Duration Of Anticoagulation Research Articles

Short-term versus extended anticoagulant treatment for unprovoked venous thromboembolism: A survey on guideline adherence and physicians' considerations

BackgroundIn patients with unprovoked venous thromboembolism (VTE), anticoagulant treatment duration should be decided by weighing bleeding risk versus risk of recurrent VTE, considering patient's preference. Because both risks differ between individuals, this recommendation presumably leads to wide variation in clinical management. ObjectivesTo identify physician's considerations when deciding between short-term and extended anticoagulation and to assess how current guidelines are put to practice. Materials and methodsAn online, 33-item survey was developed, containing questions on clinical management, considerations regarding treatment duration, risk scores, information tools and shared decision-making. It was distributed to internists, pulmonologists and residents treating patients with VTE in the Netherlands. Results69 internists and 73 pulmonologists including 24 residents participated in the survey. Extended treatment was preferred by 73% (104/142) of participants. Most important reasons for extended treatment were, in descending order: patient's preference, active malignancy, low estimated bleeding risk, history of VTE and hemodynamic instability during previous VTE. Most important reasons for short-term treatment were frequent falls, history of major bleeding, previous bleeding during anticoagulation, patient's preference and thrombocytopenia. Although existing risk scores are infrequently used, physicians express their need for scores combining risks of recurrence and bleeding to aid individualized decision-making. ConclusionOur results confirm a wide variety of considerations regarding treatment duration in patients with unprovoked VTE. Although most participants followed guidelines' recommendations to prescribe indefinite treatment in absence of contraindications, rationale is not always supported by evidence. A clinical decision tool to estimate and weigh risks of recurrence and bleeding is warranted.

Risk of Pulmonary Embolism More Than 6 Weeks After Surgery Among Cancer-Free Middle-aged Patients

The risk of postoperative pulmonary embolism has been reported to be highest during the first 5 weeks after surgery. However, how long the excess risk of postoperative pulmonary embolism persists remains unknown. To assess the duration and magnitude of the late postoperative risk of pulmonary embolism among cancer-free middle-aged patients by the type of surgery. Case-crossover analysis to compute the respective risks of pulmonary embolism after 6 types of surgery using data from a French national inpatient database, which covers a total of 203 million inpatient stays over an 8-year period between 2007 and 2014. Participants were cancer-free middle-aged adult patients (aged 45 to 64) with a diagnosis of a first pulmonary embolism. Hospital admission for surgery. Surgical procedures were classified into 6 types: (1) vascular surgery, (2) gynecological surgery, (3) gastrointestinal surgery, (4) hip or knee replacement, (5) fractures, and (6) other orthopedic operations. Diagnosis of a first pulmonary embolism. A total of 60 703 patients were included (35 766 [58.9%] male; mean [SD] age, 56.6 [6.0] years). The risk of postoperative pulmonary embolism was elevated for at least 12 weeks after all types of surgery and was highest during the immediate postoperative period (1 to 6 weeks). The excess risk of postoperative pulmonary embolism ranged from odds ratio (OR), 5.24 (95% CI, 3.91-7.01) for vascular surgery to OR, 8.34 (95% CI, 6.07-11.45) for surgery for fractures. The risk remained elevated from 7 to 12 weeks, with the OR ranging from 2.26 (95% CI, 1.81-2.82) for gastrointestinal operations to 4.23 (95% CI, 3.01-5.92) for surgery for fractures. The risk was not clinically significant beyond 18 weeks postsurgery for all types of procedures. The risk of postoperative pulmonary embolism is elevated beyond 6 weeks postsurgery regardless of the type of procedure. The persistence of this excess risk suggests that further randomized clinical trials are required to evaluate whether the duration of postoperative prophylactic anticoagulation should be extended and to define the optimal duration of treatment with regard to both the thrombotic and bleeding risks.

