Anticoagulation Withdrawal Research Articles

Cardiovascular Interventions in Patients with Hemophilia and Severe Von Willebrand Disease.

The management of cardiovascular interventions in patients with hemophilia and severe von Willebrand disease (VWD) is challenging. The procedure itself as well as the use of anti-platelet drugs and anticoagulants implies a risk of bleeding. On the other hand, factor replacement therapy as well as withdrawal of anti-platelet drugs or anticoagulants may increase the risk of cardiovascular events and thrombosis. Information on the management of such interventions is limited to very few case reports. Here, we report a retrospective analysis of 28 patients with hemophilia A (n=16), hemophilia B (n=4) or VWD (n=8, all with VWF:RCo <30 IU/dl), who underwent a total of 39 cardiovascular interventions including coronary angiography (CA, n=11), percutaneous coronary interventions (PCI, n=18), or cardiac surgery (CS, n=10) including coronary artery bypass grafting (CABG) and heart valve surgery with the use of cardiopulmonary bypass (CPB). Patients had a median age of 66 years (range 47–85) and had a median factor activity of 3 IU/dl (range <1–35). Six patients were on regular prophylaxis prior to the intervention. Patients undergoing CA received replacement therapy for a median of 2 days (range 1–15) with a median starting dose of 36 IU/kg (range 24–67). Minor bleeding at the site of puncture occurred in 5 of 11 patients. Major bleeding or bleeding requiring transfusion did not occur. Patients undergoing PCI received replacement therapy for a median of 4 days (range 1–41) with a starting dose of 40 IU/kg (range 12–63) given before or during the intervention. 12 of 14 patients receiving bare metal stents were on aspirin and clopidogrel for 4 to 6 weeks; 7 of these including all patients with severe hemophilia received prophylactic replacement therapy for the time of dual anti-platelet therapy. Two patients received shorter courses of single anti-platelet agents due to bleeding. Three patients receiving drug-eluting stents were on aspirin and clopidogrel for 8 to 12 weeks; 2 of these also received prophylactic replacement therapy, whereas one patient with mild hemophilia did not. Minor bleeding at the site of puncture occurred in 15 of 18 patients undergoing PCI; major bleeding at the site of puncture occurred in 1 patient and required transfusion. Major bleeding at distant sites occurred in 3 patients with 1 patient requiring transfusion. Two of these three patients received anti-platelet therapy without prophylactic factor replacement. No patient experienced stent thrombosis or other thromboembolic complications. Patients undergoing cardiac surgery received replacement therapy for a median of 23 days (range 11–46) with a median starting dose of 57 IU/kg (range 23–107). Unfractionated heparin was used for anticoagulation during CPB. Minor wound bleeding occurred in 8 of 10 patients. Four patients received transfusions of 2 to 5 units of packed red blood cells. Five of seven patients undergoing CABG received aspirin. One patient with VWD undergoing CABG and biological aortic valve replacement received oral anticoagulation and experienced gross hematuria; he was switched to aspirin after 6 weeks. A patient with mild hemophilia on long-term oral anticoagulation because of atrial fibrillation remained on oral anticoagulants without signs of bleeding. In summary, this is the largest cohort of patients with hemophilia and severe VWD undergoing cardiovascular interventions. Combining replacement therapy with anti-platelet agents or anticoagulants appears to be a safe strategy, despite of frequent minor bleeding. Major bleeding mainly occurred in patients on anti-platelet agents without concomitant prophylactic replacement therapy.

Anticoagulant therapy in patients with atrial fibrillation: management of bleeding

Bleeding is the most common complication of long-term anticoagulant therapy. For patients with atrial fibrillation, it is important to consider the balance of hemorrhagic and thromboembolic risks in the event of bleeding since unreasonable withdrawal of anticoagulants can worsen the prognosis. The management of patients with hemorrhagic complications is determined according to the severity of bleeding, type of anticoagulant taken, and presence of high thromboembolic risk factors. The paper presents the authors protocol for the management of patients with atrial fibrillation and various types of hemorrhagic complications against the background of anticoagulant therapy.

