Asymptomatic Thrombosis Research Articles

A Randomized, Controlled Trial of Continuous Heparin Infusion to Prevent Asymptomatic Catheter-related Thrombosis at Discharge in Infants After Cardiac Surgery: The CHIP-CRT Trial.

There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery. This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15units/kg/h for infants with CRT and 2 to 3units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms. Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge ( P =0.429) and 6 months after surgery ( P =1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus ( P =0.088), D dimer ( P =0.412), catheter in situ days ( P =0.281), and post-thrombotic syndrome ( P =1.000), except for activated partial thromboplastin time ( P =0.001). With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention.

Should all critical care patients with a central venous catheter in situ be screened for central catheter related thrombosis?

There are many studies on central catheter related thrombosis (CCRT), however, there are significantly fewer studies focusing on the incidence and evolution of CCRT in the adult critical care population. This article reviews data collected from observational studies that have performed bedside duplex ultrasound for surveillance of CCRT and discuss if we should routinely screen for CCRT. The reported CCRT incidence is 17-38%, with most thrombus being detectable on ultrasound within seven days of line placement. Nearly all CCRT are designated as asymptomatic (no associated pulmonary embolism (PE) or deep vein thrombosis (DVT)) and no significant changes in mortality rates amongst patients that develop CCRT were reported. Based on the evidence reviewed, we do not recommend screening routinely for CCRT in the adult critical care population.

Management of Asymptomatic Complete Bilateral Cavernous Sinus Thrombosis in a 63-year-old Woman with Bacterial Meningitis: Anticoagulation Dilemma (P8-13.007)

Management of Asymptomatic Complete Bilateral Cavernous Sinus Thrombosis in a 63-year-old Woman with Bacterial Meningitis: Anticoagulation Dilemma (P8-13.007)

Venous thromboembolism in patients with isolated moderate to severe traumatic brain injury

Background. Traumatic brain injury (TBI) remains a big problem of modern neurosurgery, accompanied by high rates of disability and lethality. Venous thromboembolism (VTE) including venous thrombosis and pulmonary embolism (PE) plays a significant role in the structure of mortality in this pathology. Regimens and schemes of pharmacological prevention of VTE in TBI as well as corresponding preventative measures are not yet determined completely.Aim. To identify the frequency of VTE in patients with isolated moderate and severe TBI, and to evaluate the results of prevention and treatment of these complications in patients of this category.Materials and methods. Over a 3‑year period (from 2020 to 2023) 73 patients with isolated moderate and severe TBI (51 men and 22 women, mean age 61.0 ± 13.0 years) were treated in the V. M. Buyanov City Clinical Hospital. Of these, 31 patients received only conservative therapy, and 42 patients underwent surgery (craniotomy with hematoma removal, closed external hematoma drainage, and installation of intracranial pressure sensor). Ultrasound examination of the lower limb veins was performed at patient admission, then every 7 days until discharge from the hospital. Pharmacological prevention of VTE using low molecular weight heparin in non‑surgical patients was started after 1–2 days if computed tomography of the brain 24 h after admission showed no negative hematoma dynamics. Surgical patients were prescribed preventive medications 24 h after surgery if computed tomography confirmed intracranial hemostasis.Results. Venous thrombosis was detected in 22 (30.1 %) of 73 patients. PE complicated the underlying disease in 1 (1.4 %) case and was non‑fatal. There was no fatal PE in the study group. An increase of the initial intracranial hematoma volume occurred in 3 (4.1 %) patients, in 2 (2.8 %) patients the recurrence of hemorrhage occurred before the beginning of heparin administration, and in 1 (1.4 %) case against the background of therapeutic doses of anticoagulants prescribed for venous thrombosis. In the majority of cases (82.0 %; 18 of 22 patients) thromboses were localized in deep veins of the lower leg and were asymptomatic. Intrahospital mortality was 23.3 % (17 patients), all lethal outcomes were due to the course of traumatic brain disease.Conclusion. VTE is a frequent complication of TBI with intracranial hemorrhage. Regular ultrasound diagnostics makes it possible to diagnose asymptomatic distal venous thrombosis in a timely manner and to prescribe therapeutic doses of low molecular weight heparin in time which in turn allows to avoid fatal PE. Currently, there are no clear domestic recommendations for the prevention and, most importantly, for the treatment of these complications in patients with isolated moderate and severe TBI, which requires further active study of this problem.

