Safety and Efficacy of Direct Oral Anticoagulants vs Warfarin in Patients With Obesity and Venous Thromboembolism: A Retrospective Analysis.

BACKGROUND: Current venous thromboembolism guidelines recommend using direct oral anticoagulants (DOACs) over warfarin regardless of obesity status; however, evidence remains limited for the safety and efficacy of DOAC use in patients with obesity. This retrospective analysis sought to demonstrate the safety and efficacy of DOACs compared with warfarin in a diverse population of patients with obesity in light of current prescribing practices. METHODS: A retrospective cohort study was conducted at a large academic health system between July 2014 and September 2019. Adults with an admission diagnosis of deep vein thrombosis (DVT) or pulmonary embolism, with weight greater than 120 kg or a body mass index greater than 40, and who were discharged on an oral anticoagulant were included. Outcomes included occurrence of a thromboembolic event (DVT, pulmonary embolism, or ischemic stroke), bleeding event requiring hospitalization, and all-cause mortality within 12 months following index admission. RESULTS: Out of 787 patients included, 520 were in the DOAC group and 267 were in the warfarin group. Within 12 months of index hospitalization, thromboembolic events occurred in 4.23% of patients in the DOAC group vs 7.12% of patients in the warfarin group (hazard ratio, 0.6 [95% CI, 0.32-1.1]; P = .082). Bleeding events requiring hospitalization occurred in 8.85% of DOAC patients vs 10.1% of warfarin patients (hazard ratio, 0.93 [95% CI, 0.57-1.5]; P = .82). A DVT occurred in 1.7% and 4.9% of patients in the DOAC and warfarin groups, respectively (hazard ratio, 0.35 [95% CI, 0.15-0.84]; P = .046). CONCLUSION: No significant differences could be determined between DOACs and warfarin for cumulative thromboembolic or bleeding events, pulmonary embolism, ischemic stroke, or all-cause mortality. The risk of DVT was lower with apixaban and rivaroxaban. Regardless of patient weight or body mass index, physicians prescribed DOACs more commonly than warfarin.

Management of lower-extremity venous thromboembolism: An updated review.

According to the 2021 updated guidelines of the American College of Chest Physicians, the location of venous thromboembolism, the severity of symptoms, the risk of thrombus extension vs that of bleeding, and comorbidities all affect the decision to treat, the choice of anti-thrombotic agent, and the duration of therapy. In patients with isolated distal deep vein thrombosis without high-risk features, monitoring progression is recommended over initiating anticoagulation. However, treatment of proximal deep vein thrombosis with anticoagulation is strongly recommended by the guidelines. More evidence now supports the treatment of superficial vein thrombosis with anticoagulation in high-risk patients.

International Normalized Ratio Predicts Recurrence and Bleeding in Patients With Acute Venous Thromboembolism Who Undergo Direct Oral Anticoagulants.

Prothrombin time/international normalized ratio (PT/INR) is related to both antithrombotic effect and risk of bleeding. Its role in the prediction of venous thromboembolism (VTE) recurrence and bleeding for patients with acute VTE who undergo direct oral anticoagulants (DOACs) treatment is unclear, despite previous studies revealed some association between them. The predictive efficiency of INR for VTE recurrence and bleeding were analyzed in a retrospective cohort with VTE patients who underwent DOACs treatment. Then its predictive efficiency for VTE recurrence and bleeding were validated in a prospective cohort with the acquired cutoffs range, and compared with anti-Xa level, DASH and VTE-BLEED scores. In the retrospective cohort (n = 1083), the sensitivity and specificity of INR for the prediction of VTE recurrence were 79.4% and 92.8%, respectively. The area under the curve (AUC) was 0.881 (0.803-0.960)(P = .025). The cutoff value of INR was 0.9. The sensitivity and specificity of INR for the prediction of bleeding were 85.7% and 77.9%, respectively. The AUC was 0.876 (0.786-0.967)(P < .001). The cutoff value of INR was 2.1. In the prospective cohort (n = 202), the calibration showed that there were 4 (50%) patients with VTE recurrence, 156 (97.5%) patients with non-recurrence and bleeding (non-R&B), and 20 (58.8%) patients with bleeding in the low (INR < 0.9)(n = 8), intermediate (0.9 ≤ INR ≤ 2.1)(n = 160), and high (INR > 2.1)(n = 34) groups, respectively. The baseline PT/INR value at the initiation of DOACs treatment is an independent predictor for VTE recurrence and bleeding in patients with acute VTE who undergo DOACs treatment.

