Anticoagulation For Venous Thromboembolism Research Articles

Inflammatory Bowel Disease and Risk of Major Bleeding During Anticoagulation for Venous Thromboembolism.

Little is known about the bleeding risk in patients with inflammatory bowel disease (IBD) and venous thromboembolism (VTE) treated with anticoagulation. Our aim was to elucidate the rate of major bleeding (MB) events in a well-defined cohort of patients with IBD during anticoagulation after VTE. This study is a retrospective follow-up analysis of a multicenter cohort study investigating the incidence and recurrence rate of VTE in IBD. Data on MB and IBD- and VTE-related parameters were collected via telephone interview and chart review. The objective of the study was to evaluate the impact of anticoagulation for VTE on the risk of MB by comparing time periods with anticoagulation vs those without anticoagulation. A random-effects Poisson regression model was used. We included 107 patients (52 women, 40 with ulcerative colitis, 64 with Crohn disease, and 3 with unclassified IBD) in the study. The overall observation time was 388 patient-years with and 1445 patient-years without anticoagulation. In total, 23 MB events were registered in 21 patients, among whom 13 MB events occurred without anticoagulation and 10 occurred with anticoagulation. No fatal bleeding during anticoagulation was registered. The incidence rate for MB events was 2.6/100 patient-years during periods exposed to anticoagulation and 0.9/100 patient-years during the unexposed time. Exposure to anticoagulation (adjusted incidence rate ratio, 3.7; 95% confidence interval, 1.5-9.0; P = 0.003) and ulcerative colitis (adjusted incidence rate ratio, 3.5; 95% confidence interval, 1.5-8.1; P = 0.003) were independent risk factors for MB events. The risk of major but not fatal bleeding is increased in patients with IBD during anticoagulation. Our findings indicate that this risk may be outweighed by the high VTE recurrence rate in patients with IBD.

Abstract 15444: Anticoagulation Treatment of Venous Thromboembolism Across the Weight Spectrum: Insights From the Veterans Health Administration

Introduction: In seminal trials of venous thromboembolism (VTE) treatment with direct oral anticoagulants (DOAC), few patients were enrolled at low and high body weights to estimate treatment effects in these subgroups. Consensus statements have recommended against use of DOACs in VTE for patients ≥120 kg. We sought to describe real-world use of DOACs and other anticoagulants for VTE across the weight spectrum. Methods: We performed a retrospective cohort study of patients with first-time VTE that were treated with anticoagulants in the VA health care system from 2008 to 2018. We excluded patients with 1) additional indications for anticoagulation (atrial fibrillation and mechanical valves) and 2) no documented weight in the 90 days prior to 90 days after index VTE. We stratified patients by weight (<60, 60 to 119, ≥120 kg) and determined 1) index anticoagulation prescription in the 30 days after index VTE (DOAC, warfarin, and low molecular weight heparin or fondaparinux [LMWH/F] only) and 2) variables associated with DOAC prescription, as compared to warfarin, in those ≥120 kg. Results: After excluding 3,676 patients with missing weight, there were 111,774 patients with VTE (64±13 years, 6% female). The most common therapy was warfarin (66%), followed by DOAC (21%), and LMWH/F only (13%). Median weight was 92 kg (interquartile range: 28), with 13,753 patients (12%) with weight ≥120 kg. Across weight categories, proportion of patients receiving DOAC was similar. In patients ≥120 kg, after multivariate adjustment, multiple comorbidities were associated with warfarin prescription while chronic kidney disease was associated with DOAC prescription ( Table ). Conclusion: Weight ≥120 kg is common for VTE patients, with DOAC frequently prescribed despite consensus statements recommending DOAC avoidance. For patients ≥120 kg, comorbidities influence VTE treatment selection, and determination of optimal treatment strategies across the spectrum of comorbidities is needed.