MO755SPONTANEOUS SOFT TISSUE HEMATOMAS IN ESRD PATIENTS WITH SYMPTOMATIC SARS-CO-V2 INFECTION – THE EXPERIENCE OF AN EMERGENCY NEPHROLOGY AND DIALYSIS DEPARTMENT

Background and AimsWhile actual proofs plead for an increased thrombotic risk in SARS-Co-V2 infection and need for anticoagulant therapy in severe cases, we report suspicious occurrence of hemorrhagic events in a series of ESRD patients.Method59 patients with stage 5 CKD were hospitalized in a two months interval, since our hospital was designated for the admission of mild-severe SARS-Co-V2 patients exclusive. 8 patients were admitted for RRT initiation and 51 were maintenance dialysis patients admitted with SARS-Co-V2-associated complications. Beside hemodialysis and treatment of chronic complications of ESRD, all patients were treated, according to the stage and gravity of SARS-Co-V2 infection and under continuous supervision of an infectious disease physician, with antivirals, antibiotics, anticoagulants and IL-antagonists. Daily or at 2 days laboratory monitoring was performed and consisted in evaluation of inflammatory markers, clotting tests, complete hemogram, D-dimer testing, IL-1 and IL-6 serum levels, serum urea, creatinine and albumin.ResultsIn 6 cases spontaneous soft tissue hematomas were noted, totalizing a number of 9 hematomas documented through ultrasound and CT-scan. In order of frequency, the locations were: 4 rectus abdominalis hematoma, 2 in the external oblique, 2 in gluteus maximus muscle, and one in the right psoas muscle. The source of the bleeding could not be identified in any patient. The occurrence of spontaneous hematomas was correlated with the D-dimer values (p=0.02), prolonged anticoagulation (over 7 days), albumin levels (p=0.01), platelets count (p=0.05). We found no correlation with the serum urea, creatinine, hemoglobin, INR, or with the dialysis age. In all these cases cough was severe. A conservative approach was instituted, with daily US monitoring, withdrawal of anticoagulants and antiplatelet medication, and blood transfusions. 2 patients necessitated surgical procedures and two deaths were recorded.ConclusionIn this brief report, we observed that in chronic hemodialysis patients infected with SARS-Co-V2, risk of hemorrhagic manifestations may overcome the benefits of anticoagulant routine therapy. There is a need to explore further this risk in the future; until then, a careful individualized assessment of the safety and indications for anticoagulant therapy regimens is mandatory for ESRD patients with symptomatic new Coronavirus infection.

MO378WHAT LIES BENEATH ANTICOAGULATION-RELATED ACUTE KIDNEY INJURY

Abstract Background and Aims Acute kidney injury (AKI) secondary to glomerular hemorrhage in the context of overanticoagulation, commonly known as anticoagulant-related nephropathy (ARN), is a relatively novel recognized entity. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to examine underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Method Spanish retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. The main outcome was to describe pathologic findings in kidney biopsy specimens of patients with clinical suspicion of ARN. The secondary outcome was to assess kidney outcomes during follow-up. Results Twenty-four patients were included with a median age of 76 years (interquartile range [IQR] 64-81) and a follow-up period of 10.1 (IQR 1.3-41.1) months. 79% were male, 22 (91%) had hypertension and 9 (37%) were diabetic. Most cases (91%) were on anticoagulation with vitamin K antagonists. At admission, 87% of cases presented gross hematuria with a median serum creatinine (SCr) of 4.2 mg/dl and a median INR of 2.3. During follow-up, median highest (peak) SCr was 6.3 mg/dl and 11 (45%) patients required acute dialysis. Kidney biopsy showed that all patients except one had an underlying nephropathy (confirmed IgA nephropathy in 16 [66.7%], probable IgA nephropathy in 2, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1). Tubules filled with red cells and red cell casts were observed in 66.7% of the cases and acute tubular necrosis in 70.8%. Management included anticoagulation withdrawal in 14 cases (58.3%) and immunosuppressive treatment with corticosteroids (n = 17 [70.8%]) and mycophenolic acid (n = 5 [20.8%]). At 12 weeks after discharge, 11 patients had &amp;gt;50% decrease in SCr (with respect to peak SCr), 6 had &amp;lt;50% decrease and 5 were on chronic dialysis. Conclusion IgA nephropathy was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