Biomarkers Profile in Provoked Versus Unprovoked Deep Venous Thrombosis.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.

Aspirin or enoxaparin for VTE prophylaxis after primary partial, total or revision hip or knee arthroplasty: A secondary analysis from the CRISTAL cluster randomized trial.

BACKGROUND: This study compares aspirin to enoxaparin for symptomatic VTE prophylaxis within 90 days of any type of hip or knee arthroplasty performed for any diagnosis, in patients enrolled in the CRISTAL trial. MATERIALS AND METHODS: CRISTAL was a cluster-randomised crossover, registry-nested non-inferiority trial across 31 hospitals in Australia. The primary publication was restricted to patients undergoing primary total hip or knee arthroplasty for a diagnosis of osteoarthritis. This report includes all enrolled patients undergoing hip or knee arthroplasty procedures (partial or total, primary or revision) performed for any indication. Hospitals were randomized to administer patients aspirin (100mg daily) or enoxaparin (40mg daily), for 35 days after hip arthroplasty and 14 days after knee arthroplasty. Crossover occurred after the patient enrolment target had been met for the first group. The primary outcome was symptomatic VTE within 90 days. Analyses were performed by randomization group. RESULTS: Between April 20, 2019 and December 18, 2020, 12384 patients were enrolled (7238 aspirin group and 5146 enoxaparin). Of these, 6901 (95.3%) given aspirin and 4827 (93.8%) given enoxaparin (total 11728, 94.7%) were included in the final analyses. Within 90 days, symptomatic VTE occurred in 226 (3.27%) aspirin patients and 85 (1.76%) enoxaparin patients, significant for the superiority of enoxaparin (estimated treatment difference 1.85%, 95% CI 0.59% to 3.10%, p = 0.004). Joint-related reoperation within 90 days was lower in the enoxaparin group (109/4827 (2.26%) vs 171/6896 (2.47%) with aspirin, estimated difference 0.77%; 95% CI 0.06% to 1.47%, p = 0.03). There were no significant differences in the other secondary outcomes. CONCLUSION: In patients undergoing hip or knee arthroplasty (of any type, performed for any indication) enrolled in the CRISTAL trial, aspirin compared to enoxaparin resulted in a significantly higher rate of symptomatic VTE and joint-related reoperation within 90 days. These findings extend the applicability of the CRISTAL trial results. TRIAL REGISTRATION: Anzctr.org.au, identifier: ACTRN12618001879257.

Recurrent Venous Thromboembolism in Patients on Anticoagulation: An Update Based on the Revised AWMF S2k Guideline.

In the recently updated German S2k Guideline "Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism," a new chapter was incorporated about recurrent venous thromboembolism (VTE) in patients on anticoagulation treatment. Despite the high efficacy of anticoagulation in most patients, approximately 2% experience a recurrent VTE event while receiving anticoagulant drugs. The proper diagnosis of the recurrent VTE is important and possible only with the knowledge of localization and thrombus burden of the primary VTE event. Possible reasons for recurrent VTE events in patients on anticoagulation are non-adherence to medication, sub-therapeutic drug levels due to resorption disorders or drug interactions, or concomitant disease with high thrombogenicity. Cancer is the most common underlying disease, but it is important to investigate and understand possible other causes whenever a breakthrough VTE event occurs. This results in the recommendation that in patients with VTE recurrence on therapeutic anticoagulation, in particular, the presence of malignant disease, antiphospholipid syndrome, and rare diseases like paroxysmal nocturnal hemoglobinuria or Behçet's disease should be considered. For VTE recurrence during heparin therapy, heparin-induced thrombocytopenia type II needs to be ruled out, even if platelet counts are within the normal range. Although the mechanisms of recurrence on anticoagulation can be evaluated in a certain degree, clinical evidence for the management of recurrent VTE in anticoagulated patients is minimal and mainly based on expert opinion. Switching anticoagulant medication and intensifying anticoagulant treatment are possible options.

Oral anticoagulant therapy in older adults.

