Start Of Anticoagulant Treatment Research Articles

Neutrophil extracellular trap formation is an independent risk factor for occult cancer in patients presenting with venous thromboembolism

BackgroundVenous thromboembolism (VTE), particularly unprovoked VTE, is associated with occult cancer. The optimal screening regimen remains controversial. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis, and elevated biomarkers of NET formation are associated with poor prognosis. ObjectivesTo investigate the association between NET formation and occult cancer in patients with VTE. MethodsBlood biomarkers associated with NETs and neutrophil activation (nucleosomal citrullinated histone H3 [H3Cit-DNA], cell-free DNA, and neutrophil elastase) were quantified in patients with VTE. The primary outcome was cancer diagnosed during a one-year follow-up. ResultsThis study included 460 patients with VTE, of which 221 (48%) had isolated deep vein thrombosis. Forty-three patients had active cancer at inclusion and were excluded from the primary analysis Cancer during follow-up was diagnosed in 29 of 417 (7.0%) patients. After adjustment for age and unprovoked VTE, the hazard ratio of cancer during follow-up per 500 ng/mL increase of H3Cit-DNA was 1.79 (95% CI, 1.03–3.10). Furthermore, patients with cancer-associated VTE (known active cancer or cancer diagnosed during follow-up) had higher levels of H3Cit-DNA than cancer-free patients with VTE after adjustment for age, hemoglobin, gender, chronic obstructive pulmonary disease, previous cancer, and start of anticoagulant treatment (odds ratio 2.06 per 500 ng/mL increase of H3Cit-DNA [95% CI, 1.35–3.13]). ConclusionsH3Cit-DNA is an independent predictor for occult cancer in patients with VTE and elevated in cancer-associated VTE, suggesting that H3Cit-DNA is potentially a useful diagnostic marker for cancer in patients with VTE and that elevated NET formation is a hallmark of cancer-associated VTE.

Problems of adherence to treatment with oral anticoagulants in elderly patients with atrial fibrillation in the Kyrgyz Republic

Objectives assessment of adherence to treatment in elderly patients with nonvalvular atrial fibrillation who were prescribed anticoagulant therapy with vitamin K antagonist, warfarin, and a new oral anticoagulant rivaroxaban.
 Material and methods. During the study, 322 patients with atrial fibrillation of nonvalvular etiology were observed. Depending on the type of anticoagulant taken, the patients were divided into 2 groups: the first group included 253 (78.6%) people who took warfarin, the second group 69 (21.4%) people, who were prescribed a new oral anticoagulant rivaroxaban.
 Results. By the end of the one-year follow-up from the start of anticoagulant treatment, only 8.7% of patients in the first group followed the doctor's prescription; the second group had 59.4% of adherent patients. The vast majority of patients refused warfarin therapy due to the inability to control INR. In the case of the appointment of rivaroxaban, the reason for the refusal to take was the high cost of the drugs.
 Conclusion. Effective prevention of thromboembolic complications in atrial fibrillation requires the development of appropriate measures to improve adherence to treatment.

Evolution of CT findings after anticoagulant treatment for acute pulmonary embolism in patients with and without an ultimate diagnosis of chronic thromboembolic pulmonary hypertension.

The pulmonary arterial morphology of patients with pulmonary embolism (PE) is diverse and it is unclear how the different vascular lesions evolve after initiation of anticoagulant treatment. A better understanding of the evolution of computed tomography pulmonary angiography (CTPA) findings after the start of anticoagulant treatment may help to better identify those PE patients prone to develop chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to assess the evolution of various thromboembolic lesions on CTPA over time after the initiation of adequate anticoagulant treatment in individual acute PE patients with and without an ultimate diagnosis of CTEPH. We analysed CTPA at diagnosis of acute PE (baseline) and at follow-up in 41 patients with CTEPH and 124 patients without an ultimate diagnosis of CTEPH, all receiving anticoagulant treatment. Central and segmental pulmonary arteries were scored by expert chest radiologists as normal or affected. Lesions were further subclassified as 1) central thrombus, 2) total thrombotic occlusion, 3) mural thrombus, 4) web or 5) tapered pulmonary artery. Central thrombi resolved after anticoagulant treatment, while mural thrombi and total thrombotic occlusions either resolved or evolved into webs or tapered pulmonary arteries. Only patients with an ultimate diagnosis of CTEPH exhibited webs and tapered pulmonary arteries on the baseline scan. Moreover, such lesions always persisted after follow-up. Webs and tapered pulmonary arteries at the time of PE diagnosis strongly indicate a state of chronic PE and should raise awareness for possible CTEPH, particularly in patients with persistent dyspnoea after anticoagulant treatment for acute PE.

