Duration Of Anticoagulant Treatment Research Articles

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.

Therapeutic Implications of Inherited Thrombophilia in Pregnancy.

Inherited (hereditary) thrombophilia is a genetic disorder that affects coagulation, being responsible for more than 60% of idiopathic (spontaneous or unprovoked) thromboembolic events. Association of inherited thrombophilia with pregnancy increases the risk of thromboembolic disease, and it may be related to many complications, such as preeclampsia, recurrent miscarriage intrauterine growth restriction, early detachment of placenta, and prematurity. Interpretation of a positive test for thrombophilia in pregnant women is difficult because they have many natural changes in the coagulation system. Genetic diagnosis of thrombophilia, after a thrombotic event or during a pregnancy complication, has a major importance, not only to define its etiology but also to determine the duration of anticoagulant treatment and risk stratification for prophylaxis treatment. Literature search was performed using electronic database (PubMed) between April 1981 and November 2018. We used different keywords and MeSH terms to generate the most relevant results related to the inherited thrombophilia and its impact on pregnancy. Screening for inherited thrombophilia in young women is recommended in case of personal history of venous thromboembolism, first-degree relatives with a history of high-risk thrombophilia, or personal history of second-trimester miscarriage. Decision to recommend thromboprophylaxis with anticoagulant treatment in pregnant women with inherited thrombophilia is determined by history of venous thromboembolism, type and associated risk of inherited thrombophilia, and presence of additional risk factors. Low-molecular-weight heparins are the preferred agents for prophylaxis in pregnancy, while the doses vary depending on thrombophilia type, personal history, and associated risk factors. Association between 2 procoagulant conditions, inherited thrombophilia and pregnancy, has an important impact for the mother and fetus. This review will summarize the impact of each inherited prothrombotic factor on cardiovascular and pregnancy outcomes and will discuss the role of anticoagulation treatment for women diagnosed with inherited thrombophilia.

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.

Duration of anticoagulant therapy and VTE recurrence in patients with cancer

PurposeAnticoagulant therapy for at least 3–6 months is currently recommended for treatment of venous thromboembolism (VTE) in patients with cancer, but the optimal duration of treatment is unknown. This study examines the association between the duration of anticoagulation treatment and VTE recurrence in cancer patients.MethodsThe Humana claims database was used to identify newly diagnosed cancer patients who had their first VTE diagnosis between January 1, 2013, and May 31, 2015, and initiated injectable or oral anticoagulant therapy. Follow-up was calculated from the index treatment initiation to the end of eligibility or end of data (June 2015). VTE recurrence was defined as a hospitalization with a primary diagnosis of VTE. Cox proportional hazards models were used to evaluate the risk of VTE recurrence by duration of therapy in patients who discontinued therapy.ResultsThe study included 1158 patients. Compared to patients treated for 0 to 3 months, VTE recurrences were significantly lower among patients treated for 3 to 6, or over 6 months. After adjustment for baseline characteristics, patients treated for 3 to 6 months (HR [95%CI], 0.53; 0.37–0.76) and more than 6 months (HR [95%CI], 0.48; 0.34–0.68) were still significantly less likely to have VTE recurrences compared to patients treated for 0 to 3 months (both p < 0.01). Findings were similar using a VTE event definition that included outpatient visits.ConclusionsAmong newly diagnosed cancer patients with VTE, anticoagulant therapy lasting more than 3 months was associated with a lower risk of VTE recurrence.

The Effect of Anticoagulant Therapy on Survival and Outcome of Venous Thrombosis in Children, Teenagers, and Young Adults with Acute Lymphoblastic Leukemia Treated According to ALL-MB-2008 and ALL-MB-2015 Protocols

