Subtherapeutic Anticoagulation Research Articles

Bridging therapy and risk of major bleeding and thrombosis in continuous-flow left ventricular assist device patients: a quasi-experimental study

Abstract Background Bridging with low molecular weight heparin (LMWH) on top of vitamin K antagonist treatment is recommended in continuous-flow left ventricular assist device (CF-LVAD) patients during subtherapeutic anticoagulation. However, the consequence of bridging on the risk of bleeding and thrombosis are unknown. Aim To assess the risk of major bleeding and thrombosis associated with bridging in CF-LVAD patients, through a regression discontinuity (RD) design, a quasi-experimental design. Methods We included CF-LVAD patients implanted at our university medical center between 2010-2021. Outcomes were major bleeding (INTERMACS type 3, 4, 5) and thromboembolic events (pump thrombosis, arterial non-central nervous system and venous thromboembolism). We estimated incidence rates and hazard ratios (HR) with 95% confidence intervals (95%CI) by time-dependent Cox regression. Using an RD design, a quasi-experimental design, we compared patients using LMWH due to a subtherapeutic international normalized ratio (INR) to patients with no LMWH and an INR just in target range. As LMWH treatment is initiated based on an INR threshold (i.e., when INR is below the lower target range) and INR is subject to random variability, patients just below and in the INR target range are comparable, mimicking a randomized trial. Analyses were performed five times including INRs±0.1, ±0.2, ±0.3, ±0.4 and ±0.5 around the INR threshold. Results 77 patients were included, with a median age at implantation of 69 years, 60 (78%) were male, 45 (58%) had ischemic heart failure and 35 (45%) had INTERMACS classification 3. We included 35,466 INRs during 91 patient-years of follow-up. Bridging was associated with increased major bleeding rates compared to no-bridging in all analyses (Figure 1). In particular, the risk of major bleeding was 6.9-fold increased (95%CI 1.2-38.9) during bridging compared to no-bridging considering INR+0.1, and 3.4-fold (95%CI 1.4-8.2) considering INR±0.5 (Figure 2A). While thrombotic events were infrequent, the risk of thrombosis was around unity during bridging compared to no-bridging considering INR±0.5 (HR 1.1, 95%CI 0.1-9.9, Figure 2B). Conclusions During bridging with LMWH, CF-LVAD patients had a 6.9-fold increased risk of major bleeding, while the risk of thrombosis was around unity compared to no-bridging.Incidence ratesHazard ratios

Coronary embolism due to probable clinical bioprosthetic aortic valve thrombosis: a case report

BackgroundCoronary embolism is a relatively rare but important non-atherosclerotic cause of acute coronary syndrome, mainly caused by atrial fibrillation and mechanical heart valve thrombosis due to subtherapeutic anticoagulation. There have been increasing reports of bioprosthetic valve thrombosis (BPVT), but thromboembolic events are rare and mainly affect the cerebrovascular system. Coronary embolism is an extremely rare complication of BPVT.Case presentationA 64-year-old male presented with non-ST-Elevation myocardial infarction (NSTEMI) to an Australian regional health service. Three years ago, he had undergone Bentall procedure with bioprosthetic aortic valve replacement for severe aortic regurgitation and significant aortic root dilatation. Diagnostic coronary angiography revealed embolic occlusion of first diagonal branch in the absence of underlying atherosclerosis. Prior to NSTEMI presentation, the patient was clinically asymptomatic apart from the progressive increase in transaortic mean pressure gradient on transthoracic echocardiography which was first detected seven months after surgical aortic valve replacement. Transoesophageal echocardiography showed restrictions of the aortic leaflet opening but no evidence of mass or vegetation. After eight weeks of warfarin therapy, the raised aortic valve gradient returned to normal. Lifelong warfarin was prescribed, and patient remained clinically well at 39-month follow-up.ConclusionWe experienced a case of coronary embolism in a patient with probable BPVT. Reversible bioprosthetic valve hemodynamic deterioration after anticoagulation strongly supports the diagnosis in the absence of histopathology. Early moderate-to-severe hemodynamic valve deterioration warrants further investigations, including cardiac computed tomography and sequential echocardiography, to investigate for probable BPVT and consideration of timely anticoagulation initiation to prevent thromboembolic events.

British Society for Haematology guideline for anticoagulantmanagement of pregnant individuals with mechanical heart valves.

British Society for Haematology guideline for anticoagulantmanagement of pregnant individuals with mechanical heart valves.

