Performance of CHA2DS2-VASc and HAS-BLED in predicting stroke and bleeding in atrial fibrillation and cancer.

Aims: To compare the predictive performance of CHA2DS2-VASc and HAS-BLED scores in atrial fibrillation (AF) patients with and without cancer. Methods and results: Using data from the Clinical Practice Research Datalink in England, we performed a retrospective cohort study of patients with new diagnoses of AF from 2009 to 2019. Cancer was defined as history of breast, prostate, colorectal, lung, or haematological cancer. We calculated the CHA2DS2-VASc and HAS-BLED scores for the 1-year risk of stroke and major bleeding events. Scores performance was estimated by discrimination [area under the receiver operating characteristic curve (AUC)] and calibration plots. Of 141 796 patients with AF, 10.3% had cancer. The CHA2DS2-VASc score had good to modest discrimination in prostate cancer AUC = 0.74 (95% confidence interval: 0.71, 0.77), haematological cancer AUC = 0.71 (0.66, 0.76), colorectal cancer AUC = 0.70 (0.66, 0.75), breast cancer AUC = 0.70 (0.66, 0.74), and lung cancer AUC = 0.69 (0.60, 0.79), compared with no-cancer AUC = 0.73 (0.72, 0.74). HAS-BLED discrimination was poor in prostate cancer AUC = 0.58 (0.55, 0.61), haematological cancer AUC = 0.59 (0.55, 0.64), colorectal cancer AUC = 0.57 (0.53, 0.61), breast cancer AUC = 0.56 (0.52, 0.61), and lung cancer AUC = 0.59 (0.51, 0.67), compared with no-cancer AUC = 0.61 (0.60, 0.62). Both the CHA2DS2-VASc score and HAS-BLED score were well calibrated across all study cohorts. Conclusion: Amongst certain cancer cohorts in the AF population, CHA2DS2-VASc performs similarly in predicting stroke to AF patients without cancer. Our findings highlight the importance of cancer diagnosis during the development of risk scores and opportunities to optimize the HAS-BLED risk score to better serve cancer patients with AF.

Direct oral anticoagulant therapy in adolescent venous thromboembolism: A systematic review.

Adolescent venous thromboembolism (VTE) has unique challenges in management, complications, and compliance to anticoagulants. Direct oral anticoagulants (DOACs) have been approved for pediatric VTE management, with an increasing use especially in adolescents. Primary objective is to evaluate the safety and efficacy of DOAC therapy in adolescent VTE. Secondary objectives include adverse events, bleeding events, and overall mortality. A SR protocol was registered in PROSPERO 2022 (CRD42022363928). Databases were searched from inception to September 22, 2022. Studies with children aged 10-18 years, VTE diagnosis, DOAC therapy, randomized control trials (RCTs), cohort, and relevant study types were included. Studies including prophylaxis, non-DOAC therapy, arterial thrombosis, age outliers, non-relevant study types were excluded. Findings are reported in accordance to PRISMA 2020. Nine reports from five studies, published between 2016 and 2022, were included. Rivaroxaban was the most common DOAC. VTE recurrence was 0.02% in the rivaroxaban phase III trial and one patient in the dabigatran phase IIb/III trial. Complete/partial thrombus resolution (CR/PR) was 76.6% in the rivaroxaban phase III trial, and 83.9% in the dabigatran phase IIb/III trial. CR/PR was found to be 68.4% in Dhaliwal et al. study and 83.3% in Hassan et al. study. Major bleeding occurred in one patient. Headache and gastrointestinal symptoms were commonly seen. All-cause mortality occurred in a patient due to cancer progression. DOAC therapy in adolescent VTE had CR/PR in two-thirds of the patients, with low incidence of VTE recurrence and major bleeding. As there are only two randomized controlled trial (RCTs), future adolescents' studies are required to validate our results.

Feasibility of atezolizumab and bevacizumab combination regimens in patients with hepatocellular carcinoma and lung cancer taking direct oral anticoagulants.

AIM: Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs. METHODS: This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed. RESULTS: The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105-0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157-10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin-bilirubin score (HR: 9.083, 95% CI: 1.118-73.76) was associated with bleeding events (p = 0.039). CONCLUSIONS: DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs.

Treatment strategies of the thromboembolic risk in kidney failure patients with atrial fibrillation.