Severe renal impairment and risk of bleeding during anticoagulation for venous thromboembolism

BackgroundDetection of severe renal impairment in patients with venous thromboembolism (VTE) is mandatory both for selecting anticoagulant therapy and for evaluating major bleeding risk, increased by severe renal impairment. ObjectivesTo determine whether the Cockcroft and Gault (CG) and Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) formulas identify severe renal impairment in the same VTE patients presenting the same risk of major bleeding. Patients/MethodsWe compared clinical characteristics and outcomes during the first 3 months of anticoagulation between VTE patients in the RIETE registry with severe renal impairment according to the CG and/or CKD‐EPI formula (estimated glomerular filtration rate <30 mL/min and <30 mL/min/1.73 m2, respectively). The primary outcome was major bleeding. ResultsUp to October 2017, 41 796 patients were included in RIETE. Among the 4676 patients with severe renal impairment according to at least one of the formulas, this was not confirmed by the other formula in 1904 (40.7%). Major bleeding risk was increased in every patient subgroup with severe renal impairment vs patients without this condition (CG or CKD‐EPI < 30: odds ratio [OR] = 2.26, 95% confidence interval [CI 2.01‐2.53], only CG < 30: OR = 1.72, 95% CI [1.37‐2.13], only CKD‐EPI < 30: OR = 2.34, 95% CI [1.77‐3.05], CG+CKD‐EPI < 30: OR = 2.47, 95% CI [2.16‐2.83], all vs CG+CKD‐EPI > 30). ConclusionThe CG and CKD‐EPI formulas identify different subgroups of patients with severe renal impairment, leading to discordant results in 40.7% of these patients. Irrespective of the formula used for their identification, patients with severe renal impairment have a higher risk of major bleeding under anticoagulant therapy.

Anticoagulation after intracranial hemorrhage in brain tumors: Risk of recurrent hemorrhage and venous thromboembolism

BackgroundIntracranial hemorrhage (ICH) is a common and often devastating outcome in patients with brain tumors. Despite this, there is little evidence to guide anticoagulation management following an initial ICH event. ObjectivesTo analyze the risk of recurrent hemorrhagic and thrombotic outcomes after an initial ICH event in patients with brain tumors and prior venous thromboembolism (VTE). Patients and MethodsA retrospective cohort study was performed. Radiographic images obtained after initial ICH were reviewed for the primary outcomes of recurrent ICH and VTE. Results and ConclusionsA total of 79 patients with brain tumors who developed ICH on anticoagulation for VTE were analyzed. Fifty‐four patients (68.4%) restarted anticoagulation following ICH. The cumulative incidence of recurrent ICH at 1 year was 6.1% (95% confidence interval [CI], 1.5‐15.3) following reinitiation of anticoagulation. Following a major ICH (defined as an ICH >10 mL in size, causing symptoms, or requiring intervention), the rate of recurrent ICH upon reexposure to anticoagulation was 14.5% (95% CI, 2.1‐38.35), whereas the rate of recurrent ICH following smaller ICH was 2.6% (95% CI, 0.2%‐12.0%). Mortality following a recurrent ICH on anticoagulation was 67% at 30 days. The cumulative incidence of recurrent VTE was significantly lower in the restart cohort compared to patients who did not restart anticoagulation (8.1% vs 35.3%; P = .003). We conclude that resumption of anticoagulation is lowest among patients with metastatic brain tumors with small initial ICH. Following an initial major ICH, resumption of anticoagulation was associated with a high rate of recurrent ICH.

Comparative effectiveness of oral anticoagulants in venous thromboembolism: GARFIELD-VTE

IntroductionRandomized controlled trials have shown that direct oral anticoagulants (DOACs) are a safe and effective alternative to vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE). However, there are limited post-marketing data describing the effectiveness and safety of the DOACs in the community setting. We aimed to compare the effectiveness of DOACs and VKAs on 12-month outcomes in a real-world VTE patient population. MethodsThe Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE is an observational study designed to document real-world treatment practices. This intention-to-treat analysis included 7987 VTE patients initiated on either DOACs (N = 4791) or VKAs (N = 3196) with or without pre-treatment with parenteral anticoagulants. Treatment groups were balanced according to baseline characteristics, using overlapping propensity score weights. ResultsAfter adjustment for baseline characteristics, all-cause mortality was significantly lower with DOAC than with VKAs (hazard ratio [HR]: 0.73; 95% confidence interval [CI] 0.56–0.95. Patients receiving VKAs were more likely than those receiving DOACs to die of complications of VTE (4.7% vs 2.7%) or from bleeding (4.2% vs. 1.3%). There was no significant difference in recurrent VTE (HR: 0.91, 95% CI 0.71–1.18), major bleeding (HR 1.03, 95% CI 0.69–1.54), or overall bleeding (HR 0.96, 95% CI 0.81–1.14) with DOACs or VKAs. ConclusionsIn this real-world analysis of VTE treatment, DOACs were associated with reduced all-cause mortality compared with VKAs, and similar rates of recurrent VTE and bleeding.

