Duration Of Oral Anticoagulant Therapy Research Articles

Impact of concomitant proton pump inhibitor during oral anticoagulant treatment

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Proton pump inhibitor is commonly used for gastroprotective effect in patients with a combination of antiplatelets and anticoagulants. However, data quantifying the concomitant proton pump inhibitor for clinical adverse outcomes other than gastrointestinal bleedings of oral anticoagulant is lacking. Purpose We aimed to explore the effect of concomitant proton pump inhibitor on the effectiveness and safety of oral anticoagulant in patients with atrial fibrillation. Methods The medical records were retrospectively reviewed from four tertiary referral hospitals between January 1, 2012, and December 31, 2020. Concomitant use of drug was quantified as the overlapping proportion over the duration of oral anticoagulant therapy. Primary endpoint was the time to occurrence of ischemic stroke, systemic embolism, intracardiac thrombus, major bleeding events, or death. Results Data were analyzed for 20,750 episodes with oral anticoagulant and atrial fibrillation (median [IQR] age, 71 [63-78] years; female, 42.5%; warfarin, 37.3%; median [IQR] CHA2DS2-VASc score, 3 [2-5]). The risk of primary endpoint was greatest in the group of persistent use (80% or more of overlapping proportion) of proton pump inhibitor among the other groups with less overlapping proportion (adjusted hazard ratio, 1.88; 95% confidence interval, 1.63–2.16; P for groups, <0.001). Concomitant proton pump inhibitor was not associated with the risk of major bleeding from the gastrointestinal tract. Conclusion Among patients with atrial fibrillation receiving oral anticoagulant, concomitant use of proton pump inhibitor increased the rate of thromboembolism, major bleeding, or death in proportion of overlapping period.

Optimal duration of Vitamin K antagonists anticoagulant therapy after venous thromboembolism: a systematic review and network meta-analysis of randomized controlled trials

BackgroundThe optimal duration of oral anticoagulant therapy for patients with venous thromboembolism (VTE) remains highly uncertain in clinical practice. It is essential to accurately assess the effect of anticoagulant therapy in reducing recurrent VTE against the risk of inducing major bleeding.MethodsRandomized controlled trials were identified by searching PubMed, Web of Science, Embase, and the Cochrane library, reporting rates of recurrent VTE and major bleeding in patients taking Vitamin K Antagonists (VKA) with VTE and comparing different durations.ResultsEleven RCTs with 3109 participants utilizing varied durations were included in the meta-analysis. Longer VKA therapy was associated with significantly lower rates of VTE recurrence compared with shorter duration of VKA therapy (OR 0.75, 95%CI 0.57–0.99), with significant difference noted in major bleeding risk (OR 2.31, 95%CI 1.17–4.56). During anticoagulation duration, patients treated by 6-month VKA had higher risk of major bleeding compared with 3-month VKA regimen (OR 33.45, 95%CI 2.00–559.67).ConclusionsRegimen longer than 6 months did not show statistical elevation of major bleeding risk. VKA treatment strongly reduces the risk of recurrent VTE during anticoagulation therapy. The absolute risk of recurrent VTE declines over time while the risk for major bleeding after 6 months’ treatment did not demonstrate a continuous significant increase with extended duration of VKA therapy.

Randomized Evaluation of D-dimer Guiding dUration of Oral antiCoagulation thErapy

Randomized Evaluation of D-dimer Guiding dUration of Oral antiCoagulation thErapy

Антикоагулянтная терапия при фибрилляции предсердий на фоне острого коронарного синдрома в реальной клинической практике по данным тотального регистра острого коронарного синдрома по Краснодарскому краю

to analyze patients with first-time developing atrial fibrillation (AF), against acute coronary syndrome (ACS), risk factors for arrhythmia, assessment of patients' adherence to oral anticoagulant therapy 6-24 months after the ACS episode, according to the total ACS registry for the Krasnodar Territory. A retrospective analysis of the case histories of 13,244 patients admited to the infarction departments of all setlements of the Krasnodar Territory without exception and included in the ACS registry for the Krasnodar Territory from November 20, 2015 to January 20, 2018. The study group of ACS with AF included 201 patients, among them 144 men (71.642%), women 57 (28.358%). The average age was 68,084 ± 9,606 years, a maximum of 85 years, a minimum of 25 years. The frequency of the following outcomes was assessed: hospital mortality, frequency of hemorrhagic, thromboembolic complications. The effectiveness of prognostic scales of development of hemorrhage CRUSADE and HAS BLED was evaluated and the expediency of prescribing extended OAT to patients with the first developed AF atack against the background of ACS after discharge from the hospital. Based on the obtained results, based on the data of the total ACS register for the Krasnodar Territory, we can conclude: 1. Patients with a newly developed episode of AF on the background of ACS have demographic, anamnestic data comparable with other types of AF; 2. Patients with a newly developed AF episode on the background of ACS have a more severe course of the disease, which does not affect hospital mortality, hospital complications and lethality after 6-24 months after discharge from the hospital for ACS; 3. Patients with a newly developed episode of AF on the background of ACS after discharge from the hospital do not have arrhythmia recurrences, they do not have thromboembolic complications. The decision on the duration of oral anticoagulant therapy should be carried out afer carrying out a multi-day monitoring of the ECG.

