Anticoagulant Options Research Articles

Anticoagulant therapy in pregnant women with mechanical and bioprosthetic heart valves.

The aim of the present study was to review maternal and fetal outcomes in pregnant women with prosthetic heart valves. A retrospective record review of pregnant women with prosthetic heart valves on anticoagulation was performed at the Specialist Cardiac Antenatal Clinic, Johannesburg South Africa from 2015 to 2023. Fifty pregnancies with mechanical heart valves and three with tissue valves, on anticoagulation for comorbid atrial fibrillation were identified. The majority were of African ethnicity at a mean age of 33 ± 6 years. Anti-Xa adjusted enoxaparin was commenced at 10.5 ± 5.6 weeks' gestation until delivery in 48 (90.6%) pregnancies and warfarin was continued in five (9.4%) pregnancies. The live birth rates on enoxaparin and warfarin were 56.3% (95% confidence interval [CI]: 42.3-69.3) and 20.0% (95% CI: 2.0-64.0), respectively. There were 12 (22.6%) miscarriages at a mean of 11.3 ± 3.7 weeks' gestation, four (7.5%) intrauterine fetal deaths on warfarin and two (3.8%) warfarin embryopathy/fetopathy. The rates of antepartum/secondary postpartum bleeding and primary postpartum bleeding were 29.4% (95% CI: 18.6-43.1) and 5.9% (95% CI: 1.4-16.9), respectively. Maternal complications included anemia (n = 11, 20.8%), arrhythmia (n = 2, 3.8%), heart failure (n = 2, 3.8%) and paravalvular leak (n = 2, 3.8%). There was one (1.9%) mitral valve thrombosis and one (1.9%) stuck valve in pregnancies who defaulted warfarin prior to pregnancy. There were no maternal deaths. Multidisciplinary management of pregnant women with prosthetic heart valves with anti-Xa adjusted low molecular weight heparin throughout pregnancy represents an effective anticoagulation option for low-middle-income countries.

RNAi targeting LMAN1-MCFD2 complex promotes anticoagulation in mice.

Combined deficiency of coagulation factor V (FV) and factor VIII (FVIII) is a rare bleeding disease caused by variants in either lectin mannose binding 1 (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) gene. Reducing the level of FVIII by inhibiting the LMAN1-MCFD2 complex may become a new anticoagulant approach. We aimed to find a new therapeutic option for anticoagulation by RNA interference (RNAi) targeting LMAN1 and MCFD2. siRNA sequences with cross-homology between mice and humans were designed based on LMAN1 or MCFD2 transcripts in NCBI and were screened with the Dual-Luciferase reporter assay. The optimal siRNAs were chemically modified and conjugated with three N-acetylgalactosamine molecules (GalNAc-siRNA), promoting their targeted delivery to the liver. The expression of LMAN1 and MCFD2 in cell lines or mice was examined by RT-qPCR and western blotting. For the mice administered with siRNA, we assessed their coagulation function by measuring APTT and the activity of FVIII factor. After administration, siRNAs GalNAc-LMAN1 and GalNAc-MCFD2 demonstrated effective and persistent LMAN1 and MCFD2 inhibition. 7 days after injection of 3mg/kg GalNAc-LMAN1, the LMAN1 mRNA levels reduced to 19.97% ± 3.78%. MCFD2 mRNA levels reduced to 32.22% ± 13.14% with injection of 3mg/kg GalNAc-MCFD2. After repeated administration, APTT was prolonged and the FVIII activity was remarkably decreased. The tail bleeding test of mice showed that the amount of bleeding in the treated group did not significantly increase compared with the control group. Our study confirms that therapy with RNAi targeting LMAN1-MCFD2 complex is effective and can be considered a viable option for anticoagulation drugs. However, the benefits and potential risk of bleeding in thrombophilic mice model needs to be evaluated.

