Oral Factor Xa Research Articles

3-Factor prothrombin complex concentrate versus 4-factor prothrombin complex concentrate for the reversal of oral factor Xa inhibitors.

Multiple agents exist for the reversal of oral Factor Xa inhibitor (FXa) associated bleeding, including Coagulation FXa Recombinant, Inactivated zhzo (andexanet alfa) and 4-factor prothrombin complex concentrate (4F-PCC). While classified as a 3F-PCC product, Profilnine contains up to 35IU of Factor VII (per 100IU of Factor IX) in addition to therapeutic levels of Factors II, IX, and X, and has demonstrated a similar impact on prothrombin time and blood product usage in non-warfarin related bleeding. This was a retrospective, multicenter study at four medical centers of adult patients who presented with major bleeding associated with oral FXa inhibitors and received either 4F-PCC (n = 64) or 3F-PCC (n = 61). The primary outcome was hemostatic effectiveness. Secondary outcomes included the incidence of thromboembolism, in-hospital mortality, and length of stay. The most common indication for reversal was intracranial bleeding. For the primary outcome, 84% of all patients were rated as effective with no difference noted between the groups (p = 0.81). No significant difference between groups was found in the multivariable analysis adjusting for baseline differences between groups including race, total body weight, type of bleeding, and the use of antiplatelet therapy. There was no difference in the length of stay, in-hospital mortality, or the incidence of thromboembolism between the groups. Overall, no significant differences were found in the effectiveness or safety of 4F-PCC and 3F-PCC use in the management of oral FXa inhibitor-associated bleeding. Further investigations are warranted to explore the use of 3F-PCC for this indication and its safety and effectiveness.

Typical profile of a patient with atrial fibrillation in the Russian population based on medical registries. A systematic review

Aim. To compare clinical and anamnestic characteristics of patients with atrial fibrillation (AF) included in three large international stu­dies assessing the efficacy and safety of therapy with direct oral anti­coagu­lants, with the profile of a typical Russian patient with AF in clinical practi­ce, established by medical registries in the Russian Federation (RF).Material and methods. A systematic review of scientific publications was con­ducted. The search was conducted in the E-library and Google Scholar databases. Publications from 8 registries of patients with AF, con­ducted in the Russian Federation from 2012 to 2023, were found, which present the clinical and anamnestic characteristics of patients. All studies included in the analysis meet the generally accepted require­ments for medical registries. The systematic review protocol was pre­viously recorded in the PROSPERO electronic database (CRD42024512425).Results. A Russian patient with AF is a patient with a large number of cardiovascular pathologies and a high risk of thromboembolic events. According to the analysis, Russian patient with AF has an average age of ~70 years. Most patients have a diagnosis of hypertension, heart failure, while from one third to half of patients have a diagnosis of chronic kidney disease. From 20 to 30% of patients have a history of myocardial infarction and every fifth patient has type 2 diabetes.Conclusion. In all countries around the world, including the Russian Fe­deration, for many years, medical registries have been one of the main sources of information on the characteristics of patients with AF and the disease course. They can supplement the available data from randomized clinical trials with real-world data. Comparison of clinical and anamnestic characteristics of patients in randomized clinical trials of direct oral anticoagulants with characteristics of patients in the Russian registries shows that patients included in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K An­tagonism for Prevention of Stroke and Embolism Trial in Atrial Fib­rillation (ROCKET AF trial) were most similar to Russian patients with AF.

Dual direct oral anticoagulant therapy in challenging thrombosis: a case series

BackgroundWhile anticoagulation therapy is highly effective at treating venous thromboembolism, some patients can develop rapidly progressive thrombosis in multiple organs or sites despite therapeutic anticoagulation. Effective strategies to manage life-threatening thrombosis in these patients are elusive. ObjectivesWe describe our experience using dual direct oral anticoagulant (DOAC) therapy with a factor (F)Xa inhibitor (such as rivaroxaban or apixaban) and a FIIa inhibitor (dabigatran) for refractory cases of thrombosis. MethodsA retrospective chart review of all patients treated with simultaneous dabigatran and an oral FXa inhibitor at our institution was conducted. We included all patients over the age of 18. The study was approved by the University of British Columbia Research Ethics Board (REB number: H23-02575). ResultsEight patients were included. All patients initiated standard therapeutic anticoagulation upon diagnosis of acute venous thromboembolism with a median of 3 breakthrough thrombotic events prior to dual DOAC use. Five patients had a positive heparin-induced thrombocytopenia screen, but only 2 had heparin-induced thrombocytopenia confirmed on serotonin release assay testing. There were no recurrent deep vein thrombosis, pulmonary embolism, or bleeding events during dual DOAC use. Most patients ultimately transitioned to a single oral FXa inhibitor. ConclusionDual DOAC therapy may be a useful strategy for managing challenging thrombosis cases resistant to conventional anticoagulation. Further research is warranted to validate these findings and explore the broader applicability of dual DOAC therapy in challenging thrombotic scenarios.