Residual pulmonary embolism as a predictor for recurrence after a first unprovoked episode: Results from the REVERSE cohort study

BackgroundThe optimal duration of oral anticoagulant therapy after a first, unprovoked venous thromboembolism is controversial due to tightly balanced risks and benefits of indefinite anticoagulation. Risk stratification tools may assist in decision making. ObjectivesWe sought to determine the relationship between residual pulmonary embolism assessed by baseline ventilation-perfusion scan after completion of 5–7months of oral anticoagulant therapy and the risk of recurrent venous thromboembolism in patients with the first episode of unprovoked pulmonary embolism. MethodsWe conducted a multicentre prospective cohort study of participants with a first, unprovoked venous thromboembolism enrolled after the completion of 5–7months of oral anticoagulation therapy. The participants completed a mean 18-month follow-up. Participants with pulmonary embolism had baseline ventilation-perfusion scan before discontinuation of oral anticoagulant therapy and the percentage of vascular obstruction on baseline ventilation-perfusion scan was determined. During follow-up after discontinuation of oral anticoagulant therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated with reference to baseline imaging. Measurements and main resultsDuring follow-up, 24 of 239 (10.0%) participants with an index event of isolated pulmonary embolism or pulmonary embolism associated with deep vein thrombosis and central assessment of percentage of vascular obstruction on baseline ventilation-perfusion scan had confirmed recurrent venous thromboembolism. As compared to participants with no residual pulmonary embolism on baseline ventilation-perfusion scan, the hazard ratio for recurrent venous thromboembolism was 2.0 (95% CI 0.5–7.3) for participants with percentage of vascular obstruction of 0.1%–4.9%, 2.1 (95% CI 0.5–7.8) for participants with percentage vascular obstruction of 5.0%–9.9% and 5.3 (95% CI 1.8–15.4) for participants with percentage vascular obstruction greater than or equal to 10%. ConclusionsResidual pulmonary embolism assessed by pulmonary vascular obstruction on baseline ventilation-perfusion performed after 5–7months of oral anticoagulant therapy for the first episode of unprovoked pulmonary embolism was associated with a statistically significant higher risk of subsequent recurrent venous thromboembolism. Percentage of pulmonary vascular obstruction assessment by ventilation-perfusion scans maybe a useful tool to help guide the duration of oral anticoagulant therapy after a first unprovoked pulmonary embolism. Trial registrationRegistered at www.clinicaltrials.gov identifier: NCT00261014.

Abstract 235: Impact of Short-term Anticoagulant Use on the Risk of Recurrent Venous Thromboembolism: Evidence From Insurance Claims in the United States

Background: Duration of oral anticoagulant therapy for venous thromboembolism (VTE) is debatable. Moreover, literature shows that approximately 12% of the VTE patients discontinue warfarin therapy within 3 months and 63% discontinue within 1 year. Aim: To assess the real world impact of short term use of anticoagulants on the risk of recurrent VTE in the United States. Methods: Retrospective analyses of a large national claims dataset from 01/01/2007 to 12/31/2011 were conducted. Adult patients who had at least 3 months of continuous anticoagulant use (vitamin K antagonist or low molecular weight heparin) following an incident VTE were selected. Time to recurrent VTE after anticoagulant discontinuation was assessed using Cox proportional hazard regressions, adjusting for baseline characteristics. Subgroup analyses were conducted in unprovoked VTE, provoked VTE, and VTE patients with cancer. Results: We identified 31,906 patients with incident VTE. Within 1 year after the incident VTE, therapy was discontinued among 75.4% of the patients, with an average of 6 months of treatment. Patients with treatment discontinuation were younger than those without (mean age: 57 vs. 60 years), more likely to be females (51% vs. 46%) and had more co-morbidities (all P<0.05). The adjusted rate of recurrent VTE was 94% higher in patients with treatment discontinuation than in those without (hazard ratio [HR] = 1.9, 95% CI: 1.5-2.5). The higher rate of recurrent VTE associated with anticoagulant discontinuation was observed regardless of the timing of discontinuation (discontinued in 3-6, 6-9, or 9-12 months after incident VTE). The HR was found to be similar in the subgroups. Conclusion: Even after 3 months of anticoagulant treatment, the patients remained at high risk for recurrent VTE once the treatment was stopped by the physician or discontinued by the patient. Thus, longer-term use of anticoagulants may be warranted to prevent recurrent VTE.