P5588Early versus delayed oral anticoagulation in patients with acute pulmonary embolism: determinants and outcome

Abstract Background Whether early oral anticoagulant treatment is appropriate for patients with acute pulmonary embolism (PE) regardless of PE severity is undefined. The aim of this study in patients with acute PE at intermediate risk of death were: I) to assess the determinants for the use of early vs delayed vs no oral anticoagulants in patients with acute PE and II) to assess the association between timing of oral anticoagulation and in-hospital mortality. Methods Prospective cohorts of patients with acute PE at intermediate risk of death according to the European Society of Cardiology Guidelines 2014 were merged in a collaborative database. The initiation of oral anticoagulation was classified as early (≤3 days) or delayed (between day 3 and 10 from diagnosis). Patients treated with parenteral anticoagulants for longer than 10 days were also included. In-hospital death was the primary study outcome. Results Overall, 557 patients were included in the study, 23 received thrombolytic treatment during the hospital stay. The mean duration of parenteral anticoagulation was 7±8 days (5 median), 348 patients were initiated on a direct oral anticoagulant and 79 on a vitamin K antagonist during the hospital stay. Initiation of oral anticoagulants occurred early or delayed in 209 (37%) and 218 (39%) patients, respectively and never occurred during the first 30 days in 130 (23%). Intermediate-low risk patients more commonly received early and intermediate high delayed oral anticoagulation. Simplified PESI score of zero (OR 1.9, 95% CI 1.3–2.7) was independently associated with early oral anticoagulation; among sPESI components absence of cancer (OR 5.9, 95% CI 3.3–10) and heart rate <110 (OR 1.8, 95% CI 1.01–3.16) were independent predictors of early initiation of oral anticoagulants. The presence of both right ventricle dysfunction and injury was associated with delayed initiation of oral anticoagulants. The incidence of death was 5.5%. Death occurred in 32 patients and was not related to the duration of parenteral anticoagulation (OR 1.01 per day, 95% CI 0.98–1.06) nor to right ventricle dysfunction but to sPESI 1 (OR 3.32, 95% CI 1.14–9.66). These results were partially confirmed in the 435 intermediate risk patients without cancer (OR 1.03, 95% CI 0.99–1.08 for days of parenteral treatment; OR 4.17, 95% CI 0.95–18 for sPESI 1). Conclusion The clinical severity of PE and not the timing of initiation of oral anticoagulants are associated with in-hospital death in patients with intermediate risk PE. Randomized studies are needed to definitively assess the role of heparin lead-in in patients with PE at intermediate risk for death.

3150 Deep Venous Thrombosis in Ulcerative Colitis

INTRODUCTION: Inflammatory bowel disease (IBD) has a variety of both intestinal and extraintestinal manifestations. Among the range of extraintestinal manifestations of IBD, venous thromboembolism (VTE) is a rare complication with high morbidity and mortality. VTE can present in patients with both active disease, which is more prevalent, or in well-controlled disease, which suggests a prothrombotic risk in patients with IBD. The case below is a classic presentation of VTE in IBD, and raises questions involving lifelong anticoagulation. CASE DESCRIPTION/METHODS: A 62 year old male with ulcerative colitis presented to the office with a 2-week history of constant, achy pain in his right leg associated with swelling and stiffness of his right lower extremity. A right lower extremity venous duplex ultrasound revealed extensive thrombosis from the popliteal vein up to the common femoral vein. Despite a discussion about possible sequelae of untreated VTE such as further clot extension, acute pulmonary embolism, and death, the patient opted for outpatient treatment with lifelong apixaban. His swelling improved, and although he has had prior IBD exacerbations with significant bleeding, since the patient has been on apixaban, he has not had any significant bleeding. DISCUSSION: Patients with IBD have a threefold higher risk of VTE than the general population. Research suggests that it may be due to a complex interplay between inflammation and coagulation. Treatment of acute VTE in IBD patients has not been clearly defined and currently is similar to most patients. Consequently, the duration of anticoagulation is not established, and it is imperative to establish specific guidelines due to the risk of recurrent VTE in IBD. Currently, there are no data on the role of primary VTE prophylaxis for IBD patients in the outpatient setting and no specific biomarkers to identify IBD patients at risk. Future research should assess the prothrombotic risk in IBD to assist clinicians in preventive measures. Additional studies are needed to address the use of screening tests such as ultrasound or biomarkers. In this case, the patient was placed on lifelong apixaban due to his underlying risk factor of ulcerative colitis and showed clinical improvement with no significant bleeding. This case helps highlight the concern for major bleeding in a patient who has had previous significant major bleeding episodes during IBD exacerbations. In conclusion, VTE is a significant complication that should not be overlooked in patients with IBD.

