Venous Thromboembolic Disease

Value of D-dimer testing to decide duration of anticoagulation after deep vein thrombosis: not yet.

Recent Advances in Venous Thromboembolic Prophylaxis in Major Orthopedic Surgery: A Regional Perspective

Background Cancer-associated venous thromboembolism (VTE) carries a high risk for recurrent events and major bleeding (MB) which further increases among some high-risk subgroups of patients. Purpose This study evaluates recurrent VTE and MB among VTE patients with active cancer within 6 months of initiating apixaban, low-molecular weight heparin (LMWH), or warfarin stratified by cancer type, cancer treatment, and VTE characteristics. Methods Four US commercial insurance claims databases were pooled to identify VTE patients with active cancer (defined as ≥1 claim with cancer diagnosis [any stage] or cancer treatment [chemotherapy, radiation, and cancer-related surgery] within 6 months before to 30 days after VTE diagnosis). Patients who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event (01SEP2014–31MAR2018) were included. Treatment cohorts were balanced using stabilized inverse probability treatment weighting (IPTW). Cox proportional hazards models were used to estimate hazard ratios of recurrent VTE and MB for each subgroup stratification: metastatic diagnosis, cancer treatment, chemotherapy, upper and lower gastrointestinal (GI) cancer, and VTE event type (PE with or without deep vein thrombosis [DVT] versus DVT only). Statistical significance (P<0.10) of the interaction between the subgroup strata and outcomes were evaluated. Results A total of 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients were identified with a mean follow-up of 105–166 days across cohorts. After IPTW, all patient characteristics were balanced. In the overall population, apixaban had a lower risk of recurrent VTE and MB vs. LMWH. Warfarin had a similar risk of recurrent VTE and MB vs. LMWH. Apixaban had a lower risk of recurrent VTE and a similar risk of MB vs. warfarin (Figure). Analyses stratified by metastatic diagnosis, cancer treatment, chemotherapy, VTE event type, and GI cancer show generally consistent results across the subgroups (most of the p values for interaction >0.10) and with the overall population. There was a significant interaction in cancer treatment strata: apixaban trended towards a lower risk of MB vs. LMWH with or without cancer treatment; however, patients without cancer treatment had a larger difference vs. patients with cancer treatment. Two significant interactions were observed in metastatic diagnosis strata: apixaban and warfarin had a lower risk of recurrent VTE vs. LMWH in patients without a metastatic diagnosis whereas apixaban and warfarin had similar risk of recurrent VTE vs. LMWH in patients with a metastatic diagnosis (Figure). Conclusion Across these high-risk subgroups of VTE cancer patients, apixaban generally had a lower risk of recurrent VTE and MB vs. LMWH and lower risk of recurrent VTE compared to warfarin. Warfarin patients generally had a similar risk of recurrent VTE and MB vs. LMWH. The findings are generally consistent with the overall population results. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Pfizer Inc. and Britstol-Myers Squibb Company.

