Anticoagulation for Stroke Prevention in Atrial Fibrillation and Treatment of Venous Thromboembolism and Portal Vein Thrombosis in Cirrhosis: Guidance from the SSC of the ISTH.

Whilst advanced liver disease was previously considered to be an acquired bleeding disorder, there is increasing recognition of an associated prothrombotic state with patients being at higher risk of atrial fibrillation (AF) and stroke and venous thromboembolism including portal vein thrombosis (PVT). We review the available literature on epidemiology, pathophysiology and risk factors and provide guidance on anticoagulant management of these conditions in adults with cirrhosis. In patients with Child-Pugh A or B cirrhosis and AF, we recommend anticoagulation with standard dose direct oral anticoagulants (DOACs) in accordance with cardiology guideline recommendations for patients without liver disease. In those with Child-Pugh C cirrhosis, there is inadequate evidence with respect to the benefit and risk of anticoagulation for AF. For patients with cirrhosis and acute deep vein thrombosis or pulmonary embolism, we recommend anticoagulation and suggest use of either a DOAC or low molecular weight heparin/vitamin K antagonist. We recommend anticoagulation for patients with cirrhosis and symptomatic PVT. We suggest anticoagulation for those with asymptomatic, progressing PVT and recommend continuing extended anticoagulation for liver transplant candidates with PVT.

Dural venous sinus thrombosis after vestibular schwannoma surgery: should we anticoagulate?

BACKGROUND: The incidence of Dural Venous Sinus Thrombosis (DVST) following vestibular schwannoma (VS) surgery remains understudied. The diversity of clinical presentation complicates forming anticoagulation treatment guidelines. This meta-analysis aimed to investigate the incidence of DVST post-VS surgery and to evaluate the role of anticoagulation. METHODS: A systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, was conducted. Studies reporting DVST incidence after VS surgery were included. DVST incidence stratified by detection method was the primary outcome. Adverse events per treatment strategy (anticoagulation or no anticoagulation) were the secondary outcome. Pooled incidence with respective 95% confidence intervals (CI) was calculated using the random-effects model via the DerSimonian and Laird method. RESULTS: The overall DVST incidence post-VS resection was 15.5% (95% CI: 10.3%, 22.5%; 10 studies). Stratification by detection method revealed 29.4% (19.2%, 42.3%) for magnetic resonance imaging, 8.2% (3.2%, 19.5%) for computed tomography, and 0.7% (0.2%, 2.8%) upon clinical suspicion. The pooled incidence of adverse events was 16.1% (6.4%, 35.0%) for the anticoagulation treatment and 4.4% (1.4%, 12.9%) for no anticoagulation treatment, with one mortality case being among the adverse events in this latter group. CONCLUSION: DVST after VS surgery is more common than initially perceived, predominantly presenting asymptomatically. Variability in anticoagulation protocols hinders the establishment of definitive therapeutic stances; nevertheless, there is no supporting evidence to promote anticoagulation administration for DVST. This begs the need for further institutional comparative studies with a proper adjustment for confounding and well-defined anticoagulation regimens.

Anti-Xa-guided Anticoagulation With Unfractionated Heparin and Thrombosis During Extracorporeal Membrane Oxygenation Support: A Systematic Review and Meta-analysis.

OBJECTIVE: The initiation of extracorporeal membrane oxygenation (ECMO) triggers complex coagulation processes necessitating systemic anticoagulation. Therefore, anticoagulation monitoring is crucial to avoid adverse events such as thrombosis and hemorrhage. The main aim of this work was to analyze the association between anti-Xa levels and thrombosis occurrence during ECMO support. DESIGN: Systematic literature review and meta-analysis (Scopus and PubMed, up to July 29, 2023). SETTING: All retrospective and prospective studies. PARTICIPANTS: Patients receiving ECMO support. INTERVENTION: Anticoagulation monitoring during ECMO support. MEASUREMENTS AND MAIN RESULTS: A total of 16 articles with 1,968 patients were included in the review and 7 studies in the meta-analysis (n = 374). Patients with thrombosis had significantly lower mean anti-Xa values (standardized mean difference -0.36, 95% confidence interval [CI] -0.62 to -0.11, p < 0.01). Furthermore, a positive correlation was observed between unfractionated heparin infusion and anti-Xa levels (pooled estimate of correlation coefficients 0.31, 95% CI 0.19 to 0.43, p < 0.001). The most common adverse events were major bleeding (42%) and any kind of hemorrhage (36%), followed by thromboembolic events (30%) and circuit or oxygenator membrane thrombosis (19%). More than half of the patients did not survive to discharge (52%). CONCLUSIONS: This work revealed significantly lower levels of anti-Xa in patients experiencing thromboembolic events and a positive correlation between anti-Xa and unfractionated heparin infusion. Considering the contemplative limitations of conventional monitoring tools, further research on the role of anti-Xa is warranted. New trials should be encouraged to confirm these findings and determine the most suitable monitoring strategy for patients receiving ECMO support.