Travel habits and complications in patients treated with vitamin K antagonists: A cross sectional analysis

Travel-related conditions have impact on the quality of oral anticoagulation therapy (OAT) with vitamin K-antagonists. No predictors for travel activity and for travel-associated haemorrhage or thromboembolic complications of patients on OAT are known. A standardised questionnaire was sent to 2500 patients on long-term OAT in Austria, Switzerland and Germany. 997 questionnaires were received (responder rate 39.9%). Ordinal or logistic regression models with travel activity before and after onset of OAT or travel-associated haemorrhages and thromboembolic complications as outcome measures were applied. 43.4% changed travel habits since onset of OAT with 24.9% and 18.5% reporting decreased or increased travel activity, respectively. Long-distance worldwide before OAT or having suffered from thromboembolic complications was associated with reduced travel activity. Increased travel activity was associated with more intensive travel experience, increased duration of OAT, higher education, or performing patient self-management (PSM). Travel-associated haemorrhages or thromboembolic complications were reported by 6.5% and 0.9% of the patients, respectively. Former thromboembolic complications, former bleedings and PSM were significant predictors of travel-associated complications. OAT also increases travel intensity. Specific medical advice prior travelling to prevent complications should be given especially to patients with former bleedings or thromboembolic complications and to those performing PSM.

An Unusual Case of Acute Abdominal Pain

Differential diagnosis for abdominal pain should enclose the rare occurrence of venous thromboembolism (VTE) which may be the clinical expression of a systemic disease including the complication or the unusual first clinical presentation of an inflammatory bowel disease (IBD) (Danese et al., 2005). Patients with IBD have an elevated risk of VTE compared with the general population (Kappleman et al., 2011, Grainge et al., 2010, and Miehsler et al., 2004). Mortality among patients with portal-mesenteric vein thrombosis is rather high (Quera et al., 2004), while, due to its rare occurrence, studies on splanchnic vein thrombosis are few and there are no univocal data on appropriate duration of oral anticoagulation therapy (Twing et al., 2005), long-term prognosis, morbidity, and mortality of the disease, which remain mostly unknown. The clinical case reported here describes a life-threatening, rare case of splenicmesenteric-portal vein thrombosis as the acute manifestation of ulcerative colitis. Awareness and early diagnosis of splanchnic thrombosis deserve, therefore, particular attention to ameliorate the final outcome and prognosis of the disease.

D-dimer: a useful tool in gauging optimal duration of oral anticoagulant therapy?

BACKGROUND AND AIM OF THE STUDY Optimal duration of oral anticoagulant therapy (OAT) in idiopathic venous thromboembolism (VTE) is unknown. Indefinite OAT carries an unacceptable risk of major bleeding and prospective studies have demonstrated that OAT is no longer protective after its withdrawal. How to identify the patients at risk for recurrence? D-dimer is a marker of thrombin activity. Early prospective studies showed that elevated D-dimer levels after anticoagulation had a highly predictive value for a recurrent episode. Does D-dimer assay have a role in gauging the appropriate duration of anticoagulant therapy? The PROLONG study tries to answer this question. METHOD D-dimer assay was performed one month after stopping anticoagulation. Patiens with normal D-dimer levels did not resume anticoagulation while patients with elevated D-dimer levels were randomized to discontinue or resume anticoagulation. Study end-points was the composite of recurrent VTE and major bleeding during an average follow-up of 1.4 years. RESULTS The rate of recurrence is significantly higher in patients with elevated D-dimer levels who discontinued anticoagulation. Resuming anticoagulation in this cohort of patients markedly reduces recurrent events without increasing major bleeding. DISCUSSION AND CONCLUSIONS PROLONG study is provocative, because D-dimer assay is simple, thus not requiring dedicated laboratory facilities. D-dimer test has otherwise high sensitivity but low specificity in VTE diagnosis. Aspecifically elevated D-dimer levels are available in the elderly and the majority of patients included in the study were > 65 years old, thus introducing a possible selection bias. Nonetheless the results of the study are useful for the clinician. Prolongation of vitamin K antagonists in patients with elevated D-dimer levels one month after discontinuation of OAT for a first unprovoked episode of VTE results in a favourable risk-benefit relationship. Probably this conclusion is even more appropriate for young patients.