Anticoagulation after VA-ECMO decannulation, providing new insights

Abstract Funding Acknowledgements Type of funding sources: None. INTRODUCTION Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an essential tool for the management of refractory cardiogenic shock. Little is known about the incidence of thromboembolic events after V-A ECMO decannulation, although some studies report a high incidence of cannula-related venous thrombosis after venovenous extracorporeal membrane oxygenation (VV-ECMO). Due to this fact, in our institution anticoagulation therapy is systematically prescribed for at least 3 months after VA-ECMO per protocol. AIM The main objective of this study was to explore the feasibility of 3-month anticoagulation therapy after VA-ECMO decannulation. METHODS We performed a prospective study that included 27 consecutive patients who were successfully treated with VA-ECMO in a medical ICU between 2016 and 2019 and were prescribed 3-month anticoagulation therapy per protocol after decannulation. Exclusion criteria was dying on ECMO or while on the ICU. Data analysis included demographics, mean days on ECMO, 3-month survival, and thromboembolic and bleeding events (excluding immediate post-decannulation bleeding, since anticoagulation was prescribed 24h after). RESULTS Our cohort consisted mainly of men (N = 21, 78%), with a mean age of 60 ± 11 years and a mean time on VA-ECMO of 8 ± 3 days, who primarily suffered from post-cardiotomy cardiogenic shock (N = 9, 34%) or acute myocardial infarction (N = 6, 23%). 5 patients (18%) received a heart transplant. Regarding anticoagulation, 15 patients (60%) had other indications apart from the protocol, like incidental thrombus diagnosis (N = 7, 26%) or valve surgery (N = 5, 18%). Anticoagulation therapy was not feasible in 1 patient (4%) with severe thrombopenia. No patients had severe or life-threatening bleeding events in the follow-up, although 8 patients (30%) had bleeding events, mainly gastrointestinal bleeding (N = 4, 15%), requiring withdrawal of anticoagulation in 1 patient. The incidence of thromboembolic events was 7%; two patients with low-risk pulmonary embolisms. During the 3-month follow-up survival rate was 95%. CONCLUSIONS This is the only study to date addressing the strategy of 3-month anticoagulation therapy after VAECMO, showing it is feasible and safe and may be helpful in reducing or ameliorate thromboembolic complications in the follow-up, although it is not exempt of complications. Abstract Figure. Kaplan-Meier survival analysis

The RACE to the EAST. In pursuit of rhythm control therapy for atrial fibrillation-a dedication to Harry Crijns.

The RACE trial was one of the first landmark trials to establish whether restoring and maintaining sinus rhythm could reduce morbidity and mortality in patients with atrial fibrillation (AF). Its neutral outcome shaped clinical decision-making for almost 20 years. However, there were two important treatment-related factors associated with mortality of rhythm control therapy at that time: One was safety of antiarrhythmic drug therapy, and the other one withdrawal of anticoagulation after restoration of sinus rhythm. Both concerns have been overcome, and, moreover, important knowledge considering the importance of time for the treatment of AF has been gained. These insights led to the concept of the EAST-AFNET 4 trial, and after more than two decades in the pursuit of ongoing therapeutic improvement, early rhythm control therapy has demonstrated to reduce a composite of cardiovascular death, stroke, and hospitalization for worsening of HF or acute coronary syndrome, by 21% (first primary outcome, absolute reduction 1.1 per 100 patient-years). For this entire period, Harry Crijns characterized the treatment of AF patients, and contributed decisively to realizing the benefit of rhythm control therapy. It is almost easier to list the clinical trials without Harry's involvement than to list those which he co-designed and led.