Antithrombin during veno-venous extracorporeal membrane oxygenation with heparin anticoagulation: A single-center cohort study.

INTRODUCTION: Antithrombin (AT) is a natural anticoagulant essential to enhancing the unfractionated heparin (UFH) anticoagulant effect. Its supplementation in the management of UFH-based anticoagulation during veno-venous extracorporeal membrane oxygenation (VV ECMO) has a strong pathophysiological rationale. METHODS: This is a single-center, retrospective cohort study of adult VV ECMO patients with anticoagulation maintained by UFH targeting an activated partial thromboplastin time (aPTT) of 40-50 s and AT activity >80%. We compare anticoagulation management and survival outcomes between AT subpopulations, defined by a threshold AT activity ≥80%. Linear and logistic regression analyses were used to evaluate the variation in AT activity and its association with ICU survival. RESULTS: In 244 patients enrolled from 2009 to 2022, anticoagulation was maintained by a median heparin dose of 11.4 IU/kg/h [IQR: 8.2-14.7] with a mean aPTT of 46.1 s (±7.3) and AT activity of 88.9% (±17.0). A lower mean aPTT, higher dose of UFH and shorter fraction of time without UFH were associated with higher AT activity (p < .01). Higher AT activity showed a consistent association with ICU survival (for 10% increase of AT, odds ratio for ICU mortality: 0.95; 95% CI 0.93-0.97; p value <.01). CONCLUSIONS: There is a positive association between AT activity and UFH requirements but no significant difference in the rate of bleeding events. A higher mean AT during VV ECMO was associated with ICU survival. Future studies are needed to differentiate between exogenously supplemented versus endogenous AT effect.

Antithrombin restriction in extracorporeal membrane oxygenation support (ARES): A multidisciplinary approach.

Background: Antithrombin (AT) replacement is occasionally utilized in the setting of extracorporeal membrane oxygenation (ECMO)-associated heparin resistance. Although past studies emphasized the high costs and limited clinical benefit of AT supplementation,  guidance on strategies to prevent unnecessary use remain lacking.Methods: In this retrospective study, we evaluated the cost, efficacy, and safety outcomes three years pre- and post-implementation of an AT restriction protocol in adult ECMO patients. The primary endpoint was the cost spent on anticoagulation and AT normalized to ECMO duration. Secondary endpoints included thromboembolic and bleeding outcomes.Results: 175 patients were included for analysis (pre-restriction protocol n = 87; post-restriction protocol n = 88). Implementation of the restriction resulted in complete elimination of AT use and significantly reduced the primary cost endpoint from $1009.20 to $42.99 per ECMO day (p < .001). There was no significant change in occurrence of new Venous Thromboembolism (VTE) (p = .099). Those in the pre-implementation group had significantly higher rates of transfusions (p < .001) and ISTH major bleeding (p < .001). Outcomes remained significant after exclusion of patients with coronavirus infections.Conclusion: Results of this study exemplify how AT restriction can be successfully implemented to decrease anticoagulation-associated costs without jeopardizing the risk of bleeding and thrombosis in ECMO patients.

Risk of recurrent venous thromboembolism and major bleeding according to risk factor profiles in Asian patients: a subgroup analysis EINSTEIN-Extension and EINSTEIN-CHOICE.