459Direct oral anticoagulants are an effective therapy for left ventricular thrombus formation

Abstract Background and aim Left ventricular thrombus is a frequent complication of myocardial infarction (MI) and heart failure with severely depressed ejection fraction. Once diagnosed, anticoagulation for up to 6-months is recommended, but clinical experience with direct oral anticoagulation (DOAC) is limited to a few case reports. Our aim is to test DOAC LV thrombus resolution efficacy against warfarin. Methods Single-centre retrospective cohort study of consecutive patients with recently diagnosed LV thrombus, either after acute myocardial infarction or heart failure with reduced ejection fraction, from January 2009 till December 2018. Thrombus diagnosis and subsequent assessments were performed with echocardiography and complemented with cardiac magnetic resonance, when appropriate. Decisions regarding the type, dose and duration of anticoagulation and any concomitant antiplatelet therapy were left to physician's judgement. Results In a population of 66 patients (51 male, mean age 69±12 years), 13 received DOAC therapy, with the remainder receiving vit. K antagonists. One from each group was lost to follow up. The DOAC subgroup had higher prevalence of atrial fibrillation, higher left ventricular end-diastolic volumes and worse wall motion severity score index (WMSI). The duration of anticoagulant therapy, concomitant single or dual antiplatelet therapy and overall follow up were similar between strategies. Thrombus remission was observed in 91.7% (n=11) and 59.6% (n=31) patients within DOAC and warfarin group, respectively. Risk of unsuccessful resolution was reduced by 35% relative to the warfarin group (RR 0.65; 95% CI [0.491–0.862]; p-value 0.035) (figure). figure Conclusion DOAC seems to be an effective alternative to vitamin-K antagonists in patients with LV thrombus.

P3847Deep vein thrombosis in upper extremities: clinical characteristics, management strategies and long-term outcomes from the COMMAND VTE Registry

Abstract Background/Introduction Pulmonary embolism (PE) is caused by blockage of pulmonary arteries by thrombus. The sources of thrombus are thought to be mostly veins in lower extremities, whereas deep vein thrombosis (DVT) in upper extremities rarely occurs spontaneously. Recent studies reported that DVT in upper extremities might have significant complications, and DVT in upper extremities could be increasing. However, there is a paucity of data on patients with DVT in upper extremities, leading to uncertainty in optimal treatment strategies including anticoagulation therapy. Purpose We sought to evaluate the clinical characteristics, management strategies, and long-term outcomes of patients with DVT in upper extremities in a large observational database in Japan. Methods The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE) objectively confirmed by imaging examination or by autopsy among 29 centers in Japan between January 2010 and August 2014. The current study population consisted of 2498 patients with DVT in upper or lower extremities, after excluding 381 patients with PE only, 144 patients who had thrombus in locations other than upper or lower extremities, and 4 patients with DVT in both upper and lower extremities. The study patients were divided into 2 groups: patients with DVT in upper extremities and patients with DVT in lower extremities. We compared the clinical characteristics, management strategies and long-term outcomes between the 2 groups. Results There were 74 patients (3.0%) with upper extremities DVT and 2498 patients (97%) with lower extremities DVT. Patients with upper extremities DVT more often had active cancer at diagnosis (58%) and central venous catheter use (22%). The proportion of concomitant PE at diagnosis was lower in patients with upper extremities DVT than in those with lower extremities DVT (14% and 51%, P<0.001). Discontinuation of anticoagulation therapy was more frequent in patients with upper extremities DVT (63.8% and 29.8% at 1-year, P<0.001). The cumulative 3-year incidence of recurrent VTE was not different between the 2 groups (9.8% and 7.4%, P=0.43) (Figure). After adjusting confounders, the risks of upper extremities DVT relative to lower extremities DVT for recurrent VTE remained insignificant (HR 0.94, 95% CI 0.36–2.01, P=0.89). Kaplan-Meier event curves for recurrence Conclusions The prevalence of patients with DVT in upper extremities was 3.0% in the current large-scale real-world registry. Patients with DVT in upper extremities more often had active cancer at diagnosis and central venous catheter use as a transient risk factor for VTE, and less often had concomitant PE. Patients with DVT in upper extremities had similar long-term risk for recurrent VTE as those with DVT in lower extremities despite shorter duration of anticoagulation. Acknowledgement/Funding Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

