Course Of Anticoagulant Therapy Research Articles

Short versus long-term anticoagulation for left ventricular thrombosis resolution during vitamin k antagonist therapy

Abstract Background The optimal duration of anticoagulant therapy to achieve thrombus resolution and prevent cardioembolic events in left ventricular thrombosis (LVT) has not yet been established. Purpose The purpose of our study is to evaluate the incidence of LVT resolution at 3 versus 12 months of vitamin K antagonists (VKAs) therapy. Methods Consecutive patients diagnosed with LVT and treated with VKAs for at least 12 months at 5 anticoagulant outpatient clinics in Italy were retrospectively included. The primary effectiveness outcome was on-treatment thrombus resolution while the secondary was objectively documented on-treatment acute ischemic stroke, peripheral embolism, and myocardial infarction at 12-months follow-up. Safety outcomes were on-treatment major and clinically relevant non-major bleedings at 12-months follow-up as defined by the ISTH criteria. Cumulative incidences of thrombus resolution with 95% confidence intervals (CIs) were calculated while other outcomes were descriptively reported. Multivariable Cox hazards models were calculated using age, sex, reduced left ventricular ejection fraction (EF < 35%), VKAs monotherapy, and time in therapeutic range (TTR) below 60% as covariates for thrombus persistence at 12-months of follow-up. Results Out of 95 patients, 87 were finally included (Table) and 8 excluded due to the lack of relevant data. Median age was 67 years and 75.9% were men. A total of 64.4% of patients had acute myocardial infarction as risk factor for LVT development while 21.8% and 5.7% of patients had dilated and primary hypertrophic cardiomyopathy, respectively. A reduced EF and atrial fibrillation were present in 77.0% and 19.5% of patients, respectively. All but one patient received warfarin with a median TTR of 54%, and 35.5% of patients did not receive concomitant antiplatelet therapy. All included patients received VKAs for at least 12-months. The 3 and 12 month cumulative incidences (Figure) of thrombus resolution were 34.5% (95% CI, 24.7%-44.5%) and 68.3% (95% CI, 57.2%-77.1%), respectively. At multivariable Cox regression analysis, the presence of a reduced EF appeared to be associated with a higher risk of thrombus persistence at 12-months follow-up (Hazard Ratio 3.09; 95% CI 1.27-7.55; p=0.013). During 12-months follow-up, two patients (2.3%) had acute ischemic stroke at 4 and 7 months from the start of VKAs therapy. Three patients (3.4%) had a major and 5 (5.7%) a clinically relevant non-major bleeding that occurred within the first three months of VKAs. Conclusions A 12-month course of anticoagulant therapy with VKA appeared to be effective and safe in patients with LVT and appeared to be associated with a higher cumulative incidence of LVT resolution than a 3-month course. A reduced left ventricular EF was associated with a higher risk of LVT persistence. Whether anticoagulant agents with improved ease-of-use and safety profile are effective in this setting remains undefined.Baseline patients' characteristicsCumulative incidences of LVT resolution

Comparative effectiveness and safety of extended anticoagulant therapy among Medicare beneficiaries with venous thromboembolism.

Guidelines recommend an extended course of anticoagulation therapy for patients who experienced venous thromboembolism (VTE) without transient provocation, however, optimal duration remains uncertain. We assessed effectiveness and safety of extended use of apixaban and warfarin greater than 6months of initial treatment in patients with VTE. We conducted a retrospective cohort study of Medicare beneficiaries aged greater than or equal to 18 years with deep vein thrombosis or pulmonary embolism. Patients were required to have initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6months of initial anticoagulant treatment, and received extended phase treatment with apixaban (the apixaban group) or warfarin (the warfarin group) or no extended therapy. Multivariable Cox proportional hazards modeling with inverse probability treatment weighting was used to compare recurrent VTE, mortality, and major bleeding risks among the three groups. Mean extended-treatment duration was up to 10months and 14 months in apixaban and warfarin groups, respectively. Compared with no extended treatment, apixaban use was associated with decreased risks of recurrent VTE (hazard ratio [HR]=0.08, [95% confidence interval [CI]: 0.01-0.41]) and mortality (HR=0.37, [95% CI: 0.27-0.51]) without increased major bleeding risk (HR=1.29, [95% CI: 0.68-2.45]); warfarin use was associated not with recurrent VTE risk change but with increased major bleeding risk (HR=2.14, [95% CI: 1.26-3.65]) and decreased mortality risk (HR=0.39, [95% CI: 0.29-0.51]). Compared with warfarin, apixaban use was associated with decreased recurrent VTE (HR=0.13, [95% CI: 0.03-0.63]) and major bleeding (HR=0.56, [95% CI: 0.32-0.98]) risks. Subgroup and sensitivity analyses (e.g., intention-to-treat) findings remained consistent. Compared with warfarin or no extended therapy, extended-apixaban use was associated with reduced risk of recurrent VTE without increased major bleeding risk. Continuing anticoagulant therapy with apixaban greater than 6months may be effective and safe.