BACKGROUND: Risks of recurrence and major bleeding with extended anticoagulation in Asian patients with venous thromboembolism (VTE) are similar to those in non-Asian patients but risks according to baseline risk factor profiles is not well documented. METHODS: Subgroup analysis of two randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with placebo or aspirin (100 mg) for extended treatment in Asian patients with VTE who had completed 6-12 months of anticoagulation. Index events were classified as unprovoked, provoked by major persistent risk factors, minor persistent risk factors, minor transient risk factors, or major transient risk factors. One-year cumulative risks of recurrent VTE were calculated for these risk factor profiles. RESULTS: 367 patients received rivaroxaban, 159 aspirin, and 48 placebo. For patients with unprovoked VTE, one-year cumulative incidences of recurrence in the 202 patients given rivaroxaban, the 89 given aspirin and the 28 given placebo were 1.6%, 5.8%, and 14.8%, respectively. For patients with VTE provoked by minor persistent risk factors, these incidences were 0% in the 74 patients given rivaroxaban, 9.3% in the 36 given aspirin, and 0% in the 12 given placebo. No recurrent VTE occurred in patients with VTE provoked by major persistent or transient risk factors or minor transient risk factors. Rivaroxaban was not associated with a significant increase in major bleeding. CONCLUSIONS: Rivaroxaban seems to be an effective and safe option for extended treatment in Asian patients, especially those presenting with unprovoked VTE. Subgroups of patients with provoked risk factors were too small to draw meaningful conclusions. TRIAL REGISTRATION: NCT00439725 and NCT02064439.

Oral anticoagulation in patients with left ventricular thrombus - a systematic review and meta-analysis.

AIMS: Direct oral anticoagulants (DOACs) are increasingly used off-label to treat patients with left ventricular thrombus (LVT). We analyzed available meta-data comparing DOACs and vitamin K antagonists (VKAs) for efficacy and safety. METHODS: We conducted a systematic search and meta-analysis of observational and randomized data comparing DOACs versus VKAs in patients with LVT. Endpoints of interest were stroke or systemic embolism, thrombus resolution, all-cause death, and a composite bleeding endpoint. Estimates were pooled using a random-effect model meta-analysis, and their robustness was investigated using sensitivity and influential analyses. RESULTS: We identified 22 articles (18 observational studies, 4 small randomized clinical trials) reporting on a total of 3,587 patients (2,489 VKA vs. 1,098 DOAC therapy). The pooled estimates for stroke or systemic embolism (OR 0.81; 95% CI [0.57, 1.15]) and thrombus resolution (OR 1.12; 95% CI [0.86; 1.46]) were comparable, and there was low heterogeneity overall across the included studies. DOAC use was associated with lower odds of all-cause death (OR 0.65; 95%CI [0.46; 0.92]) and a composite bleeding endpoint (OR 0.67; 95%CI [0.47; 0.97]). A risk of bias was evident particularly for observational reports, with some publication bias suggested in funnel plots. CONCLUSION: In this comprehensive analysis of mainly observational data, the use of DOACs was not associated with a significant difference in stroke or systemic embolism, or thrombus resolution compared to VKA therapy. The use of DOACs was associated with a lower rate of all-cause death and fewer bleeding events. Adequately sized randomized clinical trials are needed to confirm these findings, which could allow a wider adoption of DOACs in patients with LVT.

A targeted educational intervention increases oral anticoagulation rates in high-risk atrial fibrillation patients.

Background: Anticoagulation is the cornerstone of atrial fibrillation (AF) management for stroke prevention. Recently, we showed that oral anticoagulation (OAC) rates of AF patients in a large U.S. multispecialty health system are >80%. Objective: The purpose of this study was to improve OAC rates in AF patients via an educational intervention targeted to primary care providers with low OAC rates. Methods: Primary care clinicians were stratified by proportions of their AF patients at elevated stroke risk not taking anticoagulation medication. Clinicians with the lowest rates of anticoagulation were assigned to a target group receiving an educational program consisting of E-mail messaging summarizing anticoagulation guidelines. All other clinicians were assigned to a comparison group (CG). Data from a 6-month lead-in phase were compared with a 6-month follow-up period to determine whether the proportion of AF patients treated with OACs had changed. Results: Of the 141 primary care clinicians with patients who met the inclusion criteria, 36 (25.53%) were assigned to the educational group (EG) and 105 (74.47%) to the CG. At baseline, there was a significant difference in percent of high-risk AF patients who were untreated in the EG (20.65%) compared to the high-risk patients who were untreated in the CG (13.64%; P = .001). After the educational intervention, high-risk AF patients without anticoagulation decreased in both EG (15.47%; P = .047) and CG (10.14%; P = .07), with greater absolute reduction in the EG (5.19% vs 3.50%). Conclusion: A targeted education program was associated with increased anticoagulation rates for AF patients at high risk for stroke.

Risk of recurrence after discontinuing anticoagulation in patients with COVID-19- associated venous thromboembolism: a prospective multicentre cohort study.

Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences. Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Funding: Sanofi and Rovi, Sanofi Spain.

Thromboembolic and bleeding complications after elective cardioversion of atrial fibrillation: a nationwide cohort study.

AIMS: Elective cardioversion (ECV) is routinely used in atrial fibrillation (AF) to restore sinus rhythm. However, it includes a risk of thromboembolism even during adequate oral anticoagulation treatment. The aim of this study was to evaluate the risk of thromboembolic and bleeding complications after ECV in a real-life setting utilizing data from a large AF population. METHODS AND RESULTS: This nationwide register-based study included all (n = 9625) Finnish AF patients undergoing their first-ever ECV between 2012 and 2018. The thromboembolic and bleeding complications within 30 days after ECV were analysed. The mean age of the patients was 67.7 ± 9.9 years, 61.2% were men, and the mean CHA2DS2-VASc score was 2.6 ± 1.6. Warfarin was used in 6245 (64.9%) and non-vitamin K oral anticoagulants (NOACs) in 3380 (35.1%) cardioversions. Fifty-two (0.5%) thromboembolic complications occurred, of which 62% were ischaemic strokes, 25% transient ischaemic attacks, and 13% other systemic embolisms. Thromboembolic events occurred in 14 (0.4%) NOAC-treated patients and in 38 (0.6%) warfarin-treated patients (odds ratio 0.77; confidence interval: 0.42-1.39). The median time from ECV to the thromboembolic event was 2 days, and 78% of the events occurred within 10 days. Age and alcohol abuse were significant predictors of thromboembolic events. Among warfarin users, thromboembolic complications were more common with international normalized ratio (INR) <2.5 than INR ≥2.5 (0.9% vs. 0.4%, P = 0.026). Overall, 27 (0.3%) bleeding events occurred. CONCLUSION: The rate of thromboembolic and bleeding complications related to ECV was low without significant difference between NOAC- and warfarin-treated patients. With warfarin, INR ≥2.5 at the time of cardioversion reduced the risk of thromboembolic complications.

Periprocedural Anticoagulation Management of Patients Undergoing Colonoscopy with Polypectomy.

Introduction/Objective Colonoscopy with polypectomy is an integral component of colorectal cancer screening. There are limited data and consensus on periprocedural anticoagulation management, especially regarding bleeding risk with uninterrupted anticoagulation and thromboembolic risk with interruption. Our aim was to determine the incidence of bleeding and thromboembolic complications among colon screening participants undergoing colonoscopy following implementation of a novel patient care pathway for standardized periprocedural anticoagulation management. Methods We conducted a retrospective study including all participants (age 50-74) on an oral anticoagulant (e.g., vitamin K antagonists, direct oral anticoagulants) referred to the British Columbia Colon Screening Program for colonoscopy following abnormal fecal immunochemical test in a 6-month period (March-August 2022). Data relating to their specific periprocedural anticoagulant management and colonoscopy results including method of polypectomy were obtained. Primary outcomes were major bleeding and arterial or venous thromboembolic events from time of oral anticoagulant interruption until 14 days of postcolonoscopy. Secondary outcomes included nonmajor and minor bleeding, acute coronary syndrome, emergency room visit, hospital admission, and death due to any cause. Results Over the 6-month period, 162 participants completed standardized periprocedural anticoagulation management, colonoscopy ± polypectomy, and 14-day follow-up. One (0.6%) had a major bleeding event and one (0.6%) had an arterial thromboembolic event. Conclusions A novel patient care pathway for standardized periprocedural anticoagulation management with a multidisciplinary team is associated with low rates of major bleeding and thrombotic complications after colonoscopy with polypectomy.

Pulmonary Embolism Following Lung Transplantation: Prevention and Management.

Thromboembolic events are the third leading cardiovascular diagnosis following stroke and myocardial infarction. In the United States, 300,000 to 600,000 people per year are diagnosed with venous thromboembolism, either deep venous thrombosis or pulmonary embolism (PE). Of those patients, thousands die from PE despite heightened vigilance and improved therapies. Lung transplant recipients are at increased risk of developing PE due to multiple risk factors unique to this population. Additionally, the transplant recipients are more susceptible to morbid complications from PE. As a result, prevention, timely recognition, and intervention of PE in the lung transplant population are of the utmost importance.

Anticoagulation in the Management of Acute Pulmonary Embolism-A Review.