P1895Predictors of left atrial thrombosis in patients undergoing planned electrical cardioversion of atrial fibrillation treated with direct anticoagulant

Abstract Background Scheduled electrical cardioversion (CV) of persistent atrial fibrillation (AF) can be performed after an adequate period of oral anticoagulation (OAC) therapy to reduce thromboembolic complications. Exclusion of left atrial appendage (LAA) thrombi can be achieved by transoesophagel echocardiography (TOE), that is indicated if early CV is desired in patients (pts) with ≥48 hours-lasting arrhythmia, while is not recommended after at least 3 weeks of OAC. Purpose We investigated with TOE the presence of LAA thrombi in a consecutive series of ambulatory pts scheduled for electrical CV of AF and treated with DOAC for at least 3 weeks. Methods We evaluated 93 pts referred to our Clinic for CV of persistent AF (October 2017–December 2018), all treated with DOAC. We collected clinical history, physical examination, 12-lead ECG, lab tests and transthoracic echocardiography measures. Right before cardioversion we systematically performed TOE to exclude LAA thrombi. If absent, we proceeded to CV, while in case of grade III echo-contrast and/or thrombotic stratification we didn't perform the procedure. All values are reported, as appropriate, as mean±SD or number and percentage. All results were considered statistically significant when p<0.05. The entire analysis was performed using the Statistical Package for Social Sciences package, version 19.0 (SPSS, Chicago, Illinois). Results 76 out of 93 pts (82% – group A) were free from intracavitary thrombi and underwent successful electrical CV; the other 17 pts (18% – group B) had thrombi in LAA that contraindicated electrical CV. Group B pts (74±10 years old, 65% male sex) had higher CHA2DS2-VASc score (4,1±2 vs 3,1±1,4, p=0,014), they were significantly more affected by chronic kidney disease (CKD, 59% vs 32%, p=0.035), peripheral artery disease (PAD, 35% vs 12%, p=0.017), they had larger LA dimension (48±5 vs 45±5 mm, p=0,09 - non significant) and as expected they had reduced LAA emptying velocity (76% vs 30%, p<0.001) compared to group A pts (73±8 years old, 70% male sex). There was no significant difference neither in duration (median 7 weeks) nor in type of DOAC therapy between the two groups. Conclusions Current Guidelines recommend at least three weeks of OAC before electrical CV of persistent AF. TOE is recommended only if early cardioversion is needed. We observed that in a significant part of pts treated with DOAC for more than 3 weeks TOE still identified LAA thrombi, especially in pts with multiple comorbidities. Even if we currently don't have data on clinical endpoints in this population, CV of patients with LAA thrombi despite adequate DOAC therapy may lead to an increased risk of thromboembolic events. We think it's necessary to identify more accurate predictors (i.e. CKD) to stratify the thromboembolic risk. Further randomized studies are needed to identify whether there are patients in which CV shouldn't be performed without TOE, irrespective of anticoagulation duration.

Venous Thromboembolism Recurrence in Latvian Population: Single University Hospital Data.

Background and objectives: Recurrence of venous thromboembolism (VTE) after a primary event is common; however, no sufficient risk scores have been widely introduced in clinical practice. The aim of this study was to assess the risk factors for VTE recurrences, as well as the effect of treatment strategies on the recurrence rate in a single-center patient cohort. Materials and Methods: The prospective cohort study included consecutive patients in a single center from June 2014 till June 2018 presenting with acute VTE confirmed by imaging tests. All patients were followed up for at least one year or till death. Statistical analyses were conducted using IBM SPSS Statistics 23 and Stata 13. Competing risk of death was considered. Results: A total of 219 eligible patients were identified during the study period. Pulmonary embolism with or without deep vein thrombosis (DVT) was present in 95.9% (n = 210), isolated DVT was present in 4.1% (n = 9) of patients. The total number of documented recurrences was 13 (5.9%). Incidence rate was 5.6 per 100 person-years. Recurrent VTE predicted significantly higher mortality rate (hazard ratio (HR) 6.64 [95% CI 2.61–16.93]). In univariate analysis, active cancer was associated with higher recurrence rate (p = 0.036). In competing-risks regression model (with death as the competing risk), active cancer (subdistribution hazard ratio (SHR) 2.11 (95% CI 0.58–7.76)) did not retain statistical significance for VTE recurrence. Discontinuation and duration of anticoagulant treatment (≤6 or >6 months), and drug class in acute or long-term therapy (parenteral, vitamin K antagonist (VKA), direct oral anticoagulant (DOAC)) were not associated with recurrences (p > 0.05). Conclusions: Patients who experienced recurrent VTE had 6.6-fold higher mortality rate than patients with no recurrences. The presence of active cancer was not a statistically significant risk factor for recurrence when taking into account the competing risk of death. Duration and drug class of anticoagulation did not seem to impact recurrence rate.