Renal replacement therapy in critical ill patients

Acute kidney injury (AKI), especially when caused or accompanied by sepsis, is associated with prolonged hospitalization, progression of chronic kidney disease (CKD), financial burden on the health care system, and increases mortality in various entities. Extended renal replacement therapy (CRRT) is the predominant form of renal replacement therapy (RRT) in intensive care units (ICU) by providing hemodynamic stability in critically ill patients, more precise control of fluid balance, correction of acid-base imbalances, electrolyte disorders and achieving a stable level of osmolarity correction, including in multimorbid patients. This article examines the various aspects of CRRT in critically ill patients with severe AKI with high comorbidity, as well as in patients with sepsis and multiple organ failure. An analytical evaluation of the choice of CRRT over intermittent/intermittent hemodialysis (IHD) in selected clinical settings is being conducted. Filter/dialyzer life is assessed, including assessment of filtration fraction, use of anticoagulation options including regional citrate anticoagulation (RCA), dose of CRRT prescribed and delivered, vascular access management, general criteria, timing of initiation and cessation of CRRT, and initiation of renal replacement therapy for nonrenal indications. with AKI and/or sepsis.

Bivalirudin as a substitute for heparin in neurointervention for patients with heparin-induced thrombocytopenia

ObjectivesHeparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature. Materials and methodsHere we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients. ResultsBivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia. ConclusionsHeparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate.

Preventing venous thromboembolism for ambulatory patients with cancer: Developing the form and content of implementation strategies

BackgroundFor ambulatory cancer patients receiving systemic chemotherapy, adherence is low to recommended venous thromboembolism (VTE) prevention interventions. Previously, we identified implementation strategies to address barriers to adherence, including (1) conducting clinician education and training; (2) developing and distributing educational materials for clinicians; (3) adapting electronic health records to provide interactive assistance; and (4) developing and distributing educational materials for patients. The objective of this study was to develop these implementation strategies’ form (i.e., how and when) and content (i.e., information conveyed) as a critical step for implementation and dissemination. MethodsTo design and develop the form and content of the implementation strategies, we conducted multidisciplinary stakeholder panels with oncology clinicians, pharmacists, and hematologists. Over several panel discussions, we developed a low fidelity prototype. Participants performed preliminary usability testing, simulating patient care encounters. We also conducted interviews with three patients who provided additional feedback. ResultsThe form and content for each strategy, respectively, included (1) concise training with a slide deck; (2) succinct summary of evidence for the interventions and support for anticoagulation management; (3) automated VTE risk-assessment and clinical decision support, including bleeding risk assessment and anticoagulation options; and (4) patient education resources. During development, audit and feedback was identified as an additional strategy, for which we created report cards to implement. ConclusionWith stakeholder input, we successfully developed the form and content needed to put the implementation strategies into practice. The next step is to study the effect on the uptake of ambulatory VTE prevention recommendations in oncology clinics.

The Application of Regional Citrate Anticoagulation in Protein A Immunoadsorption: A Single-Center Retrospective Cohort Study

Introduction: Protein A immunoadsorption (IA) is proving to be an effective treatment method for autoimmune diseases and other disorders. Regional citrate anticoagulation (RCA) prevents clotting in extracorporeal circuits without increasing hemorrhage risk in high bleeding risk patients, but there are no specific guidelines for its application in IA. We aimed to evaluate the safety and adverse effects of RCA used in IA therapy. Methods: We conducted a retrospective cohort study of forty-five RCA-IA sessions in 14 HLA-incompatible kidney transplant recipients with focus on the safety and adverse effects of RCA in IA. The extracorporeal circuit was equipped with 4% trisodium citrate solution as an anticoagulant and 10% calcium gluconate solution to compensate for calcium loss. The adverse events, including coagulation and blood biochemical indexes, especially calcium level, were recorded. Results: Our study found that 93.33% of the sessions were without circuit clotting or other significant complications. A slight decrease in fibrinogen level was observed, but without significant variations in other coagulation indexes or platelet count. There was a slight elevation in the potential of hydrogen, bicarbonate, and base excess after 2 h and 6 h posttreatment relative to prior treatment, but these returned to normal levels within 24 h posttreatment. Conclusion: RCA is a feasible, effective, and safe anticoagulation option for IA treatment in HLA-incompatible kidney transplant recipients. Electrolyte disturbances, especially alkalosis, hypocalcemia, hypomagnesemia, and fluid status, should be closely monitored and managed.