Meningioma resection and venous thromboembolism incidence, management, and outcomes

BackgroundMeningioma resection is associated with the risk of venous thromboembolism (VTE). ObjectivesTo determine the incidence and risk factors for VTE following meningioma resection and VTE outcomes based on the type and timing of anticoagulation. MethodsFrom 2011 to 2019, 901 consecutive patients underwent meningioma resection. We retrospectively evaluated the postoperative incidence of VTE and bleeding. For VTE, we determined the treatment strategy and rate of VTE complications and bleeding. ResultsPharmacologic prophylaxis was administered to 665 (73.8%) patients. The cumulative incidence for total postoperative VTE was 8.7% (95% CI: 6.9%-10.6%), and for symptomatic VTE was 6.0% (95% CI: 4.6%-7.7%). A multivariable model identified the following independent predictors of symptomatic VTE: history of VTE, obesity, and lack of pharmacologic prophylaxis. Following postoperative VTE, 58 (74.3%) patients received therapeutic anticoagulation either initially (33.3%) or after a median delay of 23.5 days (41.0%). Symptomatic recurrent VTE occurred in 13 (16.6%) patients. Following VTE, the use of subtherapeutic anticoagulation was associated with a lower rate of total VTE extension than no anticoagulation (17.5% vs 42.9%, OR 0.28, 95% CI: 0.09–0.93). In total, 14 patients (1.6%) experienced clinically relevant bleeding: 4 received therapeutic anticoagulants, 8 received prophylactic anticoagulation, and 2 received no anticoagulation. Among patients with VTE, 4 (5.1%) experienced bleeding. ConclusionRecognition of risk factors for VTE following meningioma resection may help improve approaches to thromboprophylaxis. The management of postoperative VTE is highly variable, but most VTE patients are ultimately treated with therapeutic anticoagulants.

Novel Coagulation Test Detects Anticoagulation Resistance and Is Associated With Thrombotic Events in Pediatric Patients Requiring Extracorporeal Membrane Oxygenation.

OBJECTIVES:Bivalirudin, an IV direct thrombin inhibitor, and unfractionated heparin (UFH) are frequently used anticoagulants in the pediatric critical care setting. An accurate, specific, point-of-care test to quantify and detect anticoagulation resistance is not currently available. This study evaluates the ability of a rapid (< 10 min), micro-volume (< 50 uL) coagulation test to detect and quantify the anticoagulation effect of bivalirudin and UFH using a functional, clot time endpoint in pediatric critical care patients.DESIGN:Single-site retrospective laboratory sample analysis and chart review.SETTING:A 105-bed pediatric and cardiac ICUs delivering extracorporeal membrane oxygenation.SUBJECTS:Forty-one citrated, frozen, biobanked plasma specimens comprising 21 with bivalirudin and 20 with UFH from 15 anticoagulated pediatric patients were analyzed. Thirteen patients were on extracorporeal membrane oxygenation, one had a submassive pulmonary embolism, and one was on a left ventricular assist device.INTERVENTIONS:None.MEASUREMENT AND MAIN RESULTS:A Clotting Time Score (CTS) was derived on each sample. The CTS detected patients that had developed a pathologic clotting event with 100% sensitivity and 82% specificity compared with prothrombin time with 25% sensitivity/76% specificity and activated partial thromboplastin time with 0% sensitivity/0% specificity. Additionally, the CTS detected subtherapeutic anticoagulation in response to UFH in patients that were clinically determined to be UFH resistant requiring alternative anticoagulation with bivalirudin.CONCLUSIONS:The CTS appears to be a clinically valuable indicator of coagulation status in patients treated with either UFH or bivalirudin. Results outside of the therapeutic range due to inadequate dosing or anticoagulation resistance appeared to be associated with clot formation. CTS testing may reduce the risk of anticoagulation-related complications via the rapid identification of patients at high risk for pathologic thrombotic events.