The incidence and prevalence of atrial fibrillation (AF) in patients affected by kidney failure, i.e. glomerular filtration rate <15 ml/min/1.73 m2, is high and probably underestimated. Numerous uncertainties remain regarding how to prevent thromboembolic events in this population because both cardiology and nephrology guidelines do not provide clear recommendations. The efficacy and safety of oral anticoagulant therapy (OAC) in preventing thromboembolism in patients with kidney failure and AF has not been demonstrated for either vitamin K antagonists (VKAs) or direct anticoagulants (DOACs). Moreover, it remains unclear which is more effective and safer, because estimated creatinine clearance <25-30 ml/min was an exclusion criterion in the randomized controlled trials (RCTs). Three RCTs comparing DOACs and VKAs in kidney failure failed to reach the primary endpoint, as they were underpowered. The left atrial appendage is the main source of thromboembolism in the presence of AF. Left atrial appendage closure (LAAC) has recently been proposed as an alternative to OAC. RCTs comparing the efficacy and safety of LAAC versus OAC in kidney failure were terminated prematurely due to recruitment failure. A recent prospective study showed a reduction in thromboembolic events in haemodialysis patients with AF and undergoing LAAC compared with patients taking or not taking OAC. We review current treatment standards and discuss recent developments in managing the thromboembolic risk in kidney failure patients with AF. The importance of shared decision-making with the multidisciplinary team and the patient to consider individual risks and benefits of each treatment option is underlined.

Pharmacokinetics and pharmacodynamics of drug‒drug interactions in hospitalized older adults treated with direct oral anticoagulants.

PURPOSE: Polypharmacy is a frequent situation in older adults that increases the risk of drug-drug interactions (DDIs), both pharmacokinetic (PK) and pharmacodynamic (PD). Direct oral anticoagulants (DOACs) are frequently prescribed in older adults, mainly because of the high prevalence of atrial fibrillation (AF). DOACs are subject to cytochrome P450 3A4 (CYP3A4)- and/or P-glycoprotein (P-gp)-mediated PK DDIs and PD DDIs when co-administered with drugs that interfere with platelet function. The aim of our study was to assess the prevalence of DDIs involving DOACs in older adults and the associated risk factors at admission and discharge. METHODS: This was a cross-sectional study conducted in an acute geriatric unit between January 1, 2018 and December 31, 2022, including patients over 75 years of age treated with DOACs at admission and/or discharge, for whom a comprehensive collection of co-medications was performed. RESULTS: From 909 hospitalizations collected, the prevalence of PK DDIs involving DOACs was 16.9% at admission and 20.7% at discharge, and the prevalence of PD DDIs was 20.7% at admission and 20.2% at discharge. Factors associated with DDIs were bleeding history [adjusted odds ratio (ORa) 1.74, 95% confidence interval (CI) 1.13-2.68], number of drugs > 6 (ORa 2.54, 95% CI 1.88-3.46) and reduced dose of DOACs (ORa 0.39, 95% CI 0.28-0.54) at admission and age > 87 years (ORa 0.74, 95% CI 0.55-0.99), number of drugs > 6 (ORa 2.01, 95% CI 1.48-2.72) and reduced dose of DOACs (ORa 0.41, 95% CI 0.30-0.57) at discharge. CONCLUSION: This study provides an indication of the prevalence of DDIs as well as the profile of DDIs and patients treated with DOACs.

Perioperative Management in Patients with Atrial Fibrillation Treated with Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Minor Bleeding Risk Procedure: Rationale and Protocol for the PERIXa Study.

Background: While treatment interruption of non-vitamin K antagonist oral anticoagulants (NOACs) for elective surgery or procedures among patients with atrial fibrillation (AF) is becoming more prevalent, there remains insufficient evidence regarding the optimal perioperative management of NOACs, particularly procedures with minor bleeding risks. Objective: This study aims to evaluate the safety and effectiveness of a simplified, standardized protocol for perioperative management of direct factor Xa inhibitors in patients, with AF undergoing procedures associated with minor bleeding risk. Methods: This multicenter, prospective single-arm registry study plans to enroll patients undergoing procedures with minor bleeding risk who were prescribed direct factor Xa inhibitors for AF. The procedures with minor bleeding risk will include gastrointestinal endoscopy for diagnostic purposes, selected dental procedures, and ocular surgery for cataracts or glaucoma. For apixaban, patients will withhold the last evening dose and resume either from the evening dose of the procedure day or the following morning, depending on the bleeding risk of the patient. For edoxaban or rivaroxaban, patients will withhold only a single dose on the procedure day. The primary outcome is the occurrence of major bleeding events within 30 days. Secondary outcomes include systemic thromboembolism, all-cause mortality, and a composite of major and clinically relevant non-major bleeding events. Conclusion: This study has the potential to generate evidence regarding the safety of perioperative management for patients, with AF undergoing procedures associated with minor bleeding risk. Trial Registration: Clinicaltrials.gov: NCT05801068.