Venous thromboembolism (VTE) has been traditionally considered a transient acute disorder requiring a limited duration of anticoagulant therapy. Patients who suffer deep vein thrombosis (DVT) or pulmonary embolism (PE) following major surgery, major trauma, or periods of immobility are generally treated with anticoagulation for 3–6 months. After completion of anticoagulation for the initial event, the risk of VTE recurrence is believed to return to that of the general population. However, epidemiological studies suggest that VTE may be better characterized as a chronic disorder with periodic relapses. While patients who suffer unprovoked (idiopathic) VTE bear the highest risk of recurrent events, exceeding 50% over 10 years if not treated with extended duration anticoagulation, those who suffer VTE in the setting of identifiable provoking factors have an enduring risk of recurrence that exceeds 20% over 10 years. 1 Randomized controlled trials of extended duration anticoagulation for prevention of recurrent unprovoked VTE have demonstrated that the rate of recurrence increases abruptly if anticoagulation is discontinued. 2 An analysis of the Danish National Registry of Patients demonstrated that patients with VTE have increased mortality over 30 years of follow-up and that recurrent PE is an important cause of death throughout this period. 3 The efficacy of extended duration anticoagulation for prevention of recurrent events after an initial unprovoked DVT or PE further supports the classification of VTE as a chronic relapsing disease. Prolonged anticoagulation with a low- (international normalized ratio (INR) target 1.5–2.0) 4 or conventional-intensity (INR target 2.0–3.0) 5 or a non-vitamin K-dependent oral anticoagulant such as rivaroxaban, 6 dabigatran, 2 or apixaban 7 provides a 60–90% reduction in recurrent events in patients who suffer an initial unprovoked VTE. Evidence-based practice guidelines recognize the increased risk of recurrence among patients with idiopathic VTE and recommend extended duration anticoagulation in those with a low bleeding risk. Virchow’s Triad of stasis, hypercoagulability, and endothelial dysfunction and injury does not fully explain the increased risk of recurrent VTE and the need for extended duration anticoagulation. Immobility resulting in stasis is only a transient risk factor in the majority of patients with VTE. Although frequently sought as an explanation for VTE, thrombophilia is detected in only a minority of patients. 8 Furthermore, common thrombophilias such as the factor V Leiden and prothrombin gene mutations do not appear to increase the risk of recurrence. 8 Endothelial dysfunction and injury may play an important role in a subset of patients with VTE, but the underlying mechanism leading to recurrence remains unclear. Advances in our understanding of the pathophysiology of atherothrombosis may shed light on critical mechanisms for VTE recurrence. Traditionally, the burden of recurrent atherothrombotic events has been largely ascribed to dyslipidemia. However, even with intensive lipid-lowering therapy for secondary prevention, a significant burden of recurrent atherothrombotic events remains. A growing body of literature suggests that cardiovascular inflammation is a key pathophysiologic factor in recurrent atherothrombotic events. 9,10 Traditionally considered distinct and unrelated disorders, atherothrombosis and VTE are linked both epidemiologically and pathophysiologically. In fact, a reciprocal relationship exists: patients with VTE have an increased risk of myocardial infarction and stroke, and vice versa. Proven cardiovascular risk factors such as obesity, tobacco use, diabetes, stress, and diet increase the risk of atherothrombotic events and VTE. These particular risk factors share a common pathophysiological mechanism of promoting cardiovascular inflammation. In epidemiologic studies, systemic inflammation has been closely associated with an increased risk of VTE. The increased frequency of DVT and PE in patients with chronic inflammatory disorders such as inflammatory bowel disease and systemic vasculitis highlights the role of inflammation in VTE. Furthermore, increased levels of the inflammatory biomarker C-reactive protein (CRP) are associated with an increased risk of VTE. In an analysis of 10,505 participants in

Prior History of Venous Thromboembolism Is a Significant Risk Factor for Recurrence of Thrombosis after Cancer Diagnosis