Outcomes of Open Surgery for Retroperitoneal Hematoma in Covid-19 Patients: Experience from a Single Centre.

Background: Spontaneous retroperitoneal hematoma is a severe and potentially fatal complication that appears in the course of anticoagulation therapy. Therapeutic doses of low molecular weight heparin (LMWH) are used for the prevention of thrombosis in patients seriously ill with Covid-19. Methods: We describe 27 (0.14%) patients with retroperitoneal hematomas who required emergency surgery out of 19108 patients with Covid-19 who were hospitalized in Batajnica COVID Hospital between March 2021 and March 2022. All the patients were on therapeutic doses of LMWH. The existence of retroperitoneal hematoma was confirmed by abdominal ultrasound and computed tomography scans. Results: Open surgery was performed on 27 patients with spontaneous retroperitoneal hematomas (12 female and 15 male). The mean age of the study population was 71.6+-11.9 years. D-dimer was significantly elevated two days before the surgery in comparison with the values on the day of surgery (p=0.011). Six patients (22.23%) survived, while 21 (77.77%) patients died. Conclusion: Bleeding in Covid-19 patients treated by LMWH is associated with an increased risk of developing retroperitoneal hematoma. Open surgery for retroperitoneal hematoma in Covid-19 patients on anticoagulation therapy is a procedure associated with a high rate of mortality.

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

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

A Rise in Plasma Coagulability during the First 3 Months Following Provoked Venous Thromboembolism Is Associated with the Development of Post-Thrombotic Syndrome in Children and Young Adults: Analysis of the Kids-DOTT Multicenter Trial-Derived Biobank