Venous Thromboembolism in Children: The Rivaroxaban Experience.

The incidence of venous thromboembolism (VTE) in the pediatric population has increased more than 10-fold in the last 20 years, as a consequence of the advancement of resuscitation and surgical techniques and the global increase in life expectancy of children suffering from chronic pathologies. Monitoring anticoagulant therapy to achieve outcomes within the target range in childhood VTE, parenteral administration of medications, and frequent blood tests in children are often cumbersome. Availability of safe and effective oral agents with pediatric data to support use would be of clear benefit. A physiologically based pharmacokinetic model was developed to estimate the appropriate dosing schedule for rivaroxaban in children. This incorporated growth/maturation and variability in anthropometrics (e.g., body height, weight, and body mass index), anatomy (e.g., organ weight), physiology (e.g., blood flow rates), metabolism and excretion. Rivaroxaban use in pediatric population underwent a complete investigational program, consisting mainly of one phase I pharmacokinetics/pharmacodynamics trial, three phase II trials, one phase III trial. The phase III trial enrolled 500 patients from birth to <18 years and documented the efficacy and safety of rivaroxaban regimens at dose equivalent to the adult 20 mg dose for the prevention of fatal or symptomatic nonfatal recurrent VTE and major bleeding versus heparin or vitamin K antagonists. Results were similar to those in rivaroxaban studies in adults. The efficacy and safety of rivaroxaban in children reported in the EINSTEIN JUNIOR trial provide further support to previous trials in adults (EINSTEIN Program), which demonstrate a favorable profile for the use of rivaroxaban for the management of VTE in challenging patient populations. Other clinical evidence contributing to the use of rivaroxaban among different risk groups in pediatric VTE population confirms the consistency with principal trial. Our review aims to describe the rationale for using rivaroxaban oral suspension in clinical practice and to summarize its multiple indications in each vascular bed (e.g., cerebral venous thrombosis, symptomatic or asymptomatic central venous catheter-associated thrombosis), etiology, and patients setting.

Risk Factors and Clinical Prediction Modeling of Preoperative Asymptomatic Lower Extremity Venous Thrombosis in Patients with Knee Osteoarthritis

Risk Factors and Clinical Prediction Modeling of Preoperative Asymptomatic Lower Extremity Venous Thrombosis in Patients with Knee Osteoarthritis

Mesoglycan for the secondary prevention of superficial vein thrombosis: a randomized, controlled, double-blind study (METRO Study)—rationale and protocol

No data is available about pharmacological secondary prevention of superficial vein thrombosis (SVT) despite 10–15% of patients develop venous thromboembolic complications at 3–6 months after an adequate treatment of the acute phase. To verify efficacy and safety of mesoglycan in secondary prevention of SVT recurrence and venous thromboembolic complications. Phase III multicenter, double-blind, randomized, superiority trial comparing mesoglycan 50 mg bid vs placebo in consecutive patients with a SVT extended at least 5 cm, after the initial 45-day treatment course with fondaparinux 2.5 mg once-daily. Primary efficacy outcome: SVT recurrence/extension, symptomatic venous thromboembolism (VTE), asymptomatic proximal deep-vein thrombosis, death. Primary safety outcome: major bleeding. We hypothesized a 12-month 15% incidence of the primary efficacy outcome in placebo group and a 50% risk reduction in mesoglycan group. A bilateral log-rank test with a sample of 650 patients (randomization 1:1) reach a 90% power, with an α-error of 0.025, of detecting a 7.0% difference (HR = 0.51) after 12 months of treatment, considering a 10% patients drop-out. At deadline (December 31, 2022) 570 patients have been randomized (10% drop rate). Mean age was 63.9 years, 58.8% were women. SVT involved great saphenous vein in 69.3%, small saphenous vein in 13.1%, and collaterals in 17.6% of patients. SVT was the first event in 61.7%, a recurrence in 38.3%, provoked in 50.2% and unprovoked in 49.8%. Patients not experiencing a primary outcome, or not retiring their consent will be followed up to December 31, 2024 when the final data analysis will be performedClinicalTrials.gov: NCT03428711.

