Remedios Otero-Candelera

Testing for occult cancer in patients with pulmonary embolism: Results from a screening program and a two-year follow-up survey

INTRODUCTION An association between pulmonary embolism (PE) and a subsequent diagnosis of cancer has been repeatedly reported. Although screening and early detection might play a pivotal part in reducing mortality from cancer, there are currently no definite data to suggest that cancer screening may improve survival rates in patients with PE. We hereby present the results of a screening program and a two-year follow-up survey for detecting occult cancer in this patient population. MATERIALS AND METHODS A total of 107 patients with PE were consecutively enrolled. All subjects underwent an initial screening program followed by a two-year follow-up survey. We calculated the sensitivity of our screening program, and identified risk factors associated with occult cancer by means of logistic regression. RESULTS The initial screening program yielded positive results in five patients (4.7%), and four additional cases were identified during the 2-year follow-up. The overall sensitivity of our screening program in idiopathic PE was 55.5%. In the entire study cohort, the number necessary for screening was 12.1 (6.1 in idiopathic PE, and 58 in secondary PE). Logistic regression analysis revealed that a shock index >/=1 (odds ratio: 5.467; p=0.007) and idiopathic PE (odds ratio: 12.82; p=0.03) were independent risk factors for occult cancer in our PE patients. CONCLUSIONS A simple and noninvasive screening program yields an acceptable sensitivity for detecting occult cancer in idiopathic PE patients. These results highlight the importance of screening for occult cancer in patients diagnosed with PE, especially in idiopathic forms.

Rivaroxaban for the treatment of venous thromboembolism. A "real-life" perspective in 103 patients.

INTRODUCTION Randomized clinical trials have demonstrated non-inferiority of rivaroxaban compared with vitamin K antagonists (VKAs) in the treatment of venous thromboembolism (VTE). Our objective was to analyze in real life, tolerance, recurrence, bleeding and adverse events of rivaroxaban in patients with acute symptomatic VTE. MATERIAL AND METHODS Open follow-up study of a cohort of patients aged 18 and over diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) treated with rivaroxaban from December 2011 to January 2014. RESULTS The total number of patients treated with rivaroxaban was 103. The mean age was 58+/-17 years. The most frequent co-morbidities were: hypertension (30.0%), dyslipidemia (23.3%) and respiratory disease (25.2%). The type of thromboembolic event treated was: DVT (64.1%), PE (18.4%), DVT+PE (17.5%). Of the rivaroxaban-treated patients, 30% did so from the initial anticoagulant therapy and the other 70% in long-term or extended anticoagulant therapy. The median time of treatment with rivaroxaban was 6 months [corrected]. There was one recurrence and no deaths occurred. Six patients had bleeding, one of which was severe. CONCLUSIONS Rivaroxaban provides a therapeutic alternative in a group of patients with VTE with advantages over VKAs, because of the convenience in dosing, lack of requirements for periodic monitoring and limited interaction with other drugs.

Impact of sample processing on the measurement of circulating microparticles: storage and centrifugation parameters.

Abstract Background: Microparticles (MPs) have been shown to be markers of cellular activation and interactions. Pre-analytical conditions such as the centrifugation protocol and sample storage conditions represent an important source of variability in determining MPs values. The objectives of this study were to evaluate the influence of sample storage conditions and centrifugation speed and temperature on the determination of MPs in plasma. Methods: Citrate-anticoagulated blood samples obtained from 21 healthy subjects were centrifuged under four different protocols involving different speeds (2500 g or 1500 g) and temperatures (4 °C or 20 °C) to isolate platelet-poor plasma (PPP). The number of MPs in fresh and frozen-thawed PPP were analyzed by flow cytometry, and MPs-mediated procoagulant activity was determined by a thrombin generation test and phospholipid-dependent procoagulant tests. Results: The number of MPs and their procoagulant activity were affected by freeze-thaw cycling and centrifugation speed but not by centrifugation temperature. Sample freezing increased MPs number (six-fold) and thrombin generation (four-fold), and decreased clotting time (two-fold). Low centrifugation speed caused an increase in MPs number and a parallel increase in MP-mediated procoagulant activity. Conclusions: Sample storage conditions and centrifugation speed are important processing conditions affecting MPs number and activity. Before any study, the protocol for MPs isolation should be optimized to ensure a reliable characterization of MPs, which could provide important information for diagnostic purposes and for understanding the pathogenesis of diseases.