Residual vein obstruction as a predictor for recurrent thromboembolic events after a first unprovoked episode: data from the REVERSE cohort study

There is growing interest in using residual vein obstruction (RVO) to guide the duration of oral anticoagulant therapy (OAT) for unprovoked deep vein thrombosis (DVT). We sought to determine if RVO as determined by compression ultrasonography (CUS) after completion of 5-7 months of anticoagulation for unprovoked DVT is associated with an increased risk of recurrent venous thromboembolism (VTE). This was a multicentre multinational prospective cohort study undertaken in tertiary care centers. Patients with a first 'unprovoked' major VTE were enrolled over a 4-year period and completed a mean 18-month follow-up in September 2006. All 452 patients with DVT had baseline CUS at inclusion to assess any RVO before stopping OAT at 5-7 months. During follow-up off OAT, all episodes of suspected recurrent VTE were independently adjudicated with reference to baseline imaging. Forty-five out of 231 patients with abnormal CUS (19.5%) had recurrent VTE during follow-up, as compared with 32 out of 220 patients with normal CUS (14.6%), and one patient had inadequate CUS. There was no significant association between an abnormal CUS at inclusion and the risk of recurrent VTE: hazard ratio 1.4 (95% confidence interval, 0.9-2.1), P=0.19. None of the different degrees of clot resolution on baseline CUS was statistically significantly associated with the risk of recurrent VTE. In our study, the presence of RVO at the time of OAT withdrawal was not associated with a statistically significant higher risk of recurrent VTE. RVO assessment may not be useful to guide duration of anticoagulation.

EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients

Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for <1% of all strokes. Diagnosis is still frequently overlooked or delayed as a result of the wide spectrum of clinical symptoms and the often subacute or lingering onset. Current therapeutic measures which are used in clinical practice include the use of anticoagulants such as dose-adjusted intravenous heparin or body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH), the use of thrombolysis and symptomatic therapy including control of seizures and elevated intracranial pressure. We searched MEDLINE (National Library of Medicine), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library to review the strength of evidence to support these interventions and the preparation of recommendations on the therapy of CVST based on the best available evidence. Review articles and book chapters were also included. Recommendations were reached by consensus. Where there was a lack of evidence but consensus was clear we stated our opinion as good practice points. Patients with CVST without contraindications for anticoagulation (AC) should be treated either with body weight-adjusted subcutaneous LMWH or with dose-adjusted intravenous heparin (level B recommendation). Concomitant intracranial haemorrhage (ICH) related to CVST is not a contraindication for heparin therapy. The optimal duration of oral anticoagulant therapy after the acute phase is unclear. Oral AC may be given for 3 months if CVST was secondary to a transient risk factor, for 6-12 months in patients with idiopathic CVST and in those with "mild" thrombophilia, such as heterozygous factor V Leiden or prothrombin G20210A mutation and high plasma levels of factor VIII. Indefinite AC should be considered in patients with recurrent episodes of CVST and in those with one episode of CVST and 'severe' thrombophilia, such as antithrombin, protein C or protein S deficiency, homozygous factor V Leiden or prothrombin G20210A mutation, antiphospholipid antibodies and combined abnormalities (good practice point). There is insufficient evidence to support the use of either systemic or local thrombolysis in patients with CVST. If patients deteriorate despite adequate AC and other causes of deterioration have been ruled out, thrombolysis may be a therapeutic option in selected cases, possibly in those without large ICH and threatening herniation (good practice point). There are no controlled data about the risks and benefits of certain therapeutic measures to reduce an elevated intracranial pressure (with brain displacement) in patients with severe CVST. However, in severe cases with impending herniation craniectomy can be used as a life-saving intervention (good practice point).

Durée du traitement anticoagulant dans la maladie thromboembolique veineuse : utilité du dosage des D-dimères

The optimal duration of oral anticoagulant therapy after a first “unprovoked” venous thromboembolism (VTE) is uncertain. Oral anticoagulation therapy is very efficient in reducing the risk of recurrence but increases the risk of hemorrhage. The balance between the risk of recurrent VTE and bleeding complication is difficult to predict on an individual basis. D-dimer levels during and after anticoagulation cessation have been evaluated in several cohort studies to potentially identify patients at high or low risk of recurrent event. Overall, these studies showed that D-dimer measurement had a high negative predictive value. According to the recent PROLONG trial and a meta-analysis, elevated D-dimer level may help identifying patients with a higher risk for recurrent VTE. Nevertheless, D-dimers should not be used as a stand-alone test to determine whether to stop or continue anticoagulation in patients with a first unprovoked VTE. La durée du traitement anticoagulant au décours d’un premier événement thromboembolique veineux idiopathique ne fait pas l’unanimité. L’anticoagulation, bien que très efficace dans la prévention de la récidive, s’accompagne d’un risque hémorragique non négligeable. Cette balance risque–bénéfice est difficile à évaluer chez une personne donnée. Depuis quelques années, l’évolution du taux des D-dimères sous anticoagulants et à distance de l’arrêt de ces derniers a été étudiée dans l’idée de pouvoir identifier les patients à faible ou à haut risque de récidive. Plusieurs études de cohorte utilisant des seuils et des méthodes de dosage différents ont montré que ce test avait une haute valeur prédictive négative. Une étude interventionnelle ainsi qu’une récente méta-analyse ont rapporté qu’en absence de traitement anticoagulant, les patients avec D-dimères élevés étaient à risque augmenté de récidive. Toutefois, malgré ces résultats encourageants, il semble encore prématuré de recommander l’utilisation des D-dimères pour se déterminer sur la durée du traitement anticoagulant chez les patients ayant présenté un premier événement thromboembolique veineux idiopathique.