Incidence of asymptomatic catheter-related thrombosis in intensive care unit patients: a prospective cohort study

BackgroundCatheter-related thrombosis (CRT) incidence, rate, and risk factors vary in literature due to differences in populations, catheters, diagnostic methods, and statistical approaches.The aim of this single-center, prospective, observational study was to assess incidence, incidence rate (IR), cumulative incidence, and risk factors by means of IR ratio (IRR) of asymptomatic CRT in a non-oncologic Intensive Care Unit (ICU) population. CRT development was assessed daily by means of ultrasound screening. The proportions of patients and catheters developing CRT and CRT incidence rates, expressed as the number of events per catheter-days (cd), were calculated. Kalbfleisch and Prentice’s method was used to estimate the cumulative incidence of CRTs. Univariate and multivariable Poisson regression models were fitted to calculate IRR in risk factors analysis.ResultsFifty (25%, 95% CI 19–31) out of 203 included patients, and 52 (14%, 95% CI 11–18) out of 375 catheters inserted developed CRT [IR 17.7 (13.5–23.2) CRTs/1000*cd], after 5 [3–10] days from insertion. Forty-six CRTs (88%) were partial thrombosis. All CRTs remained asymptomatic. Obesity and ECMO support were patient-related protective factors [IRR 0.24 (0.10–0.60), p = 0.002 and 0.05 (0.01–0.50), p = 0.011, respectively]. The internal jugular vein had higher CRT IR than other sites [20.1 vs. 5.9 CRTs/1000*cd, IRR 4.22 (1.22–14.63), p = 0.023]. Pulmonary artery catheter and left-side cannulation were catheter-related risk factors [IRR 4.24 (2.00–9.00), p < 0.001 vs. central venous catheters; IRR 2.69 (1.45–4.98), p = 0.002 vs. right cannulation, respectively]. No statistically significant effect of the number of simultaneously inserted catheters [IRR 1.11 (0.64–1.94), p = 0.708] and of the catheterization length [IRR 1.09 (0.97–1.22), p = 0.155] was detected. The ICU length of stay was longer in CRT patients (20 [15–31] vs. 6 [4–14] days, p < 0.001), while no difference in mortality was observed.ConclusionsCRTs are frequent but rarely symptomatic. This study suggests that obesity and ECMO are protective factors, while pulmonary artery catheter, internal jugular vein and left-side positioning are risk factors for CRT.

Risk factors of worsening kidney function and mortality in patients with renal vein thrombosis: a retrospective study.

The outcome of renal vein thrombosis, in particular as for the long-termimpact on kidneyfunction, isnot fully known.We aimed to studythe natural course and outcomes of patients with renal vein thrombosis, ina large, single-center cohort. A single-center retrospective cohort study including patients who were diagnosed with renal vein thrombosis between January 2006 and September 2021was analyzed. The mainoutcomes analyzedwere worsening kidney function, defined as a decrease in eGFR of at least 40% from baseline, and all-cause mortality. Eighty-seven patients were included, 56.3% were female, median age was57years. Malignancy was the most common cause of renal vein thrombosis (60.9%), followed by post-surgery and trauma (16.1%) and nephrotic syndrome (12.6%). At initial presentation, 65.5% of the patientswere asymptomatic; the main signs andsymptoms were gross hematuria (20.7%), flank pain (18.4%), and flank tenderness (9.2%). During follow-up, 18 (21.4%) patients experienced worsening kidney function and 57 (65.5%) died. Multivariable analyses showed that the risk of worsening kidney function was higher in patients with nephrotic syndrome (hazard ratio [HR] 18.41; 95% confidence interval [CI], 1.57-216.04), body weight ≥ 60kg (HR 4.82; 95% CI 1.43-16.32), and malignancy (HR 9.10; 95% CI 1.05-78.63). Symptomatic acute renal vein thrombosis was associated with a lower risk of worsening kidney function compared to asymptomatic or symptomatic chronic renal vein thrombosis (HR 0.12; 95% CI 0.01-0.96). Malignancy (HR 5.45; 95% CI 2.58-11.54), age ≥ 75years (HR 3.44; 95% CI 1.49-7.93), and serum albumin < 3.0g/dL (HR 2.88; 95% CI 1.65-5.05) were associated with an increased mortality risk. Renal vein thrombosis is associated with a high rate of worsening kidney function and mortality. It is crucial to promptly identify patients at high risk and initiate early treatment to prevent negative outcomes.