Risk of Pregnancy-Associated Venous Thromboembolism in Sickle Cell Trait

BackgroundThe relationship between KRAS mutations and the risk of venous thromboembolism (VTE) recurrence in metastatic colorectal cancer (mCRC) patients with established cancer-associated thrombosis (CAT) remains uncertain. This study aims to (1) evaluate the predictive value of seven KRAS mutation subtypes for VTE recurrence and (2) assess the impact of incorporating these mutations into two existing VTE risk scores: the Khorana score and the Ottawa score.MethodsBetween 2019 and 2023, we identified patients with histologically confirmed mCRC who had symptomatic or incidental index VTE and received anticoagulation therapy. Regression analyses were conducted to calculate hazard ratios (HRs) for recurrent VTE associated with the seven KRAS mutation subtypes. We used receiver operating characteristic (ROC) curves to assess the performance of both the original scores and the modified scores that included KRAS mutations. To quantify the improvements of the modified scores, we calculated the net reclassification improvement (NRI).ResultsA total of 2,195 patients were enrolled. KRAS G12C, KRAS G12A, and KRAS G13D mutations were significantly associated with a higher risk of recurrent VTE compared to other subtypes, with HRs of 1.84 (95% CI: 1.09–2.97), 2.02 (95% CI: 1.07–3.79), and 1.55 (95% CI: 1.02–2.27), respectively. The original Khorana and Ottawa scores demonstrated moderate predictive ability for VTE recurrence, each with an area under the ROC curve (ROC-AUC) of 0.56 (95% CI: 0.52–0.60). Incorporating the KRAS G12C, KRAS G12A, and KRAS G13D mutations improved the AUCs to 0.70 (95% CI: 0.67–0.74) for the modified Khorana score and 0.71 (95% CI: 0.67–0.74) for the modified Ottawa score. After dichotomizing risk using thresholds from ROC analysis, the NRI values were 0.54 (95% CI: 0.43–0.65) for the modified Khorana score and 0.48 (95% CI: 0.37–0.60) for the modified Ottawa score.ConclusionsThe KRAS G12C, KRAS G12A, and KRAS G13D mutations are significantly associated with an increased risk of recurrent VTE. Incorporating these specific KRAS mutations into existing risk scores may enhance their predictive accuracy for recurrent VTE in patients with mCRC.

Objectives: The aim of this study is to assess the risk of venous thromboembolism (VTE) in surgical patients. Study Design: An Observational Study. Setting: 4 Tertiary Hospitals in Faisalabad city. Period: 6 months from July 2015 to December 2015. Material & Methods: Clinical data sheets of surgical in patients of 4 teaching hospitals in Faisalabad city were retrospectively reviewed. Caprini assessment model (CAM) was used for VTE risk assessment and the patients were classified into very high risk (VHR), high risk (HR), moderate risk (MR) and low risk (LR) groups. The data was collected on an Excel spread sheet and statistical analysis was done using SPSS version 17. Chi square test was carried out to assess the association of VTE risk with age, gender, BMI and surgical units. Results: We identified a total of 256 patients from July 2015 to December 2015. The median age was 42 years. 118 (46%) patients were male and 138 (54%) were female. 106 (41.4%) patients were VHR and 124 (48.4%) patients were HR for VTE according to CAM. Nineteen (7.4%) patients were MR and only 7 (2.7%) patients were LR. Higher age and male gender were found to be significantly associated with the high risk for VTE (p<0.001). Conclusion: Our study shows that the postoperative surgical patients are at higher risk of developing VTE. There is statistically significant association between increasing age and male gender with risk of VTE in this group of patients.

Extended Follow-up of the Multi-Center Multi-National Prospective Cohort Study That Derived the “Men Continue and HERDOO2” Clinical Decision Rule Which Identifies Low Risk Patients Who May Be Able to Discontinue Oral Anticoagulants (Oac) 5-7 Months After Treatment for Unprovoked Venous Thromboembolism (VTE).

Influence of Preceding Length of Anticoagulant Treatment and Initial Presentation of Venous Thromboembolism on Risk of Recurrence After Stopping Treatment: Analysis of Individual Participants' Data From Seven Trials

Venous thromboembolism in immobilized patients with dementia. Findings from the RIETE registry