Evaluation of acute thrombus regression effect of edoxaban for deep vein thrombosis in patients with cancer: a single-center prospective observational study.

BACKGROUND: Although there are reports on the recurrence prevention in the chronic phase using direct oral anticoagulants (DOACs) for deep vein thrombosis (DVT) in patients with cancer, acute thrombus regression effect using DOACs has not been assessed. This study aimed to assess the thrombus regression effect of initial treatment using edoxaban for acute lower-extremity DVT in patients with active cancer. METHODS AND RESULTS: In this observational study, among the inpatients with cancer and lower-extremity DVT who underwent initial treatment with edoxaban at our hospital from November 2019 to December 2021, 34 consenting patients were recruited in this study. The quantitative ultrasound thrombus (QUT) score of thrombus volume was calculated at baseline (before administration) and 7-14 days after the start of edoxaban administration, using lower-extremity venous ultrasound to evaluate changes in thrombus volume. The primary and secondary endpoints were the acute thrombus regression effect of edoxaban and the impact of patients' clinical frailty on the thrombus regression effect, respectively. Anticoagulant therapy with edoxaban significantly reduced QUT score (p < 0.001). In addition, regardless of the Clinical Frailty Scale scores, QUT score decreased significantly. CONCLUSION: Initial treatment with edoxaban was effective for lower-extremity DVT in patients with cancer. In addition, the effect was the same independent of the degree of frailty.

A Rare Case of Renal Vein Thrombosis Secondary to Oral Contraceptive Pills.

Renal vein thrombosis (RVT) is a common complication of nephrotic syndrome and renal malignancy. However, its association with oral contraceptive use has rarely been reported. We report a case of a 29-year-old female with a history of oral contraceptive use, presenting with acute flank pain. On further investigation, she was found to have unilateral RVT. Oral contraception was discontinued, and she was started on therapeutic anticoagulation, initially with low-molecular-weight heparin, and then switched to apixaban. Her symptoms improved, and she is currently doing well. This case signifies the importance of proper history-taking and how oral contraception should be considered a significant risk factor for venous thromboembolism.

Risk factors for postgastric endoscopic submucosal dissection bleeding in direct oral anticoagulant users.

OBJECTIVES: Bleeding after endoscopic submucosal dissection (ESD) for gastric tumors in patients taking antithrombotic drugs, in particular direct oral anticoagulants (DOACs), remains unresolved; therefore, we evaluated the risk factors for post-ESD bleeding and drug differences in patients taking DOACs. METHODS: We included 278 patients taking antithrombotic drugs who underwent gastric ESD between January 2017 and March 2022. Antithrombotic drugs were withdrawn following the 2017 guidelines (Appendix on anticoagulants including DOACs). To further clarify differences in antithrombotic agents' effects, the peri-cancerous mucosa in the resected specimen was pathologically evaluated according to the Updated Sydney System. Multivariate analysis was performed to assess the risk of post-ESD bleeding. RESULTS: The incidence of post-ESD bleeding in patients taking DOACs was 19.6% (10/51). Among patients taking antithrombotic drugs, DOACs were identified as a possible factor involved in post-ESD bleeding (odds ratio [OR] 4.92). Among patients taking DOACs, possible factors included resection length diameter ≥30 mm (OR 3.72), presence of neutrophil infiltration (OR 2.71), lesions occurring in the lower third of stomach (OR 2.34), and preoperative antiplatelet use (OR 2.22). Post-ESD bleeding by DOAC type was 25.0% of patients (4/16) receiving apixaban, in 20.0% (3/15) receiving edoxaban, in 21.4% (3/14) receiving rivaroxaban, and in none of those receiving dabigatran. CONCLUSIONS: The administration of DOACs was shown to be a possible factor involved in post-ESD bleeding, and risk factors for patients taking DOACs included neutrophil infiltration. The pharmacological differences in the effects of DOACs contributing to bleeding in gastric ulcers suggest comparatively less bleeding with dabigatran after ESD.

A Case of Direct-Acting Oral Anticoagulant-Induced Intramural Colon Hematoma Successfully Treated by Laparoscopic Surgery.