Venous thromboembolism (VTE) is a very frequent cardiovascular entity that encompasses deep vein thrombosis and pulmonary embolism (PE). This last entity represents a major cause of cardiovascular morbidity and mortality. The incidence of PE and the rate of PE-related morbidity significantly increase with age, race, and underlying medical conditions, such as malignancy. Given the recent advances in diagnostic strategies and algorithms, patients can be risk assessed and treated promptly to avoid disease progression. Anticoagulation is the mainstay of treatment for acute PE that is not hemodynamically unstable. Direct oral anticoagulants, such as apixaban, rivaroxaban, or edoxaban, are currently the preferred agents for the treatment of patients who present with acute PE or for long-term treatment. Treatment duration should be continued for at least 3 months, and all patients should be assessed for extended duration of therapy based on the precipitating factors that led to the development of the VTE. Novel anticoagulant agents targeting factor XI/XIa are currently being investigated in phases 2 and 3 clinical trials, representing an attractive option in anticoagulation therapies in patients with VTE. For hemodynamically unstable patients, systemic thrombolysis is the treatment of choice, and it may also be of benefit-in reduced dose-for patients with intermediate to high risk who are at risk of hemodynamic collapse.

Role of Extracorporeal Membrane Oxygenation in the Treatment of Massive Pulmonary Embolism.

Massive/high-risk pulmonary embolism (PE) is associated with a 30-day mortality rate of approximately 65%. In searching for strategies that may make a dent on this dismal mortality rate, investigators have, over the last decade, shown renewed interest in the potential beneficial role of venoarterial (V-A) extracorporeal membrane oxygenation (ECMO) in the treatment of patients with high-risk PE. There is a dearth of high-quality evidence regarding the value of ECMO in the treatment of massive PE. Studies examining this issue have generally been retrospective, often single center and frequently with small patient numbers. Moreover, these reported studies are not matched with appropriate controls, and, accordingly, it is difficult to regulate for inherent treatment bias. Not surprisingly, there are no randomized controlled trials examining the value of ECMO in the treatment of massive PE, as such trials would pose formidable feasibility challenges. Over the past several years, there has been increasing support for upfront use of V-A ECMO in the treatment of massive PE, when it is complicated by cardiac arrest. In those patients without cardiac arrest, but who have contraindications for thrombolysis, V-A ECMO combined with anticoagulation may be used to stabilize the patient. If after 3 to 5 days, such patients demonstrate persistent right ventricular dysfunction, embolectomy (either surgical or catheter based) should be performed. Well-designed, multicenter, prospective studies are urgently needed to better define the role of V-A ECMO in the treatment of patients with massive PE.

Anticoagulation Versus Antiplatelets in Spontaneous Cervical Artery Dissection: A Systematic Review and Meta-Analysis.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P=0.02; I2=0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P=0.03, I2=0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

Correction of Warfarin Coagulopathy for Non-bleeding Patients in the Outpatient Setting at an Ambulatory Care Organization: Application of Vitamin K Guidance.

BACKGROUND: Warfarin is an effective anticoagulant but requires close International Normalized Ratio (INR) monitoring and may occasionally require correction of excessive anticoagulation. Current guidelines provide limited practical guidance on the administration of vitamin K for the management of supratherapeutic INR levels ≥ 5.0 in non-bleeding outpatients. OBJECTIVE: Based on expert consensus and guidelines, the Atrius Health Anticoagulation Management Services (AMS) has developed internal guidance for oral vitamin K use in highly selected populations. This study will describe the internal guidance for oral vitamin K use and present associated results and clinical outcomes. METHODS: Episodes with INR > 5.0 were included, with vitamin K considered for episodes with INR ≥ 6. Moreover, compelling indications and exclusions to select ideal patients for vitamin K intervention were also defined. RESULTS: Overall, episodes were managed conservatively; of the 246 collected episodes of excessive anticoagulation, in 18 episodes (7%), patients received vitamin K, and in 228 (93%) episodes, patients did not receive vitamin K. The mean index INR was 6.0 (range 5.0 - 10.5, SD 1.07), with nearly 57% of episodes achieving INR correction and 15% of episodes developing INR overcorrection. High thrombotic risk patients, regardless of hemorrhagic risk, were less likely to receive vitamin K. Three episodes (1.2%) resulted in bleeding complications. No thrombotic complications occurred during the 30-day follow-up of the index INR value ≥ 5.0. CONCLUSION: Our internal guidance is a novel, standardized approach that serves as a decision support tool for the management of warfarin-associated coagulopathy and vitamin K intervention using patient-specific characteristics and index INR values. This guidance may assist other anticoagulation management services with practical applications and require validation in a prospective clinical trial.

