December 2025: New In Coagulation
by Donna Castellone • December 15, 2025
Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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Three or More Drinks a Day Linked to More Severe Brain Bleeds
A review of 1600 consecutive patients who had spontaneous, nontraumatic ICH were analyzed. Patients presented with a median age of 75, with 53% male, and 85% white. Results were adjusted for age, sex, smoking status, race, hypertension, hyperlipidemia, coronary artery disease, atrial fibrillation, diabetes, previous stroke or transient ischemic attack, previous hemorrhage, and liver disease. Results showed that people who drank three or more alcoholic drinks/day had a 70% larger, deeper brain bleed at a younger age and more signs of small-vessel brain damage when compared with people who drank less than three drinks. Additionally heavy drinkers had lower platelet counts and higher blood pressure.
Brain bleeds are one of the most difficult conditions to recover from. The leading cause of spontaneous ICH is cerebral small vessel disease, a progressive condition characterized by chronic microvascular dysfunction driven by hypertensive arteriopathy and cerebral amyloid angiopathy. Alcohol consumption may accelerate hypertensive small vessel pathology and increase this hemorrhage risk. Guidelines suggest limiting daily alcohol for two or less drinks for men and one or fewer for women. However, in 2023 the WHO issued a statement that no amount of alcohol is safe. Minimizing use will lower the risk.
Sleep Apnea Linked to Brain Microbleeds
A longitudinal cohort of people with moderate to severe obstructive sleep apnea (OSA) (15-apnea-hyopnea events/hour) correlated with the development of cerebral microbleeds which are linked to stroke and dementia risk. The study included 1441 adults mean age 58 years and 53% were women. Mild OSA was seen in 30.25%, and moderate to severe OSA in 13.39% at baseline. Subjects had in-home overnight polysomnography data and brain MRI done at baseline in 2011-2014 and at 4-year follow-ups in 2015-2018 and 2019-2022. Cumulative incidence reached 4.66% at 4 years and 7.25% at 8 years. Post multivariable adjustment demonstrated a 2.14 fold higher risk of developing cerebral microbleeds at 8 years. OSA is also linked to stroke, cerebral small vessel disease and other CVD. The moderate to severe OSA group had relative risk of 1.89-2.52 across all the adjustment models at both 4- and 8-year time points.
OSA and cerebral microbleeds mechanism may be due to chronic hypoxia triggering oxidative stress that leads to brain vasculature-damaging production of free radicals and inflammatory responses. This may lead to endothelial dysfunction and increased vascular permeability making vessels more susceptible to bleeding.
Benefit of Embolization for Subdural Hematoma Confirmed
The EMMA-CAN trial was a randomized trial of embolization of the middle meningeal artery (EMMA) post-surgery for chronic subdural hematoma showed a major drop in hematoma recurrence. EMMA is an endovascular procedure that blocks blood flow to the fragile membranes surrounding the hematoma and is minimally invasive. Patients were six times less likely to experience symptomatic hematoma recurrence during the 90 day follow up period. Chronic subdural hematoma affects 300 people/million and rises with age. Surgery is usually effective in draining the hematoma, but recurrence occurs in roughly one third of patients.
There were 192 patients assigned to receive the EMMA procedure. Results showed a large reduction in symptomatic recurrence of hematoma at 90 days versus surgery alone. Recurrence of hematoma occurred in 28% of the control group vs 4.3% of those who received the EMMA procedure. Radiographic hematoma recurrence occurred in 49.5% of the control group compared with 14% of the EMMA group.
Clear Benefit of Thrombectomy in Large-Core Stroke
A meta-analysis of the ATLAS study demonstrated consistent improvements of endovascular thrombectomy (EVT) in a wide spectrum of patients with large-core strokes compared with best medical management alone. This was shown beneficial regardless of age, sex, clinical severity, time to treatment, stroke size, and mismatch profile. However, rates of symptomatic ICH and neurological worsening were higher with EVT but did not outweigh the overall clinical benefits. Evidence supports the superiority of thrombectomy over medical management in patients with large-core strokes caused by large vessel occlusion. Endovascular clot removal was first shown to benefit patients with large-vessel occlusion who presented within 6 hours of stroke onset. A subsequent wave of trials demonstrated that this approach also benefits patients presenting up to 24 hours after onset, provided imaging shows a small infarct core and salvageable brain tissue.