Results of a multinational survey of diagnostic and management practices of thromboembolic pulmonary embolism in children

IntroductionThe incidence of thromboembolic (TE)-pediatric pulmonary embolism (PPE) is increasing. We sought to evaluate current practice patterns and gaps in the management of TE-PPE. Materials and methodsAfter Institutional Review Board approval, SurveyMonkey® questions were sent to members of the Pediatric/Neonatal Thrombosis and Hemostasis Subcommittee, of the International Society on Thrombosis and Haemostasis and the Hemostasis and Thrombosis Research Society. ResultsOf 442 members of the two groups, 134 (30%) responded, and 125 (28%) complete responses were analyzed. Eighty percent practiced at a pediatric facility, 88% at academic centers, and 59% in the USA. Computed tomography pulmonary angiography (CTPA) was the preferred diagnostic modality (89%). D-dimer testing was variably used; 22% used clinical diagnostic prediction models and 8% had specific clinical care pathways for TE-PPE management. Prognostic stratification models were used to guide therapy by 4%. Indications for thrombolytic therapy varied considerably; 40% had a standardized protocol for thrombolysis, employing various modalities (45% systemic, 25% catheter-directed, 19% pharmaco-mechanical) and tissue plasminogen activator dose intensities. Duration of anticoagulation was variable with 58% prescribing anticoagulation for duration of >3 months–6 months; 61% followed for long-term adverse outcomes. ConclusionThis multinational survey of thrombosis/hemostasis specialists mainly based at pediatric academic centers demonstrates that antithrombotic management of TE-PPE (including duration of anticoagulation and use/non-use of thrombolysis) varies considerably. Furthermore, standardized care pathways to facilitate acute evaluation and management decisions are in place in a minority of centers. These findings help to inform the design of future clinical trials in TE-PPE.

Outcome of Anticoagulation Therapy of Left Atrial Thrombus or Sludge in Patients With Nonvalvular Atrial Fibrillation or Flutter

BackgroundBoth warfarin and nonvitamin K antagonist oral anticoagulants (NOACs) are increasingly used for thromboembolic prevention in patients with nonvalvular atrial fibrillation (NVAF). However, there are limited data concerning anticoagulation for left atrial (LA) thrombus or sludge. We aimed to determine the efficacy of warfarin and NOACs in LA thrombus or sludge in patients with NVAF or atrial flutter (AFL). Materials and MethodsSeventy-two patients with LA thrombus or sludge were analyzed who were scheduled for catheter ablation of NVAF or AFL between December 2015 and November 2018. Baseline demographics, the nature and duration of anticoagulation therapy and LA thrombus or sludge resolution were recorded. ResultsAfter receiving anticoagulation therapy for 101.5 (76.3-151) days, 44 patients (61.1%) demonstrated LA thrombus or sludge resolution, including 10 (58.8%) for warfarin, 15 (57.7%) for dabigatran and 19 (65.5%) for rivaroxaban (with no significant differences among these anticoagulants). After either prolonged anticoagulation, increased dosage or a change in anticoagulant, 14 patients underwent a third transesophageal echocardiography after 194.5 days (164.8-401.0) and an additional nine patients (12.5%) demonstrated LA thrombus or sludge resolution. Finally, 53 patients (73.6%) demonstrated complete resolution of LA thrombus or sludge, and this group had a lower CHA2DS2-VASc score (P = 0.044) and a lower rate of stroke history (P = 0.041). ConclusionsCompared with warfarin, dabigatran and rivaroxaban can also effectively resolve LA thrombus or sludge with no significant differences. Increasing the duration of anticoagulation, determining the optimal dosage of anticoagulants, and switching to another anticoagulant when necessary could be considered to improve treatment effectiveness.