Safety of Once Daily Enoxaparin for Anticoagulation Bridging in Patients with HeartMate III Left Ventricular Assisted Device

<h3>Purpose</h3> Most centers bridge patients with Left Ventricular Assist Device (LVAD) patients with heparin drip to avoid thromboembolic complications based on data from HeartMate II. Because of improved hemocompatibility of third generation HeartMate III (HM3), Low molecule weight heparin like enoxaparin has been used to bridge to warfarin when the INR (International Normalized Ratio) is subtherapeutic. Once daily dosing has been used in select patients with higher bleeding risk. However, data supporting this approach is limited. We investigate the safety of using once daily Enoxaparin dosing to bridge subtherapeutic warfarin in patients on HMIII LVAD. <h3>Methods</h3> We conducted a retrospective review of patients who underwent HMIII LVAD implantation from 2018 to 2020. We identified 22 patients who received enoxaparin daily bridging after LVAD implantation. We investigated complications related to enoxaparin use and the necessary data parameters to determine the safety profile of once daily enoxaparin use. The primary outcome was in-pump thrombosis. Secondary outcomes included ischemic stroke, embolic phenomenon, acute kidney injury and bleeding events. <h3>Results</h3> 52 patients were screened, 22 patients of which bridged at least once with enoxaparin. 10 patients received multiple rounds of enoxaparin bridging over their course of follow up. The average enoxaparin course was 3-7 days and extended only if INR remains below 1.6. Enoxaparin was held once the INR reaches 1.8. There were no incidence of pump thrombosis, ischemic stroke or embolic phenomenon related to enoxaparin bridging. No significant events were noted in terms of worsening thrombocytopenia, anemia, renal function, bleeding events, or rates of infection. <h3>Conclusion</h3> Once daily enoxaparin dosing as a bridge to subtherapeutic anticoagulation with warfarin for HM III patients is a safe and effective method for preventing pump thrombosis while significantly reducing the need for hospital admissions for heparin bridging.

Adverse Events in HVAD vs. HM3 Patients under Outpatient Bridging with Low-Molecular Weight Heparin for Subtherapeutic Anticoagulation

<h3>Purpose</h3> The standard of care in patients with durable left-ventricular assist devices combines antiplatelet with anticoagulation therapy. Current guidelines recommend use of intravenous (IV) unfractionated heparin as bridge to therapeutic INR-values in the postoperative period. However, management of subtherapeutic INR in the ambulatory setting is not yet clearly defined by guidelines. The protocol at our center proposes the use of unfractionated heparin perioperatively and low-molecular weight heparin in outpatients. Therefore, we aimed to analyse outcomes in patients with continuous-flow LVAD (CF-LVAD). <h3>Methods</h3> In this single-center retrospective trial all patients after CF-LVAD implantation at our center were included between 1/2015 and 12/2020 (n=110 patients; HVAD n=80, HM3 n=30). Patients were followed up from initial discharge after LVAD implantation until death, heart transplantation or end of the observation period (9/2021). Bridging for subtherapeutic INR (≤ 0.4 below target INR) were provided with enoxaparin in a therapeutic dose adapted to weight and renal function. Only patients with an INR > 0.4 below target INR were admitted to hospital for bridging with IV unfractionated heparin. Bleeding events leading to hospital admission, cerebrovascular events and pump thromboses were evaluated and provided in percent of study population and/or events per patient year (eppy). <h3>Results</h3> Follow-up covers a total of 214.2 patient years. Overall mortality was 18.2 %. Bleeding events occurred in 42.7 %, of which GI bleeding constituted the largest group with 21.8 % (HVAD: 0.25 eppy; HM3: 0.05 eppy). Stroke/TIA/PRIND occurred in 5.5 % of the patients (HVAD: 0.07 eppy; HM3: 0.01 eppy; in total: 0.03 eppy). Intracerebral hemorrhage (overall 0.04 eppy) occurred 6.3 times more often in HVAD patients. Pump thrombosis occurred in 8.2 % of all CF-LVAD patients and was limited to HVAD (0.13 eppy). <h3>Conclusion</h3> Current studies tend to promote the use of low molecular weight heparins, especially enoxaparin for outpatient anticoagulation bridging in case of subtherapeutic INRs. However, in most cases old generation CF-LVADs were studied. Our study includes a relevant number of HM3 devices. Overall, the adverse event rates presented herein suggest feasibility of low-molecular weight heparin bridging in patients with HM3 devices.

