Duration Of Anticoagulation Research Articles

Treatment of catheter-related thrombosis in patients with hematologic malignancies: A Venous thromboEmbolism Network U.S. retrospective cohort study

IntroductionOptimal treatment of catheter-related thrombosis (CRT) is uncertain in patients with hematologic malignancy. We aimed to evaluate the treatment strategies, outcomes, and predictors of recurrent venous thromboembolism (VTE) associated with catheter-related thrombosis (CRT) in patients with hematologic malignancy. MethodsWe performed a multicenter retrospective cohort study of eight institutions through the Venous thromboEmbolism Network US. Patients with hematologic malignancies with documented CRT were identified using ICD-9 and ICD-10 diagnostic codes. Semi-competing risks proportional hazard regression models were created. Results and conclusionsOf the 663 patients in the cohort, 124 (19%) were treated with anticoagulation alone, 388 (58%) were treated with anticoagulation and catheter removal, 119 (18%) treated with catheter removal only, and 32 (5%) had neither catheter removal nor anticoagulation. 100 (15%) patients experienced a recurrent VTE event. In the 579 patients who had catheter removal, the most common reason for catheter removal was the CRT [392 (68%)]. For subjects who received any anticoagulation (n = 512), total anticoagulation duration was not associated with VTE recurrence [1.000 (0.999–1.002)]. After adjustment patients treated with catheter removal only had an increased risk of VTE recurrence [2.50 (1.24–5.07)] and death [4.96 (2.47–9.97)]. Patients with no treatment had increased risk of death [16.81 (6.22–45.38)] and death after VTE recurrence [27.29 (3.13–238.13)].In this large, multicenter retrospective cohort, we found significant variability in the treatment of CRT in patients with hematologic malignancy. Treatment without anticoagulation was associated with recurrent VTE.

POS-570 ATRIAL FIBRILLATION AND HAEMODIALYSIS: AN AUDIT OF ANTI-COAGULATION PRESCRIBING IN AN IRISH HOSPITAL.

The objective of this audit was to evaluate prescribing of anti-coagulants for atrial fibrillation in haemodialysis patients in St. Vincent’s University Hospital. The prevalence of AF is between 8 and 34 percent in patients on haemodialysis1. End stage renal disease patients were excluded from key trials evaluating direct-acting oral anticoagulants (DOACs) in AF. Nevertheless when compared to warfarin DOACs have similar or superior efficacy, less bleeding risk, and more predictable pharmacokinetic and pharmacodynamic properties2. American Heart Association guidelines have altered to reflect this and now recommend apixaban in this patient group. Patients were included if prescribed warfarin or any DOAC for the indication of atrial fibrillation on September 1st 2020. Patients were excluded if actively awaiting transplant. Patient characteristics including age, sex, weight, anti-coagulant, CHA2DS2VASc score, HAS-BLED score, INR, concurrent antiplatelet, anticoagulant on dialysis, duration of anticoagulation and bleeding events during that time were recorded. Data was collected from SVUH Clinical Portal admission records and the EMED renal database. Data analysis was completed using SPSS. Eleven patients met inclusion criteria (Table 1). Seven patients were prescribed apixaban and four warfarin. No other DOACs were prescribed. Of those patients prescribed warfarin the percentage of INR values in the sub and supra-therapeutic ranges varied from 22-38% and 2-13% respectively. One patient in the DOAC group had a recorded bleed (GI, non-fatal requiring transfusion) event and one patient was prescribed an inappropriately high dose of apixaban. View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Patients with ESRD possess both a prothrombotic state predisposing to a high risk of thromboembolism and a coagulopathy with an increased tendency for bleeding3, 4. Prudence is required when deciding whether or not to anti-coagulate5. When anticoagulation is necessary the preferred choice is Apixaban, prescribed at the appropriate dose. The CHA2DS2VASc and HAS-BLED scores are useful guides. This audit identified four patients where a switch to apixaban may be appropriate and one patient where the apixaban dose should be reduced. This audit is too small to comment on risk of bleeding events, although it is noted that one patient had a recorded non-fatal bleed event requiring hospitalisation.