Anticoagulation Management in V-V ECMO Patients: A Multidisciplinary Pragmatic Protocol

(1) Background: Extracorporeal membrane oxygenation (ECMO) is a complex procedure affecting both the risk of thrombosis and bleeding. High-quality data to personalize anticoagulation management in ECMO are lacking, resulting in a high variability in practice among centers. For this reason, we review coagulation methods and monitoring and share a pragmatic proposal of coagulation management, as performed in our high-volume ECMO Referral Centre; (2) Methods: We revised the anticoagulation options and monitoring methods available for coagulation management in ECMO through PubMed search based on words including “anticoagulation,” “coagulation assays,” “ECMO,” “ELSO,” and “ISTH”; (3) Results: Actual revision of the literature was described as our routine practice regarding ECMO anticoagulation and monitoring; (4) Conclusions: No coagulation test is exclusively predictive of bleeding or thrombotic risk in patients undergoing ECMO support. An approach that allows for a tailored regimen of anticoagulation (regardless of agent used) and monitoring is mandatory. To accomplish this, we propose that the titration of anticoagulation therapies should include multiple laboratory tests, including anti-Xa, aPTT, ACT, viscoelastic tests, AT levels, platelet count, fibrinogen, and FXIII levels. Anticoagulation regimens should be tailored to a specific patient and personalized based on this complex array of essays.

Efficacy and safety of Apixaban for the prevention of thrombosis in arteriovenous grafts.

This research aims to fill a vital gap in existing studies by evaluating the efficacy and safety of Apixaban, a direct oral anticoagulant, in the prevention of arteriovenous graft (AVG) thrombosis, thereby offering substantial insights into alternative anticoagulant options for hemodialysis patients. Conducted as a multi-center, randomized, double-blind, placebo-controlled trial, this study involved end-stage renal disease (ESRD) patients who had recently received polytetrafluoroethylene grafts. Participants were assigned to receive either Apixaban at a dose of 2.5 mg twice daily or a placebo. The primary outcome measure was the occurrence of graft thrombosis, while secondary outcomes focused on the incidence and severity of bleeding. Analytical methods included Kaplan-Meier estimates, Cox proportional hazards models, and conventional statistical tests. With 96 patients enrolled, the study found that Apixaban significantly reduced the incidence of AVG thrombosis compared to placebo (16.7% vs. 62.5%, P < 0.0001). Notably, this reduction in thrombosis incidence was not accompanied by an increase in bleeding events, thus affirming the safety profile of Apixaban as established in prior research. Apixaban is identified as an efficacious alternative to traditional anticoagulants in the prevention of AVG thrombosis among hemodialysis patients, representing a notable advancement in the care of individuals with ESRD. The results of this study support further investigations into the optimal dosing strategies specifically tailored for this patient demographic.

Choice and Duration of Anticoagulation for Venous Thromboembolism.

Venous thromboembolism (VTE) is a prevalent medical condition with high morbidity, mortality, and associated costs. Anticoagulation remains the main treatment for VTE, though the decision on when, how, and for how long to administer anticoagulants is increasingly complex. This review highlights the different phases of VTE management, with special circumstances for consideration such as antiphospholipid syndrome, coronary artery disease, cancer-associated thrombus, COVID-19, and future anticoagulation options. Anticoagulation management will continue to be a complex decision, applying evidence-based medicine to individual patients with the hope of maximizing effectiveness while minimizing risks.

Anticoagulation practices for continuous renal replacement therapy: a survey of physicians from the United States

Background During continuous renal replacement therapy (CRRT), anticoagulants are recommended for patients at low risk of bleeding and not already receiving systemic anticoagulants. Current anticoagulants used in CRRT in the US are systemic heparins or regional citrate. To better understand use of anticoagulants for CRRT in the US, we surveyed nephrologists and critical care medicine (CCM) specialists. Methods The survey contained 30 questions. Respondents were board certified and worked in intensive care units of academic medical centers or community hospitals. Results 150 physicians (70 nephrologists and 80 CCM) completed the survey. Mean number of CRRT machines in use increased ∼30% from the pre-pandemic era to 2022. Unfractionated heparin was the most used anticoagulant (43% of estimated patients) followed by citrate (28%). Respondents reported 29% of patients received no anticoagulant. Risk of hypocalcemia (52%) and citrate safety (42%) were the predominant reasons given for using no anticoagulant instead of citrate in heparin-intolerant patients. 84% said filter clogging was a problem when no anticoagulant was used, and almost 25% said increased transfusions were necessary. Respondents using heparin (n = 131) considered it inexpensive and easily obtainable, although of moderate safety, citing concerns of heparin-induced thrombocytopenia and bleeding. Anticoagulant citrate dextrose solution was the most used citrate. Respondents estimated that 37% of patients receiving citrate develop hypocalcemia and 17% citrate lock. Conclusions Given the increased use of CRRT and the lack of approved, safe, and effective anticoagulant choices for CRRT in the US, effective use of current and other anticoagulant options needs to be evaluated.