Adherence to rivaroxaban for the treatment of venous thromboembolism–Results from the FIRST registry

BackgroundMedication nonadherence can result in poor clinical outcomes and significant costs to health care providers. When treating venous thromboembolism (VTE), subtherapeutic anticoagulation may contribute to complications such as recurrent VTE or postthrombotic syndrome. ObjectivesTo describe the extent, reasons for, and predictors of nonadherence to rivaroxaban for the treatment of VTE in clinical practice in the United Kingdom reported by participants of the FIRST registry. Patients/MethodsThe FIRST registry was an observational, multicenter registry reporting on the use of rivaroxaban in routine clinical practice. FIRST registry participants completed an adherence screening questionnaire during their treatment and follow‐up. ResultsIn total, 1028 participants completed 1660 questionnaires over 2 years. One hundred thirteen of 1028 (11%) reported nonadherence at 28 days (interquartile range, 21‐45). Reasons given for nonadherence at 1 month were forgetfulness (8.6% vs 74.7%; P < .001), carelessness (2.7% vs 27.3%; P < .001) or a change in routine (7.4% vs 25.5%; P < .001) reported by adherent and nonadherent participants, respectively. Older age (10‐year increments) was the strongest predictor of good adherence (adjusted odds ratio, 1.21; 95% confidence interval, 1.06‐1.39; 1 = adherent). ConclusionsOverall adherence to rivaroxaban was high, and most nonadherence was unintentional. Identification of those at risk of nonadherence may reduce the risk of VTE recurrence and long‐term complications.

Abstract 12394: Development of a Heparin Dosing Algorithm to Maintain Therapeutic Anticoagulation During Atrial Fibrillation Ablation

Introduction: Therapeutic anticoagulation during atrial fibrillation (AF) ablation reduces the risk of cerebral thromboembolism during ablation. Heparin dosing strategies vary and can result in sub-therapeutic anticoagulation. Hypothesis: We hypothesize that a heparin dosing algorithm will improve maintenance of guideline-based therapeutic activated clotting times (ACT) during AF ablation. Methods: Starting from published guidance on heparin dosing during AF ablation, an artificial intelligence algorithm based on a decision tree and other mathematical considerations was developed. The algorithm launches directly from the electronic medical record and captures deidentified data for future improvements. The rules were modified over several months to establish the tested algorithm. The strategy utilized heparin boluses and an infusion. Dosing was adapted based on an individual patient’s response to the first heparin bolus. Goal ACT was 300-350 s. Outcomes from a month prior to algorithm introduction were compared to those from one month using the developed algorithm. The measured outcomes included time from first bolus to therapeutic ACT (&gt;300 s), number of heparin boluses to achieve goal ACT, time in left atrium below therapeutic ACT, and ACT value when below goal in left atrium. Results: Data from seventeen pre-algorithm procedures were compared to fourteen procedures completed using the dosing algorithm. Compared to procedures using typical dosing, procedures using the dosing algorithm reached goal ACT faster (16.1 ± 5.3 min compared to 26.2 ± 14.5 min, p = 0.02) with fewer heparin boluses (1.1 ± 0.3 boluses compared to 1.6 ± 0.9 boluses, p = 0.04). The ACT did drift below goal in some cases (n = 4 using algorithm and n = 5 using typical dosing). The time below goal was not different between dosing strategies (16.5 ± 8.7 min for algorithm compared to 22.4 ± 7.9 min for typical dosing). However, when the ACT drifted below goal with the dosing algorithm, it was significantly closer to goal than with typical dosing (295 ± 3 s compared to 268 ± 21 s, p = 0.02). Conclusion: An artificial intelligence algorithm based on a decision tree and adaptation to individual patient kinetics may improve maintenance of guideline based therapeutic ACT during AF ablation.

Abstract 12966: Novel, Low-Volume, Point-of-Care Coagulation Test Successfully Detects Anticoagulation Resistance in Hospitalized Patients With COVID-19

Introduction: Severe COVID-19 has been associated with aberrant coagulation factor activities, particularly in patients with a thrombotic event (TE). Management of anticoagulant is critical in the care of hospitalized patients with COVID-19. Hypothesis: Evaluation of a point-of-care (POC), functional, clot-time-based coagulation test to detect the anticoagulant effect of therapeutic unfractionated heparin (UFH) in hospitalized SARS-CoV-2-positive patients who developed a TE. Methods: An IRB-approved analysis of 36 citrated plasma specimens from 26 SARS-CoV-2-positive patients and 10 matched negative controls was performed. A Clotting Time Score (CTS), a measure of factor-specific inhibition (i.e. anticoagulant activity), was derived for each patient. CTS results were compared with traditional coagulation tests. Five UFH COVID-19 samples with low CTS scores (&lt;10) were spiked with uniform dosing of UFH, low molecular weight heparin (LMWH), apixaban, or argatroban and retested to assess anticoagulation response. Results: The CTS detected sub-therapeutic UFH anticoagulation levels more frequently in COVID-19 cases compared with controls (76% vs. 17%). Prothrombin Times, activated Partial Thromboplastin Times, anti-Xa levels, and antithrombin activity did not correlate with each other or with the CTS in the COVID-19 samples. CTS correlated with both FV and Factor X activity (R 2 =0.49, Spearman R=-0.68), which form the prothrombinase complex. The CTS was 94% sensitive and 67% specific for the occurrence of TEs in patients on UFH. CTS demonstrated a consistent anticoagulant response only to argatroban (100%) compared with other anticoagulants (60%). Conclusions: The CTS, generated using a novel, low-volume, rapid POC coagulation test is a strong indicator of the therapeutic effect of UFH anticoagulation in COVID-19 patients and may provide a predictive measure of TEs potentially occurring from anticoagulation resistance.