Intramural intestinal hematoma is a rare disease, one of the triggering factors of which is the use of anticoagulants. In previous reports, most patients were on treatment with warfarin. Herein, we report a case of direct-acting oral anticoagulant (DOAC)-induced intramural hematoma of the ascending colon in a patient refractory to conservative treatment and required laparoscopic right hemicolectomy. An 80-year-old male patient with a history of atrial fibrillation and cerebral infarction, on treatment with apixaban, was brought to our hospital with the chief complaints of abdominal pain, vomiting, and melena. Imaging revealed the cause of symptoms to be intestinal obstruction caused by a mass lesion on the wall of the ascending colon. We initially opted for conservative treatment with discontinuation of apixaban and insertion of an ileus tube. Intestinal dilatation findings showed improvement; however, subsequent imaging examinations did not reveal the shrinkage of a lesion in the ascending colon. If the mass was not removed, recurrence of bowel obstruction symptoms was expected, so we decided to perform surgical intervention. A laparoscopic right hemicolectomy was performed, and an intramural hematoma of the ascending colon was diagnosed based on the excised specimen. He needed a blood transfusion for anemia but was discharged on postoperative day 14 with no other complications. DOACs are now widely used in patients with atrial fibrillation, and the risk of bleeding as a side effect is extremely low compared to conventional anticoagulants, including warfarin. However, when abdominal pain occurs, as in the present case, an intramural hematoma should be considered in the differential diagnosis. There is no established treatment plan for intestinal intramural hematoma. Although conservative treatment is effective in some cases, it is difficult to evaluate the risk of bleeding associated with DOACs using coagulation tests. Even if conservative treatment is selected, it is essential to determine surgical resection, if necessary, based on the clinical course and imaging and blood test findings.

Dabigatran Etexilate Related Unilateral Adrenal Hemorrhage.

A 63-year-old male presented to our clinic with computed tomography data of a large tumor of the left adrenal gland. The formation is highly suspicious for malignancy with central necrosis and hemorrhage, and a total size of 197/183/201 mm. Due to elevated D-dimer values of 7.17 mg/l (reference range <0.5 mg/l), treatment with dabigatran etexilate 2x150 mg was prescribed following a cardiology consult. On the third day of therapy, the patient noticed a large swelling in the left abdominal flank, which caused discomfort. No additional symptoms were reported. No previous abdominal surgical interventions or trauma were reported. Following a thorough physical examination, the patient was referred for a computer tomography that reported a diagnosis of a tumor of the left adrenal gland. Due to the size of the neoplasm, the suspicion of malignancy, compression of adjacent structures, and significant anemia with an Hb of 112 g/L, operative treatment was chosen as the best treatment modality. The mass was reported as a large organizing adrenal hematoma with no suspicion of malignancy on histology. Following a review of available literature, no other cases of unilateral adrenal hematoma with a size of 201x197 mm, following oral anticoagulant therapy with dabigatran etexilate, without any prior surgery or trauma have been reported. Most clinical cases report bilateral adrenal hemorrhage during the postoperative period, following prophylaxis with heparin and the development of heparin-induced thrombocytopenia. The patient underwent operative treatment, after which the patient recovered normally and was discharged from the clinic without complications.

Minimally invasive left atrial appendage occlusion plus reduced dose direct oral anticoagulant to prevent stroke in patients with atrial fibrillation-the LAAO-PlusRE.

The onset of atrial fibrillation (AF) has a direct association with left atrial appendage (LAA) function, as demonstrated by recent studies demonstrating the link between left atrial (LA) wall fibrosis, impaired contractility, and the development of AF. Non-valvular AF (NVAF) affects almost 30 million people worldwide, with this number expected to increase in the next 20 years. It is the main cause of ischemic stroke, with significant subsequent economic and social impact. Currently, the mainstay of stroke prevention in patients with NVAF is oral anticoagulation (OAC), which reduces the incidence of ischemic events at the stake of increased hemorrhagic events. Despite the introduction and widespread use of direct oral anticoagulants (DOACs), which almost completely replaced vitamin K antagonists (VKAs), the adherence to OAC is still low, hindering the efficacy of stroke prevention. Percutaneous LAA occlusion (LAAO) is now indicated (class IIB) in patients with NVAF at increased ischemic risk who cannot undergo OAC. Recently published data demonstrated that a reduced dose of DOAC after percutaneous LAAO is superior to long-term dual antiplatelet therapy (DAPT) for stroke prevention in the mid-term. One of the possible pitfalls of percutaneous LAAO is postprocedural peri-device leaks (PDLs) that have been associated with increased thromboembolic events. According to LAAOS III results, surgical LAAO during cardiac surgery brings a 33% reduction in risk of stroke at five years, independently from the OAC regimen with a high rate of complete appendage occlusion. The combination of surgical LAAO and reduced dose DOAC might ensure adequate embolic prevention, lowering the hemorrhagic risk. The present manuscript aims to describe the rationale and design of the Minimally Invasive Left Atrial Appendage Occlusion Plus REduced Dose DOAC To Prevent Stroke In Patients With Atrial Fibrillation Randomized Clinical Trial (LAAO-PlusRE).