Pharmacologic Venous Thromboembolism Prophylaxis in Patients with Nontraumatic Subarachnoid Hemorrhage Requiring an External Ventricular Drain.

BACKGROUND: Optimal pharmacologic thromboprophylaxis dosing is not well described in patients with subarachnoid hemorrhage (SAH) with an external ventricular drain (EVD). Our patients with SAH with an EVD who receive prophylactic enoxaparin are routinely monitored using timed anti-Xa levels. Our primary study goal was to determine the frequency of venous thromboembolism (VTE) and secondary intracranial hemorrhage (ICH) for this population of patients who received pharmacologic prophylaxis with enoxaparin or unfractionated heparin (UFH). METHODS: A retrospective chart review was performed for all patients with SAH admitted to the neurocritical care unit at Emory University Hospital between 2012 and 2017. All patients with SAH who required an EVD were included. RESULTS: Of 1,351 patients screened, 868 required an EVD. Of these 868 patients, 627 received enoxaparin, 114 received UFH, and 127 did not receive pharmacologic prophylaxis. VTE occurred in 7.5% of patients in the enoxaparin group, 4.4% in the UFH group (p = 0.32), and 3.2% in the no VTE prophylaxis group (p = 0.08). Secondary ICH occurred in 3.83% of patients in the enoxaparin group, 3.51% in the UFH group (p = 1), and 3.94% in the no VTE prophylaxis group (p = 0.53). As steady-state anti-Xa levels increased from 0.1 units/mL to > 0.3 units/mL, there was a trend toward a lower incidence of VTE. However, no correlation was noted between rising anti-Xa levels and an increased incidence of secondary ICH. When compared, neither enoxaparin nor UFH use was associated with a significantly reduced incidence of VTE or an increased incidence of ICH. CONCLUSIONS: In this retrospective study of patients with nontraumatic SAH with an EVD who received enoxaparin or UFH VTE prophylaxis or no VTE prophylaxis, there was no statistically significant difference in the incidence of VTE or secondary ICH. For patients receiving prophylactic enoxaparin, achieving higher steady-state target anti-Xa levels may be associated with a lower incidence of VTE without increasing the risk of secondary ICH.

The imprecision of measuring activated clotting time (ACT) from the guiding catheter during percutaneous coronary interventions.

BACKGROUND: Finding the balance between the reduction in ischemic events and bleeding complications is crucial for the success of percutaneous coronary intervention (PCI). The activated clotting time (ACT) is used routinely worldwide to monitor and titrate anticoagulation therapy with unfractionated heparin (UFH) during the procedure. OBJECTIVES: We aimed to test the accuracy of ACT measurements from the guiding catheter compared to the arterial access sheath. METHODS: Patients undergoing PCI with UFH therapy were prospectively enrolled. Blood samples were drawn from the coronary guide catheter and the arterial access sheath. ACT values were determined in the same ACT machine, and potential interactions with clinical variables were analyzed. RESULTS: The study included 331 patients with post PCI ACT measurements. The mean ACT value of the catheter samples was statistically higher than the arterial access sample [294 ± 77 s Vs. 250 ± 60 s, p < 0.001]. The mean difference between the guiding catheter and the arterial line sheath samples was 43 ± 27 s (P < 0.001). We found that in 101/331 [30 %] patients the ACT from the guiding catheter was above 250 s, while from the access sheath it was below 250 s. Notably, in 40/331 [12 %] the ACT from the guiding catheter was above 200 s, while from the access sheath it was below 200 s. CONCLUSIONS: Large proportion of patient may be considered to have therapeutic ACT if measured from guide catheter during PCI, while the corresponding ACT from arterial sheath is subtherapeutic. This difference may have clinical and safety significance.

Discordance between aPTT and anti-Xa in monitoring heparin anticoagulation in mechanical circulatory support.

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance. METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23 001 pairs of simultaneously measured aPTT/anti-Xa were collected from 699 MCS patients. aPTT and anti-Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT > antiXa 61.5%; aPTT < antiXa 3.0%). Discordance with a high aPTT relative to anti-Xa (aPTT > antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre-albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT > anti-Xa than temporary MCS devices. CONCLUSIONS: aPTT and anti-Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti-Xa.