Background:Knowledge of prognostic factors for the development of post-thrombotic syndrome (PTS) is limited, particularly in the pediatric population. Elevated plasma levels of D-dimer and FVIII, both markers of coagulation activation and inflammation, are associated with an increased risk of adverse thrombosis outcomes, including PTS, in children. Similarly, increased levels of inflammatory cytokines, such as interleukin-6 (IL-6), have been associated with venous endothelial dysfunction and fibrosis, suggesting a potential role in the development of PTS. Given the strong interplay between inflammation and coagulation, the aims of this study were to: (1)Investigate a hypothesized association between increased levels of plasma cytokines during the first 3 months post-diagnosis of deep venous thrombosis (DVT) with the development of PTS in patients <21 years old; and (2) to investigate an association between increased plasma coagulability during the first 3 months post-DVT diagnosis with the development of PTS. Methods:We used banked plasma biospecimens and masked clinical data from an ongoing NHLBI-sponsored multinational multicenter trial of VTE treatment in patients <21 years old (the Kids-DOTT trial, NCT00687882). All patients with an extremity DVT who underwent PTS assessment at 1 year were included in this analysis. The Clot Formation and Lysis (CloFAL) spectrophotometric assay was performed, as previously described, on banked plasma samples obtained at 6 weeks and 3 months post-VTE diagnosis. All samples were pre-treated with heparinase prior to assay. Assay measurements included maximal amplitude of the CloFAL waveform (MA), time to maximal amplitude (T1), and area under the curve at 60 minutes, indexed to that of the pooled normal plasma standard (AUC60). Levels of IL-6, IL-8, IL-12/IL-23p40, IL-17, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, interferon (IFN)-γ and C-reactive protein (CRP) were measured via V-Plex kit (Meso Scale Discovery, Rockville, MD). For each patient, the change in each laboratory parameter between the 3 months and 6 weeks post-VTE time points was calculated. The diagnosis of PTS was made at the one year follow-up assessment using the Manco-Johnson Instrument. Descriptive statistics were used to summarize data on patient and VTE characteristics as well as PTS outcome. Putative prognostic factors for PTS (age group, complete thrombus occlusion, CloFAL parameters, and inflammatory cytokines) were evaluated via univariate logistic regression, using odds ratios (OR) and 95% confidence intervals (CI). Variables with P-values <0.1 in univariate analyses were pre-specified for inclusion in an adjusted (multivariate) regression analysis. The blind was maintained in the Kids-DOTT trial throughout data transfer and analysis. Results: A total of 80 patients were included in the present analysis. Median age was 12.7 years (range 0.04 - 20.8 years). Patient and VTE characteristics at baseline, as well as PTS outcomes, are summarized in Table 1. PTS developed in 34% of patients by the 1 year post-VTE follow up visit. Univariate logistic regression analysis identified change in CloFAL AUC60 (OR=1.46, 95%CI=1.02-2.09; P=0.036) and complete thrombus occlusion at 6 weeks post-VTE (OR=3.29, 95%CI=0.93-11.6; P=0.064) as putative prognostic factors for PTS (Table 2). After adjustment in multivariate regression, change in CloFAL AUC60 remained the only possibly-significant (P=0.06) independent prognostic factor for PTS. Specifically, for each 1 A.U. increase in CloFAL AUC from the 6 weeks to 3 months post-VTE diagnosis, the odds of PTS increased by more than 40% (OR=1.43, 95%CI=0.99-2.08; Table 3). Changes in none of the measured inflammatory cytokines were prognostic of PTS. Conclusions: PTS developed in 34% of patients <21 years old enrolled in enrolled in an ongoing multicenter trial of provoked DVT treatment. A rise in plasma coagulability during the first 3 months post-DVT diagnosis, as measured by increase in AUC60 in the CloFAL assay is a candidate prognostic factor for PTS in patients <21 years old with provoked DVT. Future work should seek to investigate the mechanisms of increased plasma coagulability following a course of anticoagulation therapy in young VTE patients, and to substantiate findings of its potential prognostic significance for the development of PTS. Disclosures Everett: ImmunArray: Consultancy, Patents & Royalties. Goldenberg:NIH: Other: research support and salary support.

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

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

Features of etiology and pathogenesis of acute deep vein thrombosis in children of different age groups. Results of a prospective cohort study in parallel groups

Aim. To study the characteristics of the etiology and clinical picture of acute deep vein thrombosis in children of different age groups. 
 Methods. The article analyzes the diagnosis and treatment of 77 children and adolescents with acute deep vein thrombosis. The features of the history of patients, previous fact of deep venous catheterization were studied. The fact of the presence and absence of clinical symptoms of thrombosis is registered. The results of ultrasound diagnostics are used. All patients underwent a course of anticoagulant therapy. The results of diagnosis and treatment were evaluated taking into account the age of the patients, the presence/absence of the history of catheterization of deep veins. 
 Results. When comparing different age groups, their distinctive characteristics were revealed: predominant presence of asymptomatic catheter-associated thrombosis in the younger age group (newborns and infants) with symptomatic deep vein thrombosis of various origin in older children. Among the surveyed, the majority (75.3%) had asymptomatic thrombosis. Pain (2.6%), edema (3.9%) and a combination of pain and edema (18.2%) were more common among symptomatic patients with the symptoms of acute vein thrombosis. In some cases, a combination of two or more complaints was noted. Asymptomatic thrombosis in the catheter-associated thrombosis group amounted to 96.6%. All patients below 1 year had a predisposing factor in the history: 95% - preceding vein catheterization, 5% - postoperative period. With a history of venous catheterization, symptoms of thrombosis were detected 9.2 times less frequently than in children without vein catheterization. In the group of children older than a year, the ratio of thrombosis without a predisposing factor was 10.5%, and the ratio of children with symptoms of thrombosis was 1.38 times higher than among children younger than a year. The only fatal outcome: a 17-year-old patient with a history of thrombophilia, thrombosis of the left iliac vein, pulmonary embolism. 
 Conclusion. Deep vein thrombosis in children of the first year of life in all cases was caused by a predisposing factor: in children during the first year of life in 95% of cases deep vein thrombosis was asymptomatic and was revealed by ultrasound examination.

