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Research and Practice in Thrombosis and... May 2024The bleeding risk associated with direct oral anticoagulants (DOACs) remains a major concern, and rapid reversal of anticoagulant activity may be required. Although...
BACKGROUND
The bleeding risk associated with direct oral anticoagulants (DOACs) remains a major concern, and rapid reversal of anticoagulant activity may be required. Although specific and nonspecific hemostatic biotherapies are available, there is a need for small-molecule DOAC reversal agents that are simple and cost-effective to produce, store, and administer.
OBJECTIVES
To identify and characterize a small molecule with procoagulant activity as a DOAC reversal agent.
METHODS
We sought to identify a small procoagulant molecule by screening a chemical library with a plasma clotting assay. The selected molecule was assessed for its procoagulant properties and its ability to reverse the effects of the DOACs in a thrombin generation assay. Its activity as a DOAC reversal agent was also evaluated in a tail-clip bleeding assay in mice.
RESULTS
The hemostatic molecule (HeMo) dose-dependently promoted thrombin generation in plasma, with dose values effective in producing half-maximum response ranging between 3 and 5 μM, depending on the thrombin generation assay parameter considered. HeMo also restored impaired thrombin generation in DOAC-spiked plasma and reversed DOAC activity in the mouse bleeding model. HeMo significantly reduced apixaban-induced bleeding from 709 to 65 μL (vs 43 μL in controls; < .01) and dabigatran-induced bleeding from 989 to 155 μL (vs 126 μL in controls; < .01).
CONCLUSION
HeMo is a small-molecule procoagulant that can counterbalance hemostatic disruption by a thrombin inhibitor (dabigatran) or factor Xa inhibitors (apixaban and rivaroxaban). The compound's effective clot formation and versatility make it a possible option for managing the inherent hemorrhagic risk during DOAC therapy.
PubMed: 38882463
DOI: 10.1016/j.rpth.2024.102426 -
Heart Rhythm Jun 2024There are no clinical trials with head-to-head comparison between the two most commonly used oral anticoagulants (apixaban and rivaroxaban) in patients with atrial...
BACKGROUND
There are no clinical trials with head-to-head comparison between the two most commonly used oral anticoagulants (apixaban and rivaroxaban) in patients with atrial fibrillation (AF). The comparative efficacy and safety between these drugs remain unclear, especially among older patients who are at the highest risk for stroke and bleeding.
OBJECTIVE
To compare the risk of major bleeding and thromboembolic events with apixaban versus rivaroxaban in older patients with AF.
METHODS
We conducted a population-based, retrospective cohort study of all adult patients (66 years or older) with AF in Ontario, Canada who were treated with apixaban or rivaroxaban between April 1, 2011 and March 31, 2020. The primary safety outcome was major bleeding and the primary efficacy outcome was thromboembolic events. Secondary outcomes included any bleeding. Rates and hazard ratios (HRs) were adjusted for baseline comorbidities with inverse probability of treatment weighting (IPTW).
RESULTS
This study included 42,617 patients with AF treated with apixaban and 30,725 patients treated with rivaroxaban. After IPTW using the propensity score, patients in the apixaban and rivaroxaban groups were well balanced for baseline values of demographics, comorbidities and medications; both groups had similar mean age of 77.4 years and 49.9% were female. At one year, the apixaban group had reduced risk for both major bleeding with an absolute risk reduction at one year of 1.1% (2.1% vs 3.2%; HR 0.65 [95% CI, 0.59-0.71]) and any bleeding (8.1% vs 10.9%; HR 0.73 [95% CI, 0.69-0.77]) with no difference in the risk for thromboembolic events (2.2% vs 2.2%; HR 1.02 [95% CI, 0.92-1.13]).
CONCLUSIONS
Among AF patients, 66 years or older, treatment with apixaban was associated with reduced risk for major bleeding with no difference in risk for thromboembolic events compared with rivaroxaban.
PubMed: 38878942
DOI: 10.1016/j.hrthm.2024.06.010 -
Thrombosis Research Jun 2024Post-thrombotic syndrome (PTS) is common in patients with deep vein thrombosis (DVT). It is unclear if different types of anticoagulant therapies (e.g. vitamin K...