Psychotropic Drugs and Outcome in Patients Receiving Anticoagulant Therapy for Venous Thromboembolism.

The influence (if any) of the use of psychotropic drugs on outcome in patients receiving anticoagulant therapy for venous thromboembolism (VTE) has not been consistently evaluated. We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the risk for VTE recurrences, major bleeding, or death during the course of anticoagulant therapy, according to the use of psychotropics at baseline. Among 49,007 patients with VTE enrolled from February 2009 to September 2019, total 5,230 (11%) were using psychotropics at baseline: antidepressants 3,273 (6.7%), antipsychotics 1,588 (3.2%), and anticholinesterases 369 (0.7%). During the course of anticoagulation, 1,259 patients developed VTE recurrences, 1,231 bled, and 3,988 died (fatal pulmonary embolism 269 and fatal bleeding 187). On multivariable analysis, patients using psychotropics at baseline had a similar risk for VTE recurrences (adjusted hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.58-1.12), a nonsignificantly higher risk for major bleeding (adjusted HR: 1.15; 95% CI: 0.97-1.35), and a higher risk for intracranial bleeding (adjusted HR: 1.83; 95% CI: 1.32-2.53) or death (adjusted HR: 1.44; 95% CI: 1.32-1.57) compared with those not using psychotropics. When separately analyzed, the highest risk for intracranial bleeding was found in patients using antidepressants (adjusted HR: 1.60; 95% CI: 1.08-2.37) or antipsychotics (adjusted HR: 2.02; 95% CI: 1.17-3.49) but not in those on anticholinesterases (adjusted HR: 1.69; 95% CI: 0.62-4.60). During the course anticoagulation for VTE, patients using psychotropics at baseline were at increased risk for intracranial bleeding.

Anticoagulation in Venous Thromboembolism: How Long and Which Dose?

Anticoagulation in Venous Thromboembolism: How Long and Which Dose? Abstract. Venous thromboembolism is quite common in daily practice. As soon as the diagnosis is confirmed, anticoagulation should be started immediately. Nowadays DOACs are the first choice for treatment of VTE. An important issue is the duration of anticoagulation in an individual patient. Generally, the anticoagulation should be continued for at least three months in any patient. While anticoagulation can be safely stopped after three months in patients with isolated distal DVT it should be continued for an unlimited period in persons with unprovoked proximal DVT and PE. In the vast majority of cases making that decision is not straightforward. Decision making involves assessing risks and benefits on an individual basis. Another important issue is dose reduction of the DOACs during treatment. The goal of this article is to show the factors that must be considered for decision making.

Abstract No. 415 Uterine artery embolization for anticoagulant-associated uterine bleeding

Abnormal uterine bleeding (AUB) affects up to two thirds of women on anticoagulation (AC) therapy. In women on AC for venous thromboembolism (VTE), AUB is linked to recurrent VTE, likely due to interrupted therapy. Treatment options for anticoagulant-associated AUB (AA-AUB) are limited, as estrogen-containing treatments increase thrombotic risk and endometrial ablation or hysterectomy lead to infertility. While uterine artery embolization (UAE) is a well-established treatment for symptomatic fibroids, its role in acute AA-AUB is limited to case reports. This study describes a series of patients who underwent UAE for the treatment of acute AA-AUB, focusing on technique, safety and outcomes. The institutional review board approved this retrospective review on 16 patients who underwent UAE for acute AA-AUB at a single academic medical center between Feb 2014 and Feb 2019. Three board-certified interventional radiologists performed UAE cases using 500-700 micron tris-acryl gelatin microspheres (Merit Medical Systems). In one case, tris-acryl gelatin microspheres were used in combination with Gelfoam. Medical, surgical, and radiologic records were reviewed. Statistical analysis were performed using MATLAB version R2018b (Mathworks). 16 patients were included with mean age 42 ± 7, on warfarin (38%), heparin drip (38%), or NOACs (25%). All patients demonstrated concurrent fibroids and/or adenomyosis and no patient had known endometrial malignancy. VTE, due to various etiologies, was the most common indication (88%) for AC. Cessation of acute AA-AUB was noted in the short term, defined as 3 days post-UAE, in 15 (94%) patients. 2 patients (12.5%) ultimately underwent hysterectomy due to failure of UAE to control AA-AUB in either the short or long term. Among patients who did not undergo hysterectomy for whom follow-up data was available, 9 (90%) maintained menses post-UAE. All patients were able to re-initiate or continue anticoagulation following UAE. UAE is an effective treatment strategy for acute AA-AUB. As an initial alternative to hysterectomy, endometrial ablation, or medical management, UAE allows patients to preserve menses and continue anticoagulation.Tabled 1Demographics Total cases16 Age (years)42 ± 7Indication for anticoagulation Cardiac valve prothesis1 Coronary arterial stent1 Venous thromboembolism14Timing of medical management of AA-AUB Concurrent with UAE7 Failure leading to UAE5 Not attempted4Anticoagulation post-UAE Re-initiated (previously held)6 Continued (not previously held)10 Stopped0Cessation of AUB post-UAE Resolved in short and long term10 Resolved in short term only; long term control with conservative or medical management3 Resolved in short term only; long term control with hysterectomy1 Resolved in short term; unable to assess long term efficacy due to hysterectomy for other indication1 Did not resolve, leading to hysterectomy1Loss of menses post-UAE No9 Yes1 N/A (hysterectomy shortly after UAE)2 N/A (inadequate follow up)4 Open table in a new tab