Dalteparin and Rivaroxaban Sequential Use in Cancer Patients with Venous Thromboembolism

To determine the effect and safety of sequential treatment with the low-molecular-weight heparin dalteparin and the direct oral anticoagulants rivaroxaban in patients with cancer- associated venous thromboembolism (VTE). Observational study. Department of Oncology, the Second Affiliated Hospital of Soochow University, between January 2017 and September 2019. Patients with active cancer, diagnosed with VTE and who received sequential treatment with dalteparin and rivaroxaban, were retrospectively reviewed. Logistic regression analysis was used to identify risk factors associated with VTE recurrence. Ninety-nine patients with active cancer were enrolled in the study. The median delteparin treatment time was nine days (5-20 days), and 2.8 months (1-6 months) for rivaroxaban. Sixty (60.6%) patients had eliminated VTE, and 39 (39.4%) had persistent VTE, but with relieved symptoms. No major bleeding was observed. Eleven (11.1%) patients had minor bleeding, including melena (5.1%), hematuria (3.0%), vaginal bleeding (1.0%), gingival bleeding (1.0%), and subcutaneous hemorrhage (1.0%). During the 6 months follow-up period, one (1.0%) developed pulmonary embolism, and seven (7.1%) experienced recurrent VTE. Univariate logistic regression analysis showed that bleeding occurrence and anticoagulant treatment duration were the two significant factors affecting VTE recurrence (p<0.05). Maintenance of rivaroxaban after initial dalteparin treatment could effectively reduce the risk of VTE recurrence and was well tolerated by patients with cancer-associated VTE. However, in the clinical practice, the treatment duration is often insufficient, so it is essential to follow-up these patients to ensure sufficient treatment time. Key Words: Venous thromboembolism, Low-molecular-weight heparins, Directly oral anticoagulants, Cancer.

Incidence and predictors of splanchnic vein thrombosis and mortality following hepatobiliary and pancreatic surgery

BackgroundIntraabdominal surgery is a known risk factor for splanchnic vein thrombosis (SVT). SVT incidence, management, and prognosis after hepatopancreatobiliary surgery are unknown. ObjectivesTo determine the incidence and prognosis of SVT following hepatopancreatobiliary surgery and describe current practices in anticoagulation for postoperative SVT. Patients/MethodsMulticenter retrospective cohort study of adults undergoing hepatopancreatobiliary surgery. Multivariable analyses for predictors of SVT, major bleeding, and 90‐day mortality were performed. ResultsOf 1815 patients included, 89 (4.9%) had cirrhosis and 1532 (84.4%) had active cancer. The most frequent surgeries were pancreaticoduodenectomy (40.6%), open (30.7%), and laparoscopic (11.0%) liver resection. Sixty (3.3%) patients experienced SVT within 90 days of surgery. Among patients with SVT, 23.3% were symptomatic and 75.0% were treated with therapeutic anticoagulation. Planned duration of anticoagulation averaged 3 to 6 months. By multivariable analysis, SVT predictors were: operative time (adjusted odds ratio [aOR] per hour increase 1.32, 95% confidence interval [CI] 1.20‐1.46), cirrhosis (aOR 3.22, 95% CI 1.28‐8.10), and postoperative intraabdominal infection (aOR 2.99, 95% CI 1.72‐5.19). Postoperative major bleeding occurred in 22.1% of patients and 4.0% died within 90 days. Predictors of postoperative mortality were age (aOR per 10‐year increase 1.79, 95% CI 1.38‐2.30), operative time (aOR 1.31 (1.17‐1.45), cirrhosis (aOR 4.42, 95% CI 1.96‐9.96), postoperative intraabdominal infection (aOR 2.66, 95% CI 1.55‐4.57), postoperative major bleeding (aOR 4.12, 95% CI 2.36‐7.30), and postoperative SVT (aOR 3.15, 95% CI 1.42‐6.97). ConclusionSVT occurred in 1 in 30 patients after hepatopancreatobiliary surgery and was associated with a 3‐fold independent increase in 90‐day mortality.

Venous thromboembolism in solid-organ transplant recipients: Findings from the RIETE registry

BackgroundVenous thromboembolism (VTE) represents a relevant cause of morbidity in patients with solid-organ transplant (SOT), but there are scarce data on the management and outcomes in these patients. MethodsRIETE is a worldwide, ongoing observational registry of patients with objectively confirmed, acute VTE. We used the RIETE database to compare the clinical characteristics, treatment and outcomes in SOT recipients vs. non-recipients. ResultsFrom January 2001 to December 2019, 83,210 patients were enrolled in RIETE. Of these, 329 (0.4%) were SOT recipients: in the kidney 221, liver 41, lung 28 and heart 25. Median duration of anticoagulation was similar in SOT recipients and non-recipients (174 vs. 182 days). During anticoagulation, 1180 patients developed deep vein thrombosis (DVT) recurrences, 1028 pulmonary embolism (PE) recurrences, 2392 had major bleeding, 3119 non-major bleeding and 8157 died. SOT recipients had a higher rate of major bleeding (hazard ratio [HR]: 2.55; 95% CI: 1.62–3.84) and clinically relevant non-major bleeding (HR: 1.94; 95% CI: 1.23–2.93) than non-recipients, with no differences in the rates of DVT recurrences (HR: 0.96; 95% CI: 0.30–2.32), PE recurrences (HR: 1.11; 95% CI: 0.35–2.67) or death (HR: 0.98; 95% CI: 0.67–1.40). On multivariable analysis, only liver transplant recipients were at an increased risk for major bleeding compared to non-recipients (adjusted HR: 3.17; 95% CI: 1.02–9.87). ConclusionsTreatment of VTE in SOT recipients is associated with an increased risk of bleeding compared to non-recipients. This is mainly due to the influence of liver transplant recipients. In non-liver SOT recipients, the risk for bleeding was similar to that in non-recipients.