BACKGROUND
Post-thrombotic syndrome (PTS) is common in patients with deep vein thrombosis (DVT). It is unclear if different types of anticoagulant therapies (e.g. vitamin K antagonists (VKA), direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH)) are associated with different risks of PTS. We sought to assess the incidence rates of PTS development following a proximal DVT of the lower extremity managed with different types of anticoagulation regimens.
METHODS
A systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2023 was performed. The primary outcome was development of PTS. The secondary outcomes included severe PTS, venous ulcers, and major bleeding. Incidence rates were pooled using the random effects model and expressed as event per 100 patient-years with its associated 95 % confidence intervals (CI) using R software.
RESULTS
A total of 21 (4342 patients) articles were included in the analysis. The adjusted pooled incidence of PTS was 15.1 (95 % CI: 8.7 to 26.1), 18.2 (95 % CI: 9.4 to 35.1) and 24.6 (95 % CI: 9.2 to 65.5) per 100 patient-years patients managed with VKA, DOAC and LMWH, respectively. The adjusted pooled incidence of severe PTS was 5.1 (95 % CI: 2.6 to 10.0) and 0.2 (95 % CI: 0.01 to 2.7) per 100 patient-years for VKAs and DOACs, respectively.
CONCLUSIONS
The development of PTS is common in patients with proximal lower extremity DVT. The incidence rates of PTS seem to be similar across the different anticoagulation regimens, but severe PTS may be lower among patients receiving a DOAC.
PubMed: 38875846
DOI: 10.1016/j.thromres.2024.109057 -
Breast Disease 2024An 85-year-old Chinese lady presented with a 5-day history of a painless left breast lump. There was no fever, nipple discharge, or history of trauma. She had a past...
An 85-year-old Chinese lady presented with a 5-day history of a painless left breast lump. There was no fever, nipple discharge, or history of trauma. She had a past medical history of atrial fibrillation that was managed with an oral anticoagulant. Mammography demonstrated a dense mass in the upper outer quadrant of the left breast. Ultrasound showed an irregular, heterogeneous 4.7 cm lesion containing debris and cystic spaces with raised peripheral vascularity at the 2 o'clock position, 3 cm from nipple. No internal vascularity was detected. This was managed as a haematoma and rivaroxaban was withheld. Follow-up imaging 3-weeks later showed persistence of the lesion. Bedside needle aspiration yielded haemoserous fluid with immediate reduction in size of the lesion. However, 2 weeks after aspiration, there was recurrence of the 'haematoma'. Multidisciplinary review of the clinical history, examination and imaging was sought, and biopsy of the irregularly thickened areas with vascularity along the periphery of the lesion was recommended. Vacuum-assisted biopsy was performed, and histology returned as metaplastic carcinoma. A recurring 'haematoma' should always prompt a search for a secondary cause, with features such as irregular thickened walls and papillary/nodular components requiring further evaluation with biopsy for histopathological correlation.
Topics: Humans; Female; Hematoma; Breast Neoplasms; Aged, 80 and over; Diagnosis, Differential; Mammography; Metaplasia; Recurrence
PubMed: 38875024
DOI: 10.3233/BD-240006 -
Annals of Medicine Dec 2024Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in...
BACKGROUND
Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF).
OBJECTIVE
To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR.
MATERIALS AND METHODS
We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban ( = 12,426), dabigatran ( = 4545), rivaroxaban ( = 12,950) and warfarin ( = 43,548).
RESULTS
The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85-2.85), 1.44 (1.18-1.75), 0.60 (0.47-0.77) and 0.72 (0.56-0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88-8.35) and 1.87 (1.41-2.49) in the two poorest TTR groups, 1.44 (1.02-1.93) on rivaroxaban, and 0.58 (0.40-0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group.
CONCLUSIONS
The outcome was unsatisfactory in the two lowest TTR quartiles - in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest.