Aim. To assess the effect of anticoagulant therapy on survival and outcome of venous thrombosis in children, teenagers, and young adults with acute lymphoblastic leukemia (ALL). Materials &amp; Methods. Venous thrombosis was diagnosed in 42 out of 592 ALL patients treated according to ALL-MB-2008 and ALL-MB-2015 protocols from 2008 to 2017. Results. A daily dose of 150-200 lU/kg low molecular weight heparin (LMWH) was administered to 30 patients. Duration of anticoagulant treatment was up to 1 month in 4 patients, 2-3 months in 8 patients, 4-6 months in 12 patients, and 7-12 months in 4 patients. To 2 patients anticoagulants were administered for more than 24 months. Complete recanalization of thrombosed vessel was achieved in 19 patients, partial recanalization was achieved in 6 patients, obliteration of predominantly internal jugular vein was found in 5 patients. During thrombocytopenia (100 to 35 x 10&lt;sup&gt;9&lt;/sup&gt;/L) 12 patients received reduced doses of LMWH for 1-4 weeks. In the period of chemotherapy-induced thrombocytopenia the daily LMWH dose was reduced in proportion to thrombocyte level. After thrombocyte recovery up to more than 100 x 10&lt;sup&gt;9&lt;/sup&gt;/L antithrombotic treatment was continued with LMWH daily dose of 150-200 anti-Xa lU/kg. The duration of anticoagulant treatment among 12 patients who received reduced doses of LMWH was up to 1 month in 3 patients, 2-3 months in 4 patients, 4-6 months in 3 patients, and 7-12 months in 2 patients. Complete recanalization of thrombosed vessel was achieved in 8 patients, partial recanalization was achieved in 2 patients, vein obliteration was found in 2 patients. No correlation between LMWH dosage and thrombosis outcome was observed (χ&lt;sup&gt;2&lt;/sup&gt; = 0.494; p = 0.78). Maintenance (accompanying) therapy was completed in 38 out of 42 ALL patients with venous thrombosis. Event-free survival was 83 ± 8 %, that was similar to the one (81 ± 2 %) in patients without thrombosis (p = 0.654). Conclusion. Anticoagulant treatment of venous thrombosis complicating ALL in children, teenagers, and young adults did not yield a decrease of either overall or event-free survival. Reduction of LMWH doses in the period of chemotherapy-induced thrombocytopenia did not affect the outcome of venous thrombosis.

Clinical Impact and Safety of Anticoagulants for Portal Vein Thrombosis in Cirrhosis.

Portal vein thrombosis (PVT) is a frequent complication of cirrhosis. Benefit, safety, and duration of anticoagulant treatment in this setting are controversial issues. The aim of this study was to analyze the course of PVT in a large cohort of cirrhotic patients undergoing or not anticoagulation therapy. The data of 182 patients who presented between January 2008 and March 2016 with cirrhosis and PVT with at least 3 months of follow-up after the first PVT detection were analyzed. Eighty-one patients received anticoagulants and 101 were untreated per physician discretion. The extension of the thrombosis decreased by >50% in 46 (56.8%, with complete recanalization in 31/46) patients under anticoagulation and in 26 (25.7%) untreated patients. Of the 46 patients who underwent recanalization, 17 (36%) suffered recurrent thrombosis after stopping anticoagulation therapy. Kaplan-Meier analysis showed a higher survival rate in the treated group (p = 0.010). At multivariate analysis, anticoagulation was an independent factor associated with longer survival (HR:0.30, CI:0.10-0.91, p = 0.014). The Child-Turcotte-Pugh classes B/C negatively influenced survival (hazard ratio, (HR):3.09, confidence interval (CI):1.14-8.36, p = 0.027 for Child-Turcotte-Pugh B and HR:9.27, CI:2.67-32.23, p < 0.001 for Child-Turcotte-Pugh C). Bleeding complications occurred in 22 (21.8%) untreated and 16 (19.7%) treated patients, but in only four cases was it judged to be related to the anticoagulant treatment. No death was reported as a consequence of the bleeding events. Anticoagulant treatment is a safe and effective treatment leading to partial or complete recanalization of the portal venous system in 56.8% of cases, improving the survival of patients with cirrhosis and PVT. Discontinuation of the therapy is associated with a high rate of PVT recurrence.

Breadth of complications of long-term oral anticoagulant care.