Treatment of Superficial Vein Thrombosis: Recent Advances, Unmet Needs and Future Directions.

Once considered relatively benign, superficial vein thrombosis (SVT) of the lower limbs is linked to deep vein thrombosis (DVT) or pulmonary embolism (PE) in up to one fourth of cases. Treatment goals include alleviating local symptoms and preventing SVT from recurring or extending into DVT or PE. Fondaparinux 2.5 mg once daily for 45 days is the treatment of choice for most patients with SVT. Potential alternatives include intermediate-dose low-molecular-weight heparin or the direct oral factor Xa inhibitor rivaroxaban, however, these require further evidence. Despite these treatment options, significant gaps remain, including the role of systemic or topical anti-inflammatory agents alone or combined with anticoagulants, and the optimal duration of anticoagulation for patients at varying risk levels. Additionally, the efficacy and safety of factor Xa inhibitors other than rivaroxaban, management of upper extremity SVT, and optimal treatment for SVT near the sapheno-femoral or sapheno-popliteal junctions are not well understood. This narrative review aims to summarize current evidence on anticoagulant treatment for SVT, highlight key unmet needs in current approaches, and discuss how ongoing studies may address these gaps.

Impact of patient selection in clinical trials: application of ROCKET AF and ARISTOTLE criteria in GARFIELD-AF

BackgroundThe extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition...

Assessment of Days Alive Out of Hospital as a Possible End Point in Trials of Stroke Prevention for Atrial Fibrillation: A ROCKET AF Analysis.

Days alive out of hospital (DAOH) is an objective and patient-centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations. ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was an international double-blind, double-dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator-reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin (P=0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively, P=0.88). DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.

Factor XI inhibitors: a new option for the prevention and treatment of cancer-associated thrombosis

Venous thromboembolism (VTE) is a relatively common complication in cancer patients with potentially dire consequences. Anticoagulants are the mainstay of treatment of cancer-associated VTE. The anticoagulants most often used are low-molecular-weight heparin (LMWH) and direct oral factor (F) Xa inhibitors, which include apixaban, edoxaban, and rivaroxaban. Most guidelines recommend primary VTE prophylaxis with LMWH, apixaban, or rivaroxaban after abdominal or pelvic cancer surgery, or in high-risk ambulatory cancer patients. Both oral FXa inhibitors and LMWH have limitations. LMWH requires daily subcutaneous injections, and because of its renal clearance, its use may be problematic in patients with severe kidney disease. The risk of bleeding with oral FXa inhibitors may be higher than with LMWH in patients with intraluminal gastrointestinal or genitourinary cancers. Other problems with oral FXa inhibitors include potential drug-drug interactions and dosing issues in patients with thrombocytopenia or severe kidney or liver disease. Therefore, there remains a need for convenient and safer anticoagulants for VTE treatment in cancer patients. FXI has emerged as a potentially safer target for anticoagulants than FXa because FXI is essential for thrombosis, but mostly dispensable for hemostasis. This review summarizes the currently available therapeutic options for cancer-associated VTE, highlights knowledge gaps, and discusses the potential of FXI inhibitors to address key unmet clinical needs in this vulnerable patient population.

Is There an Alternative Oral Anticoagulation to Vitamin-K-Antagonists for Patients with Mechanical Aortic Valve Replacement? - A Literature Review.