Is there a role for the laboratory monitoring in the management of specific antidotes of direct oral anticoagulants?

Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes.

Fragility and long-term clinical outcomes in patients with venous thromboembolism receiving direct oral anticoagulants: From the COMMAND VTE REGISTRY-2.

INTRODUCTION: There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE). MATERIALS AND METHODS: We used the COMMAND VTE Registry-2 enrolling patients with acute symptomatic VTE. The study population consisted of 3928 patients receiving DOACs, who were divided into fragile (2136 patients) and non-fragile groups (1792 patients). Fragility was defined as patients of age ≥ 75 years, creatinine clearance level ≤ 50 ml/min, and/or body weight ≤ 50 kg. RESULTS: The fragile group significantly more often received reduced doses of DOACs compared to the non-fragile group (51 % and 19 %, P < 0.001). The cumulative 5-year incidence of major bleeding was numerically higher in the fragile group than the non-fragile group (15.0 % and 11.1 %, P = 0.052), even with no significant excess risk after adjusting for confounders (HR 1.03, 95%CI 0.81-1.31, P = 0.78). The cumulative 5-year incidence of clinically relevant bleeding was significantly higher in the fragile group than the non-fragile group (28.6 % and 19.6 %, P < 0.001), even after adjusting for confounders (HR 1.28, 95%CI 1.08-1.53, P = 0.005). There was no significant difference in cumulative 5-year incidence of recurrent VTE between the groups (9.6 % and 8.9 %, P = 0.68), which was consistent after adjusting for confounders (HR 1.13, 95%CI 0.84-1.51, P = 0.41). CONCLUSIONS: Among VTE patients receiving DOACs, fragile patients were associated with a numerically higher rate of major bleeding and a significantly increased risk of clinically relevant bleeding, but not an increased risk of recurrent VTE.

Direct oral anticoagulants compared with warfarin in patients with left ventricular thrombus: a cohort study from China.

Background: Current guidelines recommend vitamin K antagonist (VKA) for left ventricular (LV) thrombus. This study aimed to compare the effectiveness and safety of direct oral anticoagulant (DOAC) and warfarin in Chinese patients with LV thrombus. Methods: Patients with LV thrombus admitted to Beijing Anzhen Hospital of Capital Medical University between January 2018 and January 2022, were enrolled in this cohort study. The primary endpoint was defined as thrombus resolution within 90 days. The secondary endpoints included thrombus resolution within 180 days, major bleeding events, and minor bleeding events. All patients were followed up for at least 90 days after diagnosis of LV thrombus. Patients were divided into the VKA and DOAC groups according to the anticoagulants. Differences in clinical endpoint events between the two groups were compared. Results: This study included 129 and 111 patients in the VKA and DOAC groups, respectively. After adjusting for gender and smoking status, no significant difference was observed in thrombus resolution within 90 days between the VKA and DOAC groups. Additionally, there was no difference between the two groups in the secondary endpoints of thrombus resolution within 180 days, major bleeding, and minor bleeding. In subgroup analysis, rivaroxaban and dabigatran did not show significant differences in primary and secondary endpoints. Conclusions: This study showed no significant difference in thrombus resolution between DOAC and warfarin. DOAC might be an alternative to warfarin for the treatment of LV thrombus. However, further large prospective studies are required to explore the efficacy and safety of DOAC in patients with LV thrombus.

Real-world experience of direct oral anticoagulant use in a single pediatric center.