Residual Thrombosis on Ultrasonography to Guide the Duration of Anticoagulation in Patients With Deep Venous Thrombosis: A Randomized Trial

Conclusion: Rates of recurrent venous thromboembolism (VTE) in adults with proximal deep venous thrombosis (DVT) can be reduced by tailoring the duration of anticoagulation on the basis of ultrasound findings. Summary: Patients with DVT are known to have an increased risk for recurrent VTE after anticoagulation (JAMA 2005;294:706-15). Anticoagulation is generally prescribed for 3 months for patients with reversible risk factors and for a minimum of 6 months for those patients with permanent risk factors or venous thrombosis (Chest 2008;133:454-5s). An association has been suggested between residual thrombosis present by ultrasound imaging at the time warfarin therapy is discontinued and an increased risk of subsequent recurrent VTE (Ann Intern Med 2002;137:955-60). The authors performed a randomized trial to evaluate the efficacy of tailoring the duration of anticoagulation based on recanalization or persistence of residual venous thrombosis as determined by ultrasound imaging. Patients with the first episode of proximal DVT who completed 3 months of anticoagulation were assigned to receive fixed-duration anticoagulation or flexible ultrasound-guided anticoagulation. This was a randomized, multicenter, open-label trial with independent and blinded assessments of study outcomes. Patients were recruited between January 1999 and July 2003, and the study ended when the last recruited patient had 3 years of follow-up. The study was conducted at nine centers in Italy. In patients assigned to the fixed-duration of anticoagulation, those with unprovoked DVT received 3 additional months of treatment for a total of 6 months, and anticoagulation was discontinued after 3 months in those with secondary DVT. Patients assigned to a flexible-duration of anticoagulation underwent ultrasound imaging after 3 months of anticoagulation. If the veins had recanalized, anticoagulation was discontinued. If the veins had not recanalized, patients were invited to undergo further ultrasound imaging after 3 and 9 months if they had a secondary DVT and to undergo further examinations after 3, 6, 9, 15, and 20 months if they had had an unprovoked DVT. Anticoagulation was discontinued when the veins had recanalized. Patients were monitored for symptomatic recurrent VTE and major bleeding episodes. Of 538 consecutive patients who underwent a 3-month period of anticoagulation, 530 completed the trial. Overall, recurrent VTE developed in 46 of 268 patients (17.2%) allocated to fixed-duration anticoagulation and 32 of the 270 (11.9%) allocated to flexible-duration anticoagulation (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.39-0.99). If patients had unprovoked DVT, the adjusted HR was 0.61 (95% CI, 0.36-1.02). In those with secondary DVT, the HR ratio was 0.81 (95% CI, 0.32-2.06). Major bleeding occurred in 0.7% of patients in the fixed-duration group and in 1.5% in the flexible-duration group (P = .67). Comment: Tailoring the duration of oral anticoagulant therapy based on follow-up ultrasound studies reduced the risk of recurrent VTE by 35% compared with a fixed-duration administration of warfarin therapy. The data also suggest the greatest benefit of flexible-duration warfarin therapy is in those with unprovoked DVT. The major problem in extrapolating these data to clinical practice is the authors' criteria for determining recanalization of a thrombosed vein. Ultrasound criteria for quantifying residual venous thrombosis are not widely used. Their criteria for a recanalized vein were that a vein was <2 mm in diameter with probe compression or <3 mm in diameter on two consecutive examinations. These criteria differ substantially from other criteria used to determine the presence of residual thrombosis after VTE (J Thromb Haemost 2006;4:1919-24). Additional studies will be needed to determine if the authors' approach and, in particular, their method of determining recanalization of a thrombosed vein is medically sound, safe, and cost-effective in routine clinical practice.