Inflow Artery Aneurysmal Degeneration After Long Term Native Arteriovenous Fistula for Haemodialysis

Inflow arterial aneurysms are a rare but serious complication after long term arteriovenous fistulae (AVF), probably due to arterial wall remodelling after an increase in flow and shear stress, and kidney transplantation with immunosuppressive therapy. This study aimed to describe the outcomes of surgical treatment and long term follow up in a large cohort. This prospective cohort study collected data from patients with a true inflow artery aneurysm after AVF creation that was surgically repaired between 2010 and 2022. Anastomotic and infected aneurysms or post-puncture pseudoaneurysms were excluded. Demographic data, access characteristics, symptoms, treatment strategies, and long term follow up were recorded; patency was estimated using Kaplan-Meier survival analysis. During the study period, 28 patients (64% men, mean age 60.1 years) were treated surgically for aneurysmal degeneration of the axillary or brachial (n= 23) or radial (n= 5) artery after an AVF (10 distal, 18 proximal) performed a mean of 18.3 ± SD 7.9 years previously. Most AVFs were ligated or thrombosed, while all patients except one had previously received kidney transplants. Most of the cases (n= 18) were symptomatic: 13 with pain or swelling, four with distal embolisation, and one rupture. They were repaired by aneurysm partial excision and graft interposition (11 great saphenous vein, six ipsilateral basilic vein, three cephalic vein, and two PTFE graft), ligation (n= 3), or direct end to end anastomosis (n= 3). No major complications occurred before discharge, after a mean hospital stay of 2.4 days. After a mean follow up of 4.8 ± 3.3 years, three cases presented complications: two recurrent proximal brachial aneurysms were repaired with an additional proximal interposition graft (one with further late infected pseudoaneurysm) and an asymptomatic post-traumatic graft thrombosis. Five year primary and secondary patency was 84% and 96%, respectively. Aneurysmal degeneration of the inflow artery is an unusual complication during long term follow up of AVFs. Aneurysm excision and, in general, autogenous graft interposition using the saphenous or ipsilateral arm vein is a safe and effective strategy.

Growth of Flow-Related Aneurysms Following Occlusion of Cerebral Arteriovenous Malformation.

Flow-related aneurysms (FRAs) associated with cerebral arteriovenous malformations (AVMs) pose a significant therapeutic challenge. Both their natural history and management strategy are still unclear and underreported. FRAs generally increase the risk of brain hemorrhage. However, following AVM obliteration these vascular lesions are expected to disappear or remain stable. We present two cases where growth of FRAs was detected following complete obliteration of an unruptured AVM. The first patient presented with proximal middle cerebral artery (MCA) aneurysm growth after spontaneous and asymptomatic thrombosis of the AVM. In our second case, a very small aneurysmal-like dilation located at the basilar apex enlarged to a saccular aneurysm following complete endovascular and radiosurgical obliteration of the AVM. The natural history of flow-related aneurysms is unpredictable. In the cases where these lesions are not managed first, there should be close follow-up. When aneurysm growth is evident, active management strategy seems mandatory.

New asymptomatic thrombosis caused by carotid web during the acute period of cerebral infarction

BackgroundAt present, the carotid web (CaW) as an important cause of cryptogenic ischemic stroke has gradually received clinical attention. CaW is associated with a high risk of stroke and patient is more likely to have recurrent stroke if the CaW is untreated. We report a patient who developed CaW related thrombosis during the acute period of cerebral infarction.Case presentationA 49-year-old male patient with CaW in the left internal carotid artery was diagnosed by computed tomography angiography (CTA) and had two cerebral infarctions in two years. Within 72 h after thrombolysis for an acute cerebral infarction, acute thrombosis was identified between the web and the posterior wall of the carotid artery on carotid ultrasound. Emergent carotid endarterectomy (CEA) was performed to remove abnormal CaW structures and thrombosis to prevent stroke. The patient recovered well and was asymptomatic at 2 months follow-up.ConclusionCarotid web related thromboembolism is a rare cause of stroke. Carotid ultrasound plays an important role in the diagnosis of asymptomatic thrombosis caused by carotid web. Carotid endarterectomy is effective for stroke prevention in patient with carotid web related thrombosis.