The majority of patients with venous thromboembolism (VTE) have a considerable long-term risk of recurrence and may require extended duration of anticoagulant treatment after the initial 3 to 6 months. The decision to extend treatment is based not only on the individual risk of recurrence, but should also consider the potential complications associated with anticoagulation, taking into account that anticoagulant drugs are among the drugs most frequently associated with hospital admission due to adverse drug reactions. The most feared complication of oral anticoagulants is bleeding, which in some cases may be fatal or may affect critical organs. Case-fatality rates of bleeding have been reported to be ∼3 times higher than case-fatality rates of recurrent VTE. Even when nonserious, bleeding may require medical intervention and/or may impact on patient quality of life or working activity. Factors associated with bleeding during anticoagulant treatment include, among others, advanced age, cancer, renal or liver insufficiency, or concomitant antithrombotic drugs, but no bleeding risk score is sufficiently accurate for use in clinical practice. Not uncommonly, bleeding occurs as a complication of trauma or medically invasive procedures. Nonbleeding complications associated with oral anticoagulants are unusual, and their relevance is extremely uncertain, and include vascular calcification, anticoagulation-related nephropathy, and osteoporosis. Finally, because VTE not uncommonly affects young individuals and the mean age of the population is ∼60 years, the costs associated with extended anticoagulation should not be forgotten. The costs of the drugs need to be balanced against health outcome costs associated with both recurrent VTE and bleeding.

Long-term outcomes of isolated superficial vein thrombosis in patients with active cancer

BackgroundCancer patients who develop a deep-vein thrombosis (DVT) or a pulmonary embolism (PE) are at higher risk of death than similar cancer patients who do not develop DVT or PE. The impact of isolated superficial venous thrombosis (SVT) (i.e. without DVT or PE) on the prognosis of cancer patients is unknown. MethodsData from the OPTIMEV, multicentre, observational study, to compare at 3 years the incidences of death, DVT-PE recurrence and bleeding of cancer patients with objectively confirmed SVT vs. cancer patients with DVT (matched 1:2 on age, sex, cancer stage) and vs. patients with SVT without cancer (matched 1:3 on age and sex). ResultsCancer patients with SVT (n = 34) had a high risk of death (23.2%patient-year(PY)), that was similar to that of cancer patients with DVT (aHR = 1.0[0.6–1.9]) and higher to that of SVT patients without cancer (aHR = 9.0[3.5–23.1]). Cancer patients with SVT received anticoagulants for a median duration of 45 days and had a high risk of DVT-PE recurrence (6.0%PY), similar to that of cancer patients with DVT (adjusted cause-specific HR (aCHR) = 1.5[0.4–5.8]) and higher to that of SVT patients without cancer (aCHR = 2.9[0.7–11.9]). In our population, venous thrombosis on varicose veins was associated with a lower risk of death (aHR = 0.6[0.3–1.0]) and DVT-PE recurrence (aCHR = 0.6[0.2–1.7]). ConclusionOur results suggest that cancer patients with SVT have a poor prognosis, similar to that of patients with cancer-related DVT. The high rate of DVT-PE recurrence suggests that such patients may need longer duration of anticoagulant treatment.

Risk factors for recurrence in deep vein thrombosis patients following a tailored anticoagulant treatment incorporating residual vein obstruction

BackgroundFinding the optimal duration of anticoagulant treatment following an acute event of deep vein thrombosis (DVT) is challenging. Residual venous obstruction (RVO) has been identified as a risk factor for recurrence, but data on management strategies incorporating the presence of RVO and associated recurrence rates in defined clinical care pathways (CCP) are lacking. ObjectivesWe aimed to investigate the long‐term clinical outcomes and predictors of venous thromboembolism (VTE) recurrence in a contemporary cohort of patients with proximal DVT and managed in a CCP incorporating the presence of RVO. PatientsAll patients treated at the Maastricht University Medical Center within an established clinical care pathway from June 2003 through June 2013 were prospectively followed for up to 11 years in a prospective management study. ResultsOf 479 patients diagnosed with proximal DVT, 474 completed the two‐year CCP (99%), and 457 (94.7%) the extended follow‐up (2231.2 patient‐years; median follow‐up 4.6 years). Overall VTE recurrence was 2.9 per 100 patient‐years, 1.3 if provoked by surgery, 2.1 if a non‐surgical transient risk factor was present and 4.0 if unprovoked. Predictors of recurrent events were unprovoked VTE (adjusted hazard ratio [HR] 4.6; 95% CI 1.7, 11.9), elevated D‐dimer one month after treatment was stopped (HR 3.3; 1.8, 6.1), male sex (HR 2.8; 1.5, 5.1), high factor VIII (HR 2.2; 1.2, 4.0) and use of contraceptives (HR 0.1; 0.0, 0.9). ConclusionsPatients with DVT managed within an established clinical care pathway incorporating the presence of RVO had relatively low incidences of VTE recurrence.