Recurrence of Venous Thromboembolism in the Context of Metabolic Syndrome

Whether or not to extend anticoagulation for venous thromboembolism (VTE) after 3 months of therapy depends on the continued presence of risk factors

Spotlight in Plastic Surgery: April 2020

Spotlight in Plastic Surgery: April 2020

Review: In patients with cancer, prophylactic anticoagulants reduce VTE and do not increase major bleeding.

Source Citation Barbarawi M, Zayed Y, Kheiri B, et al. The role of anticoagulation in venous thromboembolism primary prophylaxis in patients with malignancy: a systematic review and meta-analysis o...

Efficacy and Safety of Direct Oral Factor Xa Inhibitors in Patients after Bariatric Surgery

Background: Over 200,000 people underwent weight loss surgery in the United States in 2017. The absorption of numerous drugs has been shown to be altered in patients after bariatric procedures, as gastrointestinal absorptive surface, food volume, and gastric pH all affect bioavailability. Dosing of warfarin, which is commonly used for the treatment of venous thromboembolism (VTE), often needs to be adjusted, based on INR, after bariatric surgery. Since direct oral anticoagulants (DOACs), which are rapidly replacing warfarin as standard anticoagulant therapy, are not monitored, there is concern regarding their efficacy and safety in patients who have had bariatric surgery, particularly rivaroxaban, which is absorbed primarily in the stomach and must be taken with food at therapeutic doses. One study found that 9 out of 9 apixaban patients (but only 2 of 7 rivaroxaban patients) had levels that fell within the expected range after bariatric surgery. Effects of bariatric surgery on DOACs may be further complicated by baseline obesity and subsequent weight loss of the patients. The goal of our current study is to determine whether DOACs are safe and effective in preventing recurrent VTE in patients who have undergone bariatric surgery. Methods: Using our institutional database, we identified all adult patients (age ≥18 years) with a history of bariatric surgery (gastric banding, sleeve gastrectomy, and Roux-en-Y gastric bypass) who were started on anticoagulation with apixaban or rivaroxaban for VTE, between July 1, 2013 and June 30, 2018. We performed retrospective chart review to obtain information on patient demographics, BMI and type of bariatric surgery. We documented clinical outcomes of recurrent VTE and bleeding from the first prescription date to the earliest of a thrombotic event, discontinuation of medication, death, or the end of study period, June 30, 2018. VTE events were confirmed by a review of imaging studies (compression ultrasonography, ventilation/perfusions scans, and CT scans). Bleeding events were included if they met criteria for clinically relevant non-major bleeding and/or major bleeding according to the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Safety outcomes included major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). We also compared VTE recurrence and bleeding rates between the post-bariatric surgery patients and patients with BMI &gt;40 from our prior study. Chi- squared tests were used to assess statistical significance of the differences in recurrent VTE and bleeding rates between anticoagulant cohorts. Results: Data on 102 patients were collected: 42 patients on apixaban and 60 patients on rivaroxaban. Our population was predominantly female (82.4%) with a mean age of 48.5 years and a median BMI of 35.7 at initiation of anticoagulation. Gastric bypass was the most common bariatric procedure (51%), followed by sleeve gastrectomy (37.3%), and gastric banding (11.8%). There were no recurrent VTE events in the apixaban cohort with a median follow-up duration of 137 days. Among patients on rivaroxaban, with a median follow-up of 232 days, there was one recurrent VTE (1.7%) in a patient with a BMI of 54 at the time of event. When we compared VTE recurrence rates of our combined DOAC cohort (apixaban + rivaroxaban) between our general morbidly obese population, from a prior study at our institution, and post-bariatric surgery patients, there was no statistically significant difference (2.0% vs. 1.0%, respectively, p=0.5). In bariatric surgery patients, one CRNMB event was recorded in apixaban group (2.4%) while 4 major bleeding events occurred on rivaroxaban (6.7%), p=0.3. There was no significant difference in the rate of composite MB and CRNMB between the general obesity and bariatric surgery patients (8.0% vs. 4.9%, respectively, p=0.3). Conclusions: In a review of post-bariatric surgery patients on anticoagulation for VTE, we found low rates of recurrent VTE for patients on DOACs. Although we had a relatively small sample size, the incidence of VTE recurrence was not higher in this cohort than was found in our previously published study of general obesity population. Prospective studies are needed to further investigate the efficacy and safety of direct oral anticoagulants in patients after bariatric surgery. Table. Disclosures Kushnir: Janssen Pharmaceuticals: Research Funding. Billett:Janssen: Research Funding.