Current guidelines exclusively recommend vitamin-K-antagonists (VKA) as anticoagulation for patients after mechanical aortic valve replacement due to the increased postoperative risk of valve thrombosis and thrombo-embolism. Strict and regular assessments are mandatory during VKA therapy to ensure a potent anticoagulatory effect within the desired range. From the patients' perspective, VKA are associated with relevant interactions and side effects reducing the quality of life and contributing to a high number of patients not achieving the optimal therapeutic target. Direct oral anticoagulants (DOAC) have replaced VKA therapy in the past for several indications, e.g., atrial fibrillation. However, it is still unclear if DOACs could replace VKA therapy in patients after mechanical aortic valve replacement. While the PROACT-Xa study did not show a sufficient anticoagulatory effect of apixaban plus aspirin compared to VKA therapy in patients after mechanical aortic valve replacement, the direct thrombin inhibitor dabigatran and the oral factor Xa inhibitors apixaban and rivaroxaban showed promising results in comparable patient cohorts in smaller studies and case reports. Factor Xa inhibitors were able to prevent thrombosis and thrombo-embolic events in patients after mechanical aortic valve replacement. Therefore, factor Xa inhibitors or factor XI inhibitors could provide a potent alternative to VKA for patients after a mechanical aortic valve replacement.

Minimally modified human blood coagulation factor X to bypass direct factor Xa inhibitors

BackgroundDirect oral factor (F)Xa inhibitors are widely used as alternatives to conventional vitamin K antagonists in managing venous thromboembolism and nonvalvular atrial fibrillation. Unfortunately, bleeding-related adverse events remain a major concern in clinical practice. In case of bleeding or emergency surgery, rapid-onset reversal agents may be required to counteract the anticoagulant activity. ObjectivesThe ability of FXa variants to bypass the direct oral FXa inhibitors was assessed. MethodsHuman FXa variants were generated through substitution of phenylalanine 174 (F174) for either alanine, isoleucine, or serine. FXa variants were stably expressed in HEK293 cells and purified to homogeneity using ion-exchange chromatography. ResultsF174-substituted human FX variants demonstrated efficacy in restoring thrombin generation in plasma containing direct FXa inhibitors (apixaban, rivaroxaban, edoxaban). Their ability to bypass the anticoagulant effects stems from a significantly reduced sensitivity for the direct FXa inhibitors due to a decrease in binding affinity determined using molecular dynamics simulations and free energy computation. Furthermore, F174 modification resulted in a partial loss of inhibition by tissue factor pathway inhibitor, enhancing the procoagulant effect of F174-substituted FX. Consequently, the F174A- and F174S-substituted FX variants effectively counteracted the effects of 2 widely used anticoagulants, apixaban and rivaroxaban, in plasma of atrial fibrillation and venous thromboembolism patients. ConclusionThese human FX variants have the potential to serve as a rescue reversal strategy to overcome the effect of direct FXa inhibitors in case of life-threatening bleeding events or emergency surgical interventions.

Four-factor prothrombin complex concentrate is not inferior to andexanet alfa for the reversal or oral factor Xa inhibitors: An Eastern Association for the Surgery of Trauma multicenter study.

Andexanet alfa (AA) is the only FDA-approved reversal agent for apixaban and rivaroxaban (DOAC). There are no studies comparing its efficacy with four-factor prothrombin complex concentrate (PCC). This study aimed to compare PCC to AA for DOAC reversal, hypothesizing noninferiority of PCC. We performed a retrospective, noninferiority multicenter study of adult patients admitted from July 1, 2018, to December 31, 2019, who had taken a DOAC within 12 hours of injury, were transfused red blood cells (RBCs) or had traumatic brain injury, and received AA or PCC. Primary outcome was PRBC unit transfusion. Secondary outcome with intensive care unit length of stay. MICE imputation was used to account for missing data and zero-inflated Poisson regression was used to account for an excess of zero units of RBC transfused. Two units difference in RBC transfusion was selected as noninferior. Results: From 263 patients at 10 centers, 77 (29%) received PCC and 186 (71%) AA. Patients had similar transfusion rates across reversal treatment groups (23.7% AA vs. 19.5% PCC) with median transfusion in both groups of 0 RBC. According to the Poisson component, PCC increases the amount of RBC transfusion by 1.02 times (95% confidence interval, 0.79-1.33) compared with AA after adjusting for other covariates. The average amount of RBC transfusion (nonzero group) is 6.13. Multiplying this number by the estimated rate ratio, PCC is estimated to have an increase RBC transfusion by 0.123 (95% confidence interval, 0.53-2.02) units compared with AA. PCC appears noninferior to AA for reversal of DOACs for RBC transfusion in traumatically injured patients. Additional prospective, randomized trials are necessary to compare PCC and AA for the treatment of hemorrhage in injured patients on DOACs. Therapeutic/Care Management; Level III.