Predictors for blood loss and transfusion frequency to guide blood saving programs in primary knee- and hip-arthroplasty

Endoprosthetic surgery can lead to relevant blood loss resulting in red blood cell (RBC) transfusions. This study aimed to identify risk factors for blood loss and RBC transfusion that enable the prediction of an individualized transfusion probability to guide preoperative RBC provision and blood saving programs. A retrospective analysis of patients who underwent primary hip or knee arthroplasty was performed. Risk factors for blood loss and transfusions were identified and transfusion probabilities computed. The number needed to treat (NNT) of a potential correction of preoperative anemia with iron substitution for the prevention of RBC transfusion was calculated. A total of 308 patients were included, of whom 12 (3.9%) received RBC transfusions. Factors influencing the maximum hemoglobin drop were the use of drain, tranexamic acid, duration of surgery, anticoagulation, BMI, ASA status and mechanical heart valves. In multivariate analysis, the use of a drain, low preoperative Hb and mechanical heart valves were predictors for RBC transfusions. The transfusion probability of patients with a hemoglobin of 9.0–10.0 g/dL, 10.0–11.0 g/dL, 11.0–12.0 g/dL and 12.0–13.0 g/dL was 100%, 33.3%, 10% and 5.6%, and the NNT 1.5, 4.3, 22.7 and 17.3, while it was 100%, 50%, 25% and 14.3% with a NNT of 2.0, 4.0, 9.3 and 7.0 in patients with a drain, respectively. Preoperative anemia and the insertion of drains are more predictive for RBC transfusions than the use of tranexamic acid. Based on this, a personalized transfusion probability can be computed, that may help to identify patients who could benefit from blood saving programs.

Venous Thromboembolism in Pediatric Inflammatory Bowel Disease: A Case-Control Study.

Inflammatory bowel disease (IBD) is associated with increased risk of venous thromboembolism (VTE). Despite this recognized risk, there are limited data and no anticoagulation guidelines for hospitalized pediatric IBD patients. The objectives of this study were to characterize pediatric IBD patients with VTE and determine risk factors. This was a nested case-control study comparing hospitalized children with IBD diagnosed with VTE to those without VTE over a decade at a large referral center. Standard descriptive statistics were used to describe the VTE group. Multivariable conditional logistic regression was used to assess risk factors. Twenty-three cases were identified. Central venous catheter (CVC) presence (odds ratio [OR] 77.9; 95% confidence interval [CI]: 6.9--880.6; P < 0.001) and steroid use (OR 12.7; 95% CI: 1.3--126.4; P = 0.012) were independent risk factors. Median age at VTE was 17 years (interquartile range [IQR] 13.5--18.2), and in 48%, VTE was the indication for admission. Median duration of anticoagulation was 3.8 months (IQR 2.3--7.6), and there were no major bleeding events for patients on anticoagulation. There were no patients with known sequelae from VTE, though 22% had severe VTE that required interventions. Pediatric patients with IBD are at risk for VTE, although the absolute risk remains relatively low. The safety and efficacy of pharmacologic thromboprophylaxis needs to be further evaluated in this population with attention to risk factors, such as steroid use and presence of CVC.

Consenso multidisciplinar para el manejo de la tromboembolia de pulmón

We have updated recommendations on 12 controversial topics that were published in the 2013 National Consensus on the diagnosis, risk stratification and treatment of patients with pulmonary embolism (PE). A comprehensive review of the literature was performed for each topic, and each recommendation was evaluated in two teleconferences. For diagnosis, we recommend against using the Pulmonary Embolism Rule Out Criteria (PERC) rule as the only test to rule out PE, and we recommend using a D-dimer cutoff adjusted to age to rule out PE. We suggest using computed tomography pulmonary angiogram as the imaging test of choice for the majority of patients with suspected PE. We recommend using direct oral anticoagulants (over vitamin K antagonists) for the vast majority of patients with acute PE, and we suggest using anticoagulation for patients with isolated subsegmental PE. We recommend against inserting an inferior cava filter for the majority of patients with PE, and we recommend using full-dose systemic thrombolytic therapy for PE patients requiring reperfusion. The decision to stop anticoagulants at 3 months or to treat indefinitely mainly depends on the presence (or absence) and type of risk factor for venous thromboembolism, and we recommend against thrombophilia testing to decide duration of anticoagulation. Finally, we suggest against extensive screening for occult cancer in patients with PE.