Long‐term outcomes of elderly patients with CYP2C9 and VKORC1 variants treated with vitamin K antagonists

Background The long-term effect of polymorphisms of the vitamin K-epoxide reductase (VKORC1) and the cytochrome P450 enzyme gene (CYP2C9) on clinical outcomes remains unclear. Objectives We examined the association between CYP2C9/VKORC1 variants and long-term clinical outcomes in a prospective cohort study of elderly patients treated with vitamin K antagonists for venous thromboembolism (VTE). Methods We followed 774 consecutive patients aged ≥ 65 years with acute VTE from nine Swiss hospitals for a median duration of 30 months. The median duration of initial anticoagulant treatment was 9.4 months. The primary outcome was the time to any clinical event (i.e. the composite endpoint of overall mortality, major and non-major bleeding, and recurrent VTE. Results Overall, 604 (78%) patients had a CYP2C9 or VKORC1 variant. Three hundred and thirty-four patients (43.2%) had any clinical event, 119 (15.4%) died, 100 (12.9%) had major and 167 (21.6%) non-major bleeding, and 100 had (12.9%) recurrent VTE. After adjustment, CYP2C9 (but not VKORC1) variants were associated with any clinical event (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.08-1.66), death (HR, 1.74; 95% CI, 1.19-2.52) and clinically relevant non-major bleeding (sub-hazard ratio [SHR], 1.39; 95% CI, 1.02-1.89), but not with major bleeding (SHR, 1.03; 95% CI, 0.69-1.55) or recurrent VTE (SHR, 0.95; 95% CI, 0.62-1.44). Patients with genetic variants had a slightly lower anticoagulation quality. Conclusions CYP2C9 was associated with long-term overall mortality and non-major bleeding. Although genetic variants were associated with a slightly lower anticoagulation quality, there was no relationship between genetic variants and major bleeding or VTE recurrence.

Clinical course of isolated distal deep vein thrombosis in patients with active cancer: a multicenter cohort study

Background Although isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer, no study has specifically evaluated the long-term clinical course of IDDVT in this setting. Aim To provide data on the rate of recurrent venous thromboembolism (VTE), major bleeding events and death in IDDVT patients with active cancer. Patients and Methods Consecutive patients with active cancer and an objective IDDVT diagnosis (January 2011 to September 2014) were included from our files. We collected information on baseline characteristics, IDDVT location and extension, VTE risk factors, and type and duration of anticoagulant treatment. Results A total of 308 patients (mean age 66.2 [standard deviation (SD), 13.2 years]; 57.1% female) with symptomatic IDDVT and a solid (n = 261) or hematologic (n = 47) cancer were included at 13 centers. Cancer was metastatic in 148 (48.1%) patients. All but three (99.0%) patients received anticoagulant therapy, which consisted of low-molecular-weight heparin in 288 (93.5%) patients. Vitamin K antagonists were used for the long-term treatment in 46 (14.9%) patients, whereas all others continued the initial parenteral agent for a mean treatment duration of 4.2 months (SD, 4.6 months). During a total follow-up of 355.8 patient-years (mean, 13.9 months), there were 47 recurrent objectively diagnosed VTEs for an incidence rate of 13.2 events per 100 patient-years. During anticoagulant treatment, the annual incidence of major bleeding was 2.0 per 100 patient-years. Conclusions Cancer patients with IDDVT have a high risk of VTE recurrence. Additional studies are warranted to investigate the optimal intensity and duration of anticoagulant treatment for these patients.

Inferior Vena Cava Agenesis and Deep Vein Thrombosis in the Young: A Review of the Literature and Local Experience.