COST-EFFECTIVENESS ANALYSIS OF ANTICOAGULANT USAGE IN COVID-19 PATIENTS AT 45 KUNINGAN HOSPITAL

Cost-effectiveness analysis (CEA) is a pharmacoeconomic method that compares prices from all sources consumed (cost) with the outcome value of a program or intervention to obtain objective answers to the selection of drugs that are effective in terms of benefits and costs. COVID-19, or Coronavirus Disease 2019, is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2) and causes acute respiratory distress, including fever, coughing, and shortness of breath. Fondaparinux, aside from heparin and enoxaparin, can be given as an anticoagulant therapeutic option in hospitalized COVID-19 patients, according to the third edition of the COVID-19 care recommendations. This study aimed to find the most cost-effective therapy among heparin, enoxaparin, and fondaparinux in COVID-19 patients at the RSUD’45 Kuningan. It also applied descriptive non-experimental research methods with retrospectively collected data. The intervention that had been studied was the administration of anticoagulant medication, where the effectiveness of the drug was observed in the reduction of D-dimer levels to normal levels. Meanwhile, the costs were observed from the perspective of a healthcare provider, specifically the RSUD’45 Kuningan. The study sample included 107 patients, with 13 receiving heparin, 41 receiving enoxaparin, and 53 receiving fondaparinux. Bivariate analysis using the chi-square test revealed no significant difference between the drug groups in the proportion of patients who improved and did not improve (sig. value = 0.610)...

Treatment Complications of Venous Thromboembolism in Patients with Central Nervous System Tumors

Introduction: In the last decade, landmark studies have been conducted in patients with cancer-associated venous thromboembolism (CA-VTE), helping to guide treatment decisions of anticoagulant therapy. Although these trials outlined new treatment opportunities, they either completely excluded or included only a small number of patients with primary brain tumors or central nervous system (CNS) metastasis. Additionally, there are very limited data on complication rates of anticoagulants in patients with spinal metastasis. Consequently, there is an ongoing knowledge gap for safe and effective anticoagulation options for patients with acute VTE in this high-risk patient population. Methods: We conducted a single institution IRB-approved retrospective study evaluating the rates of hemorrhage and recurrent thromboses in patients with CA-VTE and a diagnosis of a primary brain tumor or brain and/or spinal metastases. Our investigation was conducted at The Preston Robert Tisch Brain Tumor Center and the Center for Brain and Spine Metastasis at Duke between 2017 and 2021. The cohort was built through identifying patients by ICD-10 codes searched within the electronic medical records. Inclusion criteria consisted of patients ≥ 18 years of age, a history of confirmed primary brain tumor or brain and/or spinal metastases prior to VTE, treatment with anticoagulation or an inferior vena cava (IVC) filter, and followed up at least once since starting treatment beyond 1 month of VTE diagnosis . We compared complication event rates and the anticoagulant selected for treatment. Data obtained included patient demographic information, medical and social histories, cancer-related history, VTE history and treatment, recurrent thrombotic and hemorrhagic events, and patient mortality. Results: We identified 3584 total patients during the study timeframe. Eight hundred and twenty-five patients were included and 2759 were excluded for not meeting our inclusion criteria. Of the 825 included patients, 766 were treated with either apixaban (348/766; 45%), rivaroxaban (178/766; 23%), or enoxaparin (240/766; 31%) for their initial CA-VTE (Table 1). The other 59 patients were treated with another anticoagulant or received an IVC filter without anticoagulation. The median age for our cohort of 766 patients was 61.0 (20.0 - 87.0). There was no significant statistical association between relevant past medical histories of obesity or hypertension among the 3 anticoagulant groups. There was no significant statistical association between the 3 anticoagulant cohorts and primary brain tumors, or brain and/or spinal metastases ( p= 0.06). Although it trended towards significance, there was no statistically significant difference in the proportion of patients receiving anti-VEGF inhibitors at time of initial VTE among the 3 anticoagulant cohorts ( p = 0.052). When looking at our primary outcomes of recurrent thrombosis, major hemorrhage, or clinically relevant non-major bleeding, 171 individual patients experienced a total of 188 unique events that occurred during treatment with apixaban, rivaroxaban, or enoxaparin (Table 2). Of the 171 unique patients, enoxaparin use was the most common (80/171; 47%), followed by apixaban (61/171; 36%), rivaroxaban (28/171; 16%), and a small percentage (2/171; 1%) were treated with a combination of apixaban, rivaroxaban, or enoxaparin during their unique event. When excluding the 2 patients with multiple anticoagulant treatments, there was no statistical difference among anticoagulant rates and any event of recurrent thrombosis, major hemorrhage, clinically relevant non-major bleeding, or any multiple events ( p = 0.07). Conclusions: We present the largest unique data set comparing anticoagulant use in a known high-risk patient population of primary brain tumors, brain and/or spinal metastases. Our data demonstrate up to 22% of patients with CA-VTE and primary brain tumors, brain and/or spinal metastases have a subsequent hemorrhagic or recurrent thrombotic complication during treatment with apixaban, rivaroxaban, or enoxaparin for their initial event. However, our data did not demonstrate a statistically significant difference in complication rates between these 3 anticoagulants. These findings indicate a need for future large-scale prospective investigations to determine optimal treatment in this high-risk patient population.