Efficacy and safety of oral factor Xa inhibitors versus vitamin-K antagonists in the early phase after acute ischemic stroke or TIA in the real-world setting: The PRODAST study.

Factor Xa (FXa) inhibitors are superior to vitamin K antagonists (VKAs) in terms of avoiding hemorrhagic complications. However, no robust data are available to date as to whether this also applies to the early phase after stroke. In this prospective registry study, we aimed to investigate whether anticoagulation with FXa inhibitors in the early phase after acute ischemic stroke or transient ischemic attack (TIA) is associated with a lower risk of major bleeding events compared with VKAs. The Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) study is a prospective, multicenter, observational, post-authorization safety study at 86 German stroke units between July 2015 and November 2020. Primary outcome was a major bleeding event during hospital stay. Secondary endpoints were recurrent strokes, recurrent ischemic strokes, TIA, systemic/pulmonary embolism, myocardial infarction, death and the composite endpoint of stroke, systemic embolism, life-threatening bleeding and death. In total, 10,039 patients have been recruited. 5,874 patients were treated with FXa inhibitors and 1,050 patients received VKAs and were eligible for this analysis. Overall, event rates were low. We observed 49 major bleeding complications during 33,297 treatment days with FXa-inhibitors (rate of 14.7 cases per 10,000 treatment days) and 16 cases during 7,714 treatment days with VKAs (rate of 20.7 events per 10,000 treatment days), translating into an adjusted hazard ratio (aHR) of 0.70 (95% confidence interval (95% CI): 0.37-1.32) in favor of FXa inhibitors. Hazards for ischemic endpoints (63 vs 17 strokes, aHR: 0.96 (95% CI: 0.53-1.74), mortality (33 vs 6 deaths, aHR: 0.87 (95% CI: 0.33-2.34)) and the combined endpoint (154 vs 39 events, aHR: 0.99 (95% CI: 0.65-1.41) were not substantially different. This large real-world study shows that FXa inhibitors appear to be similarly effective in terms of bleeding events and ischemic endpoints compared to VKAs in the early post-stroke phase of hospitalization. However, the results need to be interpreted with caution due to the low precision of the estimates.

Clinical Pathways and Outcomes of Andexanet Alfa Administration for the Reversal of Critical Bleeding in Patients on Oral Direct Factor Xa Inhibitors.

Background Andexanet is U.S. Food and Drug Administration (FDA) approved for the reversal of critical bleeding from factor Xa inhibitors and off-label for surgical reversal. Data are lacking on andexanet administration processes. Methods We retrospectively studied patients at a 23-hospital system who received andexanet from November 2019 to March 2023. Abstractors coded demographics, comorbidities, anticoagulant use, andexanet indication, and process times. The primary outcome was presentation-to-andexanet time; diagnosis, ordering, and administration times were calculated. Secondary outcomes included in-hospital postandexanet major thromboembolism/bleeding and mortality. Results In total, 141 patients were analyzed. Andexanet indications were predominantly neurologic bleeding (85.8%). Twenty-four patients (17.0%) were transferred from nontertiary/academic centers to tertiary/academic centers. The median presentation-to-administration time was 192.5 minutes (interquartile range [IQR]: 108.0-337.0 minutes). Components were as follows: 72.5 minutes (IQR: 39.0-137.5 minutes) for bleeding diagnosis; 35.5 minutes (IQR: 0-96.5 minutes) for andexanet ordering; and 53.0 minutes (IQR: 38.5-78.5 minutes) for administration, which was longer at tertiary/academic hospitals (ratio 1.5, 95% confidence interval [CI]: 1.2-2.0, p = 0.002). Gastrointestinal or other critical bleeding (ratio 2.59, 95% CI: 1.67-4.02, p < 0.001), and tertiary/academic center treatment (ratio 1.58, 95% CI: 1.15-2.18, p = 0.005), were associated with increased time. Major thromboembolism, bleeding, and mortality occurred in 10.6, 12.0, and 22.9% of patients, respectively. Conclusions In our cohort, the median presentation-to-administration time was over 3 hours. Cumulative times were longer at tertiary/academic hospitals and for gastrointestinal/other bleeding. Postandexanet major thromboembolism/bleeding occurred more at tertiary/academic hospitals, possibly related to transfers. Prospective studies may elucidate clinical decision-making bottlenecks.

Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity: Prespecified Subgroup Analysis of the ANNEXA-4 Study in Japan.

Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been approved for clinical use in several countries, including Japan, based on the results from the phase 3 trial ANNEXA-4. We aimed to assess the efficacy and safety of andexanet alfa treatment in FXa inhibitor-related acute major bleeding in patients enrolled for ANNEXA-4 in Japan. This prespecified analysis included patients enrolled at Japanese sites in the prospective, open-label, single-arm ANNEXA-4 trial. Eligible patients had major bleeding within 18 hours of oral FXa inhibitor administration. The coprimary efficacy endpoints were percent change in anti-FXa activity and proportion of patients achieving excellent or good hemostatic efficacy 12 hours post-treatment. A total of 19 patients were enrolled, all of whom had intracranial hemorrhage; 16 patients were evaluable for efficacy. Median percent reduction in anti-FXa activity from baseline to nadir was 95.4% in patients taking apixaban, 96.1% in patients taking rivaroxaban, and 82.2% in patients taking edoxaban. Overall, 14/16 patients (88%) achieved excellent or good hemostasis (apixaban, 5/5; rivaroxaban, 6/7; edoxaban, 3/4). Within 30 days, treatment-related adverse events (AEs) and serious AEs occurred in 2 and 5 patients, respectively. One patient died during follow-up, and 2 patients experienced thrombotic events. Treatment with andexanet alfa rapidly reduced anti-FXa activity with favorable hemostatic efficacy in Japanese patients with acute major bleeding. Serious AEs of thrombotic events during rapid reversal of anti-FXa activity arose as particular safety concerns in this population as with previous studies.

Proteomic analysis of extracellular vesicle cargoes mirror the cardioprotective effects of rivaroxaban in patients with venous thromboembolism.

Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality worldwide. Rivaroxaban, a direct oral factor Xa inhibitor, mediates anti-inflammatory and cardiovascular-protective effects besides its well-established anticoagulant properties; yet, these remain poorly characterized. Extracellular vesicles (EVs) are considered proinflammatory messengers regulating a myriad of (patho)physiological processes and may be highly relevant to the pathophysiology of VTE. The effects of Rivaroxaban on circulating EVs in VTE patients remain unknown. We have established that differential EV biosignatures are found in patients with non-valvular atrial fibrillation anticoagulated with Rivaroxaban versus warfarin. Here, we investigated whether differential proteomic profiles of circulating EVs could also be found in patients with VTE. We performed comparative label-free quantitative proteomic profiling of enriched plasma EVs from VTE patients anticoagulated with either Rivaroxaban or warfarin using a tandem mass spectrometry approach. Of the 182 quantified proteins, six were found to be either exclusive to, or enriched in, Rivaroxaban-treated patients. Intriguingly, these proteins are involved in negative feedback regulation of inflammatory and coagulation pathways, suggesting that EV proteomic signatures may reflect both Rivaroxaban's anti-coagulatory and anti-inflammatory potential. These differences suggest Rivaroxaban may have pleiotropic effects, supporting the reports of its emerging anti-inflammatory and cardiovascular-protective characteristics relative to warfarin.

How do oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors compare with conventional anticoagulation for the treatment of pulmonary embolism?

How do oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors compare with conventional anticoagulation for the treatment of pulmonary embolism?

Efficacy and Safety of a New Selective Oral Factor Xa Inhibitor Amidine Hydrochloride for Prevention of Thromboembolic Events in Hospitalized Patients with COVID-19: a Multiple-Center Prospective Randomized Controlled Study

Efficacy and Safety of a New Selective Oral Factor Xa Inhibitor Amidine Hydrochloride for Prevention of Thromboembolic Events in Hospitalized Patients with COVID-19: a Multiple-Center Prospective Randomized Controlled Study

Use of Andexanet Alfa for Factor Xa Inhibitor Reversal in US Verified Trauma Centers: A National Survey.