Impact of Adding Aspirin to Direct Oral Anticoagulant Therapy without an Apparent Indication

Introduction: The direct oral anticoagulants (DOACs: apixaban, dabigatran, edoxaban and rivaroxaban) may be used for the treatment and secondary prevention of venous thromboembolism (VTE) and for the prevention of stroke in the setting of non-valvular atrial fibrillation (NVAF). Adding aspirin (ASA) to a DOAC is often appropriate after acute coronary syndromes or percutaneous coronary intervention. However, many patients receive oral anticoagulation and ASA without a clear need for combination therapy. Current data, largely from patients treated with warfarin and ASA, suggest that the addition of ASA may increase bleeding risk without reducing thrombotic events. However, it is uncertain if this applies to patients on DOACs with ASA, and patients on combination DOAC+ASA therapy were not well represented in clinical trials. We sought to evaluate the impact of adding ASA to DOAC therapy for patients without an apparent indication for combination therapy. Methods: We conducted a registry-based cohort study of adults on DOAC therapy for NVAF or VTE followed at 6 anticoagulation clinics in Michigan between January 2009 to June 2019, recruited through the Michigan Anticoagulation Quality Improvement Initiative (MAQI2). Patients were excluded if they had a history of heart valve replacement, recent myocardial infarction, or less than 3 months of follow-up. Two propensity matched cohorts (DOACs vs. DOAC+ASA) of patients were analyzed based on aspirin use at the time of study enrollment. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of arterial or VTE, bleeding event type (fatal, life threatening, major, clinically relevant non-major, non-major bleeding (CRNMB), and intracranial or intraspinal), and death. Random chart audits were done to confirm the accuracy of the abstracted data. Results: Of the study cohort of 2,045 patients, 647 (31.6%) patients without a clear indication for ASA received ASA with a DOAC. We compared two groups of 639 matched patients. Patient demographics, co-morbidities, and concurrent medications were well-balanced after propensity score matching. After an average of 15.2 months of follow-up we found that patients on combination therapy (DOAC+ASA) had a significantly higher rate of bleeding compared to patients on DOAC monotherapy (319 bleeding events vs. 261 bleeding events, P=0.02; 0.41 bleeds per patient vs. 0.33 bleeds per patient). This difference was largely driven by CRNMB events (151 with DOAC+ASA vs. 109 with DOAC monotherapy, P=0.01), with the only 2 fatal bleeding events observed with DOAC monotherapy. We did not observe a significant difference between the groups in other bleeding event classifications. Bleeding sites were most commonly cutaneous, gastrointestinal, and genitourinary. Observed rates of thrombosis (stroke, VTE, myocardial infarction, or other) were similar between the groups (19 events with DOAC+ASA vs. 18 events for DOAC monotherapy, P=NS). Patients on combination therapy had more emergency room visits and hospitalizations but these differences were not statistically significant. Conclusion: Patients on oral anticoagulation for VTE or NVAF with a DOAC, without a clear need for ASA, experienced more bleeding events with the addition of ASA compared to DOAC monotherapy, without an apparent improvement in the incidence of thrombosis. Further study is needed to assess if DOAC+ASA is safer than warfarin+ASA, to compare the outcomes of the individual DOACs, and to confirm these findings in a larger cohort. Until such assessment is complete, clinicians should carefully consider the need to add aspirin in patients on DOAC therapy. Disclosures Kaatz: Portola: Honoraria; Pfizer: Honoraria; Janssen: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria. Kline-Rogers:AC Forum: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; QUANTUM-AF: Membership on an entity's Board of Directors or advisory committees. Sood:Bayer: Research Funding. Froehlich:Fibromuscular Dysplasia Society: Research Funding; Janssen: Honoraria; Pfizer: Honoraria; Boehringer-Ingelheim: Honoraria; Merck: Honoraria; Blue Cross Blue Shield of Michigan: Research Funding; Novartis: Honoraria. Barnes:Portola: Honoraria; Janssen: Honoraria; Blue Cross Blue Shield of Michigan: Research Funding; Bristol Myers Squib: Honoraria; AMAG Pharmaceuticals: Honoraria; Pfizer/Bristol Myers Squib: Research Funding; Pfizer: Honoraria.