Left Atrial Thrombus Mimicking Myxoma Secondary to Rebound Hypercoagulable State

Novel oral anticoagulants (NOACs) have made the use of anticoagulation in patients with atrial fibrillation (AFib) much more convenient and predictable. It is a very common practice to hold anticoagulation either in anticipation of surgical procedures (to prevent excessive bleeding) or in case of acute bleeding episodes. This abrupt withdrawal of anticoagulation tilts the balance in favor of pro-thrombotic state in the body. We present a case of a 60-year-old man with past medical history of AFib who abruptly discontinued his apixaban (Eliquis). This patient presented to emergency room with the complaint of weakness and numbness of left arm and left half of the face. Stroke code was activated, and patient received tissue plasminogen activator (t-PA). This resulted in significant improvement of symptoms within hours of receiving treatment. Later during the same day, patient developed numbness and tingling of fingers of left hand. On physical exam, left hand was cold to touch and radial pulse was absent. Arterial duplex revealed occluded ulnar and radial arteries. Vascular surgery performed embolectomy to establish blood flow in the radial and ulnar arteries. Transthoracic echocardiogram revealed large left atrial mass attached to the atrial septum. Most likely t-PA infusion in the setting of atrial mass led to distal showering of emboli resulting in stenosis of radial and ulnar arteries. The left atrial mass was most likely thrombus as patient had cardiac imaging including transthoracic echocardiogram and computed tomography of heart prior to these events which did not reveal any mass in left atrium. In short, as clinicians we should be aware of the hypercoagulability associated with withdrawal of anticoagulation. In addition, we should be wary of the challenges associated with differentiating cardiac masses of different etiology. J Med Cases. 2021;12(6):243-247 doi: https://doi.org/10.14740/jmc3656

A case of idiopathic acquired haemophilia - A with massive subcutaneous bleeding

We report a case of a 69-year-old male, a known epileptic on phenytoin for 40 years, presented with ecchymotic patches over the right upper and lower extremities. There was a history of right leg pain 3 weeks before presentation, when he was misdiagnosed as deep venous thrombosis (DVT) on the basis of venous Doppler at a nursing home. He was treated with low-molecular-weight heparin followed by acenocoumarol. Subsequently, he developed subcutaneous bleeding followed by sudden drop in haemoglobin, and anticoagulant measures were withheld. He continued to have fresh crops of ecchymosis even 10 days after withdrawal of anticoagulants; hence, he was shifted to our hospital. On evaluation, his activated partial thromboplastic time (APTT) was found elevated and anaemia was present, while prothrombin time and thrombin time were normal. His factor VIII level was identified as low (1%) and factor VIII inhibitor level was elevated. With diagnosis of acquired haemophilia A, he was treated with recombinant factor VII, steroid and cyclophosphamide. There was no cause identified for acquired haemophilia A, even after extensive work-up for malignancy, viral diseases, connective disorders and coagulating disorders. Hence, the diagnosis of idiopathic acquired haemophilia was considered.

Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion.

The withdrawal of oral anticoagulation (OAC) in patients with SLE and secondary aPL syndrome (SAPS) who become seronegative has not been clearly investigated to date. Our aim was to evaluate the prevalence of aPL seroconversion and the prognosis of SLE patients with SAPS who withdrew OAC after aPL negativization. We retrospectively analysed data of all SLE patients (ACR criteria) with SAPS (Sydney criteria) prospectively followed-up in our clinic. aPL seroconversion was defined as negativization of lupus anticoagulant, aCL, and anti-β2glycoprotein-1 antibodies on two or more consecutive measurements, at least 12 weeks apart. OAC discontinuation was defined as the definitive withdrawal of all anticoagulants. Fifty-five out of 513 (10.7%) SLE patients had vascular SAPS. Sixteen patients (29.1%) became aPL seronegative during follow-up. Immunosuppressive therapy predicted aPL negativization (odds ratio 5.211, 95%CI 1.341, 20.243), whereas APS diagnosis prior to that of SLE (odds ratio 0.078, 95%CI 0.008, 0.799) and triple-positive profile (odds ratio 0.264, 95%CI 0.115, 0.609) were negative predictors of aPL negativization. OAC was discontinued in 13/55 patients (23.6%), after a median follow-up of 45 months (range 1-276) from aPL seroconversion. SLE-related modifiable risk factors for thrombosis were observed in 10/13 patients (77%) at the time of the thrombotic event. No thrombotic recurrences were observed during a mean follow-up time of 44 (19) months from OAC discontinuation. Our results suggest that OAC can be safely discontinued in SLE patients who became persistently seronegative for aPL, at least when aPL-related thrombotic events occurred in presence of other thrombotic risk factors.

Antithrombotic Treatment after Atrial Fibrillation Ablation.

