Essentials Predicting recurrences may guide therapy after unprovoked venous thromboembolism (VTE). We evaluated the DASH score in 827 patients with unprovoked VTE to verify prediction accuracy. A ...DASH score ≤ 1 had a cumulative recurrence risk at 1 year of 3.6%, as predicted by the model. The DASH score performed better in younger (< 65 years old) subjects.
Background The DASH prediction model has been proposed as a guide to identify patients at low risk of recurrence of venous thromboembolism (VTE), but has never been validated in an independent cohort. Aims To validate the calibration and discrimination of the DASH prediction model, and to evaluate the DASH score in a predefined patient subgroup aged > 65 years. Methods Patients with a proximal unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) who received a full course of vitamin K antagonist or direct oral anticoagulant (> 3 months) and had D-dimer measured after treatment withdrawal were eligible. The DASH score was computed on the basis of the D-dimer level after therapy withdrawal and personal characteristics at the time of the event. Recurrent VTE events were symptomatic proximal or distal DVT/PE, and were analyzed with a time-dependent analysis. Observed 12-month and 24-month recurrence rates were compared with recurrence rates predicted by the DASH model. Results We analyzed a total of 827 patients, of whom 100 (12.1%) had an objectively documented recurrence. As compared with the original DASH cohort, there was a greater proportion of subjects with a 'low-risk' (≤ 1) DASH score (66.3% versus 51.6%, P < 0.001). The slope of the observed versus expected cumulative incidence at 2 years was 0.71 (95% confidence interval 0.51-1.45). The c-statistic was lower for subjects aged > 65 years (0.54) than for younger subjects (0.72). Conclusions These results confirm the validity of DASH prediction model, particularly in young subjects. The recurrence risk in elderly patients (> 65 years) was, however, > 5% even in those with the lowest DASH scores.
Cancer-associated Thrombosis (CAT) is a common complication among patients with cancer which is associated with significant morbidity and mortality. The risk of CAT varies widely depending on cancer ...types and treatments and its cumulative incidence increases over time. Although patients with cancer have a high risk of developing venous thromboembolism, pharmacological thromboprophylaxis is not routinely recommended for ambulatory patients receiving chemotherapy but is suggested for those deemed as high-risk. Risk assessment models can help clinicians identify ambulatory patients at high risk who would most benefit from thromboprophylaxis with low molecular weight heparin or direct oral anticoagulants (apixaban or rivaroxaban). This narrative review will summarize the data on pharmacological thromboprophylaxis in ambulatory patients with cancer, provide further insights into the safety and efficacy of different anticoagulants, and suggest implementation methods using a multidisciplinary approach leading to an optimization of preventative strategies in this patient population.
Essentials Isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer. No study has specifically evaluated the long-term clinical course of cancer-associated IDDVT. Patients ...with cancer-associated IDDVT are at very high risk of symptomatic recurrence and death. We observed low rates of major bleeding during anticoagulation.
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.
Atrial fibrillation (AF) is common among patients with cancer. Patients with cancer and AF require anticoagulant therapy direct oral anticoagulants (DOAC) or vitamin K antagonist (VKA) for stroke and ...systemic embolism (SE) prevention. We sought to assess the rates of stroke/SE and major bleeding in patients with cancer and AF on oral anticoagulant therapy (DOAC or VKA).
A systematic search of MEDLINE and EMBASE was conducted. The primary efficacy and safety outcome were stroke/SE and major bleeding (as per the International Society on Thrombosis and Haemostasis definition), respectively. Incidence rates (IR) were pooled using random effects model (event per 100 patient-years). Incidence rate ratios (IRR) were computed using a Poisson regression model with associated 95% confidence intervals (CI) using R software (version 4.0.3).
Of the total 2,153 article records that were screened, 22 observational studies from 12 different countries were included in the meta-analysis (n = 94,980 patients). The IR of stroke/SE was 1.81 (95% CI: 0.89 to 3.68) and 3.41 (95% CI: 1.38 to 8.41) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.63 (95%CI: 0.47–0.84)). The IR of major bleeding was 2.59 (95%CI: 1.54 to 4.38) and 3.60 (95% CI: 1.68 to 7.71) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.76 (95% CI: 0.55 to 1.04)).
DOACs compared to VKA seem to provide a significant reduction in the risk of stroke/SE and a good risk-benefit ratio profile for safety outcomes in this patient population.
•Patients with cancer and atrial fibrillation are at high risk of stroke and bleeding.•Direct oral anticoagulants (DOACs) are associated with a lower risk of stroke compared to vitamin K antagonists.•DOACs seem to provide a good risk-benefit ratio as it may also be associated with lower risk of major bleeding.
Antifibrinolytics combined with aPCC are not routinely administered to patients with acquired hemophilia A due to increased thrombotic risk. This association normalizes clot stability, and improves ...the efficacy of therapy, but can increase the risk of severe side effects. Due to these premises it has always raised doubts and perplexities in the clinics. We now report the data of the “FEIBA® on acquired haemophilia A Italian Registry (FAIR Registry)”, a retrospective-prospective study that included 56 patients. This is the first study that assessed the clinical response of the combination of aPCC and antifibrinolytic agents in patients with acquired haemophilia A. A total of 101 acute bleeds were treated with aPCC. Antifibrinolytic agents were used in the treatment of 39.6% of total bleeds, based on both, a clinical assessment and an evaluation of bleeding. Twenty-five of the 30 patients (57.1%) treated with antifibrinolytic drugs showed serious co-morbidity. Among them, 40% presented severe cardiovascular diseases. All bleeds treated with combined therapy had a shorter duration of treatment (mean reduction 16.3%). All the treated patients presented a good tolerability and no arterial or venous thromboembolic events were reported. In our retrospective registry the combination of antifibrinolytics and aPCC appears safe and effective in the treatment of patients with AHA, especially in the case of severe and life-threatening bleeding, but this hypothesis needs to be confirmed in adequate, larger clinical trials.
Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of ...treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo.
We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500 s(-1). The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function.
Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.
After acute proximal deep vein thrombosis (DVT) the thrombotic mass decreases, especially during the first months of anticoagulation. The persistence of residual vein obstruction (RVO) may predict ...future recurrence in patients with cancer-associated DVT. We aimed to evaluate the proportion of patients with RVO after an episode of cancer associated isolated distal DVT (IDDVT), to identify variables associated with RVO, and to provide initial evidence of its association with recurrent VTE. We performed a post-hoc analysis of a multicenter cohort study of patients with isolated cancer-associated acute IDDVT. We included patients who underwent a control ultrasonography at the end of the anticoagulant treatment between day 30 and day 365 after index IDDVT, given that no recurrent VTE had already occurred on anticoagulant treatment. A total of 153 patients had ultrasonographic follow-up after a median of 92 days from index IDDVT: 45.8% had RVO and 54.2% exhibited complete recanalization. Female sex, Body Mass Index > 30 Kg/m
2
and involvement of axial calf veins showed the strongest association with RVO. The risk of recurrence was twofold higher in patients with (versus without) RVO. RVO persisted in approximately half of patients with an episode of cancer-associated IDDVT at anticoagulant discontinuation. Patients with RVO appeared to be at a higher risk for recurrent events.
Introduction Isolated distal deep vein thrombosis (IDDVT) accounts for one-fourth to one-half of all deep vein thrombosis (DVT) of the leg. Patients with IDDVT are frequently treated for a shorter ...period of time compared to patients with proximal DVT and/or pulmonary embolism (PE) due to a perceived lower risk of recurrence. About 10-20% of patients with venous thromboembolic events (VTEs) have concomitant cancer. Guidelines recommend long-term anticoagulant treatment in this group of patients due to their high risk of VTE recurrence. Unfortunately, information on the clinical history of IDDVT patients is limited and, to date, no study has evaluated the long-term risk of VTE recurrence in IDDVT patients with cancer. Aim To provide information on the clinical history of IDDVT patients with active cancer. Materials and Methods A multicenter, cohort study including active-cancer patients with an objective diagnosis of IDDVT (between January 2011 and September 2014) was conducted. Information on baseline characteristics, thrombosis location and extension, concomitant risk factors, type and duration of treatment was collected. All patients were followed for a minimum of 12 months and up to 24 months. During follow-up, VTE recurrence, major bleeding episodes and death were registered. Potential risk factors for VTE recurrence were evaluated. Results 308 patients (mean age 66.2 ± 13.2 years, female 57.1%) in 13 centers were included, Table 1; 261 patients had solid cancer and 47 patients hematologic cancer. At the time of IDDVT diagnosis, the disease was metastatic in 148 patients (48.1%); 99.0% of patients received anticoagulant treatment: 288 patients (93.5%) were initially treated with low molecular weight heparin, 15 with fondaparinux (5.2%) and 1 with unfractionated heparin; vitamin K antagonists were used in 46 patients (14.9%) only. Total follow-up was 389 patient-years, mean follow-up 15.2 months. Mean duration of treatment was 4.2 months. During the study period there were 47 episodes of VTE recurrence (36 proximal DVT or PE) for a incidence rate of 13.2 events per 100 patient-years; 7 patients had major bleeding (2.3%) and 137 died (44.5%). At multivariate analysis, previous VTE was associated with an increased risk of recurrence (OR 2.10; 95% 1.06, 4.14), whereas patients with gastrointestinal cancer had a lower risk of recurrence (OR 0.26; 95% CI 0.08, 0.86). Table 1 Baseline characteristics of the population Number of patients 308 Age (years), mean ± SD 66.2 ± 13.2 Women 176 (57.1%) Men 132 (42.9%) Body-mass index > 30 Kg/m2 25 (8.1%) Concomitant risk factors for VTE Recent surgery or trauma 79 (25.6%) In-patients/immobilization 45 (14.6%) Prolonged bed rest 47 (15.3%) Local or systemic infections 19 (6.2%) Qualifying distal venous thrombosis Axial calf veins 135 (43.8%) Muscolar calf veins 149 (48.4%) Medial gastrocnemius veins 113 (36.7%) Lateral gastrocnemius veins 45 (14.6%) Soleal veins 73 (23.7%) Bilateral venous thrombosis 22 (7.1%) More than one vein involved 127 (41.2%) Previous history of VTE 45 (14.6%) Family history of VTE 16 (5.2%) Primary cancer site Breast 54 (17.5%) Gastrointestinal 51 (16.6%) Pancreas 18 (5.8%) Hepatic 9 (2.9%) Lung 44 (14.3%) Hematologic 47 (15.3%) Prostate 17 (5.5%) Brain 15 (4.9%) Other 53 (17.2%) Metastases 148 (48.1%) Cancer therapy Systemic chemotherapy 174 (56.5%) Radiotherapy 20 (6.5%) Hormonal therapy 36 (11.7%) Anticoagulant therapy 305 (99%) Low-molecular-weight heparin 288 (93.5%) Fondaparinux 16 (5.2%) Unfractionated heparin 1 (0.3%) Heparin-Vitamin K antagonists 46 (14.9%) VTE = venous thromboembolism. Conclusions Cancer patients with IDDVT have a high risk of VTE recurrence. Other studies are warranted to address the adequate management of these patients.
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