Long-Term Risk Factors for Occult Cancer Detection in Patients with Unprovoked Venous Thromboembolism: A Post-Hoc Analysis of the Reverse Study

Background: The diagnosis of an unprovoked (i.e., in the absence of any risk factors) venous thromboembolism (VTE) may be a sign of an underlying cancer. Previous estimates of the incidence rate of occult cancer in patients with unprovoked VTE are as high as 5-10%. However, screening methods to detect cancer early in these patients are of limited clinical value and previous identification of risk factors focused on short-term cancer diagnosis. Therefore, this study will assess the long-term incidence and risk factors of cancer in unprovoked VTE patients.Methods: This retrospective study is a post-hoc analysis of the REVERSE (Recurrent Venous Thromboembolism Risk Stratification Evaluation) study. Patient data was collected following an initial six-month course of anticoagulation therapy and were followed for a mean time period of 5.0 years (range 1 month-8 years). We performed univariable analysis to test the strength of association between each potential predictor variable and occult cancer diagnosis. Furthermore, using forward model selection we created a multivariable model with optimal predictive value for cancer diagnosis.Results: Among 663 patients presenting with unprovoked VTE, 38 (5.7%) subsequently developed a new cancer diagnosis during the follow-up period. The most common types of cancers diagnosed were prostate (21%) and colorectal cancer (16%). Univariate analysis revealed age > 65 (OR 2.59; 95% CI 1.31-4.49, P= 0.0036), elevated D-Dimer (OR 2.71; 95% CI 1.38-5.31, P=0.026) and pulmonary vein obstruction (PVO) score (OR 4.34 95% CI 1.26-14.92, P=0.023) as the strongest predictors of occult cancer. Only D-Dimer (Adj.-OR 2.72 95% CI 1.39-5.32) remained in the multivariate model and no other factor significantly improved the model's fit.Conclusion: Patients with an unprovoked VTE remain at an elevated risk of developing cancer following anticoagulation therapy. Age > 65 years old, elevated D-Dimer, and PVO in pulmonary embolism patients are among potential risk factors for developing occult cancer. More studies are needed to validate these potentially important risk factors. DisclosuresCarrier:BMS: Honoraria, Research Funding; Leo Pharma: Research Funding; Pfizer: Honoraria; Bayer: Honoraria. Rodger:Biomerieux: Research Funding. Kovacs:Daiichi Sankyo Pharma Development: Research Funding; Bayer: Research Funding.

Anemia and bleeding in patients receiving anticoagulant therapy for venous thromboembolism.

In patients receiving anticoagulant therapy for venous thromboembolism (VTE), the important issue of anemia influence on the risk of bleeding has not been consistently studied. We used the large registry data RIETE (Registro Informatizado Enfermedad Tromboembólica) to compare the rate of major bleeding in patients receiving anticoagulant therapy for VTE according to the presence or absence of anemia at baseline. Patients with or without cancer were separately studied. Until August 2016, 63492 patients had been enrolled. Of these, 21652 (34%) had anemia and 14312 (23%) had cancer. Anemia was found in 57% of the patients with cancer and in 28% without (odds ratio 3.46; 95% CI 3.33-3.60). During the course of anticoagulant therapy, 680 patients with cancer had a major bleeding event (gastrointestinal tract 43%, intracranial 14%, hematoma 12%). Cancer patients with anemia had a higher rate of major bleeding (rate ratio [RR]: 2.52; 95% CI 2.14-2.97) and fatal bleeding (RR 2.73; 95% CI 1.95-3.86) than those without anemia. During the course of anticoagulation, 1133 patients without cancer had major bleeding (gastrointestinal tract 32%, hematoma 24%, intracranial 21%). Patients with anemia had a higher rate of major bleeding (RR 2.84; 95% CI 2.52-2.39) and fatal bleeding (RR 2.76; 95% CI 2.07-3.67) than those without. On a multivariable analysis, anemia independently predicted the risk for major bleeding in patients with and without cancer (hazard ratios: 1.66; 95% CI 1.40-1.96 and 1.95; 95% CI 1.72-2.20, respectively). During anticoagulation for VTE, both cancer- and non-cancer anemic patients had a higher risk for major bleeding than those without anemia. In anemic patients (with or without cancer), the rate of major bleeding during the course of anticoagulant therapy exceeded the rate of VTE recurrences. In patients without anemia the rate of major bleeding was lower than the rate of VTE recurrences.