Residual Thrombosis on Ultrasonography to Guide the Duration of Anticoagulation in Patients With Deep Venous Thrombosis

The optimal duration of oral anticoagulant therapy in patients with deep venous thrombosis (DVT) of the lower extremities remains uncertain. To assess whether tailoring the duration of anticoagulation on the basis of the persistence of residual thrombi on ultrasonography reduces the rate of recurrent venous thromboembolism (VTE) compared with the administration of conventional fixed-duration treatment in adults with proximal DVT. Parallel, randomized trial from 1999 to 2006. Trained physicians who assessed outcomes were blinded to patient assignment status, but patients and providers were not. 9 university or hospital centers in Italy. 538 consecutive outpatients with a first episode of acute proximal DVT at completion of an uneventful 3-month period of anticoagulation. Patients were randomly assigned (stratified by center and secondary vs. unprovoked DVT by using a computer-generated list that was accessible only to a trial nurse) to fixed-duration anticoagulation (no further anticoagulation for secondary thrombosis and an extra 3 months for unprovoked thrombosis) or flexible-duration, ultrasonography-guided anticoagulation (no further anticoagulation in patients with recanalized veins and continued anticoagulation in all other patients for up to 9 months for secondary DVT and up to 21 months for unprovoked thrombosis). For the primary outcome assessment, 530 patients completed the trial. The rate of confirmed recurrent VTE during 33 months of follow-up. Overall, 46 (17.2%) of 268 patients allocated to fixed-duration anticoagulation and 32 (11.9%) of 270 patients allocated to flexible-duration anticoagulation developed recurrent VTE (adjusted hazard ratio [HR], 0.64 [95% CI, 0.39 to 0.99]). For patients with unprovoked DVT, the adjusted HR was 0.61 (CI, 0.36 to 1.02) and 0.81 (CI, 0.32 to 2.06) for those with secondary DVT. Major bleeding occurred in 2 (0.7%) patients in the fixed-duration group and 4 (1.5%) patients in the flexible-duration group (P = 0.67). The trial lacked a double-blind design. The sample size was not powered to detect differences in bleeding between groups and to detect effectiveness of the intervention in the subgroups of patients with unprovoked and secondary DVT. Patients with previous thromboembolism, permanent risk factors for thrombosis, and thrombophilic abnormalities other than factor V Leiden and prothrombin mutation were excluded. Tailoring the duration of anticoagulation on the basis of ultrasonography findings reduces the rate of recurrent VTE in adults with proximal DVT. None.

VTE recurrence in patients with inherited deficiencies of natural anticoagulants

Thromb Haemost 2009; 101: 5–6 Venous thromboembolism (VTE) is a serious clinical condition manifesting as deep venous thrombosis (DVT) and/or pulmonary embolism (PE). Patients with VTE have a considerable risk of recurrent VTE that persists for many years (1, 2). In a population based cohort study, Heit et al. (1) found an overall cumulative percentage of VTE recurrence at 180 days, 1 and 10 years of 10.1%, 12.9%, and 30.4%, respectively. In another recent prospective cohort study, Prandoni et al. (2) reported, in patients with a first episode of VTE followed for eight years after oral anticoagulant therapy (OAT) withdrawal, a cumulative incidence of recurrence of 17.5% after two years, 24.6% after five years, and 30.3% after eight years. OAT is effective in reducing the VTE recurrence rate. However, anticoagulant treatment is associated with an increased risk for bleeding complications (3). Thus, anticoagulation has to be discontinued when the benefit of treatment no longer outweighs its risks and this clearly depends on the estimated risk of recurrence. The optimal duration of OAT is established, either after a first episode of VTE, in patients with a transient or with a persistent risk factor for VTE with an average risk of bleeding. Patients with a persistent risk factor for VTE had a high risk of recurrence. In patients with cancer, the risk of recurrent VTE after stopping anticoagulant therapy is as high as 10% to 20% in the first year, particularly among those with metastatic disease or among those who received concurrent chemotherapy (2, 4). Thus, in view of the persistently high risk of VTE recurrence, a prolonged anticoagulant treatment is currently recommended in patients as long as the cancer remains active. Conversely, in patients with major reversible risk factor such as surgery, immobilization or trauma, the risk of recurrence is relatively low (5), and to stop anticoagulant therapy after three months of treatment appears to be a reasonable option. On the other hand, the optimal duration of OAT in patients with a first unprovoked episode of VTE is still uncertain, and recent guidelines of the American College of Chest Physician suggested to carefully assess the potential risks and benefits of long-term OAT in each patient (6). Recently, several studies have assessed the role of some individual features evaluated at the end of conventional anticoagulant treatment as risk factors for recurrence (7, 8). The main aim of this approach was to identify those patients with unprovoked VTE who could benefit from extended anticoagulant treatment. In a randomized controlled study, Palareti et al. showed that patients one month after discontinuation of anticoagulation with an abnormal D-dimer level had a significantly higher incidence of recurrent VTE compared to patients with normal D-dimer, and that resumption of anticoagulation was effective in reducing thromboembolic complications in these patients (7). In a prospective cohort study on 313 consecutive symptomatic outpatients with proximal DVT, Prandoni et al. showed that persistence of residual venous thrombosis at follow-up visits was associated with an increased risk VTE recurrence (8). Several studies and a meta-analysis have revealed that men have at higher risk of recurrence than women (9) and first manifestation of thrombosis as PE seems to be associated with an increased risk of VTE recurrence (10). During the last decade several abnormalities in the coagulation system have been shown to be associated with an increased risk of thrombosis. Their impact on the recurrence rate has been the focus of several clinical studies. Factor V Leiden and the prothrombin G20210A variation, the commonest inherited risk factors for thrombosis, are associated with an increased risk of VTE recurrence (11). However, the magnitude of the risk conferred by the presence of one of these risk factors is modest and not sufficient to warrant long-term anticoagulation. Inherited deficiencies of natural anticoagulants antithrombin, protein C, and protein S are present in less than 10% of VTE patients (12). Patients with these deficiencies are considered at higher risk for VTE (13). On the other hand, only few studies with a limited number of included patients have assessed the risk of recurrence associated with these thrombophilic abnormalities (14, 15). In these studies, the risk of recurrence in patients with first VTE and a thrombophilic defect and in patients without a thrombophilic defect was similar. However, these studies also included patients with other thrombophilic defects such as factor V Leiden, prothrombin G20210A mutation and included a relatively small number of patients with deficiencies of natural anticoagulants.