Abelacimab in Cancer-Associated Thrombosis: The Right Drug at the Right Time for the Right Purpose. A Comprehensive Review.

Cancer-associated thrombosis (CAT) is a devastating complication of cancer that can significantly impact a patient's health and life. The incidence of CAT is approximately 20%, and 1 in 5 cancer patients will develop CAT annually. Indeed, CAT can promote pulmonary embolism and deep vein thrombosis, leading to increased morbidity and mortality that dramatically impact survival. CAT can also provoke delay or discontinuation of anticancer treatment, which may result in a lack of treatment efficacy and high costs for patients, institutions, and society. Current guidelines advocate direct oral anticoagulants (DOACs) as the first-line anticoagulant option in CAT. Compared to low-molecular-weight-heparins (LMWHs), DOACs are advantageous in that they typically have an oral route of administration, do not require laboratory monitoring, and have a more predictable anticoagulant effect. However, in patients with thrombocytopenia, renal failure, or those receiving anticancer regimens with potential for drug-drug interactions, LMWH is still the mainstay of care. The main limitation of current anticoagulant agents is related to bleeding risk (BR), both for DOACs and LMWHs. Specifically, DOACs have been associated with high BR in gastrointestinal and genitourinary cancers. In this challenging scenario, abelacimab, an anti-factor XI agent, could represent a viable option in the management of CAT due to its "hemostasis sparing" effect. The safe profile of abelacimab could be useful in patients with active malignancy and CAT, as long-term anticoagulant therapy is often required. Two ongoing international phase III trials (Aster and Magnolia) compare abelacimab with the standard of care (i.e., apixaban in patients with CAT and dalteparin in those with CAT and high BR, respectively). Abelacimab is a new and attractive anticoagulant for the management of CAT, especially in the insidious and critical scenario of active cancer patients with venous thromboembolism and high BR. The aim of this narrative review is to discuss the updated evidence on the performance of DOACs and LMWHs in the treatment of CAT and to focus on the potential role of abelacimab in CAT and its promising associated clinical trials.

PB0923 Treatment and Outcomes of Cancer-Associated Thrombosis, from “Traditional” Anticoagulation Options to Direct Oral Anticoagulants: A Ten-Year Experience

PB0923 Treatment and Outcomes of Cancer-Associated Thrombosis, from “Traditional” Anticoagulation Options to Direct Oral Anticoagulants: A Ten-Year Experience

Anticoagulants in adult extracorporeal membrane oxygenation: alternatives to standardized anticoagulation with unfractionated heparin.

Extracorporeal membrane oxygenation (ECMO) is a vital technique for severe respiratory or heart failure patients. Bleeding and thrombotic events are common during ECMO and negatively impact patient outcomes. Unfractionated heparin is the primary anticoagulant, but its adverse effects limit its use, necessitating alternative anticoagulants. Review available alternative anticoagulants for adult ECMO patients. Explore potential novel anticoagulants for future ECMO use. Aim to reduce complications (bleeding and thrombosis) and improve safety and efficacy for critically ill ECMO patients. Comprehensive literature review of existing and emerging anticoagulants for ECMO. Identified a range of alternative anticoagulants beyond unfractionated heparin. Evaluated their potential utility in mitigating ECMO-related complications. Diverse anticoagulant options are available and under investigation for ECMO. These alternatives may enhance patient safety and outcomes during ECMO support. Further research and clinical studies are warranted to determine their effectiveness and safety profiles.