Comparison of Anticoagulation Regimens Following Stent Placement for Nonthrombotic Lower Extremity Venous Disease

PurposeTo determine whether subtherapeutic anticoagulation regimens are noninferior to therapeutic anticoagulation regimens following stent placement for nonthrombotic lower extremity venous disease. Materials and MethodsFifty-one consecutive patients (88% women; mean age, 44 years) who underwent stent placement for nonthrombotic lower extremity venous disease between 2002 and 2016 were retrospectively identified. The patients were divided into 2 cohorts: those who received prophylactic enoxaparin or no anticoagulation (subtherapeutic) after the procedure and those who received therapeutic doses of anticoagulation with enoxaparin, warfarin, and/or rivaroxaban (therapeutic) after the procedure. Baseline demographic characteristics, procedure characteristics, and outcomes were compared between the 2 groups using the Student t test, Fisher exact test, and χ2 test. The subtherapeutic and therapeutic anticoagulation groups did not differ significantly in the baseline demographic characteristics (eg, sex, race, and age) or procedure characteristics (eg, number of stents placed, stent brand, stent diameter, etc). ResultsThe mean clinical follow-up time was 4.4 years (range, 0–16.3 years). There were no thrombotic adverse events or luminal obstructions due to in-stent restenosis in either group. There were 5 minor bleeding adverse effects in the therapeutic group and no bleeding adverse effects in the subtherapeutic group (P = .051). There were no statistically significant differences in subjective symptom improvement (P = .75). ConclusionsIn this retrospective cohort, the subtherapeutic and therapeutic anticoagulation regimens produced equivalent outcomes in terms of adverse event rates, reintervention rates, and symptomatic improvement, suggesting that therapeutic doses of anticoagulation do not improve outcomes compared with subtherapeutic anticoagulation regimens following nonthrombotic venous stent placement.

Direct-Acting Oral Anticoagulant Choice for Stroke Prevention in Obese Patients With Atrial Fibrillation

Anticoagulation with direct-acting oral anticoagulants (DOACs) is recommended over warfarin for stroke prevention in patients with atrial fibrillation (AF). The efficacy of DOACs over warfarin in obese patients with AF is less defined and may carry the potential for subtherapeutic anticoagulation and reduced efficacy. The best available evidence to guide DOAC use in obese patients with AF is from analysis of obese subgroups of all the major landmark DOAC trials. From these subgroup analyses of the RE-LY, ARISTOTLE, ENGAGE-AF TIMI 48, and ROCKET-AF trials, DOAC use in obese patients demonstrated efficacy similar or superior to warfarin for stroke reduction. Major bleeding rates were similar or higher with DOACs compared with warfarin in these obese subgroup analyses. Meta-analysis of the above major clinical trials concluded that DOACs were more effective compared with warfarin for stroke prevention in obese patients (up to a body mass index [BMI] of 50 kg/m2) and had lower incidence of major bleeding. The totality of evidence supports that DOACs are as effective, if not superior, to warfarin in obese patients with AF. We propose an algorithm, based on the available evidence and current guidelines, to guide the use of DOACs based on severity of obesity. Any DOAC can be used in obese patients with BMI < 40 kg/m2. In patients with a BMI of 40-50 kg/m2, warfarin should be used, but apixaban or edoxaban can be considered. In obese patients with a BMI > 50 kg/m2, warfarin should be used.

Anticoagulant therapy management of venous thromboembolism recurrence occurring during anticoagulant therapy: a descriptive study.