Venous thromboembolism: current management

SUMMARYAnticoagulation is indicated in most cases of venous thromboembolismMonotherapy with rivaroxaban or apixaban is the preferred option for most adults with acute venous thromboembolismThere are no recommended dose reductions for rivaroxaban or apixaban in venous thromboembolism, unlike for atrial fibrillationThe initial duration of anticoagulation is usually three monthsExtended treatment with low-dose rivaroxaban or apixaban is effective in preventing recurrence in patients with a continuing increased risk of thromboembolism. Both drugs have low rates of major bleeding

Pharmacomechanical catheter thrombolysis for pregnancy-related proximal deep venous thrombosis: prevention of post-thrombotic syndrome

Objective The efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) in preventing post thrombotic syndrome (PTS) for pregnancy related deep vein thrombosis (DVT) is unknown. Study design An observational cross section study of women with pregnancy related proximal (femoral/iliofemoral) DVT who underwent PCDT followed by anticoagulation (study group), and women who were treated with anticoagulation alone (control group). Women were evaluated for PTS using the Villalta scale (primary outcome) and VEINES-QOL/Sym questionnaires. Results Eleven women with iliofemoral DVT underwent PCDT, two during their first trimester and nine postpartum; 18 women were treated with anticoagulation only. There were no significant differences in age, number of previous pregnancies, and duration of anticoagulation or thrombophilia between the groups. The time between DVT diagnosis and study inclusion was longer in the study group [median 50.5 (range 16–120) months] compared to the control group [median 27 (range 11–64) months], p = .4. None of the women in the PCDT group developed PTS, compared to six (33.3%, p = .03) in the control group, four of whom developed severe PTS. One patient in each group developed recurrent DVT, and one patient in the study group developed a calf hematoma. A reduced frequency of lower extremity symptoms was observed in the PCDT group (VEINES-Sym questionnaire), but no differences in quality of life (VEINES-QOL questionnaire) were reported. Conclusion This study suggests that PCDT may reduce the incidence of PTS in women with pregnancy related proximal DVT. Bullet points DVT involving the iliofemoral veins and development of post thrombotic syndrome is frequent among pregnant or postpartum women Studies of pharmacomechanical catheter-directed thrombolysis (PCDT) for deep vein thrombosis did not include pregnant or postpartum women In our observational cross section study women who underwent PCDT (mainly in the postpartum period) had reduced frequency of post-thrombotic syndrome compared to women who received anticoagulation only Larger studies are required to confirm the use of PCDT for prevention of PTS in this population

Evaluation of anticoagulant and antiplatelet therapy after iliocaval stenting: Factors associated with stent occlusion

ObjectiveIliocaval stenting has gained increased use over recent years for a variety of indications, including May-Thurner syndrome (MTS), post-thrombotic syndrome (PTS), and acute deep vein thrombosis (DVT). MethodsA retrospective review of 155 patients undergoing iliocaval venous stenting at a large teaching hospital was performed. Clinical and procedural data, mode and duration of anticoagulation or antiplatelet therapy, and outcomes were recorded. ResultsForty-five patients were treated for MTS, 49 for PTS. and 61 for acute DVT. The median follow-up was 19 months (interquartile range, 9-30 months). Primary patency rates were 97.8% in the MTS group, 85.7% in PTS, and 85.2% for the acute DVT group. Stent restenosis or occlusion occurred in one patient with MTS (2.2%), seven patients with PTS (14%), and nine patients with acute DVT (15%). An ipsilateral DVT recurred in 7 patients with PTS (14%) and 15 patients with acute DVT (25%). The stents that occluded had a tendency toward longer length (162.2 vs 125.2 mm; P = NS) and extension into the common femoral vein (18.8 vs 5.3%; P = NS). The patent stent group had statistically larger nominal diameter stents (P = .013). The duration of anticoagulation did not seem to be a significant factor in stent patency. ConclusionsStent diameter has a significant influence on iliocaval stent patency rates.