Anticoagulation Options for Cranial Procedures: A Comparative Review of Aspirin, Plavix, and Aggrastat.

Anticoagulation therapy is critical to avoiding thrombotic events in patients following cranial surgery. Although Aspirin, Plavix, and Aggrastat are used as anticoagulants for this purpose, there is no consensus on which agent is the most effective and safe. In this comparative study, we analyze the current evidence on the efficacy and safety of these three anticoagulants in the context of cranial surgeries. This review focuses on the advantages and disadvantages of each anticoagulant, such as its pharmacokinetics, indications, contraindications, and possible consequences. The outcomes of this study will help physicians choose the best anticoagulant for their patients based on individual patient characteristics and the kind of cranial procedure. Aggrastat's potential to be included as a recommended anticoagulant for cranial procedures warrants further study.

Comparative Efficacy of Oral Apixaban and Subcutaneous Low Molecular Weight Heparins in the Treatment of Cancer-Associated Thromboembolism: A Meta-Analysis.

Cancer patients' risk of developing venous thromboembolism (VTE) is four to seven times higher than the general population. Cancer-associated VTE (CA-VTE), is a leading cause of morbidity and mortality in cancer patients. Low Molecular Weight Heparin (LMWH) has historically been the mainstay treatment ofCA-VTE; however, complications such as bleeding and recurrent VTE make it challenging to manage these patients. Recent randomized controlled trials (RCTs) have proven that direct oral anticoagulants (DOACs) are as efficacious as LMWHs in treating CA-VTE. We conducted a systematic review and meta-analysis to ascertain the efficacy and safety of LMWH and Apixaban for the treatment of CA-VTE.A systematic review was conducted using Medline, Embase, and Scopus, databases for all cohort studies, case-control studies, and RCTs in English comparing cancer patients undergoing treatment with Apixaban or LMWH to treat CA-VTE from inception-May 2023. The Review Manager program, version 5.4.1, was used for statistical analysis and the Mantel-Haenszel fixed-effects models to calculate the risk ratio (RR) and 95% confidence intervals (CIs) and the inverse variance approach to get the weighted mean difference for the continuous outcomes. Q-test for heterogeneity was used to examine statistical heterogeneity and an I2 statistics value >50%was defined as significant heterogeneity. A total of four studies were included, and the total number of patients was 1,632 across all studies. The Apixaban group was associated with a statistically significant increase in minor bleeding (RR 1.57; 95% CI (1.12, 2.21); p=0.009; I2=0%), but not for major and total bleeding. The Apixaban group showed a statistically significant lower risk of recurrent VTE when compared to the LMWH group (RR: 0.61; 95% CI (0.41, 0.92); p=0.02; I2 = 7%), and there was no statistically significant difference in terms of mortality between the two groups (RR: 0.89;95% CI (0.73, 1.09); I2=0). Our findings suggest that Apixaban may be a favorable anticoagulant option for managing cancer-associated thromboembolism, as it demonstrated a lower risk of recurrent VTE. The risk of bleeding with DOAC in gastrointestinal cancers warrants further investigation.

Impact of type of anticoagulant on clinical outcomes in cancer patients who had atrial fibrillation

To date, evidence on optimal anticoagulant options in patients with AF who concurrently have active cancer remains elusive. To describe anticoagulant patterns and clinical outcomes among patients with a concomitant diagnosis of AF and cancer. Data were obtained from the University of Utah and Huntsman Cancer Institute (HCI) Hospitals. Patients were included if they had diagnosis of AF and cancer. Outcome was type and pattern of anticoagulant. Clinical outcomes were stroke, bleeding and all-cause mortality. From October 1999 to December 2020, there were 566 AF patients who concurrently had active cancer. Mean age ± standard deviation was 76.2 ± 10.7 and 57.6% were males. Comparing to warfarin, patients who received direct oral anticoagulant (DOACs) were associated with similar risk of stroke (adjusted hazard ratio, aHR 0.8, 95% confidence interval [CI] 0.2–2.7, P = 0.67). On contrary, those who received low-molecular-weight heparin (LMWH) were associated with significantly higher risk of stroke comparing to warfarin (aHR 2.4, 95% CI 1.0–5.6, P = 0.04). Comparing to warfarin, DOACs and LMWH was associated with similar risk of overall bleeding with aHR 1.1 (95% CI 0.7–1.6, P = 0.73) and aHR 1.1 (95% CI 0.6–1.7, P = 0.83), respectively. Patients who received LMWH but not DOACs were associated with increased risk of death as compared to warfarin, aHR 4.5 (95% CI 2.8–7.2, P < 0.001) and 1.2 (95% CI 0.7–2.2, P = 0.47). In patients with active cancer and AF, LMWH, compared to warfarin, was associated with an increased risk of stroke and all-cause mortality. Furthermore, DOACs was associated with similar risk of stroke, bleeding and death as compared to warfarin.