Quality of Life in Cancer Patients Undergoing Anticoagulant Treatment for Venous Thromboembolism: The Quavitec Study

Introduction: Treatment and prevention of VTE is crucial, yet anticoagulation is under-prescribed in cancer patients. The recommended treatment for established VTE in cancer patients is low molecular weight heparin (LMWH) once daily for at least 3 months, and termination or continuation of treatment after 3-6 months is still based on individual evaluation of the benefit-risk ratio, tolerability, drug availability, patient preference, and cancer. Despite important concerns about long-term patient tolerance for LMWH treatment (after 10 days) and its side effects, no study has analyzed the overall impact of LMWH on quality-of-life (QoL) in cancer patients.Methods: In this prospective, longitudinal, multicenter study, consecutive eligible adult cancer patients (>18 years), diagnosed with either deep vein thrombosis or a pulmonary embolism (PE), were recruited at participating centers between February 2011 and 2012. Patients were asked to answer three questionnaires administered at time of VTE diagnosis (M0), and 3 (M3) and 6 (M6) months after start of anticoagulant treatment: 1) the Medical Outcome Study 36-item Short-Form Health Survey (MOS SF-36) for generic Health-Related Quality of Life (HRQoL), 2) the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire, and 3) the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL questionnaire.Results (median[iqr], Wilcoxon Signed Rank Test): At M0, 400 cancer patients (51.5% female) were included, 60.4% with metastatic disease and 67.0% on chemotherapy. The choice of anticoagulant was made by the attending physician. 88.75% of patients received LMWH, 5.5% a vitamin K antagonist, 1.5% unfractionated heparin, and 3.75% a direct oral anticoagulant. Throughout the study, 18.9% of patients on LMWH reported at least one side effect with injection (number of reports: pain, 26 (7.3%); ecchymosis, 57(16.1%); pruritis, 2(0.6%); nodules, 28 (7.9%)). Mortality rate was 24.73%, with 79 deaths attributable to cancer progression and 3 to VTE.At M3, patients on LMWH showed a significant increase of 3.9 [5.7-14 ] points in the MOS SF-36 global HRQoL score (p=0.0007) and 8.3 [-8.3;17] points in the EORTC global Health status/QoL survey (p=0.0001). The veinsQoL score decreased by 2 [-5.2-4] points (p=0.022). Logistic regression analysis identified predictive factors common to both MOS SF-36 and EORTC: ECOG scores (MOS SF-36, p=0.050; EORTC, p=0.006) and whether patients were ambulatory as opposed to bedridden (MOS SF-36, p=0.001; EORTC, p=0.019). Cancer surgery (p=0.005), presence of central venous catheter (CVC) (p=0.018) or PE (p=0.029), and absence of chemotherapy (p=0.017), or acute infection (p=0.048) were also positive predictors of cancer-related QoL in the EORTC survey. No predictive factors were identified for veinsQoL.At M6, patients on LMWH showed sustained point increases of 5.5 [-5.6; 22] in the MOS SF-36 global HRQoL score (p<0.0001) and 8.3 [-8.3;33] in the EORTC global Health status/QoL score (p<0.0001), with no change in VeinsQoL. Logistic regression identified the pattern of change in QoL in the first three months of anticoagulation as a strong predictor of QoL scores at the M6 follow-up (MOS SF-36, p<0.0001; EORTC, p<0.0001; veinesQoL, p<0.0001). Tumor histology (p=0.005), CVC (p=0.024), absence of acute infection (p=0.034), and being ambulatory as opposed to bedridden (p=0.045), were additional predictive factors in the MOS SF-36.There was no change in the MOS SF-36 global HRQoL score between 3 and 6 months, but there was significant improvement in the sub-dimensions of general health (1.9 pts, p=0.057) and vitality (3.7 pts; p=0.016). The improved global health status/QoL score in the EORTC was also maintained between 3 and 6 months, with a significant 4.7 point reduction in the fatigue symptom subscale (p=0.016). No change was observed in the VeinsQoL. Painful side effects of LMWH treatment did not predict diminished QoL in the logistic regression analysis. Cancer progression was a negative predictor of MOS SF-36 global HRQoL in these patients (p=0.051).Conclusion: In cancer patients with established VTE who survive to 3 and 6 month follow-ups under recommended anticoagulant treatment, QoL increases despite long term treatment with LMWH. This analysis is the first to show that LMWH treatment from 3 to 6 months does not diminish QoL in cancer patients diagnosed with VTE. DisclosuresNo relevant conflicts of interest to declare.