Topics: Humans; Warfarin; Atrial Fibrillation; Male; Female; Aged; Anticoagulants; Finland; Rivaroxaban; Pyridones; Middle Aged; Pyrazoles; Dabigatran; Administration, Oral; Aged, 80 and over; Cohort Studies; Intracranial Hemorrhages; Stroke; Ischemic Stroke; International Normalized Ratio; Treatment Outcome
PubMed: 38873855
DOI: 10.1080/07853890.2024.2364825 -
Alternative Therapies in Health and... Jun 2024To evaluate the impact of Pender-based health education on outcomes in rivaroxaban-treated lower limb DVT patients.
OBJECTIVE
To evaluate the impact of Pender-based health education on outcomes in rivaroxaban-treated lower limb DVT patients.
METHODS
103 patients with DVT of the lower limbs treated with rivaroxaban admitted to The First Affiliated Hospital of Xi'an Jiaotong University from January 2022 to January 2023 were included in the study and were randomly divided into the conventional group (n=52, receiving routine care with medication instruction, exercise instruction, and psychological care as the main components) and the Pender group (n=51, giving health education based on the Pender health promotion model in addition to conventional care) to compare the recurrence rate of DVT of the lower limbs, DVT of the lower limbs clinical condition, complication rate, quality of life score, coagulation index and nursing satisfaction rate in the two groups.
PRIMARY RESULTS
The recurrence rate of lower limb DVT, circumference of the affected limb, time to get out of bed, and time to reduce swelling in the Pender group were lower (shorter) than those in the conventional group (P < .05); after the intervention, all quality of life scores in the Pender group were higher than those in the conventional group (P < .05).
SECONDARY RESULTS
The complication rate, fibrinogen (FIB) and D-dimer (D-D) levels were lower (shorter) in the Pender group than in the conventional group (P < .05). After the intervention, the levels of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) were higher in the Pender group than in the conventional group (P < .05).
CONCLUSION
The health education based on the Pender health promotion model is effective in patients with lower limb DVT treated with rivaroxaban, which can effectively reduce recurrence and complications, optimize coagulation indexes, and improve the quality of life and nursing care satisfaction by improving the patients' health cognition and health behaviors, which is of great value in clinical application and promotion.
PubMed: 38870500
DOI: No ID Found -
Clinical and Applied... 2024To examine the effectiveness of rivaroxaban compared to enoxaparin in patients diagnosed with cancer and venous thromboembolism. (Meta-Analysis)
Meta-Analysis Comparative Study Review
OBJECTIVE
To examine the effectiveness of rivaroxaban compared to enoxaparin in patients diagnosed with cancer and venous thromboembolism.
METHODS
A search of Pub Med, Scopus, and Google Scholar, from inception through April 2023 was conducted. Articles comparing rivaroxaban with enoxaparin in patients with cancer and VTE/PE/DVT were included. Review Manager Version 5.2 was utilised for the analysis of the following outcomes; VTE, PE, DVT, major bleeding, and mortality.
RESULTS
A total of 8 articles and 2276 patients were included in the final analysis. Pooled analysis showed that rivaroxaban had a statistically insignificant reduced association with VTE occurrence (RR:0.83, 95% CI:0.58-1.18, P:0.3) as well as a statically insignificant reduction in major bleeding (RR:0.79, 95% CI:0.53-1.18, P:0.25). Analysis showcased that there was an insignificant reduction of mortality rivaroxaban as compared to enoxaparin (RR:0.74, 95% CI: 0.46-1.20, P:0.23).
CONCLUSION
Rivaroxaban can serve as a viable alternative to enoxaparin, with no appreciable drawbacks, for preventing and managing VTE in patients with malignancy.
Topics: Humans; Anticoagulants; Enoxaparin; Hemorrhage; Neoplasms; Recurrence; Rivaroxaban; Venous Thromboembolism
PubMed: 38870350
DOI: 10.1177/10760296241261364 -
Thrombosis and Haemostasis Jun 2024Prethrombin-1 is a Gla-domain lacking enzymatically inactive split product that results from the cleavage of fragment 1 from prothrombin by thrombin in a feedback...
INTRODUCTION
Prethrombin-1 is a Gla-domain lacking enzymatically inactive split product that results from the cleavage of fragment 1 from prothrombin by thrombin in a feedback reaction.