Vitamin K Antagonists After 6 Months of Low-Molecular-Weight Heparin in Cancer Patients with Venous Thromboembolism

BackgroundLow-molecular-weight heparin (LMWH) is the treatment of choice in cancer patients with venous thromboembolism. However, data on continuing LMWH treatment beyond 6 months remain scanty. MethodsWe used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the rate of venous thromboembolism recurrences and major bleeding appearing beyond the first 6 months of anticoagulant therapy in cancer patients with venous thromboembolism, according to therapy with LMWH or vitamin K antagonists (VKA). We performed a propensity score-matched cohort study. ResultsAfter propensity matching, 482 cancer patients continued to receive LMWH and 482 switched to VKA. During the course of anticoagulant therapy (mean 275.5 days), 57 patients developed venous thrombosis recurrences (recurrent pulmonary embolism 26, recurrent deep vein thrombosis 29, both 2), 28 had major bleeding, 38 had nonmajor bleeding, and 129 died. No patient died of recurrent venous thrombosis, and 5 patients died of bleeding (2 were on LMWH, 3 on VKA). Patients who continued with LMWH had a similar rate of deep vein thrombosis recurrences (relative risk [RR] 1.41; 95% confidence interval [CI], 0.68-2.93), pulmonary embolism recurrences (RR 0.73; 95% CI, 0.34-1.58), major bleeding (RR 0.96; 95% CI, 0.51-1.79), or nonmajor bleeding (RR 1.15; 95% CI, 0.55-2.40), compared with those who switched to VKA, but a higher mortality rate (RR 1.58; 95% CI, 1.13-2.20). ConclusionsIn cancer patients with venous thromboembolism who completed 6 months of LMWH therapy, switching to VKA was associated with a similar risk of venous thrombosis recurrences or bleeding when compared with patients who continued LMWH.

Uterine bleeding during anticoagulation in women with venous thromboembolism

Women presenting with uterine bleeding during the course of anticoagulant therapy for venous thromboembolism (VTE) present a difficult therapeutic dilemma due to the absence of evidence-based recommendations. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics of women presenting with uterine bleeding during anticoagulation for VTE, its frequency, time course, management and 30-day outcomes. As of October 2016, 31,951 women with VTE were recruited in RIETE. During the course of anticoagulant therapy, 53 (0.17%) developed major uterine bleeding, 118 (0.37%) non-major uterine bleeding and 948 (2.97%) had major bleeding in other sites. Median time elapsed from VTE to bleeding was: 32, 71 and 22 days, respectively. Mean age was: 56±17, 52±20 and 75±14 years, respectively. Women with major uterine bleeding more likely had cancer (51%), anemia (72%), raised platelet count (19%) or recent major bleeding (11%) at VTE presentation than those in the other subgroups. During the first 30 days after bleeding, 17%, 1.7% and 31% of women died, respectively. Of 11 women with uterine bleeding who died, 9 (82%) had cancer, two (18%) died of bleeding and one (9.1%) died of pulmonary embolism after discontinuing anticoagulation. Uterine bleeding during the course of anticoagulation for VTE is not uncommon and mostly affects young women. Those with cancer, anaemia, raised platelet count or recent bleeding at baseline are at an increased risk for uterine bleeding during anticoagulation.

Gender differences in patients with venous thromboembolism and five common sites of cancer

The outcome of cancer patients with venous thromboembolism (VTE) may differ according to gender. We used the RIETE database to compare the rate of VTE recurrences, major bleeding and mortality in patients with lung, colorectal, pancreatic, hematologic or gastric cancer during the course of anticoagulation, according to gender. As of January 2016, 11,055 patients with active cancer were enrolled: 1,727 had lung cancer, 1,592 colorectal, 840 hematologic, 517 pancreatic and 459 had gastric cancer. Compared with men (N = 3,130), women (N = 2,005) were more likely to have colorectal, pancreatic or hematologic cancer, and less likely to have lung cancer. Most patients (91%) were initially treated with low-molecular-weight heparin (LMWH), but women received higher daily doses per body weight. Then, 66% kept receiving LMWH for long-term therapy. During the course of anticoagulation, 302 patients developed recurrent VTE, 220 bled and 1,749 died. Compared with men, women had a similar rate of VTE recurrences or major bleeding, and a lower mortality (risk ratio [RR]: 0.90; 95% CI: 0.82-0.99). When separately comparing outcomes according to cancer site, women with lung cancer had a lower mortality (RR: 0.79; 95% CI: 0.70-0.92), those with colorectal cancer had a higher mortality (RR: 1.25; 95% CI: 1.02-1.54) and those with gastric cancer had a higher rate of VTE recurrences than men (RR: 2.47; 95% CI: 1.04-5.89). VTE women with lung, colorectal, pancreatic, haematological or gastric cancer experienced a similar outcome during the course of anticoagulant therapy than men with similar cancers.