AbstractCongenital agenesis of the inferior vena cava (AIVC) is a rare vascular abnormality with a prevalence of 0.0005 to 1% in the general population. This condition is found in almost 5% of young patients (younger than 30 years) with proximal, typically bilateral, deep venous thrombosis (DVT) of the lower limbs, often in the absence of apparent risk factors. However, AIVC in young patients with DVT is probably underestimated because AIVC cannot be detected by the standard DVT diagnostic workup. Inherited thrombophilia has been reported in patients with AIVC-associated DVT, as an additional risk factor, but its role is poorly investigated. The best therapeutic strategy and the optimal duration of anticoagulant treatment of DVT in patients with AIVC are still unclear. Here, we describe 14 young patients (2 females and 12 males, mean age at first DVT: 27.8 ± 10.1 years), with color Doppler ultrasound (US) and abdominal computed tomography scan confirmed AIVC-associated DVT and discuss their characteristics in the framework of a literature review on this topic. Our patients were mainly males (10/12) and experienced proximal DVT events, not complicated by pulmonary embolism. DVT-precipitating factors were detected only in five cases, the two female patients (oral contraceptives and puerperium), and three male patients (one after leg fracture and two after abdominal surgery). Thrombophilic abnormalities were found in eight patients (heterozygous factor V Leiden mutation, n = 3; mild/moderate hyperhomocysteinemia, n = 3; reduced protein C activity, n = 1; antiphospholipid syndrome, n = 1). The majority of patients (13/14) were treated with long-term oral anticoagulant therapy and elastic stockings (ES), with a very low rate of DVT recurrence (1/14, mean follow-up 7 years). These clinical characteristics were largely consistent with those of 161 patients identified by review of the literature. On the whole, although many aspects are still poorly known, our case series and literature review suggest that a search should be undertaken for AIVC in young patients with proximal idiopathic, particularly when bilateral, DVT, which should then be treated with prolonged anticoagulation and ES.

Symptomatic Venous Thromboembolism After Adolescent Knee Arthroscopy

The frequency of knee arthroscopy procedures is increasing in pediatric and adolescent patients. In general, complications after these procedures in adolescents are uncommon. The purposes of this study are to report the incidence of venous thromboembolism (VTE) in adolescent patients after knee arthroscopy procedures, as well identify risk factors in this patient population. Medical records were reviewed in all pediatric and adolescent patients (≤19 y) who underwent an arthroscopic knee procedure from 2010 to 2014 and were diagnosed with a symptomatic VTE in the postoperative period. Demographic features were recorded, and included age, sex, body mass index, clinical characteristics (diagnosis, type of surgical intervention, tourniquet time), VTE risk factors [family history of VTE, obesity (body mass index >30), oral contraceptive use, and smoking use/exposure] and treatment (anticoagulation type/duration). Out of 2783 patients who underwent knee arthroscopy during the 5-year study period, 7 patients (3 males, 4 females, mean age, 16.9 y, range, 15 to 18) developed a symptomatic postoperative VTE (incidence, 0.25%, 95% confidence interval, 0.11%-0.54%). There were 6 unilateral deep venous thrombosis, and 1 bilateral deep venous thrombosis. Arthroscopic procedures performed in this cohort included anterior cruciate ligament reconstruction (3), isolated lateral release (1), meniscectomy (2), and patellar realignment with arthroscopic lateral release, open tibial tubercle osteotomy, and open proximal medial retinacular reefing (1). VTE was diagnosed an average of 9 days following surgery (range, 3 to 16). All patients were initially treated with low-molecular-weight heparin, and 2 were converted to warfarin. Mean duration of anticoagulation treatment was 64 days (range, 28 to 183). All patients had at least 1 identifiable medical or surgical risk factor, including oral contraceptive use (2), smoking (2), obesity (2), an arthroscopically assisted open procedure (4), or tourniquet time >60 minutes (3). VTE after adolescent knee arthroscopy has not been well described. The incidence is ∼0.25%. Previously established risk factors for VTE were present in 100% of the affected population. Low-molecular-weight heparin was used to successfully treat this complication. Level IV.