Limited evidence exists regarding management of recurrent venous thromboembolism (VTE) that occurs during anticoagulant therapy. We aimed to describe patient characteristics, drug therapy management, and outcomes of patients with VTE recurrence during anticoagulant therapy.We identified 30 relevant episodes of VTE recurrence. Mean age was 48.9 (15.9) years, 56.7% were male, and 93.3% were White. Common VTE risk factors included cancer (46.6%), recent surgery (33.3%), and prolonged immobility (30.0%). At the time of recurrent VTE, 40.0% were receiving enoxaparin, 30.0% warfarin, and 23.3% direct oral anticoagulants. Potential causes for VTE recurrence included indwelling venous catheters (40.0%), cancer (33.3%), subtherapeutic anticoagulation (26.7%), and nonadherence (23.3%). Recurrent VTE management strategies included switching anticoagulants (26.7%), increasing anticoagulant dose (20.0%), temporarily adding enoxaparin or unfractionated heparin to oral anticoagulation therapy (13.3%), or no change in anticoagulation therapy (43.3%). Only four adverse 90-day outcomes occurred among 17 patients who received anticoagulant therapy changes in response to VTE recurrence, whereas eight adverse outcomes occurred in the 13 patients who received no change in anticoagulation therapy in response to a recurrent VTE episode (Pvalue 0.04).Regardless of the potential etiology of recurrent VTE during anticoagulant therapy; switching anticoagulants, temporarily adding injectable anticoagulants, or increasing anticoagulant intensity appears preferable to continuing current anticoagulant therapy unchanged.

ANTICOAGULATION CONTROL AMONG PATIENTS WITH ATRIAL FIBRILLATION

Objective: To assess adequacy of anticoagulation in Warfarin treated patients with atrial fibrillation&#x0D; Study Design: Prospective observational study.&#x0D; Place and Duration of Study: Armed Forces Institute of Cardiology/National Institute of Heart Diseases, Rawalpindi, from Nov 2019 to Apr 2020.&#x0D; Methodology: All individuals fulfilling the inclusion criteria were enrolled in the study after their consent. Based upon their serial International Normalized Ratio (INR) values, Time in Therapeutic Range (TTR) was calculated using Rosendaal method. A TTR&gt;70% was a marker of adequate anticoagulation. Factors associated with TTR &lt;70% were identified.&#x0D; Results: Total 70 participants were included in the study. Mean age (± SD) was 51.43 (± 11.27) years. Thirty four (48.6%) were males and 36 (51.4%) were females. Twenty four (34.3%) had valvular atrial fibrillation while 46 (65.7%) had non-valvular atrial fibrillation. Overall, TTR&gt;70% was observed in 29 (41.4%) of study participants. Poly-pharmacy and multiple co-morbidities were identified as statistically significant factors associated with subtherapeutic anticoagulation (TTR&lt;70%).&#x0D; Conclusion: Determined TTR of study population indicates poor anticoagulation control in majority of patients being anticoagulated with Warfar in highlighting the need for focused interventions such as dedicated anticoagulation clinics and patient education.

Dialysis Filter Life, Anticoagulation, and Inflammation in COVID-19 and Acute Kidney Injury.

In recent studies, 5%–20% of hospitalized patients with coronavirus disease 2019 (COVID-19) developed AKI requiring RRT (CoV-AKI-RRT) (1,2) (L. Chan et al., unpublished observations). Hypercoagulability has been recognized as a salient feature of COVID-19 in the critically ill (3,4) and there have been anecdotal accounts of unexpectedly frequent dialysis filter clotting. However, there are limited data describing the magnitude of the problem. A recent report described clotting events in 28 of 29 patients with CoV-AKI-RRT and shorter filter lifespan compared with a historical control, but no details were provided regarding anticoagulation (4). Our objective was to examine the delivery of RRT and circuit interruptions in patients with CoV-AKI-RRT in comparison with those in the pre-COVID-19 era. With approval of the Institutional Review Board, waiver of informed consent, and in accordance with the Declaration of Helsinki, we conducted a retrospective single-center study, ancillary from our previously reported cohort (2). We identified hospitalized patients with COVID-19 (positive severe acute respiratory syndrome coronavirus 2 RNA PCR by nasopharyngeal swab) and AKI, who underwent RRT by sustained low-efficiency dialysis (SLED) for ≥8 hours in an intensive care unit between March and April of 2020 (study period: 4 weeks) by either prolonged intermittent or continuous RRT modality (5,6) using Fresenius 2008K/K2 (Bad Homburg, Germany) machines. At our hospital, continuous venovenous hemodiafiltration (CVVHDF) with PrismaFlex (Deerfield, IL) machines was restricted to the neurointensive care unit and was not expanded during the pandemic due to logistics. As pre-COVID-19 control, we included consecutive patients (reverse chronological order) with AKI without COVID-19 who underwent SLED in December of 2019. Electronic medical records were accessed and RRT flowsheets were manually reviewed to extract timing of initiation and interruption, blood flow rate (BFR), dialysate flow rate, and filter transmembrane pressure (TMP). Standard BFR was 200 …