The association of fracture risk in atrial fibrillation patients and long-term anticoagulant therapy category: a systematic review and meta-analysis.

ObjectiveOur study aimed to assess the risk of all fractures and hip fractures in patients with atrial fibrillation (AF) who took non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin.MethodsWe searched PubMed, Embase, and Cochrane Library and Clinical Trials.gov Website. Reviewed related researches up to January 31, 2020, to identify studies with more than 12 months of follow-up data. The protocol for this systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO Number: CRD42020156893).ResultsWe included five RCT studies, and five observational studies that contained a total of 326,846 patients in our meta-analysis. Our meta-analysis showed that patients taken NOACs had no significant all fracture risk (RR = 0.91, 95% CI [0.81–1.01]) and hip fracture risk (RR = 0.92, 95% CI [0.82–1.03]) compared with those taken warfarin. Subanalysis showed that the risk of all fractures and hip fractures treated by NOACs were significant lower compared with warfarin in observational studies compared with RCT studies. Also, a subanalysis across the duration of anticoagulation showed the NOACs users have lower all fracture risk than warfarin users when the duration of anticoagulation ≤2 years (RR = 0.89, 95% CI [0.80–0.99]). Further analysis, significant lower all fracture risk in the rivaroxaban therapy (RR = 0.81; 95% CI [0.76–0.86]) compared with warfarin but no statistical significance in hip fracture. There were no significant difference of all fracture risk and hip fracture risk in dabigatran, apixaban, and edoxaban therapy compared with warfarin.ConclusionThe meta-analysis demonstrated that NOACs associated with a significantly lower all fracture risk compared with warfarin when the duration of anticoagulation more than 2 years. Rivaroxaban users had lower risk of all fracture than warfarin users in AF patients. But there was no evidence to verify apixaban, edoxaban, and dabigatranin could decrease all fracture and hip fracture risk compared with warfarin.

Assessment of provider practices regarding venous thromboembolism management and prevention in pediatric acute leukemia patients.

Despite the known occurrence of venous thromboembolism (VTE) in the pediatric oncology population, there are no leukemia-specific VTE treatment guidelines. The primary objective of this study was to assess current practices regarding the management and prevention of VTE in the pediatric acute lymphoblastic leukemia (ALL) population. We performed a cross sectional, anonymous, electronic survey of members of the American Society of Hematology and the pediatric subcommittee of VENUS (VTE Network US of the Hemostasis and Thrombosis Research Society). Survey items included questions on demographics and clinical practice. Of 870 surveys distributed, 154 were submitted, giving a 17.7% response rate. Treatment duration, re-imaging timeline, and class of anticoagulants used were reported for catheter-associated deep vein thrombus, pulmonary embolism, and cerebral venous sinus thrombosis. While there are some common themes regarding VTE management, there is notable variation in the overall practice as well as with the decision to continue anticoagulation in the presence of thrombocytopenia. Given the variation seen, a multi-center, prospective clinical trial is urgently needed for developing consensus guidelines for the management of VTE in children with ALL.

Prediction models for recurrence and bleeding in patients with venous thromboembolism: A systematic review and critical appraisal

IntroductionPrediction models for recurrence and bleeding are infrequently used when deciding on anticoagulant treatment duration after venous thromboembolism (VTE) due to concerns about performance and validity. Our aim was to critically appraise these models by systematically summarizing data from derivation and validation studies. Materials and methodsMEDLINE and CENTRAL were searched until November 15th, 2019. Studies on prediction models for recurrence or bleeding after at least 3 months of anticoagulation in adult patients with VTE were included. The PROBAST, ROBINS-I and RoB2 tools were used to assess risk of bias and applicability. ResultsSelection yielded 18 studies evaluating 8 models for recurrence (7 on development; 9 on validation; 1 update). Generally, models for recurrent VTE appeared to perform poorly to moderately in external validation studies (C-statistics 0.39–0.66, one 0.83). However, impact studies show that HERDOO2 and Vienna prediction model may identify patients with unprovoked VTE at low recurrence risk. Sixteen studies evaluating 14 models for anticoagulation-related bleeding were identified (7 on development; 9 on validation). Although some models seemed promising in development studies, their predictive performance was poor to moderate in external validation (C-statistics 0.52–0.71). All but 3 studies were considered at high risk of bias, mainly due to limitations in the statistical analysis. ConclusionsPrognostic models for recurrence and anticoagulation-related bleeding risk often have important methodological limitations and insufficient predictive accuracy. These findings do not support their use in clinical practice to weigh risks of recurrence and bleeding when deciding on continuing anticoagulation after initial treatment of VTE.