Apolipoprotein M and the risk of unprovoked recurrent venous thromboembolism

Approximately a decade has passed since the addition of venous thromboembolism to the list of significant adverse reactions of antipsychotic drugs. However, only a few studies have investigated the relationship between antipsychotic use and venous thromboembolism in the Japanese population. We aimed to evaluate the risk of recurrent venous thromboembolism in users of antipsychotic drugs and update the evidence on venous thromboembolism in the Japanese population. A cross-sectional retrospective analysis of data from a large Japanese claims database, managed by Medical Data Vision Co. Ltd., was conducted. Adult patients who experienced venous thromboembolism between October 2014 and September 2018 in acute care hospitals were identified. The risk of recurrent venous thromboembolism was evaluated with logistic regression using demographic variables. The data of patients using antipsychotic drugs within specific therapeutic classes were also evaluated. We included 8960 patients (mean age, 69years; 59.2% female). Recurrent venous thromboembolism was observed in 686 patients (7.7%). The risk of recurrent venous thromboembolism was significantly higher in younger patients [<65years: reference; 65-74years: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66-0.99, p = 0.04; ≥75years: OR 0.77, 95% CI 0.64-0.94, p = 0.01], those with history of surgery (OR 1.39, 95% CI 1.18-1.65, p = 0.01), and anticoagulant users (OR 2.25, 95% CI 1.46-3.48, p = 0.01) and was significantly lower in the presence of comorbidities (OR 0.68, 95% CI 0.58-0.81, p< 0.01) and fractures (OR 0.49, 95% CI 0.26-0.94, p = 0.03). Long-term antipsychotic drug prescriptions (>14days) were associated with a higher risk of venous thromboembolism than short-term prescriptions (≤14days) (OR 1.56, 95% CI 1.04-2.34, p = 0.03). In patients with a history of venous thromboembolism, particular attention should be paid to recurrence in younger patients. If antipsychotic drugs are prescribed for >14days to patients with a history of venous thromboembolism, they should be administered carefully, guided by reported findings. Further evaluations using different databases or populations are required to generalize the findings of this study.

In 1993, individuals with a hereditary predisposition to venous thromboembolism whose plasmas exhibited a poor response to activated protein C (APC) in an activated partial thromboplastin time assay were identified.1 The molecular basis for this laboratory phenotype of resistance to APC was a guanine to adenine mutation at nucleotide 1691 in the factor V gene.2 This results in the replacement of arginine (R) at position 506 by glutamine in the resulting protein, a defect which has been termed factor V Leiden. R506 is the first of three sites at which APC normally cleaves and inactivates procoagulant factor Va. The Q506 substitution causes factor Va to be inactivated approximately l0-fold more slowly than normal, thereby making the cofactor relatively resistant to the anticoagulant action of APC.3 This allows for increased factor Va availability within the prothrombinase complex, thereby enhancing thrombin generation and the development of a hypercoagulable state. See page 1012 Factor V Leiden is the most common inherited risk factor for venous thromboembolism, increasing the risk of venous thrombosis by 4- to 10-fold in heterozygotes and 50- to 100-fold in homozygotes.4,5⇓ Heterozygosity can be identified in 12% to 20% of unselected white patients presenting with venous thrombosis and 40% to 50% of patients with a strong positive family history. Approximately 3% to 7% of normal white patients are heterozygous carriers of factor V Leiden, but the mutation is rare in …

To evaluate venous thromboembolism (VTE) risk in patients who underwent a major operation, including the use of, and factors influencing, American College of Chest Physicians-recommended types of VTE prophylaxis. The Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) survey, conducted in 358 hospitals in 32 countries, reported that globally, more than 40% of at-risk patients do not receive VTE prophylaxis. Limited data are available regarding VTE prophylaxis practices according to surgery type and patient characteristics. Patients aged >or=18 years undergoing major surgery were included in this prespecified subanalysis. VTE risk and use of prophylaxis were determined from hospital medical records according to the 2004 American College of Chest Physicians guidelines. Multivariable analyses were performed to identify factors associated with VTE prophylaxis use. Of the 18,461 patients in ENDORSE who had undergone major surgery, 17,084 (92.5%) were at-risk for VTE and 10,638 (62.3%) received prophylaxis. Use of prophylaxis varied according to major surgery type from 86.0% for orthopedic surgery to 53.8% in urologic/gynecologic and 53.6% in other procedures. Major orthopedic surgery was most strongly associated with prophylaxis use (hip replacement: odds ratio 6.2, 95% confidence interval [CI] 5.0-7.6; knee replacement: odds ratio 5.9, 95% CI 4.6-7.8). The majority of surgical patients are at high-risk for VTE. Despite long-standing recognition of the high-risk for VTE in surgical patients, thromboprophylaxis remains underutilized.