. Trials in which passengers wore a stocking on one leg but not the other, or those comparing stockings and another intervention were also eligible. Two review authors independently selected trials for inclusion and extracted data. We sought additional information from trialists where necessary. One new study that fulfilled the inclusion criteria was identified for this update. Twelve randomised trials (n = 2918) were included in this review: ten (n = 2833) compared wearing graduated compression stockings on both legs versus not wearing them; one trial (n = 50) compared wearing graduated compression tights versus not wearing them; and one trial (n = 35) compared wearing a graduated compression stocking on one leg for the outbound flight and on the other leg on the return flight. Eight trials included people judged to be at low or medium risk of developing DVT (n = 1598) and two included high-risk participants (n = 1273). All flights had a duration of more than five hours. Fifty of 2637 participants with follow-up data available in the trials of wearing compression stockings on both legs had a symptomless DVT; three wore stockings, 47 did not (odds ratio (OR) 0.10, 95% confidence interval (CI) 0.04 to 0.25, P < 0.001; high-certainty evidence). There were no symptomless DVTs in three trials. Sixteen of 1804 people developed superficial vein thrombosis, four wore stockings, 12 did not (OR 0.45, 95% CI 0.18 to 1.13, P = 0.09; moderate-certainty evidence). No deaths, pulmonary emboli or symptomatic DVTs were reported. Wearing stockings had a significant impact in reducing oedema (mean difference (MD) -4.72, 95% CI -4.91 to -4.52; based on six trials; low-certainty evidence). A further three trials showed reduced oedema in the stockings group but could not be included in the meta-analysis as they used different methods to measure oedema. No significant adverse effects were reported. There is high-certainty evidence that airline passengers similar to those in this review can expect a substantial reduction in the incidence of symptomless DVT and low-certainty evidence that leg oedema is reduced if they wear compression stockings. The certainty of the evidence was limited by the way that oedema was measured. There is moderate-certainty evidence that superficial vein thrombosis may be reduced if passengers wear compression stockings. We cannot assess the effect of wearing stockings on death, pulmonary embolism or symptomatic DVT because no such events occurred in these trials. Randomised trials to assess these outcomes would need to include a very large number of people.

Knowledge of and attitude toward venous thromboembolism among professional drivers in Saudi Arabia

Evidence suggests that professional drivers are at risk for venous thromboembolism (VTE), a life-threatening yet preventable disease. Awareness of VTE among this population has not been assessed in the Middle East. The study aimed to assess professional drivers’ awareness of VTE and attitudes toward VTE preventive measures. We used a validated VTE awareness questionnaire to interview 324 drivers in Saudi Arabia during February-March 2020. Knowledge about VTE was the lowest compared to other medical conditions. Less than a third (31.8%) of the drivers were aware of VTE. Only 15.7% of those with prior awareness correctly identified all four deep vein thrombosis symptoms, and only 7.4% correctly identified all five pulmonary embolism symptoms. A significant proportion believed in unrelated practices for VTE prevention. Health promotion campaigns are urgently needed to raise awareness and to promote healthy behaviors.

Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period.

Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period.

The Effect of Foot Massage on Hemodynamic among Patients Admitted in to the Intensive Care Unit of General Public Hospital, Indonesia

Several studies have suggested the effectiveness of foot massage on reducing stress and blood pressure. However, few studies examine the effect of foot massage on hemodynamic status especially among patients admitted to intensive care units, when the hemodynamics status was unstable and became a significant concern. This study aimed to examine the effects of on hemodynamic status especially among patients admitted to intensive care unit. This study was quasi-experimental with pre- and post-test in one group. Subjects were recruited from the intensive care unit of one general public hospital located in Garut, West Java, Indonesia. Patients who used a partial mode control of ventilator, mean arterial pressure &gt; 70 mmHg, heart rate &gt; 60 times per minute, respiration rate &gt; 12 times per minutes, and oxygen saturation ≤ 100% were considered as eligible criteria in this study. The exclusion criteria were patients who have fractures, trauma, or leg injuries, in an anxious state, or diagnosed with deep vein thrombosis symptoms. A paired t-test was used to examine the effect of the intervention of mean arterial pressure, heart rate, respiration rate, and oxygen saturation. Of the 30 patients recruited, the mean age was 41.7 (SD=3.10) with the majority female (63.3%). We found that foot massage has a significant impact on the improvement of the mean arterial pressure, heart rate, respiration rate, and oxygen saturation at the second time measurement after 30 minutes intervention (p&lt;0.05). Foot massage improves the hemodynamic status among patients admitted in intensive care unit. Future studies using a rigor method with large sample size is needed with control therapy and disease-associated factors.&#x0D; &#x0D; Keywords: foot massage, hemodynamic, intensive care unit, intervention study

Association Between Asymptomatic Proximal Deep Vein Thrombosis and Mortality in Acutely Ill Medical Patients.

BackgroundAsymptomatic proximal deep vein thrombosis (DVT) is an end point frequently used to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Recently, the clinical relevance of asymptomatic DVT has been challenged.Methods and ResultsThe objective of this study was to evaluate the relationship between asymptomatic proximal DVT and all‐cause mortality (ACM) using a cohort analysis of a randomized trial for the prevention of venous thromboembolism (VTE) in acutely ill medical patients. Patients who received at least 1 dose of study drug and had an adequate compression ultrasound examination of the legs on either day 10 or day 35 were categorized into 1 of 3 cohorts: no VTE, asymptomatic proximal DVT, or symptomatic DVT. Cox proportional hazards model, with adjustment for significant independent predictors of mortality, were used to compare the incidences of ACM. Of the 7036 patients, 6776 had no VTE, 236 had asymptomatic DVT, and 24 had symptomatic VTE. The incidence of ACM was 4.8% in patients without VTE. Both asymptomatic proximal DVT (mortality, 11.4%; hazard ratio [HR], 2.31; 95% CI, 1.52–3.51; P<0.0001) and symptomatic VTE (mortality, 29.2%; HR, 9.42; 95% CI, 4.18–21.20; P<0.0001) were independently associated with significant increases in ACM. The analysis was post hoc, and ultrasound results were not available for all patients. Adjustment for baseline variables significantly associated with ACM may not fully compensate for differences.ConclusionsAsymptomatic proximal DVT is associated with higher ACM than no VTE and remains a relevant end point to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT00571649.