Clinical controversies in the treatment of cancer-associated venous thromboembolism.

Cancer-associated venous thromboembolism (VTE) is a common complication of malignancy. Patients with cancer exhibit risk factors for both recurrent VTE and major or minor bleeding. Direct oral anticoagulants (DOACs) are an attractive treatment option; however, there is a lack of consensus among national guidelines for choice between DOACs and LMWH, agent selection, dosing strategy, and duration of anticoagulation. Characteristics of the thrombotic event, the malignancy, the patient, and the anticoagulant must be considered. A systematic search of online databases was performed to identify literature on the management of cancer-associated VTE. Multiple controversies remain surrounding the optimal treatment of cancer-associated VTE.

Anticoagulation Duration After First Venous Thromboembolism: Real-Life Data From the International, Observational WHITE Study.

BackgroundInternational guidelines recommend at least three months anticoagulation in all patients after acute venous thromboembolism (VTE) and suggest those with unprovoked events be considered for indefinite anticoagulation if the risk of recurrence is high and the risk of bleeding during treatment non-high. Other authors have recently argued against using a dichotomy unprovoked/provoked events to decide on anticoagulation duration and suggest instead using overall risk factors present in each patient as the basis for deciding.AimThis sub-analysis of the WHITE study aimed at assessing the reasons for the treatment decisions taken by doctors in different countries.Results1240 patients were recruited in 7 countries (China, Czechia, Poland, Portugal, Russia, Slovakia, and Tunisia). Anticoagulation was extended in 51.7% and 49.3% of patients with unprovoked or provoked events (n.s.); stopped in 15.4% versus 28.9% (P < .0001), and changed to antithrombotic drugs (sulodexide or aspirin) in 32.9% versus 21.8% (P < .0001). In the 430 subjects with isolated distal deep vein thrombosis (IDDVT) anticoagulation was stopped in 34.4%, continued in 37.0% (mainly those with post-thrombotic syndrome [PTS]) and switched to antithrombotics in the balance. High risk of recurrence was the most prevalent reason (>83% of cases) given to continue anticoagulation, regardless of nature and site of the index events, followed by risk of bleeding and presence of PTS signs.ConclusionOn average, attending physicians estimated the risk of recurrence in real life conditions, and the consequent therapeutic decision, using all the information available, not limiting to the location or nature of the index event.

Risk assessment of recurrent venous thromboembolism

Venous thromboembolism (VTE) recurrence risk is determined by risk factors that were present at the time of the initial VTE episode. The most significant determinant of risk for recurrent VTE is whether the VTE occurred in the setting of provoked or unprovoked condition. As anticoagulation reduces the risk of recurrent VTE, initial anticoagulant treatment at the time of VTE diagnosis is indicated with consideration given to an associated risk of bleeding. After three months of initial anticoagulation, recurrence risk and bleeding risk should be assessed again to decide if anticoagulation should be stopped or continued indefinitely. If indefinite anticoagulation is recommended, annual assessment of both risks should guide decisions about further treatment. Knowledge about the various risk factors for VTE recurrence and the risk factors for bleeding associated with anticoagulation should guide anticoagulant duration.

Impact of Chemoprophylaxis on Thromboembolism Following Operative Fixation of Pelvic Fractures

Venous thromboembolism (VTE) is a common cause of serious morbidity and mortality. While chemoprophylaxis decreases VTE, there is the theoretical risk of increased hemorrhagic complications. The purpose of this study was to evaluate the impact of preoperative anticoagulation on VTE and bleeding complications in patients with blunt pelvic fractures requiring operative fixation. Patients with blunt pelvic fractures requiring operative fixation over 10.5years were identified. Patients were stratified by age, severity of shock, operative management, and timing and duration of anticoagulation. Outcomes were evaluated to determine risk factors for bleeding complications and VTE. 310 patients were identified: 212 patients received at least one dose of preoperative anticoagulation and 98 received no preoperative anticoagulation. 68% were male with a mean injury severity score and Glasgow Coma Scale of 26 and 13, respectively. Bleeding complications occurred in 24 patients and 21 patients suffered VTE. Patients with VTE had a greater initial severity of shock (resuscitation transfusions, 4 vs. 2 units, P = .02). Despite longer time to mobilization (4 vs. 3days, P = .001), patients who received their scheduled preoperative doses within 48hours of arrival had no significant differences in the number of deep vein thrombosis events (5.2% vs. 5.7%, P = .99), but fewer episodes of pulmonary embolism (PE) (1.5% vs. 6.8%, P = .03) with no difference in bleeding complications (7.5% vs. 8%, P = .87) compared to either patients who had their doses held until after 48hours of arrival or received no preoperative anticoagulation. Preoperative anticoagulation prior to pelvic fixation reduced the risk of PE without increasing bleeding complications. Preoperative anticoagulation is safe and beneficial in this group of patients.