BACKGROUND: Pediatric venous thromboembolism has increased by 130%-200%, specifically in hospitalized children, and direct oral anticoagulants (DOACs) offer several therapeutic advantages. METHODS: This study aims to evaluate the real-world epidemiological and outcome data from a retrospective review of pediatric patients treated with DOACs from January 1, 2013 to December 31, 2022. In this single-center, IRB-approved study, 65 patients were identified and analyzed using SPSS statistical software, and a descriptive statistical analysis was conducted. RESULTS: Of the 65 patients, 37% were on apixaban, 61.5% were on rivaroxaban, and 1.5% were on dabigatran. Per the 2023 ISTH outcome definitions, one (2%) patient had a major bleeding episode, six (9%) had clinically relevant non-major bleeding, three (5%) patients had patient-important heavy menstrual bleeding (HMB), and one (1.5%) patient had minor bleeding. Seven (19%) of 37 postmenarchal patients had evidence of HMB. Six (9.2%) patients had recurrent venous thromboembolism while on a DOAC (one was on apixaban, and five were on rivaroxaban) and were transitioned to other forms of anticoagulation. CONCLUSION: Thus, bleeding rates after DOAC therapy are comparable to previous DOAC trials, as well as other anticoagulants in pediatrics. HMB is an important outcome measure and should continue to be investigated. This study reports a higher rate of recurrent thrombosis (9.2%) compared to other trials. However, this observation may be attributed to patients who had ongoing risk factors, as well as a longer duration of study follow-up. Additional multicentered outcome studies evaluating DOAC use in children are needed to determine long-term recurrence and HMB risks.

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.

Comparing Anticoagulation Strategies for Venous Thromboembolism Associated With Active Cancer: A Systematic Review and Meta-Analysis.

Background: Current guidelines recommend several direct oral anticoagulant agents (DOACs) equally for managing cancer-associated venous thromboembolism (VTE). Objectives: The aim of this study was to assess the efficacy and safety of DOACs in patients with active cancer. Methods: Literature searches were conducted in PubMed, Embase, and Cochrane Central in November 2022. Randomized controlled trials investigating anticoagulation strategies (vitamin K antagonists, parenteral anticoagulation [eg, low-molecular weight heparin], and DOACs) for VTE in patients with active cancer were identified for network meta-analysis. The outcomes included recurrent VTE, recurrent pulmonary embolism, recurrent deep venous thrombosis, major bleeding, clinically relevant nonmajor bleeding (CRNMB), and a composite outcome of major bleeding or CRNMB. Pooled HRs and 95% CIs were estimated using either the HR or relative risk provided from each study. Random-effects models were used for all the analyses. Results: Seventeen randomized controlled trials involving 6,623 patients with active cancer were included. No significant differences were found among the DOACs for efficacy outcomes (recurrent VTE, pulmonary embolism, and deep venous thrombosis). In terms of major bleeding, apixaban was similarly safe compared with dabigatran and rivaroxaban but was associated with a decreased risk compared with edoxaban (HR: 0.38; 95% CI: 0.15-0.93). Regarding CRNMB, edoxaban was similarly safe compared with apixaban but was associated with a decreased risk compared with rivaroxaban (HR: 0.31; 95% CI: 0.10-0.91). Compared with parenteral anticoagulation, apixaban was associated with a reduced risk for recurrent VTE (HR: 0.60; 95% CI: 0.38-0.93) without increasing bleeding, edoxaban was associated with an increased risk for major bleeding or CRNMB (HR: 1.35; 95% CI: 1.02-1.79), and rivaroxaban was associated with an increased risk for CRNMB (HR: 3.76; 95% CI: 1.43-9.88). Conclusions: DOACs demonstrate comparable efficacy but exhibit different safety profiles. Apixaban may confer an antithrombotic benefit without an increased risk for bleeding, distinguishing it from other contemporary anticoagulation strategies in patients with active cancer and VTE.

An Unusual Case of Apixaban-Induced Small Vessel Vasculitis: Leukocytoclastic Vasculitis.

Apixaban is a rare cause of drug-induced leukocytoclastic vasculitis (LCV). We report a case of apixaban-induced LCV in a 55-year-old male with deep vein thrombosis who developed systemic symptoms and pruritic rash in the bilateral lower extremity after 17 days of apixaban therapy. A skin biopsy confirmed the LCV, and he was diagnosed with apixaban-induced LCV after ruling out all other possible causes. His condition improved after apixaban discontinuation, supportive management, and oral prednisone. Our case highlights the early diagnosis and management of drug-induced LCV and also describes the existing literature to highlight existing knowledge and potential mechanisms underlying anticoagulant-induced vasculitis.