METHODS
A prethrombin-1 preparation derived from human plasma was tested for its hemostatic and thrombogenic properties. Animal models of nail clipping (for rabbits) and tail clipping (for mice) were developed to measure blood loss in FVIII-inhibitor or rivaroxaban anticoagulated rabbits and mice, respectively. A modified Wessler test was used in rabbits to assess the thrombogenic potential by Wessler score and clot weight. Studies were performed in groups of three to six for prethrombin-1 dose escalation and comparison with prothrombin, Beriplex®, FEIBA®, and saline as a control. Data were analyzed using t-statistics or the Mann Whitney U test as applicable.
RESULTS
Prethrombin-1 has excellent hemostatic properties in anticoagulated mouse and rabbit bleeding models. Wessler tests suggest that in contrast to activated and nonactivated prothrombin complexes, prethrombin-1 has negligible thrombogenic potential.
CONCLUSION
The thrombin zymogen prethrombin-1 promotes hemostasis with reduced risk of thrombosis. Prethrombin-1 may have potential to become a life-saving treatment for patients who bleed or are at risk of bleeding.
PubMed: 38866044
DOI: 10.1055/s-0044-1787720 -
Scientific Reports Jun 2024This review used traditional and network meta-analyses (NMA) to conduct a comprehensive study of antithrombotic therapies in children with thromboembolic disease. We... (Meta-Analysis)
Meta-Analysis
This review used traditional and network meta-analyses (NMA) to conduct a comprehensive study of antithrombotic therapies in children with thromboembolic disease. We searched the PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases from their inception to 26 February, 2023. And we finally included 16 randomized controlled trials. In the prevention of thromboembolic events (TEs), the use of anticoagulants had a low risk of TEs (relative risk (RR) 0.73, 95% CI 0.56 to 0.94) and a high risk of minor bleeding (RR 1.43, 95% CI 1.09 to 1.86) compared with no anticoagulants. In the treatment of TEs, direct oral anticoagulants (DOACs) were not inferior to standard anticoagulation in terms of efficacy and safety outcomes. In NMA, rivaroxaban and apixaban showed the lowest risk for TEs and major or clinically relevant nonmajor bleeding. According to the overall assessment of efficacy and safety, dabigatran may be the best choice for children with thromboembolic disease. The results of our study will provide references and suggestions for clinical drug selection.
Topics: Humans; Child; Thromboembolism; Fibrinolytic Agents; Hemorrhage; Anticoagulants; Treatment Outcome; Pyrazoles; Dabigatran; Rivaroxaban; Randomized Controlled Trials as Topic; Pyridones
PubMed: 38862574
DOI: 10.1038/s41598-024-64334-8 -
Circulation Reports Jun 2024Factor Xa inhibitors, such as rivaroxaban, are increasing the convenience of treatment for deep vein thrombosis (DVT). Limited evidence exists regarding clot evaluation...
Factor Xa inhibitors, such as rivaroxaban, are increasing the convenience of treatment for deep vein thrombosis (DVT). Limited evidence exists regarding clot evaluation at 3 months after treatment for DVT. We retrospectively analyzed the clinical course of symptomatic proximal DVT in patients who received 3 months of anticoagulation treatment at our hospital. Patients treated with the rivaroxaban single-drug approach were classified as group A (n=42). Patients treated with unfractionated heparin (UFH) or subcutaneous fondaparinux followed by vitamin K antagonist comprised group B (n=60) as an historical cohort. The quantitative ultrasound thrombosis (QUT) score was used to quantify clot burden before and after treatment. No significant differences were observed in patient characteristics between the groups. Serum D-dimer levels in both groups significantly improved after treatment. Clot volume assessed using QUT also reduced significantly in both groups. The QUT score in groups A and B improved from 7.5 [4.8, 12.0] to 3.0 [1.8, 5.0; P=0.000] and 7.0 [4.0, 9.8] to 3.0 [2.0, 5.0; P=0.000], respectively. The change in QUT (∆QUT) was significantly greater in group A compared with group B (-4.5 [-8.25, -2.0] vs. -2.0 [-6.0, 0.0]; P=0.005). We were able to demonstrate the effectiveness of DVT treatment using rivaroxaban over a period of 3 months from onset, in terms of clot regression evaluated using the QUT score.
PubMed: 38860185
DOI: 10.1253/circrep.CR-24-0042