The ATLAS meta-analysis included data from six trials RESCUE-Japan LIMIT, ANGEL-ASPECT, SELECT2, TENSION, TESLA, and LASTE which included a total of 1886 patients with acute anterior circulation stroke who presented within 24 hours of onset. Symptomatic ICH and neurological worsening were higher with EVT. Symptomatic ICH occurred in 5.5% of patients in the EVT group vs 2.7% of those in the control group (aRR, 2.02; P = .017). Neurological worsening occurred in 22% vs 17% of patients. Favorable functional outcomes were also strongly positive. An mRS score of 0-2 was achieved in 9.5% of EVT patients compared with 7.5% of control individuals.
There is heterogeneity among the trials, allowing generalizability of finding but highlights the need for a deeper understanding of treatment effects overall and across subgroups based on severity, size, ASPECTS score and core volume. This meta-analysis showed the benefit of EVT across both early and late time windows, older and younger patients, those with low ASPECT scored in the early window and in those with large core volumes of up to 150 ml.
Low AF Burden After CABG May Lessen Need for Anticoagulants
A study in JAMA questions the need for OAC in patients who develop AF after CABG. While arrythmia may be more frequent, the occurrence of episodes is negligible. In 198 patients who underwent CABG half developed AF within a year of the surgery the arrythmia events were <1% and occurred during the first week of surgery. Previously it was indicated that AF emerges in 30% of patients undergoing CABG, however post CABG AF seems to be self-limiting. These results challenge current guideline recommendations which state the administration of long-term anticoagulants for new-onset AF post cardiac surgery thus making the benefit of extended anticoagulation questionable. Studies have shown the bleeding risk outweighs the reduction in stroke. If anticoagulation is initiated, it should be reassessed 30 days after surgery. Long term therapies in these patients should be the exception rather than the norm.
Transcatheter LAA Closure Not a Good Setting for DAPT After All
The ANDES randomized trial showed a course of DOAC may be the safer choice of antithrombotic treatment after LAA occlusion. The trial randomized 1:1 DOAC (apixaban 76.3%, rivaroxaban 12.3%) or DAPT (aspirin and clopidogrel) for 60 days, average age 77, 35% female, half had permanent Afib with mean CHA2DS2-VASc and HAS-BLED scores around 4.2 and 3.5, respectively. LAA occluders were split between the Watchman/FLX and Amplatzer Amulet devices.
Short-term DOAC was not significantly better than dual antiplatelet therapy at preventing device related thrombosis at 60 days. The DOACs showed reduced bleeding (17.4% vs 24.9%) and site-reported device-related thrombosis (0.8% vs 3.5%). ANDES is the largest randomized trial (n=500) to address this question. DAPT after LAA closure should be discouraged due to high bleeding events. It is possible that clopidogrel alone could be an option for managing these patients.
Spread the Word: AF Patients With Stents Don’t Need Dual Antithrombotic Therapy
The ADAPT AF-DES trial looked at monotherapy or combination therapy with a DOAC plus clopidogrel in patients with AF who had a drug-eluting stent. This is a repeat of the AQUATIC trial which demonstrated superiority of anticoagulation monotherapy over anticoagulation plus low dose aspirin. The primary endpoint was net adverse events, a composite of death, myocardial infarction, stent thrombosis, stroke, systemic embolism, or major bleeding.
There were 960 patients with chronic coronary artery disease (CAD) who were taking OAC randomly assigned to DOAC monotherapy or combination DOAC and clopidogrel. Average age was 71, 79% male, median CHA2DS2VASc score was 4.1 and DOAC use was apixaban (61%), rivaroxaban (34%), and edoxaban (4%). At 12 months, the incidence of the primary endpoint was 9.6% in the monotherapy group and 17.2% in the combination-therapy group. Bleeding was also substantially worse in the combination arm. (5.2% monotherapy versus 13.2% combination). The rates of thrombotic events rates were lower in the monotherapy arm (3.3% vs 4.0%). AFIRE, EPIC CAD, and AQUATIC trials, all favored monotherapy over combination therapy.
This changes the previous practice that antiplatelet drugs were needed for CAD and DOAC for AF. The evidence strongly suggests that after the acute phase of stent placement, it is not only safe but preferred to use oral anticoagulation alone.
Anticoagulation After AF Ablation: The OCEAN Trial Still Leaves Questions
AF can be asymptomatic after ablation or ablation in the left atrium can be prothrombotic. It is hard to explain that patients should continue OAC after AF ablation. The OCEAN trial looked at rivaroxaban versus aspirin in this cohort. In the trial 1300 patients (average age of the patients was 66 years; 29% were female) who had no documented AF 1 year post AF ablation were randomly assigned to 15mg rivaroxaban or low dose aspirin. Patients had a CHA2DS2VASc score > 1 (men) or > 2 (women). AF was monitored using Holter monitors and symptoms. The primary endpoint was stroke, embolism, or covert stroke diagnosed on MRI. Primary safety outcome was fatal or major bleeding. The trial was terminated early due to futility.