P2773Evaluation of the bleeding prediction score VTE-BLEED for predicting recurrent VTE

Abstract Introduction VTE-BLEED is a validated score for identification of patients at a 3 to 5-fold increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE; table 1). It is unknown whether VTE-BLEED high-risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score. Methods This was a post-hoc analysis of the randomised double-blind placebo-controlled PADIS-PE trial, in which patients with a first unprovoked pulmonary embolism (PE) initially treated for 6 months were randomised to receive an additional 18-month of warfarin versus placebo. Primary outcome of the current analysis was recurrent VTE during 2-year follow-up after anticoagulant discontinuation, i.e. after the initial 6-month treatment in the placebo arm and after 24 months of anticoagulation in the active treatment arm. This rate, adjusted on study treatment allocation, was compared between patients in the high- versus low-risk VTE-BLEED group. Results In complete case analysis (n=308; 82.4% of total population), 89 (28.9%) patients were classified as VTE-BLEED high risk. A total of 44 VTE events occurred after anticoagulant discontinuation during 668 patient-years. The cumulative incidence of recurrent VTE was 16.4% (95% CI 10.0–26.1%; 14 events) and 14.6% (95% CI 10.4–20.3%; 30 events) in the high-risk and low-risk VTE-BLEED groups, respectively, for an adjusted Hazard Ratio of 1.16 (95% CI 0.62–2.19; Figure 1). Figure 1 Conclusion In this study, patients with unprovoked PE classified at high risk of major bleeding by VTE-BLEED did not have a higher incidence of recurrent VTE after cessation of anticoagulant therapy, supporting the potential yield of the score for making management decisions on the optimal duration of anticoagulant therapy.

Use of Direct Oral Anticoagulants in Patients with Sickle Cell Disease and Venous Thromboembolism: A Prospective Cohort Study of 12 Patients

Patients with sickle cell disease have an increased risk of venous thromboembolism (VTE) and with a mortality 2-fold higher. The anticoagulation of VTE in a young population is an important question. Indeed, hemorrhagic complications of anticoagulation may occur more frequently than in the general population. The use of a direct oral anticoagulant (DOAC) is not recommended for VTE in patients with sickle cell disease because those patients were not included in the clinical studies. We aimed to study the safety of using DOACs in a prospective cohort of patients with sickle cell disease and VTE. We prospectively followed the cohort of all sickle cell disease patients undergoing recent DOAC treatment for VTE at a sickle cell disease reference center. Twelve patients received rivaroxaban for VTE (eight women and four men). The median age was 27 years (20–45). The sickle cell disease variants included homozygous Hb SS (HBB: c.20A>T) in eight patients, Hb S-β+-thalassemia (Hb S-β+-thal) in two, Hb S-β0-thal in one and Hb S-Hb C (HBB: c.19G>A) in one. The cumulative duration of follow-up was 3134 days under rivaroxaban treatment. There were two thrombotic events, including a patient with a double positivity of antiphospholipid antibodies. No major bleeding was observed, and 6/12 patients presented minor bleeding (epistaxis: n = 4; anal fissure bleeding: n = 1; menorrhagia n = 4). Of these, 3/6 required their treatment to be switched to apixaban, which stopped the bleeding. Direct oral anticoagulants may be an alternative treatment for VTE in patients with sickle cell disease, except for an associated antiphospholipid syndrome.