Patients aged ≥65 years not only account for the majority of patients with atrial fibrillation (AF) and venous thromboembolism (VTE), they are also at a higher risk of morbidity, mortality, and undertreatment than younger patients. Several age-related physiological changes with effects on drug pharmacokinetics/-dynamics and blood vessel fragility as well as the higher prevalence of geriatric conditions such as frailty, multimorbidity, polypharmacy, fall risk, dementia, and malnutrition make older persons more vulnerable to disease- and anticoagulation-related complications. Moreover, because older patients with AF/VTE are underrepresented in oral anticoagulation (OAC) trials, evidence on OAC in older adults with AF/VTE is mainly based on subgroup analyses from clinical trials and observational studies. A growing body of such limited evidence suggests that direct oral anticoagulants (DOACs) may be superior in terms of efficacy and safety compared to vitamin K antagonists in older persons with AF/VTE and that specific DOACs may have a differing risk-benefit profile. In this narrative review, we summarize the evidence on epidemiology of AF/VTE, impact of age-related physiological changes, efficacy/safety of OAC, specifically considering individuals with common geriatric conditions, and review OAC guideline recommendations for older adults with AF/VTE. We also propose a research agenda to improve the evidence basis on OAC older individuals with AF/VTE, including the conduct of advanced age-specific and pragmatic studies using less restrictive eligibility criteria and patient-reported health outcomes, in order to compare the effectiveness and safety of different DOACs, and investigate lower-dose regimens and optimal OAC durations in older patients.

Subclass phenotypes in patients with unprovoked venous thromboembolisms using a latent class analysis.

BACKGROUND: Patients with unprovoked venous thromboembolisms (VTEs) can be sub-classified based on the different phenotypes using a latent class analysis (LCA), which might be useful for selecting individual management strategies. METHODS: In the COMMAND VTE Registry-2 database enrolling 5197 VTE patients, the current derivation cohort consisted of 1556 patients with unprovoked VTEs. We conducted clustering with an LCA, and the patients were classified into subgroups with the highest probability. We compared the clinical characteristics and outcomes among the developed subgroups. RESULTS: This LCA model proposed 3 subgroups based on 8 clinically relevant variables, and classified 592, 813, and 151 patients as Class I, II, and III, respectively. Based on the clinical features, we named Class I the younger, Class II the older with a few comorbidities, and Class III the older with many comorbidities. The cumulative 3-year anticoagulation discontinuation rate was highest in the older with many comorbidities (Class III) (39.9 %, 36.1 %, and 48.4 %, P = 0.02). There was no significant difference in the cumulative 5-year incidence of recurrent VTEs among the 3 classes (12.8 %, 11.1 %, and 4.0 % P = 0.20), whereas the cumulative 5-year incidence of major bleeding was significantly higher in the older with many comorbidities (Class III) (7.8 %, 12.7 %, and 17.8 %, P = 0.04). CONCLUSION: The current LCA revealed that patients with unprovoked VTEs could be sub-classified into further phenotypes depending on the patient characteristics. Each subclass phenotype could have different clinical outcomes risks especially a bleeding risk, which could have a potential benefit when considering the individual anticoagulation strategies. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm COMMAND VTE Registry-2: Unique identifier, UMIN000044816 COMMAND VTE Registry: Unique identifier, UMIN000021132.

D-dimer and risk of venous thromboembolism recurrence: Comparison of two studies with similar designs but different laboratory and clinical results.

BACKGROUND: D-dimer testing may help deciding the duration of anticoagulation in subjects at high risk of venous thromboembolism (VTE) recurrence. Two management studies on this issue have been published (DULCIS in 2014 and APIDULCIS in 2022). They had similar designs but had important different results. Aim of this article is to compare their results. METHODS: Both studies were finalized to extend anticoagulation [with vitamin K anticoagulants (VKAs) in DULCIS or apixaban 2.5 mg BID (kindly provided by BMS-Pfizer Collaboration) in APIDULCIS] only in patients with positive D-dimer results. RESULTS: More D-dimer assays resulted positive in APIDULCIS than in DULCIS (61.1 % vs 47.7 %, respectively; p < 0.0001). While only 4 (0.5 %) refused low dose apixaban in APIDULCIS, the 22.6 % of patients with positive D-dimer refused to resume VKAs in DULCIS; their rates of recurrence were 187 and 8.8 per 100 person-years, respectively (incidence rate ratio [IRR]: 21.2). The incidence of bleeding was low in those receiving apixaban vs those who resumed VKAs (0.4 vs 2.3 per 100 person-years, respectively; IRR 0.17;). While the recurrence rate was low and similar in the studies in subjects who resumed anticoagulation, it was significantly higher in APIDULCIS than in DULCIS in those who stopped anticoagulation for negative D-dimer (5.6 vs 3.0 per 100 person-years, respectively; IRR 1.9). CONCLUSION: The low dose Apixaban for extended VTE treatment is effective and safe, and well accepted by patients. Why subjects who stopped anticoagulation for negative D-dimer had a higher recurrence rate in APIDULCIS than in DULCIS remains to be explained.