Gender-related differences in the outcome of patients with venous thromboembolism and thrombophilia

In patients with venous thromboembolism (VTE) and factor V Leiden (FVL) or prothrombin 20210G-A mutation (PTM), the influence of gender on outcome has not been consistently studied. We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to assess the existence of gender differences in the rate of VTE recurrences (deep vein thrombosis [DVT] or pulmonary embolism [PE]) or major bleeding during the course of anticoagulation and after its discontinuation in FVL and PTM carriers. From March 2001 to September 2016, 11,224 VTE patients underwent thrombophilia testing. Of these, 1,563 were FVL carriers (863 men and 700 women) and 1,231 were PTM carriers (659 men and 572 women). During the course of anticoagulant therapy, men with FVL had a 6-fold higher rate of VTE recurrences than major bleeds (31 vs. 5 events). In women with FVL, the rate of VTE recurrences was 2-fold higher (16 vs. 8), as was in men (17 vs. 8) or women (17 vs. 9) with PTM. After discontinuing anticoagulation, men with FVL had a 3-fold higher rate of DVT recurrences than women (hazard ratio [HR]: 3.13; 95% CI: 1.79-5.67), with no differences in PE recurrences. Among patients with PTM, there were no gender differences in the rate of DVT (HR: 1.89; 95% CI: 1.00-3.65) or PE recurrences (HR: 1.82; 95% CI: 0.83-4.12). During the anticoagulation course, men with FVL are at a much higher risk for VTE recurrences than bleeding. After discontinuing anticoagulation, men with FVL are at an increased risk for DVT recurrences.

Dynamics of Residual Venous Obstruction after Electrical Stimulation of Crural Muscles following the Completion of the Standard Course of Anticoagulation Therapy in Patients with Postthrombotic Syndrome: the Results of the Comparative Non-Randomized Study

Dynamics of Residual Venous Obstruction after Electrical Stimulation of Crural Muscles following the Completion of the Standard Course of Anticoagulation Therapy in Patients with Postthrombotic Syndrome: the Results of the Comparative Non-Randomized Study

Predictors of active cancer thromboembolic outcomes. RIETE experience of the Khorana score in cancer-associated thrombosis.

Even though the Khorana risk score (KRS) has been validated to predict against the development of VTE among patients with cancer, it has a low positive predictive value. It is also unknown whether the score predicts outcomes in patients with cancer with established VTE. We selected a cohort of patients with active cancer from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the prognostic value of the KRS at inception in predicting the likelihood of VTE recurrences, major bleeding and mortality during the course of anticoagulant therapy. We analysed 7948 consecutive patients with cancer-associated VTE. Of these, 2253 (28 %) scored 0 points, 4550 (57 %) 1-2 points and 1145 (14 %) scored ≥3 points. During the course of anticoagulation, amongst patient with low, moderate and high risk KRS, the rate of VTE recurrences was of 6.21 (95 %CI: 4.99-7.63), 11.2 (95 %CI: 9.91-12.7) and 19.4 (95 %CI: 15.4-24.1) events per 100 patient-years; the rate of major bleeding of 5.24 (95 %CI: 4.13-6.56), 10.3 (95 %CI: 9.02-11.7) and 19.4 (95 %CI: 15.4-24.1) bleeds per 100 patient-years and the mortality rate of 25.3 (95 %CI: 22.8-28.0), 58.5 (95 %CI: 55.5-61.7) and 120 (95 %CI: 110-131) deaths per 100 patient-years, respectively. The C-statistic was 0.53 (0.50-0.56) for recurrent VTE, 0.56 (95 %CI: 0.54-0.59) for major bleeding and 0.54 (95 %CI: 0.52-0.56) for death. In conclusion, most VTEs occur in patients with low or moderate risk scores. The KRS did not accurately predict VTE recurrence, major bleeding, or mortality among patients with cancer-associated thrombosis.

Low discriminating power of the modified Ottawa VTE risk score in a cohort of patients with cancer from the RIETE registry.