Efficacy and Safety of Rivaroxaban for Postoperative Thromboprophylaxis in Patients After Bariatric Surgery

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality after bariatric surgery. Clinical end point studies on thromboprophylaxis with direct oral anticoagulants in patients undergoing bariatric surgery are lacking. To assess the efficacy and safety of a prophylactic dose of 10 mg/d of rivaroxaban for both 7 and 28 days after bariatric surgery. This assessor-blinded, phase 2, multicenter randomized clinical trial was conducted from July 1, 2018, through June 30, 2021, with participants from 3 academic and nonacademic hospitals in Switzerland. Patients were randomized 1 day after bariatric surgery to 10 mg of oral rivaroxaban for either 7 days (short prophylaxis) or 28 days (long prophylaxis). The primary efficacy outcome was the composite of deep vein thrombosis (symptomatic or asymptomatic) and pulmonary embolism within 28 days after bariatric surgery. Main safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and mortality. Of 300 patients, 272 (mean [SD] age, 40.0 [12.1] years; 216 women [80.3%]; mean body mass index, 42.2) were randomized; 134 received a 7-day and 135 a 28-day VTE prophylaxis course with rivaroxaban. Only 1 thromboembolic event (0.4%) occurred (asymptomatic thrombosis in a patient undergoing sleeve gastrectomy with extended prophylaxis). Major or clinically relevant nonmajor bleeding events were observed in 5 patients (1.9%): 2 in the short prophylaxis group and 3 in the long prophylaxis group. Clinically nonsignificant bleeding events were observed in 10 patients (3.7%): 3 in the short prophylaxis arm and 7 in the long prophylaxis arm. In this randomized clinical trial, once-daily VTE prophylaxis with 10 mg of rivaroxaban was effective and safe in the early postoperative phase after bariatric surgery in both the short and long prophylaxis groups. ClinicalTrials.gov Identifier: NCT03522259.

Prevalence of perioperative asymptomatic venous thromboses of the lower extremity in 30 consecutive patients undergoing transsphenoidal surgery for Cushing’s disease

Cushing´s disease is a rare endocrinological disorder which is caused by an adrenocorticotropic hormone secreting pituitary adenoma. The condition is associated with an increased risk for venous thromboembolism. While there exist reports on symptomatic venous thromboses complicating Cushing’s disease, the prevalence of incidental leg vein thromboses accompanying pituitary surgery for Cushing’s disease is yet unknown. 30 consecutive patients (9 male; age 25–77 years) with histologically confirmed Cushing’s disease underwent transsphenoidal adenomectomy between October 2018 and September 2019. All patients received perioperative pharmacological thromboprophylaxis. Whole leg compression ultrasound was performed within one week after surgery (median 2 days) to exclude leg vein thromboses (primary endpoint). Preoperative laboratory values including plasma cortisol and various coagulation parameters were evaluated as secondary outcome measures. A comparison was made between patients with and without thrombotic events (p value ≤ 0.05). A total of 2 out of 30 patients (6.7%; CI 0.8–24.1%) presented with asymptomatic perioperative deep vein thromboses of the lower legs. Thrombosis patients differed not significantly from their counterparts with respect to age, sex, and comorbidities, but preoperative morning plasma cortisol was significantly higher in patients with venous thromboses (421.0 ± 49.5 μg/l vs. 188.1 ± 78.2 μg/l; p = 0.01). Moreover, von Willebrand factor activity was markedly increased in one case (409.0%) compared to the mean value obtained from 28 patients without phlebothromboses (146.9 ± 60.7%; p < 0.01). Perioperative asymptomatic leg vein thrombosis can be found with the aid of compression ultrasound in a considerable proportion of patients undergoing transsphenoidal adenomectomy for Cushing’s disease despite the administration of pharmacological thromboprophylaxis.