Quality of life in patients with venous thromboembolism and atrial fibrillation treated with coumarin anticoagulants

IntroductionLittle is known about the overall quality of life (QOL) in patients newly diagnosed with venous thromboembolism (VTE) and atrial fibrillation (AF).We studied QOL in patients with VTE and AF immediately after the start of anticoagulant therapy, and after three months of treatment. Furthermore we identified whether QOL was affected by age, gender and nationality. Materials and MethodsThe European pharmacogenetics of anticoagulant therapy (EU-PACT) study was a multicentre, randomized controlled trial of patients aged >18years diagnosed with VTE or AF. QOL was assessed using EuroQol 5 dimensions (EQ-5D) questionnaires. ResultsThe EQ-5D questionnaires were completed by 187 patients with VTE and 660 patients with AF. The QOL in patients diagnosed with VTE or AF was significantly impaired, however, during a 3months treatment period, patients experienced an improvement (p<0.05). The QOL in patients diagnosed with VTE improved with increasing age, with similar effects seen in men and women. Men and women diagnosed with AF differed in QOL (respectively 0.84 and 0.74, p<0.05), and QOL decreased with age. Comparison between countries showed significant differences in the EQ-Index score at follow-up of patients with VTE, and in both EQ-Index score and EQ-VAS of patients with AF. ConclusionsThe QOL in patients with VTE and AF is strongly reduced directly after the start of anticoagulant treatment, but improves within 3months. Moreover, QOL is influenced by demographic and disease-specific variables. These findings provide useful information for future cost-effectiveness studies.

Anticoagulant Therapy in Very Old Patients

Older patients are less likely than younger patients to receive anticoagulation and are more likely to be underanticoagulated. Although the use of warfarin in the elderly has been increasing, fewer than half of eligible patients take warfarin. Evidence suggests that stroke recurrence in patients on oral anticoagulation is mainly ischemic, and hemorrhagic complications that derive from oral anticoagulation would be related to overdosing. Several risk factors for developing hemorrhagic complications have been described, and clinical criteria have been designed to help clinicians in decision-making concerning the start of anticoagulation treatment. Finally, given the promising results of recent studies on new anticoagulant drugs, it is possible that vitamin K antagonists will be replaced in the coming years.

Authors' reply

<h3>Introduction</h3> The pulmonary arterial morphology of patients with pulmonary embolism (PE) is diverse and it is unclear how the different vascular lesions evolve after initiation of anticoagulant treatment. A better understanding of the evolution of computed tomography pulmonary angiography (CTPA) findings after the start of anticoagulant treatment may help to better identify those PE patients prone to develop chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to assess the evolution of various thromboembolic lesions on CTPA over time after the initiation of adequate anticoagulant treatment in individual acute PE patients with and without an ultimate diagnosis of CTEPH. <h3>Methods</h3> We analysed CTPA at diagnosis of acute PE (baseline) and at follow-up in 41 patients with CTEPH and 124 patients without an ultimate diagnosis of CTEPH, all receiving anticoagulant treatment. Central and segmental pulmonary arteries were scored by expert chest radiologists as normal or affected. Lesions were further subclassified as 1) central thrombus, 2) total thrombotic occlusion, 3) mural thrombus, 4) web or 5) tapered pulmonary artery. <h3>Results</h3> Central thrombi resolved after anticoagulant treatment, while mural thrombi and total thrombotic occlusions either resolved or evolved into webs or tapered pulmonary arteries. Only patients with an ultimate diagnosis of CTEPH exhibited webs and tapered pulmonary arteries on the baseline scan. Moreover, such lesions always persisted after follow-up. <h3>Conclusions</h3> Webs and tapered pulmonary arteries at the time of PE diagnosis strongly indicate a state of chronic PE and should raise awareness for possible CTEPH, particularly in patients with persistent dyspnoea after anticoagulant treatment for acute PE.

Clotting Factor Levels in Patients with Coronary Atherosclerosis

The clotting system was studied in a number of patients with coronary atherosclerotic disease, with special regard to antihemophilic A factor (AHA) and antihemophilic C factor (AHC).The levels of a number of clotting factors were determined in plasma samples from 14 patients with atherosclerotic coronary disease before the start of anticoagulant treatment. A similar study was made in 80 patients with the same disease under long-term anticoagulant treatment with phenylindanedione or dicoumarol for more than 3 months.AHA was found on the average higher in both groups of patients than in a group of 30 normal healthy persons. The AHA values did not seem to be definitely correlated with age, judged from the variations within the group of normal persons and within the group of treated patients. The high AHA values were not found to he correlated in any definite way with the duration of the anticoagulant treatment.The investigations confirmed the findings of other workers that average fibrinogen levels in these ...