Treatment of patients with cancer-associated venous thromboembolism (VTE) remains a major challenge. The modified Ottawa score is a clinical prediction rule evaluating the risk of VTE recurrences during the first six months of anticoagulant treatment in patients with cancer-related VTE. We aimed to validate the Ottawa score using data from the RIETE registry. A total of 11,123 cancer patients with VTE were included in the analysis. According to modified Ottawa score, 2,343 (21 %) were categorised at low risk for VTE recurrences, 4,525 (41 %) at intermediate risk, and 4,255 (38 %) at high risk. Overall, 477 episodes of VTE recurrences were recorded during the course of anticoagulant therapy, with an incidence rate for low, intermediate, and high risk groups of 6.88 % (95 % CI 5.31-8.77), 11.8 % (95 % CI 10.1-13.6), and 21.3 % (95 % CI 18.8-24.1) patient-years, respectively. Overall mortality had an incidence rate of 21.1 % (95 % CI 18.2-24.3), 79.4 % (95 % CI: 74.9-84.1), and 134.7 % (95 % CI: 128.3-141.4) patient-years, respectively. The accuracy and discriminating power of the modified Ottawa score for VTE recurrence was modest, with low sensitivity, specificity and positive predictive value, and a C-statistics of 0.58 (95 % CI: 0.56-0.61). In our analysis, the modified Ottawa score did not accurately predict VTE recurrence among patients with cancer-associated thrombosis, thus hindering its use in clinical practice. It is time to define a new score including other clinical predictors.

Acute Ischemic Events in Patient Receiving Direct Oral Anticoagulants for Atrial Fibrilation: Incidence, Outcome and Clinical Profile

▪IntroductionThe use of direct oral anticoagulants (DOACs) is increasing for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Despite the good efficacy/safety balance, clinicians will be confronted with patients under treatment with DOAC presenting with ischemic events. Currently, there is a paucity of data from investigational studies regarding the clinical profile, risk factors and most suitable therapeutic intervention after therapeutic failure with these anticoagulants.AimsTo describe the clinical profile and assess the rate of subsequent ischemic events appearing during the course of anticoagulant therapy and tried to identify risk factors for these events in "real life" population treated with DOACs.MethodsIn this multicenter and retrospective study we included patients with NVAF who had recived DOACs. Ischemic Events during february 2013 to february 2016 was analyzed.ResultsWe enrolled, 3353 patients with NVAF who had recived DOACs. During the course of anticoagulation (mean, 9.4 months), 39 patients (1.16%) developed ischemic events (stroke, 22; transient ischemic attack (TIA), 7; peripheral embolism, 10). Rate of ischemic events was 0.9/100 patient-years. Median age was 76 years (range: 51-92) and 25 (64.1%) were female. Among them, 19 patients received dabigatran, 14 rivaroxaban and 6 apixaban. As per the thrombotic risk score, 66.7% of the patients were classified as "high risk" (CHA2DS2-VASc score > 5). Thirty-eight patients (97.4%) received vitamin K antagonists (VKA) prior to use of DOAC. Ischemic events patients had a higher incidence of hypertention (94.9% ), diabetes (64.1%), history of previous ischemic stroke (74.4%) and therapeutic failure with VKA (79.5%). Nonadherence to treatment was identified only in 6 patients (15.4%). On multivariable analysis, previous ischemic stroke/ TIA (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.21-2.61), female sex (HR, 1.54; 95% CI, 1.05-2.26), and CHA2DS2-VASc score>5 (HR, 1.72; 95% CI, 1.25-2.36) were independently associated with the risk for ischemic events.For the management of acute ischemic event, 20 patients received endovascular treatment, 12 patients switched from DOAC to unfractionated heparin or low molecular weight heparin and intravenous fibrinolysis was performed in 7 patients; intracranial hemorrhage being observed in two patients after treatment with thrombolytic therapy. Regarding the subsequent anticoagulation continuation at discharge, 19 patients switched to concomitant therapy with DOAC and antiplatelets, 12 patients to other DOAC and only 8 to VKA. There was a 5.1% 30 day mortality after ischemic event and 15.4% of patients had neurologic complications after ischemic event.ConclusionsWe described a low rate of stroke in patients treated with DOACs, but further studies are necessary in order to identify very high-risk patients with special emphasis in those with high CHA2DS2-VASC score, previous stroke and a correct anticoagulation. DisclosuresNo relevant conflicts of interest to declare.