Asymptomatic EVAR thrombosis: a Role For the Winslow Collateral Pathway

Asymptomatic EVAR thrombosis: a Role For the Winslow Collateral Pathway

Feasibility of edoxaban for asymptomatic cancer-associated thrombosis in Japanese patients with gastrointestinal cancer: ExCAVE study

BackgroundAlthough initial therapy with a parenteral anticoagulant is required before edoxaban, this strategy is frequently avoided in actual clinical practice because of its complexity. This study assessed the feasibility of edoxaban without initial heparin usage for asymptomatic cancer-associated thrombosis (CAT) in Japanese patients with gastrointestinal cancer (GIC) at high risk of bleeding.MethodsIn this multicenter prospective feasibility study conducted at 10 Japanese institutions, patients with active GIC who developed accidental asymptomatic CAT during chemotherapy were recruited. Edoxaban was orally administered once daily without initial parenteral anticoagulant therapy within 3 days after detecting asymptomatic CAT. The primary outcome was the incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) during the first 3 months of edoxaban administration.ResultsOf the 54 patients enrolled from October 2017 to September 2020, one was excluded because of a misdiagnosis of CAT. In the remaining 53 patients, the primary outcome occurred in six patients (11.3%). MB occurred in four patients (7.5%), including gastrointestinal bleeding in three patients and intracranial hemorrhage in one patient. CRNMB occurred in two patients (3.8%), including bleeding from the stoma site and genital bleeding in one patient each. There were no deaths attributable to bleeding, and all patients who experienced MB or CRNMB recovered.ConclusionsThe risk of bleeding after edoxaban without heparin pretreatment was acceptable, demonstrating new treatment options for asymptomatic CAT in patients with GIC.

Abstract 11530: Edoxaban For Pediatric Patients With Cardiac Diseases: A Randomized, Open Label, Multicenter Study

Introduction: Standard of care (SOC) anticoagulation for thromboembolism (TE) prevention in patients &lt;18 years old with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exist comparing direct oral anticoagulants as edoxaban with conventional anticoagulants in this population. Hypothesis: Edoxaban is at least as safe as the current standard-of-care (low molecular weight heparins and/or vitamin K antagonists) with regard to the incidence of major and clinically relevant nonmajor bleeding in pediatric patients with cardiac diseases at risk of thromboembolism. Methods: We performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients &lt;18 years old with cardiac disease (ENNOBLE-ATE, NCT00687882). Children were randomized 2:1 to age- and weight-based oral edoxaban once-daily versus SOC for 3 months (main study). Randomization was stratified by concomitant use of aspirin and by underlying disease groups, as follow: history of Fontan procedure; Kawasaki disease; heart failure; other. Both groups continued in an extension with edoxaban through 1 year. The primary endpoint was adjudicated International Society on Thrombosis and Haemostasis defined clinically-relevant bleeding (CRB). The main secondary endpoint was a composite of symptomatic TE and asymptomatic intracardiac thrombosis. Results: We randomized 168 children from May 2018 to September 2021. The CRB event rates were similar between groups during the main period. One subject per group experienced a nonmajor CRB. Treatment-emergent adverse events occurred in 46.8% (51/109) with edoxaban and 41.4% (24/58) with SOC. One SOC subject experienced 2 TE events (DVT with PE). In 152 subjects continuing in the extension, one CRB event (0.7%; trauma related) and 4 TEs occurred (2.8%; 2 strokes and 2 coronary artery thromboses and/or myocardial infarctions). Conclusion: Bleeding and TE occurred rarely for both groups and during the extension,suggesting that edoxaban is safe and effective for TE prevention in this population. Once daily edoxaban may provide advantage for children considering difficulties with enoxaparin injections and food and drug interactions with warfarin.