Seguimiento de la tromboembolia pulmonar

The aims of follow-up of pulmonary thromboembolism (PTE) are to avoid recurrence and possible sequels, such as pulmonary hypertension and postthrombotic syndrome of the lower limbs. Recurrences are reduced by anticoagulant therapy. In most PTE triggered by a transitory risk factor, without additional risk factors, the duration of oral anticoagulant therapy (OAT) is well established. However, in at least half of all cases, the triggering factors are not clear, the risk of recurrence is higher, and the duration of OAT has not been well-defined. Consequently, the factors that increase the risk of recurrence should be identified and monitored. These factors include cancer, some thrombophilias, and recurrent PTE or deep veinous thrombosis (DVT). In the last few years, idiopathic etiology, residual venous thrombosis, and other factors such as persistent right ventricular dysfunction, have also been demonstrated to be markers of recurrence. In some patients, D-dimers also seem to predict the risk of recurrence. Finally, the duration of OAT will be defined by periodically weighing the risk of recurrence against hemorrhagic risk in each individual patient. Current evidence on the balance of risks indicates a tendency toward indefinite anticoagulation, especially in idiopathic PTE. Moreover, functional monitoring through echocardiography, at least in the first 2 years, is essential to detect pulmonary hypertension associated with chronic pulmonary thromboembolism.

Absence of Residual Vein Thrombosis after an Episode of Idiopathic Deep Vein Thrombosis: Short-Term Anticoagulation Is Safe. The “Extended Dacus Study”.

Background. The optimal duration of Oral Anticoagulant Therapy (OAT) for Deep Vein Thrombosis (DVT) can be tailored by Residual Vein Thrombosis (RVT) (Siragusa S et al. Blood 2003; 102(11):OC183), a marker able to assess the individual risk for recurrent thrombosis. However, in patients with idiopathic DVT the safety of early interruption of OAT, because of absence of RVT, is still debated.Objective of the study. In the present study, we evaluated the safety of withholding OAT, in patients with idiopathic DVT and without RVT, three months after the index thrombotic episode.Study design. Prospective controlled study with two groups: patients without RVT stopped OAT after 3 months while those with RVT continued for additional 3 months.Materials and Methods. Consecutive patients with a first episode of idiopathic DVT of the lower limbs; patients with cancer or known thrombophilia were excluded. At the third months of OAT, RVT was assessed as previously described; briefly, RVT was considered absent when a clot occupying less than 40% of the vein lumen was detected by compression ultrasonography. Events, classified as recurrent DVT and/or Pulmonary Embolism (PE) and/or major and minor bleeding were evaluated; all patients were followed-up for at least 12 months after OAT discontinuation.Results. During the period 1999–2006, 518 patients were included in the study. In 206 (39.7%) RVT was considered absent (RVT negative group) and they stopped OAT; the remaining 312 patients continued anticoagulants for additional 3 months (RVT positive group). Total duration of follow-up (FU) was 184.7 years for RVT negative group (with a mean FU of 3.0 ± 0.83 years) and 191.3 years for RVT positive group (with a mean FU of 3.1 ± 0.89 years). The rate and type of events during FU is reported in table and figure.Conclusions. This investigation shows that in patients without RVT, three months of OAT are safe even after an episode of idiopathic DVT. This hold for at least 30% of the entire DVT population and has an important clinical impact; in fact, it is possible to select a group of patients with a very low risk for recurrences over a period of 3 years. This approach carries also a negligible risk for bleeding.Events between RVT Negative and Positive GroupsOutcomesRVT Neg. group (206)RVT Pos. group (312)"p" valueRecurrences, n/total (%)*2/206 (0.9)63/312 (20.2)<0.0005Recurrences, n/100 person-year (%)*2/184.7 (1.1)63/191.3 (32.9)<0.0005Type of recurrent VTEDVT143DVT + PE06Isolated PE03Controlateral111Major bleeding, n/total (%)**0/2063/312 (0.9)Major bleeding, n/100 person-Yr (%)**0/184.73/191.3 (1.5)*After OAT discontinuation, **During OAT [Display omitted]