Ovarian Vein Thrombosis: A Narrative Review.

Ovarian vein thrombosis (OVT) is a rare type of venous thromboembolism. The most common risk factors for OVT include pregnancy, oral contraceptives, malignancies, recent surgery, and pelvic infections; however, in 4 to 16% of cases, it can be classified as idiopathic. Most of the available information regards pregnancy-related OVT, which has been reported to complicate 0.01 to 0.18% of pregnancies and to peak around 2 to 6 days after delivery or miscarriage/abortion. The right ovarian vein is more frequently involved (70-80% of cases). Clinical features of OVT include abdominal pain and tenderness, fever, and gastrointestinal symptoms. The most typical finding is the presence of a palpable abdominal mass, although reported in only 46% of cases. OVT can be the cause of puerperal fever in approximately a third of women. Ultrasound Doppler is the first-line imaging, because of its safety, low cost, and wide availability. However, the ovarian veins are difficult to visualize in the presence of bowel meteorism or obesity. Thus, computed tomography or magnetic resonance imaging is often required to confirm the presence and extension of the thrombosis. In oncological patients, OVT is often an incidental finding at abdominal imaging. Mortality related to OVT is nowadays low due to the combination treatment of parenteral broad-spectrum antibiotics (until at least 48 hours after fever resolution) and anticoagulation (low-molecular-weight heparin, vitamin K antagonists, or direct oral anticoagulants). Anticoagulant treatment duration of 3 to 6 months has been recommended for postpartum OVT, while no anticoagulation has been suggested for incidentally detected cancer-associated OVT.

Abstract 15803: Effectiveness of Direct Oral Anticoagulant versus Warfarin in the Treatment of Left Ventricular Thrombus

Introduction: Left ventricular thrombus (LVT) is associated with a higher risk of ischemic stroke and peripheral embolization. Societal guidelines recommend the use of warfarin, with direct oral anticoagulants (DOACs) only for patients unable to tolerate warfarin. Data on natural history and thrombus resolution with anticoagulation (AC), especially with DOACs is scarce. We studied the natural history of LVT with AC with emphasis on comparing warfarin and DOACs use. Methods: This is a single center, retrospective study conducted in an academic medical center. We identified patients (echocardiogram, CT or MRI) with a confirmed LVT study who were followed at our center. Chart review was conducted to collect clinical information at presentation and on follow up. Type and duration of anticoagulation, INR levels and clinical outcomes (bleeding, ischemic stroke or peripheral embolization, mortality) were recorded. Thrombus resolution on follow up imaging was also recorded. Results: LVT was confirmed in a total of 110 patients. Mean age was 59±14 years. 79% were men. Underlying etiology was chronic ischemic cardiomyopathy in 58%, non-ischemic cardiomyopathy in 23%. AC was started in 96 (87%) patients (in remaining patients AC was thought to be contraindicated). Of those on long-term AC, 60 patients (63%) were treated with warfarin, 3 patients (3%) with enoxaparin and 32 patients (33%) with a DOACs. At one year follow up, 11 patients (10%) had a stroke while on any AC. Two of these patients had hemorrhagic stroke (both on warfarin) and 9 patients had ischemic stroke. Of those with ischemic stroke 7 were on warfarin and 2 patients on DOACs had ischemic strokes. Of those with ischemic stroke on warfarin, 71% had subtherapeutic INR. The 1-year risk of any stroke was 15% in warfarin group (12% risk of ischemic stroke) compared to 6% in the DOACs group (p= 0.33). Total of 55 (57%) of patient started on AC had resolution of thrombus. 37 (63%) patients on warfarin and 18 (53%) on DOACs had resolution of thrombus (p= 0.85). Conclusions: One year risk of stroke with LVT is high (10%) even with AC. Most patients with ischemic stroke on warfarin had subtherapeutic INR. There was no statistical difference in stroke risk or rate of thrombus resolution between warfarin and DOACs treated patients.