Incidence of stroke was 1.5% in the rivaroxaban arm vs 3.8% in the aspirin arm. A primary outcome event occurred in only five patients (0.8%) in the rivaroxaban arm vs 9 patients (1.4%) in the aspirin arm. Fatal or major bleeding occurred in 10 patients in the rivaroxaban group and in 4 patients in the aspirin group. Clinically relevant nonmajor bleeding occurred in 5.5% of patients in the rivaroxaban group vs 1.6% of those in the aspirin group. These results should be interpreted with caution due to the low event rates, resulting in wide confidence intervals ranging from rivaroxaban being 81% better or 65% worse than aspirin. That is largely uninformative, and you can't tell which arm is better. It is the same is for the assessment of bleeding.
FDA Probes Child Death Linked to Drug for Blood Clotting Disorder
The FDA has gotten postmarketing reports of neutralizing antibodies to ADAMTS13 in patients with congenital TTP who were treated with recombinant ADAMTS13 protein (Adzynma) including one death. Prior to treatment, the patient who died had severe allergic reactions to FFP. The patient presented with neurologic symptoms which progressed. The presence of neutralizing antibodies to ADAMTS13 was identified 10 months post beginning prophylactic treatment. There are no assays that can distinguish neutralizing antibodies to recombinant ADAMTS13 from neutralizing antibodies to endogenous ADAMTS13 leads.
ADZYNMA was approved in 2023 for ADAMTS13. This is a rare blood clotting disorder caused by a mutation in the ADAMTS13 gene. The mutation leads to blood clots in small vessels resulting in bleeding episodes, strokes and damage to organs. Neutralizing antibodies were not reported in the clinical trial.
JOURNAL CLUB
Major Bleeding With Apixaban vs Aspirin A Subanalysis of the ARTESiA Randomized Clinical Trial
Deborah M. Siegal, MD, MSc; Christian Sticherling, MD; Jeff S. Healey, MD, MSc, JAMA Cardiol, Published Online: November 12, 2025
Abstract
Importance The Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation (ARTESiA) randomized clinical trial showed that in patients with subclinical atrial fibrillation (SCAF) apixaban, compared with aspirin, reduced stroke/systemic embolism but increased major bleeding.
Objectives To characterize major bleeding events (site and severity) and identify factors associated with major bleeding.
Design, Setting, and Participants This was a prespecified subanalysis of the ARTESiA population who received treatment. This was an international, double-blind, double-dummy randomized clinical trial. Included were patients with 1 or more episodes of SCAF lasting 6 minutes to 24 hours with stroke risk factors (CHA2DS2-VASc score ≥3) or prior stroke without other risk factors. Study data were analyzed from August to November 2024.
Interventions Apixaban, 5 mg, twice daily (2.5 mg twice daily when indicated) or aspirin, 81 mg, once daily.
Main Outcomes and Measures Major bleeding adjudicated by a blinded committee according to International Society on Thrombosis and Hemostasis criteria.
Results A total of 3961 patients (mean [SD] age, 76.8 [7.6] years; 2535 male [64%]) were included in this analysis. After a mean (SD) follow-up of 3.5 (1.8) years, 1 or more major bleeding episodes occurred in 133 patients, 86 of 1989 taking apixaban and 47 of 1972 taking aspirin (1.71 vs 0.94 per 100-patient-years; hazard ratio [HR], 1.80; 95% CI, 1.26-2.57). The rates of intracranial (0.33 vs 0.40 per 100 patient-years; HR, 0.82; 95% CI, 0.43-1.57) and fatal (0.10% vs 0.16% per 100 patient-years; HR, 0.63; 95% CI, 0.20-1.91) bleeding were similar in the apixaban and aspirin groups, whereas the rate of gastrointestinal bleeding was higher in the apixaban group (0.89% vs 0.40% per 100 patient-years; HR, 2.23; 95% CI, 1.32-3.78). Among 133 index major bleeding events, those that occurred with apixaban were less likely to occur at critical sites (27.9% [24 of 86] vs 46.8% [22 of 47];
Conclusions and Relevance Results of this subanalysis of the ARTESiA randomized clinical trial found that although the rate of major gastrointestinal bleeding was higher in patients with SCAF who were treated with apixaban vs aspirin, rates of fatal and intracranial bleeding were not different. Most major bleeding events were nonemergencies characterized by a decrease in hemoglobin level greater than or equal to 2 g/dL. NSAID use, cancer, randomization to apixaban, and increasing age were associated with an increased risk of major bleeding.