Direct oral factor Xa inhibitors are replacing vitamin K-dependent antagonists as anticoagulation treatment in many clinical scenarios. Trauma centers are noting an increase in patients presenting on these medications. The 2018 Food and Drug Administration approval of andexanet alfa provides an alternative anticoagulation reversal. Barriers may limit utilization of new medications including a lack of grade 1A evidence supporting the use of prothrombin complex concentrate (PCC) versus andexanet alfa and cost. To evaluate barriers of andexanet alfa utilization by trauma surgeons, a 15-question survey was conducted. There was a 9% completion rate (n = 89). The results revealed 23.5% would choose andexanet alfa as first-line treatment in children, and 25.8% as first-line treatment in adults. The majority of respondents, 64.7% and 67.4%, would use PCC preferentially in children and adults, respectively. Respondents indicated that cost burden was an overriding factor (76.3%); 42.4% cited lack of high-level efficacy data of andexanet alfa for reversal of factor Xa inhibitors. Additional double-blinded multi-institutional randomized controlled trials comparing 4F-PCC and andexanet alfa for factor Xa inhibitor reversal are needed to support efficacy especially with the increased cost associated.

Oral factor Xa inhibitors for stroke prevention in patients with device-detected atrial fibrillation : Recent evidence from the NOAH-AFNET 6 and ARTESiA trials

Oral factor Xa inhibitors for stroke prevention in patients with device-detected atrial fibrillation : Recent evidence from the NOAH-AFNET 6 and ARTESiA trials

Successful Treatment With the Oral Factor Xa Inhibitor Edoxaban in Heparin-Induced Thrombocytopenia With Thrombosis.

Heparin-induced thrombocytopenia with thrombosis (HITT) is a rare immune reaction to the drug heparin that causes increased blood clotting, putting patients at risk for arterial and venous thromboembolism which can have severe consequences. We present a case of HITT successfully treated with the direct oral anticoagulant (DOAC), edoxaban. A 56-year-old man had surgery to remove a colorectal mass. After discharge, he developed chest discomfort, shortness of breath, and low oxygen levels and was diagnosed with a right-sided lobar pulmonary embolism. His platelet count dropped, his tests confirmed a diagnosis of HITT, and he was initially treated with fondaparinux. After showing clinical and laboratory improvement, he was switched to edoxaban. Despite being diagnosed with colonic adenocarcinoma during follow-up, the patient's platelet count returned to normal, and he did not experience any more blood clots or serious bleeding events. The use of DOACs like edoxaban as potential therapies for HITT is promising; further research is being conducted to evaluate their effectiveness, safety, and potential benefits for treating this acquired high-risk thrombophilia.

Venous thromboembolism, chronic liver disease and anticoagulant choice: effectiveness and safety of direct oral anticoagulants versus warfarin

BackgroundLittle to no data exist to guide treatment decision in patients with venous thromboembolism (VTE) and chronic liver disease. ObjectivesTo assess the effectiveness and safety of direct oral anticoagulants (DOACs)—individually and as a class—vs warfarin and between 2 DOACs in patients with acute VTE and chronic liver disease. MethodsWe conducted a retrospective, US claims–based, propensity score–matched cohort study in adults with acute VTE and chronic liver disease who had newly initiated oral anticoagulants between 2011 and 2017. The primary outcome was a composite of hospitalization for recurrent VTE and hospitalization for major bleeding. ResultsThe cohorts included 2361 DOAC-warfarin, 895 apixaban-warfarin, 2161 rivaroxaban-warfarin, and 895 apixaban-rivaroxaban matched pairs. Lower risk of the primary outcome was seen with DOACs (hazard ratio [HR], 0.72; 95% CI, 0.61-0.85), apixaban (HR, 0.48; 95% CI, 0.35-0.66) or rivaroxaban (HR, 0.73; 95% CI, 0.61-0.88) vs warfarin but not apixaban-rivaroxaban (HR, 0.68; 95% CI, 0.43-1.08). The HRs of hospitalization for major bleeding were 0.69 (95% CI, 0.57-0.84) for DOAC-warfarin, 0.43 (95% CI, 0.30-0.63) for apixaban-warfarin, 0.72 (95% CI, 0.58-0.89) for rivaroxaban-warfarin, and 0.60 (95% CI, 0.35-1.06) for apixaban-rivaroxaban. Recurrent VTE risk was lower with apixaban (HR, 0.47; 95% CI, 0.26-0.86), but not DOACs (HR, 0.81; 95% CI, 0.59-1.12) or rivaroxaban vs warfarin (HR, 0.81; 95% CI, 0.57-1.14) or apixaban-rivaroxaban (HR, 0.92; 95% CI, 0.42-2.02). ConclusionWhile the magnitude of clinical benefit varied across individual DOACs, in adults with acute VTE and chronic liver disease, oral factor Xa inhibitors (as a class or individually) were associated with lower risk of recurrent VTE and major bleeding.