Pregnancy and non-pregnancy related ovarian vein thrombosis: Clinical course and outcome

ObjectiveTo collect and summarize demographic, clinical, laboratory and radiologic characteristics, as well as management and follow-up data, of patients diagnosed with ovarian vein thrombosis. MethodsA multicenter retrospective review of all patients diagnosed with ovarian vein thrombosis between January 2000 and May 2015 at three university hospitals. ResultsData of 74 women were analyzed. Mean age was 31±9years. Sixty (81.1%) cases were pregnancy-related. The presence of at least one underlying risk factor (most commonly active infection or surgery) was more common among pregnancy than non-pregnancy related cases (61.7% vs. 14.3%, P=0.002). Anticoagulation therapy was administered in 98.6% of patients and adjunctive antibiotic therapy in 39 (52.7%). At a median follow-up of 40±38months, only one recurrent thrombotic event was observed, and no events of death. Median duration of anticoagulation treatment tended to be longer among patients with non-pregnancy related OVT (6months [3–14] vs. 3months [3–6], P=0.1). Thrombophilic evaluation detected any thrombophilic risk factor in 12 (20%) and 6 (42.9%) women with pregnancy and non-pregnancy related ovarian vein thrombosis, respectively (P=0.09). ConclusionPregnancy-related ovarian vein thrombosis is characterized by a provoked nature and a high rate of resolution after short term treatment. Treatment of three months duration of anticoagulation following this condition appeared in this study to be safe, with no recurrences encountered during a median follow up of 40months. Thrombophilia seems to have an important role in ovarian vein thrombosis and should be evaluated in non-pregnancy related cases.

Drug Treatment of Venous Thromboembolism in the Elderly.

Half of all patients with acute venous thromboembolism are aged over 70years; they then face the added hazard of an age-related increase in the incidence of major bleeding. This makes it even more important to weigh the balance of benefit and risk when considering anticoagulant treatment and treatment duration. Traditional treatment with a heparin (usually low molecular weight) followed by a vitamin K antagonist such as warfarin is effective but is often complicated, especially in the elderly. The direct-acting oral anticoagulants (DOACs), i.e. the thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban and edoxaban, are given in fixed doses, do not need laboratory monitoring, have fewer drug-drug interactions and are therefore much easier to take. Randomised trials, their meta-analyses and 'real-world' data indicate the DOACs are no less effective than warfarin (are non-inferior) and probably cause less major bleeding (especially intracranial). It seems the relative safety of DOACs extends to age above 65 or 70years, although bleeding becomes more likely regardless of the chosen anticoagulant. Renal impairment, comorbidities (especially cancer) and interventions are special hazards. Ways to minimise bleeding include patient selection and follow-up, education about venous thromboembolism, anticoagulants, drug interactions, regular checks on adherence and avoiding needlessly prolonged treatment. The relatively short circulating half-lives of DOACs mean that time, local measures and supportive care are the main response to major bleeding. They also simplify the management of invasive interventions. An antidote for dabigatran, idarucizumab, was recently approved by regulators, and a general antidote for factor Xa inhibitors is in advanced development.

Venous thromboembolism associated with acute cytomegalovirus infection: epidemiology and predisposing conditions

Background: Venous thromboembolism has been reported in association with cytomegalovirus (CMV) infection both in immunocompromised and immunocompetent patients. In this population, it is yet undetermined whether CMV alone provokes VTE or other predisposing conditions are involved.Materials and methods: 1007 VTE patients consecutively recruited in one academic hospital were analyzed retrospectively in order to identify acute CMV infection. Acquired and inherited risk factors were screened. Only adults and immunocompetent patients were included.Results: Among 1007 consecutive VTE patients, we identified 10 patients with synchronous acute CMV infection. Patients with coexistent VTE and acute CMV infection were younger (37.5 years vs. 56.6 years; p = 0.0088) and exhibited a female predominance (90% vs. 56%; p = 0.026), in comparison to the whole cohort. Hereditary thrombophilia was identified in 9 out of 10 patients. Acquired risk factors for VTE like estrogens administration and pregnancy were equally prevalent in patients with and without CMV infection.Conclusion: Acute CMV infection is a potential contributor to VTE whenever other prothrombotic conditions are required. This should help clinicians to privilege a limited duration of anticoagulant treatment like in other provoked VTE.

Treatment of pregnancy-associated venous thromboembolism - position paper from the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH).