Atrial fibrillation is a major cause of debilitating strokes and anticoagulation is an established and indispensable therapy for reducing their rate. Ablation of the arrhythmia has emerged as a putative means of disrupting its natural course by isolating its triggers and modifying its substrate, dependent on the chosen method. An important dilemma lies in the need for continuation of anticoagulation therapy in those previously receiving it following an, apparently, successful intervention, purportedly preventing arrhythmia recurrence with considerably high rates. Current guidance, given scarcity of high-quality data from randomized trials, focuses on established knowledge and recommends anticoagulation continuation based solely on estimated thromboembolic risk. In the present review, it will be attempted to summarize the pathophysiological rationale for maintaining anticoagulation post-successful ablation, along with the latter's definition, including the two-fold effects of the procedure per se on thrombogenicity. Available evidence pointing to an overall clinical benefit of anticoagulation withdrawal following careful patient assessment will be discussed, including ongoing randomized trials aiming to offer definitive answers. Finally, the proposed mode of post-ablation anticoagulation will be presented, including the emerging, guideline-endorsed, role of direct oral anticoagulants in the field, altering cost/benefit ratio of anticoagulation and potentially affecting the very decision regarding its discontinuation.

Risk of recurrent venous thromboembolism in patients with HIV infection: A nationwide cohort study.

Multiple studies have described a higher incidence of venous thromboembolism (VTE) in people living with an HIV infection (PWH). However, data on the risk of recurrent VTE in this population are lacking, although this question is more important for clinical practice. This study aims to estimate the risk of recurrent VTE in PWH compared to controls and to identify risk factors for recurrence within this population. PWH with a first VTE were derived from the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort (2003-2015), a nationwide ongoing cohort following up PWH in care in the Netherlands. Uninfected controls were derived from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) follow-up study (1999-2003), a cohort of patients with a first VTE who initially participated in a case-control study in the Netherlands who were followed up for recurrent VTE. Selection was limited to persons with an index VTE suffering from deep vein thrombosis in the lower limbs and/or pulmonary embolism (PE). Participants were followed from withdrawal of anticoagulation to VTE recurrence, loss to follow-up, death, or end of study. We estimated incidence rates, cumulative incidence (accounting for competing risk of death) and hazard ratios (HRs) using Cox proportional hazards regression, adjusting for age, sex, and whether the index event was provoked or unprovoked. When analyzing risk factors among PWH, the main focus of analysis was the role of immune markers (cluster of differentiation 4 [CD4]+ T-cell count). There were 153 PWH (82% men, median 48 years) and 4,005 uninfected controls (45% men, median 49 years) with a first VTE (71% unprovoked in PWH, 34% unprovoked in controls) available for analysis. With 40 VTE recurrences during 774 person-years of follow-up (PYFU) in PWH and 635 VTE recurrences during 20,215 PYFU in controls, the incidence rates were 5.2 and 3.1 per 100 PYFU (HR: 1.70, 95% CI 1.23-2.36, p = 0.003). VTE consistently recurred more frequently per 100 PYFU in PWH in all predefined subgroups of men (5.6 versus 4.8), women (3.6 versus 1.9), and unprovoked (6.0 versus 5.2) or provoked (3.1 versus 2.1) first VTE. After adjustment, the VTE recurrence risk was higher in PWH compared to controls in the first year after anticoagulant discontinuation (HR: 1.67, 95% CI 1.04-2.70, p = 0.03) with higher cumulative incidences in PWH at 1 year (12.5% versus 5.6%) and 5 years (23.4% versus 15.3%) of follow-up. VTE recurred less frequently in PWH who were more immunodeficient at the first VTE, marked by a better CD4+ T-cell recovery on antiretroviral therapy and during anticoagulant therapy for the first VTE (adjusted HR: 0.81 per 100 cells/mm3 increase, 95% CI 0.67-0.97, p = 0.02). Sensitivity analyses addressing potential sources of bias confirmed our principal analyses. The main study limitations are that VTEs were adjudicated differently in the cohorts and that diagnostic practices changed during the 20-year study period. Overall, the risk of recurrent VTE was elevated in PWH compared to controls. Among PWH, recurrence risk appeared to decrease with greater CD4+ T-cell recovery after a first VTE. This is relevant when deciding to (dis)continue anticoagulant therapy in PWH with otherwise unprovoked first VTE.