Incidence, clinical impact and treatment outcomes of valve thrombosis after transcatheter mitral valve implantation

Abstract Background Transcatheter mitral valve implantation (TMVI) is a new treatment option for high-risk surgical patients with degenerated bioprosthesis (ViV), failed annuloplasty rings (ViR) and severe mitral annular calcification (ViMAC). However, limited data exist on transcatheter heart valve thrombosis. Purpose The aim of this study was to report the incidence, clinical impact and treatment outcomes of transcatheter heart valve (THV) thrombosis in patients undergoing TMVI. Methods All consecutive patients undergoing TMVI in our center between July 2010 and September 2019 were included. A transoesophageal echocardiography and a computed tomography (CT) were performed before hospital discharge and at each clinical visit, at 3 months, at 1 year and yearly after. THV thrombosis was defined as the presence of at least one thickened leaflet with restricted motion suggestive of thrombus confirmed by TOE and/or contrast CT. All patients received anticoagulation therapy with vitamin K antagonists (VKA) and a low dose of aspirin for the first 3 months. Results A total of 132 patients underwent TMVI (62 ViV, 36 ViR and 34 ViMAC). Among them, 16 (12.1%) patients had a THV thrombosis. Median age was 67 years old and 56.2% of patients were women. Median time to diagnosis of THV thrombosis was 78 days. Early THV thrombosis was observed in 7 (43.7%) and in 13 (81.2%) patients THV thrombosis occurred within the first 6 months after the procedure. 8 out 9 patients with subacute or late THV thrombosis were not anticoagulated or with subtherapeutic anticoagulation. No stroke or thromboembolic events occurred in these patients. No change in mitral gradient was observed in 14 out 16 patients. VKA were indicated in all patients. THV thrombosis resolved in all but one patient. Conclusion THV thrombosis is frequent after TMVI, occurs mainly within the first 6-months after the procedure, are mostly subclinical and resolves after optimization of anticoagulation treatment. An anticoagulation therapy for at least 6 months may be necessary. Timing of THV thrombosis Funding Acknowledgement Type of funding source: None

Anticoagulation and bleeding risk in patients with COVID-19

BackgroundThere is no current standardized approach to anticoagulation in patients with Coronavirus Disease 2019 (COVID-19) while potential bleeding risks remain. Our study characterizes the patterns of anticoagulation use in COVID-19 patients and the risk of related bleeding. MethodsThis is a single center retrospective analysis of 355 adult patients with confirmed diagnosis of COVID-19 from March 1 to May 31, 2020. Chi-square was used to analyze the relationship between degree of anticoagulant dose and bleeding events by site. Multivariable logistic regression was used to look at factors associated with inpatient death. Results61% of patients were being treated with prophylactic doses of anticoagulation, while 7% and 29% were being treated with sub-therapeutic and therapeutic anticoagulation (TA) doses respectively. In 44% of patients, we found that the decision to escalate the dose of anticoagulation was based on laboratory values characterizing the severity of COVID-19 such as rising D-dimer levels. There were significantly higher rates of bleeding from non-CNS/non-GI sites (p = 0.039) and from any bleeding site overall (p = 0.019) with TA. TA was associated with significantly higher rates of inpatient death (41.6% vs 15.3% p < 0.0001) compared to those without. All patients who developed CNS hemorrhage died p = 0.011. After multivariable logistic regression, only age OR 1.04 95% CI (1.01 to 1.07) p = 0.008 and therapeutic anticoagulation was associated with inpatient mortality OR 6.16 95% CI (2.96 to 12.83) p ≤ 0.0001. ConclusionThe use of TA was significantly associated with increased risk of bleeding. Bleeding in turn exhibited trends towards higher inpatient death among patients with COVID-19. These findings should be interpreted with caution and larger more controlled studies are needed to verify the net effects of anticoagulation in patients with COVID-19.

Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation

Background and purposeUnderstanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. MethodsThe Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR <2) anticoagulation status. We used binary logistic regression models to determine factors independently associated with anticoagulation status after adjustment for pertinent confounders. In particular, we sought to determine whether atherosclerosis with 50% or more luminal narrowing in an artery supplying the infarct (a marker for a competing atherosclerotic mechanism) and small stroke size (≤ 10 mL; implying a competing small vessel disease mechanism) related to anticoagulant status. ResultsOf the 2084 patients enrolled in the IAC study, 382 patients met the inclusion criteria. The mean age was 77.4 ± 10.9 years and 52.4% (200/382) were women. A total of 222 (58.1%) subjects presented with subtherapeutic INR. In adjusted models, small stroke size (OR 1.74 95% CI 1.10–2.76, p = 0.019) and atherosclerosis with 50% or more narrowing in an artery supplying the infarct (OR 1.96 95% CI 1.06–3.63, p = 0.031) were independently associated with INR ≥2 at the time of their index stroke. ConclusionSmall stroke size (≤ 10 ml) and ipsilateral atherosclerosis with 50% or more narrowing may indicate a competing stroke mechanism. There may be important opportunities to improve stroke prevention strategies for patients with AF by targeting additional ischemic stroke mechanisms to improve patient outcomes.

Quality of initial anticoagulant treatment and risk of CTEPH after acute pulmonary embolism.

BackgroundThe pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood. Poor-quality anticoagulation may contribute to a higher risk of CTEPH after acute pulmonary embolism (PE), partly explaining the transition from acute PE to CTEPH. We assessed the association between the time in therapeutic range (TTR) of vitamin-K antagonist (VKA) treatment and incidence of CTEPH after a PE diagnosis.MethodsCase-control study in which the time spent in, under and above therapeutic range was calculated in 44 PE patients who were subsequently diagnosed with CTEPH (cases). Controls comprised 150 consecutive PE patients in whom echocardiograms two years later did not show pulmonary hypertension. All patients were treated with VKA for at least 6 months after the PE diagnosis. Time in (TTR), under and above range were calculated. Mean differences between cases and controls were estimated by linear regression.ResultsMean TTR during the initial 6-month treatment period was 72% in cases versus 78% in controls (mean difference -6%, 95%CI -12 to -0.1), mainly explained by more time above the therapeutic range in the cases. Mean difference of time under range was 0% (95%CI -6 to 7) and 2% (95CI% -3 to 7) during the first 3 and 6 months, respectively. In a multivariable model, adjusted odds ratios (ORs) for CTEPH were around unity considering different thresholds for ‘poor anticoagulation’, i.e. TTR <50%, <60% and <70%.ConclusionSubtherapeutic initial anticoagulation was not more prevalent among PE patients diagnosed with CTEPH than in those who did not develop CTEPH.

What Causes LVAD-Associated Ischemic Stroke? Surgery, Pump Thrombosis, Antithrombotics, and Infection.

Acute ischemic stroke (AIS) is a major complication in left ventricular assist device (LVAD) population. A better understanding of clinical risk factors associated with AIS may help mitigate risk of stroke. We reviewed prospectively collected data of 477 LVAD patients from a tertiary center from October 1, 2004 to December 31, 2016. Supplemental data abstraction was performed on patients with AIS. Fifty-seven (12%) developed 61 AIS. Of 61, 17 (28%) AIS occurred perioperatively. The median time from implant to perioperative AIS was 5 days (interquartile range: 3-9). Pump thrombosis accounted for 19 (31%) of 61 AIS, and 7 (37%) presented initially with AIS before the pump thrombosis. The median lactate dehydrogenase (LDH) at the time of AIS in the pump thrombosis group (806) was higher than LDH at 1 month (437, P = 0.27) at 3 months (334, P = 0.01), and 6 months (286, P = 0.001) before AIS. Thirty-three (54%) AIS occurred while receiving inadequate antithrombotic therapy. Acute infections were common (31, 51%) in AIS and 12 (20%) were associated with acute bloodstream infection. All AIS were explained by a combination of four clinical risk factors. All LVAD-associated AIS occurred perioperatively or in conjunction with pump thrombosis, subtherapeutic anticoagulation, and bloodstream infection. The common underlying thread is occurrence of a prothrombotic state. The results of this study underscore the potential consequences of disruption of delicate hemostatic balance in patients with LVAD.