Venous thromboembolism (VTE) is a major cause of maternal morbidity during pregnancy and the postpartum period. However, because there is a lack of adequate study data, management strategies for pregnancy-associated VTE must be deduced from observational stu-dies and extrapolated from recommendations for non-pregnant patients. In this review, the members of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH) have summarised the evidence that is currently available in the literature to provide a practical approach for treating pregnancy-associated VTE. Because heparins do not cross the placenta, weight-adjusted therapeutic-dose low molecular weight heparin (LMWH) is the anticoagulant treatment of choice in cases of acute VTE during pregnancy. No differences between once and twice daily LMWH dosing regimens have been reported, but twice daily dosing seems to be advisable, at least peripartally. It remains unclear whether determining dose adjustments according to factor Xa activities during pregnancy provides any benefit. Management of delivery deserves attention and mainly depends on the time interval between the diagnosis of VTE and the expected delivery date. In particular, if VTE manifests at term, delivery should be attended by an experienced multidisciplinary team. In lactating women, an overlapping switch from LMWH to warfarin is possible. Anticoagulation should be continued for at least 6 weeks postpartum or for a minimum period of 3 months. Although recommendations are provided for the treatment of pregnancy-associated VTE, there is an urgent need for well-designed prospective studies that compare different management strategies and define the optimal duration and intensity of anticoagulant treatment.

APPLICATION OF RIVAROXABAN IN ACUTE CORONARY SYNDROME: EVIDENCE AND CURRENT GUIDELINES

The analytical article focuses on the data concerning duration of anticoagulation treatment in acute coronary syndrome patients. The information provided on the evidence for impossibility of widespread usage of vitamin K antagonists in acute coronary syndrome — the novel selective oral anticoagulants that differ from rivaroxaban. The main evidence is showed for efficacy and safety of rivaroxaban in acute coronary syndrome, conditions of its application and fundamentals for dosage selection as 2,5 mg two times per day. European and Russian Guidelines arepresented that permit usage of rivaroxaban in acute coronary syndrome.

Post-thrombotic syndrome in patients treated with rivaroxaban or enoxaparin/vitamin K antagonists for acute deep-vein thrombosis. A post-hoc analysis.

Post-thrombotic syndrome (PTS) is a common complication of deep-vein thrombosis (DVT). Poor quality treatment with vitamin K antagonists (VKA) is a risk factor for PTS. We hypothesised that treatment with the direct oral anticoagulant (DOAC) rivaroxaban may lower PTS incidence as compared to enoxaparin/VKA, as DOACs have a more stable pharmacologic profile than VKA. We performed a post-hoc subgroup analysis of the Einstein DVT trial (n=3449). Kaplan-Meier survival analysis was performed to compare the cumulative incidence of PTS between the rivaroxaban and enoxaparin/VKA groups. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards models. We included 336 patients with a mean age of 58 ± 16 years and a median follow-up after index DVT of 57 months (interquartile range 48-64). Of these, 162 (48 %) had been treated with rivaroxaban and 174 (52 %) with enoxaparin/VKA. The cumulative PTS incidence at 60 months follow-up was 29 % in the rivaroxaban group and 40 % in the enoxaparin/VKA group. After adjusting for age, gender, body mass index, previous VTE, ipsilateral recurrent DVT, extent of DVT, idiopathic DVT, duration of anticoagulant treatment, compliance to assigned study medication, elastic compression stocking use and active malignancy, the HR of PTS development for rivaroxaban was 0.76 (95 % CI: 0.51-1.13). In conclusion, treatment of acute DVT with rivaroxaban was associated with a numerically lower but statistically non-significant risk of PTS compared to enoxaparin/VKA treatment. The potential effect on reducing PTS deserves evaluation in a large randomised trial.

Deep Vein Thrombosis – Current Management Strategies

Deep vein thrombosis (DVT) is a frequent and potentially life-threatening condition, and acute and late complications are common. The diagnostic approach to DVT needs to be reliable, widely available, and cost-effective. Furthermore, several therapeutic options are available for DVT treatment and the choice of anticoagulant drug, dosage, and treatment duration has to reflect the specific situation of the individual DVT patient. This review was aimed to provide bedside guidance for clinicians faced with common (and less common) clinical scenarios in DVT treatment.