Risk of Recurrence After Withdrawal of Anticoagulation in Patients With Unprovoked Venous Thromboembolism: External Validation of the Vienna Nomogram and the Dash Prediction Score

IntroductionScales for predicting venous thromboembolism (VTE) recurrence are useful for deciding the duration of the anticoagulant treatment. Although there are several scales, the most appropriate for our setting has not been identified. For this reason, we aimed to validate the DASH prediction score and the Vienna nomogram at 12 months. MethodsThis was a retrospective study of unselected consecutive VTE patients seen between 2006 and 2014. We compared the ability of the DASH score and the Vienna nomogram to predict recurrences of VTE. The validation was performed by stratifying patients as low-risk or high-risk, according to each scale (discrimination) and comparing the observed recurrence with the expected rate (calibration). ResultsOf 353 patients evaluated, 195 were analyzed, with an average age of 53.5±19 years. There were 21 recurrences in 1 year (10.8%, 95% CI: 6.8%–16%). According to the DASH score, 42% were classified as low risk, and the rate of VTE recurrence in this group was 4.9% (95% CI: 1.3%–12%) vs. the high-risk group that was 15% (95% CI: 9%–23%) (P<.05). According to the Vienna nomogram, 30% were classified as low risk, and the rate of VTE recurrence in the low risk group vs. the high risk group was 4.2% (95% CI: 0.5%–14%) vs. 16.2% (95% CI: 9.9%–24.4%) (P<.05). ConclusionsOur study validates the DASH score and the Vienna nomogram in our population. The DASH prediction score may be the most advisable, both because of its simplicity and its ability to identify more low-risk patients than the Vienna nomogram (42% vs. 30%).

Circumstances of provoked recurrent venous thromboembolism: the Austrian study on recurrent venous thromboembolism

Patients with unprovoked deep-vein thrombosis (DVT) of the leg or pulmonary embolism (PE) have a high recurrence risk. How often these recurrences are provoked by a temporary risk condition is unknown. In a cohort of patients with unprovoked venous thromboembolism (VTE), we evaluated the clinical circumstances of recurrence. We studied patients with DVT of the leg and/or PE. End point was recurrence of objectively verified symptomatic VTE. Provoked recurrence was defined according to guidance criteria. 1188 patients were followed for a median of 8.9 years after withdrawal of oral anticoagulants. 312 patients had recurrent VTE, which was provoked in 42 (13%). Recurrence was related to a major risk factor in 19, to a minor risk factor in 22, and to a persistent risk factor in one patient(s). 14 recurrences occurred after major surgery and 5 during hospitalization. Ten recurrences occurred after minor surgery, eight after trauma and three during female hormone intake. Four recurrences occurred during heparin prophylaxis. The incidence of provoked VTE recurrence appears to be low. VTE can recur when prevention is stopped or even during thromboprophylaxis. Surgery and trauma are frequent risk factors.

Risk Factors for Delayed Bleeding after Therapeutic Gastrointestinal Endoscopy in Patients Receiving Oral Anticoagulants: A Multicenter Retrospective Study

Background/Aims: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. Methods: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. Results: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. Conclusion: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.

Fatal Leaflet Thrombus Following Transcatheter Aortic Valve Replacement During Temporary Anticoagulation Withdrawal

A 91-year-old woman underwent transcatheter aortic valve replacement (TAVR) due to severe aortic stenosis (23-mm Sapien 3, Edwards Lifesciences, Irvine, California). She was on apixaban (2.5 mg twice daily) as an antithrombotic therapy due to atrial fibrillation. She was admitted to our hospital

D-dimer levels during and after anticoagulation withdrawal in patients with venous thromboembolism treated with non-vitamin K anticoagulants.