Anticoagulation for three versus six months in patients with deep vein thrombosis or pulmonary embolism, or both: randomised trial

Objective To determine the optimum duration of oral anticoagulant therapy after an episode of deep vein thrombosis or pulmonary embolism, or both.Design Multicentre, prospective, randomised study with follow-up for one...

Acceptibility of Patient Self-Testing of Oral Anticoagulation in New Patients.

Monitoring oral anticoagulation therapy (OAT) remains a significant burden on health care resources. Patient self-testing (PST) of OAT using point of care devices may alleviate these demands and improve the quality of treatment. Previous studies have shown limited benefit, as recruitment amongst patients previously established on OAT has proven to be difficult with only around 10–15 % of those invited agreeing to participate, suggesting that PST may only be suitable for a minority of patients. We aimed to assess whether PST is more acceptable to patients if offered at the commencement of treatment. 216 consecutive adults referred to anticoagulation clinics were assessed for their suitability for PST. Exclusion criteria included: short therapeutic duration (e.g. pre-cardioversion); known drug/alcohol abuse; atypical INR target values; language barriers; physical/intellectual impairment. Suitable patients were offered the opportunity to perform PST with 2 training sessions and thereafter monitor their INR every 1–2 weeks using CoaguChek S (Roche Diagnostics). It was noted during recruitment of the first 100 patients, that patients awaiting cardioversion accounted for a large proportion of the patients excluded (15/54, 28%), but many patients awaiting cardioversion received OAT in excess of six months. We therefore modified initial entry criteria, to include those with atrial fibrillation awaiting cardioversion. Of the 116 patients subsequently approached 37 (32%) were then recruited to PST (compared with only 17 cardiac patients from the first 100 enrolled into the study). 98 (45%) patients fulfilled our entry criteria for PST, of whom 54 (25%) consented to PST. Of the 118 ineligible patients: 23 had previously received OAT; 15 were awaiting cardioversion; the expected duration of OAT was less than 6 months in 13 patients; and PST was logistically impractical in 32 other patients. A further 35 were excluded for a wide variety of reasons including non-standard INR ranges, language barriers, discontinuation of OAT and planned surgical procedures. Only two of the 54 patients who started PST elected to return to hospital testing. Overall 53 % (52/98) of eligible patients have continued to self-test. The INR values obtained from these patients showed that their oral anticoagulant control remained stable (mean time in therapeutic range of 71%), and compared favourably to those patients electing to attend our routine anticoagulant clinic. Our data show that patients offered PST as an alternative to routine clinic management during induction of anticoagulation were more likely to participate in PST than established patients. Furthermore, the vast majority of patients (96%) continued to self-test, a higher figure than previous studies involving established patients.

Retinal Vein Occlusion Associated With Antithrombin Deficiency Secondary to a Novel G9840C Missense Mutation

To describe a novel missense mutation in the antithrombin gene associated with antithrombin deficiency type I in a 40-year-old man with retinal vein occlusion. Investigational case report. Ophthalmoscopy of the right eye showed hemicentral retinal vein occlusion. The patient's medical history was negative for glaucoma or cardiovascular risk factors. Screening for thrombophilic disorders revealed antithrombin deficiency type I. Based on a genetic analysis, a novel missense mutation of a transition of guanosine to cytosine at nucleotide position 9840 was detected, predicting the replacement of aspartic acid by histidine encoded by codon 366 (D366H) in exon 5. Selective screening may be helpful in identifying patients with retinal vein occlusion with thrombophilic defects. When ordering laboratory tests in patients with retinal vein occlusion, antithrombin deficiency type I should be considered in the differential diagnosis. Our results contribute to a better understanding of the molecular bases of antithrombin deficiency, adding a novel entry for the molecular defects causing antithrombin deficiency type I. Moreover, the identification of this thrombophilic disorder in retinal vein occlusion may be relevant to the issue of the initiation and duration of oral anticoagulant therapy.