Anti-Xa Monitoring of Apixaban (ZyQuis) in Venous Thrombo-Embolism and Atrial Fibrillation.

Apixaban is a direct oral Xa inhibitor and is indicated for the treatment of venous thrombo-embolism (VTE) and prevention of stroke in atrial fibrillation (AF). Recently, a generic (ZyQuis, Zydus Lifesciences Limited, India) has received Food and Drug Administration approval. While bioequivalence has been demonstrated with Eliquis (Bristol-Myers Squibb/Pfizer, UK), it is necessary to monitor its effectiveness prior to acceptance in medical practice. This prospective study independently evaluated Apixaban (ZyQuis) at two accredited laboratories. Participants were converted from Warfarin or Rivaroxaban to Apixaban 5 mg bd for a duration of one month. Peak anti-Xa levels were measured 3-4 h post the morning dose. The samples were processed on the Atellica COAG 360 (Siemens Healthineers, Marburg, Germany) analyzers with a chromogenic anti-Xa assay (Innovance, reference interval 69-321 ng/mL). There were 26 participants; 5 men, 21 women; mean ± standard deviation age of 46 ± 12 years. Indications for anticoagulation included: VTE (88.5%) and AF (11.5%). 69.2% of the participants had at least one comorbidity. 96.2% of the anti-Xa levels were within the laboratory's 95% reference interval. Mean anti-Xa activity was 191 ± 69 ng/mL and 186 ± 68 ng/mL measured at respective laboratories. Mean differences in anti-Xa measurements represented by Bland-Altman statistics were small (bias of -2.6%, 95% confidence interval -1.11 to -4.09) and a strong correlation was observed on Deming regression analysis (0.995). Apixaban (ZyQuis) was effective for the management of VTE and AF as evidenced by anti-Xa activity.

Potential treatment option of rivaroxaban for breastfeeding women: A case series.

The use of direct oral anticoagulants (DOACs) in breastfeeding women is currently challenging due to limited safety data for breastfeeding infants, and there have been no previous studies on the drug concentration in breastfeeding infants. We treated 2 patients (one case was twin pregnancy) with venous thromboembolisms in breastfeeding women administered rivaroxaban at our institution. Blood samples from the mothers and breastmilk samples were collected at time 0 and 2 h after the rivaroxaban administration, breastfeeding was conducted 2 h after the rivaroxaban administration, and blood samples from the infants were collected 2 h after breastfeeding (4 h after maternal rivaroxaban administration). The milk-to-plasma (M:P) ratios were 0.27 in Case 1 and 0.32 in Case 2. The estimated relative infant dose (RID) was 0.82 % in Case 1 Children 1 and 2, and 1.27 % in Case 2. The rivaroxaban concentration in the infant plasma was below the lower limit of quantification in all infants. In addition, even in the high-exposure case simulation based on 5 days of breastfeeding in Case 2, the infant plasma concentration level was below the lower limit of quantification. At 3 months of follow-up, breastfeeding was continued, and all infants grew and developed without any health problems including bleeding events. The current case series showed that there were no pharmacokinetic or clinical concerns for breastfeeding women or breastfed infants, and provides support for rivaroxaban as a safe treatment option for these patients.

Venous thromboembolism chemical prophylaxis after skull base surgery.

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.