The Current Practice of Management of Asymptomatic Central Venous Catheters Associated Venous Thromboembolism in Children: A Result of Saudi Arabian Pediatric Hematology/Oncology Society Survey

Introduction:Central venous catheters (CVCs) are the main cause of venous thromboembolism (VTE) in critically ill children. The optimal first-line treatment for children with asymptomatic CVC-related VTE is unknown. Due to a paucity of clinical trials, clinical practice guidelines can offer only weak recommendations for the management of asymptomatic CVC- related VTE. This case-based survey was designed to assess current trends in local management strategies for pediatric patients with an asymptomatic CVC- related thrombosis. The survey focused on the use of the thrombophilia testing, management approach, duration of anticoagulation, and the use of secondary prophylaxis. We hypothesize that there will be significant variation in these four management areas, in large part due to the aforementioned paucity of available data. Method:After Institutional Review Board approval, REDCap® questions were sent to members of the Saudi Arabian Pediatric Hematology/Oncology Society (SAPHOS) clinical forum/email database. We used a hypothetical case to assess management strategies for asymptomatic CVC-related VTE and secondary prophylaxis. Result:Seventy-one (30%) physicians responded to the survey. The majority of the respondents (83.3%) did not use thrombophilia testing. 95% treated with anticoagulation, of which 20% treated only if clot propagation was identified on follow-up and 3.3% treated only if a thrombophilia was identified. In contrast, the survey respondents varied widely in the duration of anticoagulation (19% for 6 weeks, 41.4% for 12 weeks, 29.3% until CVC removal). Secondary prophylaxis was used by 20% of the respondents, whereas 21.4% did so, only if there was a previously identified thrombophilia. Conclusion:Asymptomatic CVC-related VTE is a common clinical entity with limited data guiding management. In Saudi Arabia there remains considerable variability in clinical management; particularly, in the duration of treatment and use of secondary prophylaxis. These findings will help identify crucial knowledge gaps in the management of asymptomatic CVC-related VTE and facilitate clinical trials that will help establish evidence-based treatment guidelines. Disclosures No relevant conflicts of interest to declare.

Prospective Cohort of Catheter Related Thrombosis in Patients Treated with One Month of Anticoagulation after Catheter Removal

Background: The duration of anticoagulation in patients with catheter-related thrombosis (CRT) has not been studied in a systematic fashion and is not standardized in clinical practice. Consensus guidelines have a weak recommendation for anticoagulation for 3 months after catheter removal in patients with upper extremity CRT, but this is mainly extrapolated from treatment of lower extremity deep vein thrombosis. Shorter durations of anticoagulation have been used in practice to balance the risk of bleeding and recurrent thrombosis; however, prospective data are lacking to evaluate the efficacy and safety of this practice. CRT is a frequent complication in the cancer population, who commonly requires central venous catheters for treatment. We proposed a prospective cohort study to determine the incidence of post-thrombotic syndrome (PTS), thrombosis recurrence, and bleeding in cancer patients with CRT treated with one month of anticoagulation after catheter removal. Methods: This is a multi-institutional prospective cohort study in patients with cancer and documented upper extremity CRT. Enrolled patients were treated with a standardized protocol with therapeutic doses of enoxaparin for one month after catheter removal. Patients with platelet count &amp;lt;50 x 109/L, creatinine clearance &amp;lt;30 ml/min, history of thrombosis, or ongoing need for catheters were excluded. Demographics, catheter data, and cancer history were collected at baseline visit when catheter was removed. Incidence of bleeding, recurrent thrombosis, PTS using the modified Villalta scale, and functional limitation using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire were assessed at months 1, 3, and 6 after catheter removal. A modified Villalta score of 5 or higher was classified as the presence of PTS and a score of 15 or higher as severe PTS. Higher DASH scores indicated worse functional disability. Binomial tests with 95% confidence intervals (CI), Skillings-Mack and Wilcoxon signed ranks tests, and Pearson correlations on log transformed values were done. Unadjusted p-values &amp;lt;0.05 were considered statistically significant. Results: Twenty-seven patients from three institutions were enrolled. Seven (26%) patients discontinued study prior to month 1, with median study duration for those who continued of 176 [interquartile range (IQR): 158-186] days. The etiologies of study discontinuation were change in therapy (n=3, 11%), requiring another catheter (n=2, 7%), bleeding (n=1, 4%), and lost to follow-up (n=1, 4%). Eleven (41%) were female, and 21 (78%) were Caucasian (Table 1). Median age was 59 (IQR: 48-65) years. The most proximal location of the veins involved with the thrombus included veins proximal to subclavian (n=5, 19%), subclavian (n=6, 22%), internal jugular (n=6, 22%), and axillary (n=7, 26%). Patients with hematologic malignancies comprised 70% (n=19) of the cohort. All patients were treated with therapeutic doses of enoxaparin for a median of 32 (IQR: 30-52) days after catheter removal. During the 6-month study duration, the incidence of recurrent thrombosis was 0% (n=0/20, 95% CI: 0%-17%), and that of major hemorrhage was 5% (n=1/20, 95% CI: 0.13%-25%). Number of patients who had at least one PTS occurrence in any visit and either arm was 15% (n=3/20, 95% CI: 3.2%-38%), and no patients had severe PTS. Higher DASH scores were associated with higher PTS scores (Table 2). DASH score differed across all visits [month 1: median 6.16 (IQR: 2.08-19.97), month 3: 1.28 (0-11.67), month 6: 0 (0-10.42), p=0.040]. Pairwise comparisons revealed that no differences in DASH scores were seen between month 1 versus 6 (p=0.44) and month 3 and 6 (p=0.098). In contrast, month 6 had significantly lower and improved DASH score compared to month 1 (p=0.0066). No deaths occurred. Conclusions: Cancer patients with CRT frequently require central venous catheters. Treatment with anticoagulation for one month after catheter removal was associated with a low incidence of PTS, no recurrent thrombosis, and an improvement in functional disability over time in a cohort of 27 patients. The presence of PTS was associated with higher functional disability. Disclosures Baumann Kreuziger: Quercegen pharmaceuticals: Consultancy; CSL Behring: Consultancy.