Quality Assessment of Oral Anticoagulation by Time in Therapeutic Range in Patients with Venous Thromboembolism in Korea

Purpose To assess the efficacy and safety of oral anticoagulation with warfarin by time in therapeutic range in patients with venous thromboembolism (VTE) in South Korea. Methods This was a retrospective, single-center study to evaluate patients diagnosed with VTE and managed with adjusted dose of warfarin over two-thirds of follow-up period in Thrombosis Clinic between February 2009 and August 2010. Validated dosing algorithm was used to manage the international normalized ratio (INR). Time in therapeutic range was calculated by Rosendaal method. Results The period of predetermined warfarin interruption for peri-operative management (1 week preoperatively and 3 weeks post-operatively) was censored. It was not analyzed in 34 episodes. Out of 76 patients with VTE, 47 (23 men; mean age 64.9 years) were analyzed. Approximately two-thirds (31/47) of patients were warfarin-naïve. Total number of admissions was 84. Expected duration of anticoagulation was 6 months in 22 patients (47%), 12 months in 1 (2%), and indefinite in 24 (51%). There were various comorbidities, including active malignancy in 7 patients (15%), mycobacterium tuberculosis on rifampicin in 4 (8.5%), chronic kidney disease in 4 (8.5%), and hemorrhagic cerebral infarct in 1 (2%). Overall time in therapeutic range (TTR) was 52.4%. Most proportion of out-of-range was below the therapeutic range (29.5%). There was no thromboembolic complication, although two cases of major bleeding complications were observed. Conclusion The validated dosing algorithm is effective for managing INRs in patients with VTE in Korea. Keywords: Time in therapeutic range, Warfarin, International normalized ratio, Venous thromboembolism

Direct oral anticoagulants for extended treatment of venous thromboembolism: insights from the EINSTEIN CHOICE study.

The risk of recurrence of venous thromboembolism (VTE) persists after interruption of the initial anticoagulation therapy. New evidence shows that direct oral anticoagulants are effective for extended treatment of VTE and may reduce the risk of all-cause mortality. The optimal duration of anticoagulation after VTE is, however, controversial and complicated by the need for individualised assessment and balance between thrombosis and bleeding risks. Three direct oral anticoagulants (rivaroxaban, apixaban and dabigatran) have been studied for extended treatment of VTE. Dabigatran was shown to be safer than vitamin K antagonists and similarly effective for the prevention of recurrent VTE. Dabigatran, apixaban and rivaroxaban resulted in significant decreases in the rate of recurrent symptomatic VTE when compared to placebo, without a statistically significant difference in the risk of major bleeding. The latest guidelines of the American College of Chest Physicians suggest the use of low-dose aspirin to prevent VTE recurrence in patients who want to stop anticoagulation. In the randomised, double-blind, phase 3 EINSTEIN CHOICE trial, once-daily rivaroxaban at doses of 20 mg or 10 mg and 100 mg of aspirin were compared in VTE patients for whom there was clinical equipoise for extended anticoagulation. Either a treatment dose (20 mg) or a prophylactic dose (10 mg) of rivaroxaban significantly reduced the risk of VTE recurrence without a significant increase in bleeding risk compared with aspirin. The EINSTEIN CHOICE trial included patients with provoked or unprovoked VTE. Patients with VTE provoked by minor persistent or minor transient risk factors enrolled in this trial had not-negligible VTE recurrence rates. These new findings on extended therapy suggest the possibility of anticoagulation regimens at intensities tailored to the patients' risk profiles and VTE characteristics, with a shift of the risk-benefit balance in favour of extended treatment.

The D-dimer assay.

D-dimer is an indirect marker of fibrinolysis and fibrin turnover; this molecule exhibits unique properties as a biological marker of hemostatic abnormalities as well as an indicator of intravascular thrombosis. D-dimer is a soluble fibrin degradation product that results from the systematic degradation of vascular thrombi through the fibrinolytic mechanism. Because of this, the D-dimer serves as a valuable marker of activation of coagulation and fibrinolysis in a number of clinical scenarios. Most commonly, D-dimer has been extensively investigated for excluding the diagnosis of venous thromboembolism (VTE) and is used routinely for this indication. In addition, D-dimer has been evaluated for determining the optimal duration of anticoagulation in VTE patients, for diagnosing and monitoring disseminated intravascular coagulation, and for monitoring other conditions in which the patient is at high risk of bleeding or thrombosis. Limitations of the assay include D-dimer elevation in a constellation of clinical scenarios (age, pregnancy, and cancer) and lack of clinical standardization.