BackgroundD-dimer levels measured during and after vitamin K antagonist withdrawal may be used in clinical practice to assess the individual risk of recurrent venous thromboembolism. Currently, direct oral anticoagulants (DOACs) are frequently used in venous thromboembolism treatment; however, their pharmacokinetics and pharmacodynamics characteristics are completely different than vitamin K antagonists. The present study aimed at comparing the results of D-dimer levels during and after anticoagulation withdrawal in patients with venous thromboembolism treated with DOACs or warfarin.Material and methodsD-dimer levels were measured in 527 patients (“cases”) during DOACs treatment (T0) and after 15 (T15), 30 (T30), 60 (T60) and 90 (T90) days after their discontinuation and in 527 patients (“controls”) enrolled in the DULCIS study (all treated with warfarin), matched for sex, age (+/-3 y), type of D-dimer assay and site of venous thromboembolism. Both cases and controls received anticoagulant treatment after a first venous thromboembolism event that was unprovoked or associated with weak risk factors.ResultsThe rate of positive D-dimer results was significantly higher in cases than in controls at T0 (10.8% vs 5.1%, p = 0.002) and at T30 (18.8% vs 11.8%, p = 0.019), as well as at the other time-points, though not statistically significant.ConclusionD-dimer levels during and after stopping an anticoagulant treatment for a venous thromboembolism episode differ between patients treated with a DOAC than in those treated with warfarin. Specifically designed prospective studies are warranted to reassess the use of D-dimer as predictor of the risk of recurrent venous thromboembolism in patients treated with DOACs.

ECMO without anticoagulation in patients with disease-related severe thrombocytopenia: Feasible but futile?

Severe thrombocytopenia poses a high risk for bleeding thus representing a relative contraindication for anticoagulation and therefore extracorporeal membrane oxygenation (ECMO). We herein report on a series of immunocompromised patients with severe thrombocytopenia undergoing long-term ECMO without systemic anticoagulation. We retrospectively identified seven adult patients with anticoagulation withdrawal for ≥3 days (range 5-317) during venovenous ECMO therapy due to thrombocytopenia < 50 G/L treated in a university-affiliated hospital from January 2013 to April 2017. All ECMO systems used were heparin coated. Overall, 530 ECMO days were observed, 404 (76%) of them without systemic anticoagulation. Platelet count during ECMO treatment was 24 G/L (median, range 1-138), ECMO duration was 35 days (5-317), and ECMO was run without any anticoagulation for 20 days (5-317). Altogether, five clotting events were seen leading to oxygenator exchanges. Bleeding was common including one fatal intracerebral hemorrhage. Altogether, 29 platelet concentrates per patient (7-207) were administered, which correspond to 0.8 per day (0.6-1.3). One patient survived ICU and hospital. In patients with thrombocytopenia, ECMO can be run without anticoagulation even for considerably long periods of time. Bleeding remains common, while clotting events seem to be rare. However, prognosis of this patient population undergoing ECMO support seems grim.

Drug Management in End-of-Life Hospitalized Palliative Care Cancer Patients: The RHESO Cohort Study

Objective: Little data about the management of drugs in terminally ill palliative care cancer patients is available. The present study aimed at describing the evolution of anticancer and non-anticancer treatments (NACTs) in cancer patients in palliative care units. The second objective was to identify factors leading to the medical decision to withdraw or not NACTs. Methods: Data from 1,091 cancer patients hospitalized in palliative care units were prospectively collected in 2010–2011, through a multicenter, observational French cohort. Results: The median overall survival after admittance in palliative care units was 15 days. Specific anticancer treatments were systematically stopped in the first 24 h in palliative care units, but for 4.5% of patients. Regarding NACTs, patients were heavily treated with strong opioids (74%), corticosteroids (51%), and antidepressants (21.8%) until death. Antiulcer agents (63.4%), antibiotics (25.7%), thrombosis prevention (21.8%), antidiabetics (7.6%), and transfusions (4%) were often also continuously prescribed. In multivariate analysis, ECOG PS 4 was an independent predictor of continuous prescription of morphine and an independent predictor of discontinuation of corticosteroids, proton-pump inhibitors, antidiabetics, and preventive anticoagulant therapy. Infection symptoms independently predicted continuous prescription of paracetamol. Paralysis and cancer palpable mass independently predicted corticosteroid withdrawal. Brain metastases independently predicted antiulcer withdrawal. Hemorrhage independently predicted preventive anticoagulant withdrawal. Availability to a venous access independently predicted paracetamol and antiulcer continuous prescriptions. Co-prescriptions independently predicted continuous prescriptions (antibiotics with antiulcer, antifungals with antibiotics) or withdrawal (preventive anticoagulant with antiplatelets and antifungals). Conclusions: NACT prescription remained commonplace in terminally ill palliative cancer patients, although their benefit is questionable.