Retrospective Comparison of Doac with Enoxaparin in Gastrointestinal and Urothelial Cancers

Introduction: Venous thromboembolic disease (VTE) is a common cause of morbidity and mortality in patients with cancer. Cancer associated thrombosis (CAT) is associated with poor prognosis, worse survival and increased care costs. Previous trials demonstrated the non-inferiority of DOACs to LMWH for the treatment of CAT, but there is concern for a possible increased incidence of bleeding, particularly in patients with gastrointestinal (GI) and urothelial (GU) cancers. Current guidelines suggest a preference for enoxaparin with these diagnoses. The aim of our study is to elucidate the safety of DOACs in the treatment of GI and GU cancer associated thrombosis at our institution. Methods: Retrospective chart review of patients with GI or GU cancer associated thrombosis who received either enoxaparin or DOACs (apixaban or rivaroxaban) was performed. The baseline characteristics, duration of anticoagulation (AC) and bleeding events (BEs) were compared between the two groups. The bleeding events were classified according to ISTH categories. Statistical analysis was done using R studio (V1.3.1056). Results: All patients from 01/2001 - 01/2020 with active GI or GU cancer and associated thrombosis who had received enoxaparin or a DOAC were included in the study. Of 262 patients reviewed, 206 (78.6 %) received a DOAC and 56 (21.4%) received enoxaparin. The baseline characteristics between the two groups are depicted in Table 1. Patients in the DOAC group had lower ECOG scores than those on enoxaparin: 79.7% of DOAC and 26.8% of enoxaparin patients had ECOG scores of 1-2. Patients on DOACs were less likely to have metastatic disease (58.7% vs. 78.6%) but were more likely to have additional risk factors for bleeding (p=0.004): 24 patients (11.7%) on DOACs were also on an antiplatelet agent (19 on aspirin, 5 on clopidogrel), compared to 4 patients (7.1%) in enoxaparin group (3 on aspirin, 1 on clopidogrel). Clot distribution was similar between the two groups. The majority of patients, 70.4% in the DOAC group and 73.2% in the enoxaparin group, had no BEs. There was no statistically significant difference in the cumulative incidence (CI) of bleeding between the DOAC and enoxaparin groups (p-value 0.65) Figure 1. In the DOAC group, 109 patients (52.9%) received apixaban and 97 patients (47.1%) received rivaroxaban. There were 26 (23.9%) and 35 (36.8%) BE in the apixaban and rivaroxaban subgroups respectively, Table 2. Of those on apixaban, 13/26 had GI bleeding (12 had underlying GI and 1 patient had GU cancer) and 10/26 had GU bleeding(all with underlying GU cancer). Of those on rivaroxaban 18/35 had GI bleeding (all with underlying GI cancer) and 11/35 had GU bleeding (6 patients had GU and 5 had GI cancer). Conclusion: Our study suggests that physician preferences play a major role in the choice of AC. Most physicians preferred DOACs even for patients with GI/GU cancers when patients had better ECOG scores and non-metastatic disease. However, these were also the same patients that were then more likely to have been exposed to additional risk factors for bleeding. BEs between DOACs and enoxaparin were similar and, between the DOACs, somewhat more favorable with apixaban than rivaroxaban. Randomized clinical trials, controlling for physician choice and bleeding risk factor, are necessary valid comparisons for the best choice of anticoagulation. Disclosures No relevant conflicts of interest to declare.