Treatment of venous thromboembolism in acute leukemia: A systematic review

BackgroundThe safety and efficacy of venous thromboembolism (VTE) treatment in patients with acute leukemia (AL) are not well understood and the optimal treatment strategy is unclear. MethodsWe conducted a systematic review of the literature aiming to identify observational studies and randomized trials describing treatment of VTE in the setting of AL including, acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), and acute lymphoblastic leukemia (ALL). Due to the heterogeneity of findings, no meta-analysis was attempted. ResultsA total of 13 observational studies (11 cohorts and 2 case-control) totaling 5359 participants were included. The number of patients with VTE among the total population was 304 (5.7%; 95% CI 5.1–6.3). In patients with VTE, 221 patients received treatment with anticoagulation using either of low-molecular-weight heparin, unfractionated heparin, and/or vitamin K antagonists. Most studies adjusted the anticoagulant dose based on platelet count. The reported recurrence rate ranged from 0 to 29% among different studies and varied according to the duration of anticoagulant treatment and follow up. Bleeding events were not uniformly reported but the total number was low among anti-coagulated patients. ConclusionThere is a significant lack of data in this area with a high degree of heterogeneity in the choice of anticoagulant, dose adjustments for thrombocytopenia, and duration of anticoagulation. Further studies are required to develop guidelines and suggestions for treatment of VTE in AL.

Risk of Recurrent Venous Thromboembolism After an Initial Episode: Risk Stratification and Implications for Long-term Treatment.

Venous thromboembolism (VTE) is a common condition with significant associated morbidity and mortality. Recurrent VTE after an initial episode is a preventable medical condition. The following review discusses data supporting recurrence risk estimates after an initial VTE episode as well as treatment strategies to mitigate risk of recurrent VTE. This review particularly highlights methods for stratifying the risk of recurrent VTE and recent studies that have evaluated direct oral anticoagulants for the prevention of recurrent VTE. Risk assessment for VTE recurrence should guide anticoagulation duration. In patients who present with unprovoked VTE events, there remains a high risk of recurrence that is significantly mitigated with extended duration anticoagulation with either a vitamin K antagonist or direct oral anticoagulant.

DEVELOPMENT OF A PREDICTION MODEL FOR RECURRENCE RISK AFTER INCIDENT VENOUS THROMBOEMBOLISM: A DANISH NATIONWIDE COHORT STUDY

Optimal duration of anticoagulation after venous thromboembolism (VTE) is an ongoing critical clinical concern. Detailed clarification of risk factors associated with recurrence risk is needed to optimize decision making of treatment duration. We aimed to derive a novel risk prediction score for

Characterisation of acute ischemic stroke in patients with left ventricular thrombi after myocardial infarction.

Acute ischemic stroke (AIS) is a feared complication in post-acute myocardial infarction (AMI) patients who develop left ventricular (LV) thrombus. There is limited data available on the incidence of stroke in this population, and characterisation of stroke subtypes has not been previously reported. Our study aims to evaluate the incidence of AIS in post-AMI patients with LV thrombus and to characterise the pattern of stroke subtypes. We screened 5829 patients with echocardiogram reports containing the "thrombus" keyword from August 2006 to September 2017. AIS that occurred after LV thrombosis was captured and relevant clinical data was collected. We identified 289 post-AMI patients with acute LV thrombus formation. Mean age was 59.3 ± 13.4years. AIS occurred in 34 patients (11.8%), median duration of 20.5days (IQR = 5.5-671.8) after LV thrombosis. Despite initial thrombus resolution, nine (5.2%) encountered AIS subsequently. Cardioembolic stroke subtype was identified in 76.5% of AIS, whilst 14.7% was small vessel disease and 8.8% was of large artery atherosclerosis subtype. Presence of thrombus protrusion (HR 3.04, 95% CI 1.25-7.41, p = 0.01), failure of initial thrombus resolution (HR 3.03, 95% CI 1.23-7.45, p = 0.02) and thrombus recurrence (HR 4.20, 95% CI 1.46-12.11, p < 0.01) were significant independent predictors for stroke. Incidence of AIS in this Asian population of post-AMI patients with LV thrombus was 11.8%. Duration of anticoagulation may need to be individualised for patients with higher risk for stroke occurrence after LV thrombosis.