Assessment of the reporting quality of RCTs for novel oral anticoagulants in venous thromboembolic disease based on the CONSORT statement.

Randomized controlled trials (RCTs) are the cornerstone of evidence based medicine. Ιt is crucial that RCTs have transparent reporting to facilitate their interpretation. Thepurpose of the present study is the evaluation of the reporting quality of RCTs for novel oral anticoagulants (NOACs) in venous thromboembolism (VTE) based on the CONSORT statement. MEDLINE was meticulously searched, while quoted references by retrieved RCTs were manually screened. The primary objective was to establish the mean CONSORT compliance of RCTs for NOACs in VTE. Secondary objectives were the calculation of compliance per CONSORT item and the investigation for probable determining factors with regards to the reporting quality of RCTs. Reporting above 70% of the items was defined as adequate compliance to the CONSORT statement. A total of 83 articles were considered eligible. Mean adherence to the CONSORT statement was 61.84%, standard deviation (SD) = 18.72. Among retrieved studies, 35 (42.17%) reported above 70% of the items, while 48 (57.83%) described less than 70% of the items. Inter-rater agreement was satisfactory (Cohen's kappa ≥ 0.75). Items with respect to randomization and blinding were principally underreported, whereas the rest of the methodological features and results were more sufficiently reported. Logistic regression failed to demonstrate significant effect for any of the factors investigated. Impact factor [odds ratio (OR) = 1.347, 95% confidence interval (CI) (0.994, 1.826), p = 0.055], number of authors [OR = 1.277, 95% CI (0.975, 1.672), p = 0.076] and presentation of participant flow-diagram [OR = 55.358, 95% CI (0.914, 3351.765), p = 0.055], came closer to significance. Exploratory analysis revealed significant, strong, positive correlation between abstract and article adherence to the CONSORT guidelines (r = 0.851, p < 0.001). Reporting quality of RCTs for NOACs in VTE is moderate. A superior reporting quality is desirable, especially relating to randomization and blinding.

Natural history of patients with venous thromboembolism and hereditary hemorrhagic telangiectasia. Findings from the RIETE registry

BackgroundLimited data exist about the clinical presentation, ideal therapy and outcomes of patients with hereditary hemorrhagic telangiectasia (HHT) who develop venous thromboembolism (VTE).MethodsWe used the data in the RIETE Registry to assess the clinical characteristics, therapeutic approaches and clinical outcomes during the course of anticoagulant therapy in patients with HHT according to initial presentation as pulmonary embolism (PE) or deep venous thrombosis (DVT).ResultsOf 51,375 patients with acute VTE enrolled in RIETE from February 2009 to January 2019, 23 (0.04%) had HHT: 14 (61%) initially presented with PE and 9 (39%) with DVT alone. Almost half (47.8%) of the patients with VTE had a risk factor for VTE. Most PE and DVT patients received low-molecular-weight heparin for initial (71 and 100%, respectively) and long-term therapy (54 and 67%, respectively). During anticoagulation for VTE, the rate of bleeding events (major 2, non-major 6) far outweighed the rate of VTE recurrences (recurrent DVT 1): 50.1 bleeds per 100 patient-years (95%CI: 21.6-98.7) vs. 6.26 recurrences (95%CI: 0.31–30.9; p = 0.020). One major and three non-major bleeding were epistaxis. No patient died of bleeding. One patient died shortly after being diagnosed with acute PE.ConclusionsDuring anticoagulation for VTE in HHT patients, there were more bleeding events than VTE recurrences. Most bleeding episodes were non-major epistaxis.