A Trial of Complete Withdrawal of Anticoagulation Therapy in the Heartmate 3 Pump

Summary of Objectives The HeartMate 3 Left Ventricular Assist System has demonstrated absence of confirmed de-novo pump thrombosis and reduction in stroke. However, bleeding related adverse events persist under standard anticoagulation targeting a INR range of 2.0-3.0. In an initial experience we demonstrated safety of transition to low intensity anticoagulation (INR target 1.5-1.9, n=15, follow up of at least 6 months). Whether complete cessation of anticoagulation maintains “thromboresistance” in the HeartMate 3 pump remains unknown. Methods We previously reported on a strategy of low-intensity warfarin anticoagulation in patients implanted with HeartMate 3 (J Heart Lung Transplant. 2018;37(5):579-586). Following completion of this study phase, a staged trial was approved by the single site's ethics committee and registered as NCT03704220. All patients enrolled in the low intensity warfarin study (target INR of 1.5-1.9) were considered eligible for enrollment in the “anticoagulation withdrawal” study, if they were continuing on long-term support. All patients had to meet safe eligibility criteria including pump speed reduction to facilitate aortic valve opening (to avoid root thrombus), absence of thrombus in the pre-pump cardiac system, and absence of signs of poor unloading at reduced device speed. Careful surveillance for pump thrombosis was algorithmically mandated with biomarker and serial pump log file analyses. If enrolled, they were withdrawn from warfarin therapy and followed for survival free of pump thrombosis, disabling stroke or major bleeding for at least 3 months as the primary safety end point. Endpoints Enrollment and follow up in the low intensity anticoagulation study has been reported (n=15); 13 men, mean age 57 years (18-72), with intended goal of therapy of either BTT or DT, INTERMACS Profile mean 3 (2-5), Cardiac Index mean 1.62 l/min/m2. Of 10 patients followed beyond 1 year on reduced anticoagulation, 5 patients have qualified for complete withdrawal of anticoagulation and the safety endpoint analysis will be completed prior to the ISHLT meeting in March 2019. This pivotal study is the first indication-independent anticoagulation withdrawal study in the HeartMate 3 designed to establish thrombo-resistance for the device and form the rationale for a large scale multicenter trial.

Abstract TP226: Impact of Non-Vitamin K Antagonist Oral Anticoagulant Withdrawal on Stroke Outcomes

Introduction: Discontinuation of antithrombotics can be associated with an increased risk of cardiovascular events and poor outcomes. Abrupt warfarin withdrawal may also induce a rebound or a paradoxical prothrombotic state, subsequently leading to an increased incident risk of stroke for up to 3 months. Hypothesis: Considering the potent anticoagulant effect of non-vitamin K oral anticoagulants (NOACs) on the suppression of thrombogenesis, NOAC withdrawal may be associated with profound hypercoagulable state, leading to severe stroke and poor outcomes in patients with non-valvular atrial fibrillation (NVAF) related stroke. The aim of this study was to compare the initial stroke severity and functional outcome associated with NOAC withdrawal to those associated with other prior medication statuses including warfarin withdrawal in patients with NVAF. Methods: A total of 719 patients with ischemic stroke or transient ischemic attack and NVAF who were admitted at five regional hospitals between January 2013 and December 2016 were included. Prior medication status was categorized into seven groups such as no antithrombotics, antiplatelet-only, warfarin with a subtherapeutic intensity, warfarin with a therapeutic intensity, NOAC, warfarin withdrawal, and NOAC withdrawal. We compared initial National Institute of Health Stroke Scale (NIHSS) scores between groups. Results: The mean age was 73.9 ±10.2 years, and 397 (55.2%) patients were men. Median CHA 2 DS 2 -VASc score was 4 (interquartile range [IQR] 3-5). Among 719 patients, the NOAC withdrawal group had the highest median NIHSS scores at stroke onset (16, interquartile range, IQR [4-20]), followed by the warfarin withdrawal group (11, IQR [3-17]), the no antithrombotic group (5, IQR [2-16]), and the warfarin with subtherapeutic intensity group (5, IQR [2-13]). Multivariable analysis demonstrated that NOAC withdrawal was independently associated with higher NIHSS scores at stroke onset (B 4.645, 95% CI 0.384-8.906, P=0.033). Conclusions: Stroke occurred after discontinuing oral anticoagulants, particularly NOAC, was independently associated with severe stroke severity.