The Clinical Course of Venous Thromboembolism May Differ According to Cancer Site

BackgroundWe hypothesized that the clinical course of venous thromboembolism in patients with active cancer may differ according to the specificities of primary tumor site. Aim and MethodsWe used data from RIETE (international registry of patients with venous thromboembolism) to compare the clinical venous thromboembolism-related outcomes during the course of anticoagulation in patients with one of the 4 more frequent cancers (breast, prostate, colorectal, or lung cancer). ResultsAs of September 2014, 3947 cancer patients were recruited, of whom 938 had breast, 629 prostate, 1189 colorectal, and 1191 lung cancer. Overall, 55% had metastatic disease (42%, 36%, 53%, and 72%, respectively). During the course of anticoagulant therapy (mean duration, 139 days), the rate of thromboembolic recurrences was similar to the rate of major bleeding in patients with breast (5.6 [95% confidence interval (CI), 3.8-8.1] vs 4.1 [95% CI, 2.7-5.9] events per 100 patient-years) or colorectal cancer (10 [95% CI, 7.6-13] vs 12 [95% CI, 9.4-15] per 100 patient-years). In contrast, in patients with prostate cancer, the rate of venous thromboembolic recurrences was half the rate of major bleeding (6.9 [95% CI, 4.4-10] vs 13 [95% CI, 9.2-17] events per 100 patient-years), whereas in those with lung cancer, the rate of thromboembolic recurrences was twofold higher than the rate of major bleeding (27 [95% CI, 22-23] vs 11 [95% CI, 8.6-15] per 100 patient-years). ConclusionsSignificant differences in the clinical profile of venous thromboembolic-related outcomes were observed according to the site of cancer. These findings suggest the development of cancer-specific anticoagulant strategies as an area for further research.

Outcome during and after anticoagulant therapy in cancer patients with incidentally found pulmonary embolism.

Current guidelines suggest treating cancer patients with incidental pulmonary embolism comparably to patients with symptomatic pulmonary embolism.We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry to compare the rate of major bleeding and symptomatic pulmonary embolism during the course of anticoagulation and after its discontinuation in cancer patients with incidental pulmonary embolism.As of March 2016, 715 cancer patients with incidental pulmonary embolism had been enrolled in RIETE. During the course of anticoagulant therapy (mean 235 days), the rate of major bleeding was higher than the rate of symptomatic pulmonary embolism (10.1 (95% CI 7.48-13.4) versus 3.17 (95% CI 1.80-5.19) events per 100 patient-years, respectively), and the rate of fatal bleeding was higher than the rate of fatal pulmonary embolism (2.66 (95% CI 1.44-4.52) versus 0.66 (95% CI 0.17-1.81) deaths per 100 patient-years, respectively). After discontinuing anticoagulation (mean follow-up 117 days), the rate of major bleeding was lower than the rate of symptomatic pulmonary embolism (3.00 (95% CI 1.10-6.65) versus 8.37 (95% CI 4.76-13.7) events per 100 patient-years, respectively); however, there were no differences in the rate of fatal events at one death each.The risk/benefit ratio of anticoagulant therapy in cancer patients with incidental pulmonary embolism is uncertain and must be evaluated in further studies.

Venous thromboembolism in centenarians: Findings from the RIETE registry

BackgroundThe balance between the efficacy and safety of anticoagulant therapy in patients aged ≥100years receiving anticoagulant therapy for venous thromboembolism (VTE) is uncertain. MethodsWe used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the rate of VTE recurrences, bleeding events, and mortality appearing during the course of anticoagulant therapy in VTE patients aged ≥100years. ResultsOf 61,173 patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged ≥100years. Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and 26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti-inflammatory drugs. Most patients (95%) were treated initially with low-molecular-weight heparin (LMWH) (mean daily dose, 168±42IU/kg). Then, 14 (30%) switched to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy (mean, 148±51IU/kg/day). During the course of anticoagulant therapy (mean duration, 139days), mortality was high (15/47; 32%). Two patients died of PE (initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major bleeding was reported. ConclusionsAmong patients with acute VTE aged ≥100years, the risk of VTE recurrences during the course of anticoagulation outweighed the risk of bleeding. Our data suggest the use of standard anticoagulant therapy in this patient population, even if they have severe renal insufficiency.