Implementation of the Caprini risk assessment model (RAM) in surgical patients to decrease postsurgical venous thromboembolism and enoxaparin prescription at hospital discharge.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been an increasingly common post-surgical complication for surgical patients. In the United States, VTE has become a leading cause of preventable hospital death with more than half occurring after discharge and are directly linked to a recent (within 30 days) hospitalization or surgery [1]. In large, hospital-associated/acquired VTE (HA-VTE) are preventable through measures such as the use of risk stratification tools and chemoprophylaxis. The project institution, a community, academic, medical center, for multiple years has consistently remained a high outlier for postoperative VTE. Also, the choice of VTE chemoprophylaxis in surgical patients at the time of discharge depended on, and varied between, the individual prescribing physician. The goal was to implement and determine the efficacy of a standardized intervention tool, the Caprini risk assessment model (RAM), for reducing postoperative VTE complications and its influence on the physician's prescription of enoxaparin at discharge. Results: Risk assessment scoring pre-operatively increased from 0% baseline to 26.3% at Plan-Do-Study-Act (PDSA) cycle 1 and demonstrated a statistically significant change (p-value = 0.006). Risk assessment scoring pre-operatively was 42.9% by PDSA cycle 2 but was not statistically significantly different from PDSA cycle 1. Risk assessment scoring post-operatively (for eligible patients) remained the same throughout all three cycles at 0%. Appropriate prescription of anticoagulation declined from baseline (12.5%) to PDSA cycle 1 (0%), and improved at PDSA cycle 2 (33.3%), however no differences were significant (p-value 0.302). The National Surgical Quality Improvement Project (NSQIP) database showed a decline in VTE occurrences at the projects institution from baseline (1.02%, 6 occurrences, 2021) to PDSA cycle 2 (0.92%, 4 occurrences, 2022) when compared to the national benchmark (1.0%) for the first time since 2018. Given the significant national problem HA-VTE pose to the public, and the rise in occurrences, this quality improvement (QI) project is clinically relevant.

The incidence of major bleeding in adult patients with urogenital and gynecological cancer being treated with direct oral anticoagulants (DOACs): a systematic review.

BACKGROUND: Direct oral anticoagulants (DOACs) are the mainstay of treatment for venous thromboembolism (VTE) and non-valvular atrial fibrillation (AF), with or without an underlying cancer. Patients with cancer have a 2-3-fold increase in risk for bleeding complications compared to non-cancer patients taking anticoagulant therapy, however the incidence of bleeding for urogenital and gynecological cancers on DOACs are uncertain. AIMS: To assess the bleeding risk associated with the use of DOACs in patients with urogenital and/or gynecological cancers. METHOD: We conducted a systematic review of randomized controlled trials (RCTs) and prospective cohort studies to address the safety of DOACs for VTE and AF when used in patients with urogenital and/or gynecological malignancy. The primary outcomes assessed were major and clinically relevant non-major (CRNMB) bleeding, with minor bleeding considered as a secondary outcome. MEDLINE, EMBASE and COCHRANE Central Registry of Controlled Trials were searched up to and including Oct 28, 2022. The study protocol was registered in PROSPERO (CRD42022370981). Studies were independently assessed for inclusion and data extracted in duplicate. RESULT: Seven studies met our inclusion criteria (Fig. 1): 2 RCTs and 5 prospective cohort studies. A total of 676 patients treated with DOACs were included, 628 (92.8%) had VTE and 48 (7.1%) had AF. In patients with VTE treated with DOACs, the pooled major bleeding rate was 2.1%, 95% confidence intervals (CI) 0.9-3.3% (Fig. 2). Pooled estimates could not be determined for AF patients given small event and patient numbers. CONCLUSION: Major bleeding rates in urogenital and/or gynecological cancer patients treated with DOACs are similar to that of the general cancer population.

Superficial vein thrombosis and its relationship with malignancies: a prospective observational study.

BACKGROUND: The interrelation of cancer with venous thromboembolism is established, yet the specific impact on the incidence and progression of superficial vein thrombosis (SVT) remains unclear. OBJECTIVES: To investigate the association between SVT and malignancies, focusing on risk factors, presentation, course and complications. METHODS: A single-center prospective observational study of patients diagnosed with DVT or SVT referred to a venous thromboembolism clinic between January 2013 and April 2018. RESULTS: Of the 632 patients, 205 presented with SVT at referral, 16.6% having active cancer. Significant associations were found between active cancer and the risk of developing proximal SVT (RR 1.54 [1.18-2.03] p < 0.01), SVT within 3 cm from junction (RR 2.01 [1.13-3.72] p = 0.019), bilateral SVT (RR 8.38 [2.10-33.43] p < 0.01) and SVT affecting multiple veins (RR 2.42 [1.40-4.20] p < 0.01), with a higher risk of persistence (RR 1.51 [1.18-1.95] p < 0.01) and progression (RR 5.75 [2.23-14.79] p < 0.01) at initial assessment. Patients with SVT and no malignancy history demonstrated an elevated risk for new-onset cancer during follow-up (RR 1.43 [1.13-1.18] p = 0.022), especially in cases of proximal or bilateral SVT, initial progression or subsequent DVT or PE. No significant differences were observed in persistence, recurrence or complications during initial evaluation or follow-up across different pharmacological treatments. CONCLUSIONS: Research suggests a probable link between cancer history and the development of SVT. SVT presented more severely in cancer patients. SVT, especially in its more complex forms, could serve as a predictive marker for the future development of cancer. Treatment approaches varied, no significant differences in outcomes were noted.