#6376 TREATMENT OF DABIGATRAN INTOXICATION IN CRITICALLY ILL PATIENTS WITH ACUTE KIDNEY INJURY: THE ROLE OF SUSTAINED LOW-EFFICIENCY DIALYSIS

Abstract Background and Aims Dabigatran, a direct thrombin inhibitor, is a commonly used direct oral anticoagulant (DOAC) prescribed for non-valvular atrial fibrillation. Despite its benefits in term of safety/effectiveness along with the possibility to treat patients who were ineligible for vitamin K inhibitors (VKAs), a great degree of attention is required in elderly patients with multiple comorbidities. Notably, dabigatran mainly undergoes renal elimination, and dose adjustment is recommended in patients with Chronic Kidney Disease (CKD). In this regard, the onset of an abrupt decrease of kidney function may further affect dabigatran pharmacokinetic profile, increasing the risk of acute intoxication. Idarucizumab is the approved antagonist in the case of dabigatran-associated major bleeding or concomitant need of urgent surgery, but its clinical use is limited by the lack of data in patients with Acute Kidney Injury (AKI). Given the dabigatran PK parameters (low MW, low Vd, negligible protein binding), the early start of Extracorporeal Kidney Replacement Therapy (EKRT) may represent the optimal reversal strategy. We present a case series of three critically ill patients with AKI and dabigatran overdose treated with Sustained Low-Efficiency Dialysis (SLED). Methods Three critically ill patients (Table 1) were admitted to the Renal Intensive Care Unit (ICU) for stage 3 AKI and intercurrent dabigatran intoxication. SLED sessions with Regional Citrate Anticoagulation (RCA) were prescribed with SURDIAL X machine, ELISIO-21M filter (Nipro Co., Osaka, Japan) [blood flow rate 200 mL/min, dialysis fluid rate 300 mL/min; citrate flow rate 350 mL/h (ACD Fresenius Kabi, Italia)]. Dabigatran plasma levels (dilute thrombin time, dTT) along with coagulation parameters were monitored before, during and after SLED session. Results A rapid and sustained decreased of plasma dabigatran level was observed in each patient in course of SLED sessions. No clinically relevant post-treatment rebound was reported (Figure 1). Conclusions SLED meets the requirements to be a viable reversal anticoagulation option in the context of dabigatran overdose. Indeed, it efficiently provides dabigatran removal, by reaching a safe plasma concentration within the first hours and avoiding significant rebound effect.

Safety and Effectiveness of Direct Oral Anticoagulants for the Treatment of Gastrointestinal Cancer-Associated Venous Thromboembolism.

Patients with gastrointestinal cancer (GICA) are at high risk for venous thromboembolism (VTE). Data from randomized clinical trials in cancer-associated VTE suggest that direct oral anticoagulants (DOACs) conferred similar or superior efficacy but a heterogeneous safety profile in patients with GICA. We compared the safety and effectiveness of DOACs in patients with GICA and VTE at MD Anderson Cancer Center. This was a retrospective chart review of patients with GICA and VTE receiving treatment with DOACs for a minimum of 6 months. Primary outcomes were the proportion of patients experiencing major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and recurrent VTE. Secondary outcomes were time to bleeding and recurrent VTE. A cohort of 433 patients with GICA who were prescribed apixaban (n = 300), or rivaroxaban (n = 133) were included. MB occurred in 3.7% (95% confidence interval [CI] 2.1-5.9), CRNMB in 5.3% (95% CI 3.4-7.9), and recurrent VTE in 7.4% (95% CI 5.1-10.3). The cumulative incidence rates of CRNMB and recurrent VTE were not significantly different when comparing apixaban to rivaroxaban. Apixaban and rivaroxaban had a similar risk of recurrent VTE and bleeding and could be considered as anticoagulant options in selected patients with GICA and VTE.