Edoxaban for Thromboembolism Prevention in Pediatric Patients With Cardiac Disease

BackgroundStandard of care (SOC) anticoagulation for thromboembolism (TE) prevention in children with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exists for alternate use of direct oral anticoagulants in children. ObjectivesThe investigators aimed to obtain safety and efficacy data for edoxaban in children. MethodsWe performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients <18 years of age with cardiac disease (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease] trial). Patients were randomized 2:1 to age- and weight-based oral edoxaban once daily vs SOC for 3 months (main study period), stratified by cardiac diagnosis. Both groups could continue in an open-label edoxaban extension arm through 1 year. The primary endpoint was adjudicated clinically relevant bleeding (CRB). The main secondary endpoint was symptomatic TE or asymptomatic intracardiac thrombosis. ResultsThe modified intention-to-treat cohort included 167 children. One patient per group experienced a nonmajor CRB in the main period. Treatment-emergent adverse events occurred in 46.8% (51 of 109) with edoxaban and 41.4% (24 of 58) with SOC. One SOC patient experienced 2 TE events (DVT with PE). Among 147 children in the extension, 1 CRB event (0.7%) and 4 TEs occurred (2.8%; 2 strokes and 2 of 33 Kawasaki disease patients with coronary artery thromboses and/or myocardial infarctions). ConclusionsEdoxaban is a potential alternative mode of thromboprophylaxis in children with cardiac disease showing low rates of CRB and TEs with advantages of once daily dosing and infrequent monitoring requirement. (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots] (Thrombotic Events) in Children at Risk Because of Cardiac Disease trial; NCT03395639).

Extended Thromboprophylaxis in Hospitalized Patients with Heart Failure: A Post Hoc Analysis of the MAGELLAN Study.

This post hoc subgroup analysis examined efficacy and safety outcomes with extended thromboprophylaxis rivaroxaban compared with in-hospital enoxaparin in 2,078 patients from the MAGELLAN study who had a hospitalization for heart failure or a history of heart failure and a lower risk of bleeding. A significant 36% reduction in the composite endpoint of asymptomatic proximal deep vein thrombosis (DVT) in the lower extremity, symptomatic DVT in the lower extremity (proximal or distal), symptomatic nonfatal pulmonary embolism, and venous thromboembolism-related death was observed with rivaroxaban. Major bleeding was low in both groups and not significantly increased with rivaroxaban.

Impact of Asymptomatic Superior Mesenteric Vein Thrombosis on the Outcomes of Patients with Liver Cirrhosis.

The impact of asymptomatic superior mesenteric vein (SMV) thrombosis on the outcomes of cirrhotic patients remains uncertain. Nonmalignant cirrhotic patients who were consecutively admitted between December 2014 and September 2021 and underwent contrast-enhanced computed tomography/magnetic resonance imaging scans were screened. Portal venous system thrombosis (PVST) was identified. Death and hepatic decompensation were the outcomes of interest. Nelson-Aalen cumulative risk curve analysis and competing risk regression analysis were performed to evaluate the impact of asymptomatic SMV thrombosis and portal vein thrombosis (PVT) on the outcomes. Overall, 475 patients were included, of whom 67 (14.1%) had asymptomatic SMV thrombosis, 95 (20%) had PVT, and 344 (72.4%) did not have any PVST. Nelson-Aalen cumulative risk curve analyses showed that the cumulative incidences of death (p = 0.653) and hepatic decompensation (p = 0.630) were not significantly different between patients with asymptomatic SMV thrombosis and those without PVST, but the cumulative incidences of death (p = 0.021) and hepatic decompensation (p = 0.004) were significantly higher in patients with PVT than those without PVST. Competing risk regression analyses demonstrated that asymptomatic SMV thrombosis was not a significant risk factor for death (subdistribution hazard ratio [sHR] = 0.89, p = 0.65) or hepatic decompensation (sHR = 1.09, p = 0.63), but PVT was a significant risk factor for death (sHR = 1.56, p = 0.02) and hepatic decompensation (sHR = 1.50, p = 0.006). These statistical results remained in competing risk regression analyses after adjusting for age, sex, and Child-Pugh score. Asymptomatic SMV thrombosis may not influence the outcomes of cirrhotic patients. The timing of intervention for asymptomatic SMV thrombosis in liver cirrhosis should be further explored.