Outcomes of venous thromboembolism in patients with inherited thrombophilia treated with direct oral anticoagulants: insights from the RIETE registry.

While direct oral anticoagulants (DOACs) are frequently used to treat venous thromboembolism (VTE), the outcomes of patients with inherited thrombophilia (IT) receiving DOACs for VTE remain understudied. We used data from the international RIETE registry to compare the rates of VTE recurrences, major bleeding, and mortality during anticoagulant treatment in VTE patients with and without IT, grouped by the use of DOACs or standard anticoagulant therapy. Among 103,818 enrolled patients, 21,089 (20.3%) were tested for IT, of whom 8422 (39.9%) tested positive: Protein C deficiency 294, Protein S deficiency 726, Antithrombin deficiency 240, Factor V Leiden 2248, Prothrombin gene mutation 1434, combined IT 3480. Overall, 14,189 RIETE patients (6.2% with IT) received DOACs, and 89,629 standard anticoagulation (8.4% with IT), mostly with heparins followed by vitamin K antagonists. Proportions of patients receiving DOACs did not differ between IT-positive and IT-negative patients. Rates of VTE recurrence on anticoagulant treatment were highest in patients with AT deficiency (P < 0.01). Rates of on-treatment major bleeding and all-cause mortality were lowest among patients with Factor V Leiden (FVL) or PT G20210A mutations, compared with patients who tested negative. Patients with IT who received DOACs had lower rates of major bleeding than those receiving standard anticoagulation. Excluding FVL and Protein S deficiency, patients with IT had lower rates of VTE recurrence with DOACs than with standard anticoagulation. DOACs are equally safe and effective in VTE patients with IT, with lower bleeding rates than those on standard anticoagulation.

Management of DOAC-related bleeding in cancer patients: a single center-case series.

Venous thromboembolism (VTE) and stroke carry significant mortality and morbidity in cancer patients. Direct oral anticoagulants (DOACs) have been demonstrated to be effective for the treatment of VTE and prevention of stroke in atrial fibrillation (AF). Bleeding rates are variable and are based on the cancer type and the patient's specific risk factors. There are approved specific antidotes for DOAC-associated bleeding. Other strategies are available for bleeding reversal, including the use of prothrombin complex concentrate (PCC). No randomized studies have compared head-to-head the efficacy and safety of reversal agents. We aim to examine the safety and effectiveness of hemostatic agents in cancer patients with DOAC-related major bleeding. A retrospective chart review study of patients at MD Anderson Cancer Center with DOAC-related major bleeding between 2014 and 2019. Bleeding severity and clinical hemostasis were described based on ISTH guidelines and the Sarode criteria, respectively. The rates of thrombotic complications and mortality at 30-day from the index bleeding event were described. We identified 23 patients with DOAC-related major bleeding; 14 patients received PCC and 9 patients received andexanet alfa. The most common sites of bleeding were the gastrointestinal tract and intracranial. Effective hemostasis and 30-day mortality were similar to reported results from other reports of outcomes of reversal agents for DOAC related-bleeding in non-cancer patients. One patient in each treatment group experienced a thrombotic event. Further larger scale studies are needed to confirm our findings in cancer patients.

Anticoagulation in venous thromboembolism for the general physician.

Venous thromboembolism (VTE) is frequently encountered across various specialties. The management of VTE has become more nuanced, requiring consideration of several factors when deciding on the choice and duration of anticoagulation. This evidence-based review article summarises the current practice and evidence behind anticoagulation in VTE, incorporating national and international guidelines. Factors influencing decision-making around the choice and duration of anticoagulation, along with special circumstances such as cancer and antiphospholipid syndrome, are discussed. The clinical utility of thrombophilia screening is also addressed.