Safety of direct oral anticoagulants versus traditional anticoagulants in venous thromboembolism.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality worldwide. For decades, low molecular weight heparins (LMWH) and vitamin K-antagonists have been the gold standard of anticoagulation for VTE. Recently, direct oral anticoagulants (DOACs) that can be administered in fixed doses, without laboratory monitoring and dose adjustment have revolutionized anticoagulation management in VTE. Here, we report on recent evidence regarding the safety of DOACs compared to traditional anticoagulants in surgical and medical prophylaxis as well as in acute and extended treatments of VTE. Additionally, we provide data on special situations such as elderly, cancer and renal impairment patients. Regarding antithrombotic prophylaxis, data are lacking on DOAC use in general surgical patients, while DOACs appear to be more effective than and as safe as LMWHs in VTE prophylaxis for major orthopedic surgical patients. Whether a medically ill patient may benefit from extended VTE prophylaxis remains unclear. In fact, in these patients, DOACs showed an increased risk of bleeding compared to conventional therapy. In the acute treatment of VTE, DOACs were non-inferior and probably safer than conventional anticoagulation therapy while in the extended VTE treatment DOACs were more effective than placebo or aspirin with a comparable risk of major bleeding. These favorable results were also confirmed in elderly, cancer and renal impairment patients. However, further investigations are needed in order to generalize the safe use of DOACs in these specific subgroups of patients.

Vena cava filters in patients presenting with major bleeding during anticoagulation for venous thromboembolism.

The association between inferior vena cava filter (IVC) use and outcome in patients presenting with major bleeding during anticoagulation for venous thromboembolism (VTE) has not been thoroughly investigated. We used the RIETE registry to compare the 30-day outcomes (death, major re-bleeding or VTE recurrences) in VTE patients who bled during the first 3months of therapy, regarding the insertion of an IVC filter. A propensity score matched (PSM) analysis was performed to adjust for potential confounders. From January 2001 to September 2016, 1065 VTE patients had major bleeding during the first 3months of anticoagulation (gastrointestinal 370; intracranial 124). Of these, 122 patients (11%) received an IVC filter. Patients receiving a filter restarted anticoagulation later (median, 4 vs. 2days) and at lower doses (95 ± 52IU/kg/day vs. 104 ± 55 of low-molecular-weight heparin) than those not receiving a filter. During the first 30days after bleeding (after excluding 246 patients who died within the first 24h), 283 patients (27%) died, 63 (5.9%) had non-fatal re-bleeding and 19 (1.8%) had recurrent pulmonary embolism (PE). In PSM analysis, patients receiving an IVC filter (n = 122) had a lower risk for all-cause death (HR 0.49; 95% CI 0.31-0.77) or fatal bleeding (HR 0.16; 95% CI 0.07-0.49) and a similar risk for re-bleeding (HR 0.55; 95% CI 0.23-1.40) or PE recurrences (HR 1.57; 95% CI 0.38-6.36) than those not receiving a filter (n = 429). In VTE patients experiencing major bleeding during the first 3months, use of an IVC filter was associated with reduced mortality rates.Clinical Trial Registration NCT02832245.

French vascular physicians' practices in indicating antiplatelet and anticoagulation therapy in venous thromboembolism.

Background: As antiplatelet therapy becomes widespread, physicians face the issue patients being treated with antiplatelet agents (APA) and anticoagulants for venous thromboembolism (VTE). Bleeding risk of this combination is increased 1.5-2.5-fold. The aim of this survey is to assess French vascular physician's management of this combination at the beginning of the treatment and at 6 months of treatment for VTE. Patients and methods: French vascular physicians were surveyed between September and December 2017, using 4 fictional scenarios regarding a VTE event diagnosed in a patient under antiplatelet therapy plus isolated questions in an online questionnaire, sent by the French Society of Vascular Medicine to its members. Out of 1812 physicians, 179 returned valid questionnaires: the response rate was 9.9%. Results: Firstly 97.2% of respondents acknowledged extra risk with this combination; and 63% ceased antiplatelet therapy when initiating anticoagulants; while 36% did not. Secondly, four strategies emerged: 31.4% ceased APA and prescribed full-dose anticoagulants at initiation and at 6 months; 32% associated reduced-dose anticoagulation with APA at 6 months, regardless of what they decided at initiation; 16.5% prescribed isolated full-dose anticoagulants at initiation and reduced-dose at 6 months; lastly 11.2% associated full-dose anticoagulant with antiplatelet therapy at initiation and at 6 months. Conclusions: French vascular physicians adopted different strategies according to estimated risk/benefit ratio. Prospective randomized controlled trials should compare these strategies in order to make recommendations.