High correlation between 2 flow cytometry platforms in the microparticles analysis using a new calibrated beads strategy

Microparticles (MPs) are potential noninvasive biomarkers for diagnosis or prognosis in pathologic conditions. However, the lack of standardization of the preanalytical and analytical methods leads to a wide variability in MPs results. The recently developed Megamix-Plus beads, a new bead-based standardization tool optimized to specific types of flow cytometers, could help circumvent this problem. The aim of the present study was to determine whether the number of total MPs and platelet-derived MPs (PMPs) is similar using 2 different cytometer platforms calibrated with the Megamix-Plus beads. Blood samples from 65 patients with deep venous thrombosis were collected and processed to obtain platelet poor plasma (PPP). The number of total MPs and PMPs in each PPP sample was measured using 2 flow cytometers. Megamix-Plus side scatter channel beads were used to calibrate the LSRFortessa flow cytometer from Becton Dickinson, whereas Megamix-Plus forward scatter channel beads were applied to the Navios flow cytometer from Beckman Coulter. High correlation of total MPs and PMPs values between the flow cytometers was found (r = 0.908, P < 0.01 and r = 0.910, P < 0.001, respectively). However, the absolute numbers of total MPs and PMPs were significantly higher measured with the Navios flow cytometer compared with the LSRFortessa cytometer. Therefore, both platforms are valid for MPs determination in general, although a similar platform with the same calibration tool could be a better choice for multicenter studies.

Dyslipidemia as a long-term marker for survival in pulmonary embolism

OBJECTIVES To analyse survival rate after 24 months in consecutive patients with a diagnosis of PE as well as associated factors. METHODS Prospective cohort study during a follow-up period of two years in a series of consecutive patients with PE. RESULTS During the follow-up period, 34 out of 148 patients died (23%). Factors independently associated with reduced survival rate were: creatinine levels > 2 (OR, 8.8; 95% CI, 1.1 - 70.87), previous neoplasm (OR, 8.8; 95% CI, 3.69 - 20.98), dementia (OR, 6.85; 95% CI, 2.1 - 22.33) and dyslipidemia (OR, 5.07; 95% CI, 1.92 - 13.44). Forty four percent of the patients with dyslipidemia died vs. 20.8% of patients without this condition. CONCLUSIONS In our study dyslipidemia shows as a long-term negative prognostic marker for survival in patients with EP.

Towards a precision medicine in venous thromboembolism associated to lung cancer

Oncological patients have a higher risk for venous thromboembolism (VTE) (1,2), and also have an elevated risk of VTE recurrence and bleeding (3-5). Actually, guidelines in oncological patients with VTE recommend anticoagulant treatment, although these recommendations are the same, irrespectively of cancer and VTE location (6-9).

Survivin is a negative prognostic factor in malignant pleural effusion

Survivin is a well‐known member of the inhibitor of apoptosis family, and has been related to increased tumour aggressivity, both in tissue and in pleural fluid.

D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis

BackgroundOptimal duration of anticoagulation for cancer-associated thrombosis (CAT) remains unclear. This study assessed D-dimer (DD) and high-sensitivity C-reactive protein (hs-CRP) levels after the withdrawal of anticoagulation treatment to predict the risk of venous thromboembolism (VTE) recurrence among patients with CAT.MethodsProspective, multicentre study to evaluate CAT with ≥3 months of anticoagulation that was subsequently discontinued. Blood samples were taken when patients stopped the anticoagulation and 21 days later to determine the DD and hs-CRP levels. All patients were followed up for 6 months to detect VTE recurrence.ResultsBetween 2013 and 2015, 325 patients were evaluated and 114 patients were ultimately enrolled in the study. The mean age was 62 ± 14 years and nearly 40% had metastasis. Ten patients developed VTE recurrence within 6 months (8.8%, 95% confidence interval [CI]: 4.3–15.5%). The DD and hs-CRP levels after 21 days were associated with VTE recurrence. The subdistribution hazard ratios were 9.82 for hs-CRP (95% CI: 19–52) and 5.81 for DD (95% CI: 1.1–31.7).ConclusionsThis study identified that hs-CRP and DD were potential biomarkers of VTE recurrence after discontinuation of anticoagulation in CAT. A risk-adapted strategy could identify low-risk patients who may benefit from discontinuation of anticoagulation.

Clinically relevant bleeding and thrombotic events in non-cirrhotic splanchnic vein thrombosis. Long-term follow up

• Patients with splanchnic vein thrombosis have a high risk of thrombotic and bleeding events.

Treatment of venous thromboembolism in cancer patients with tinzaparin beyond 6 months. TiCAT study

Background: Treatment of venous thromboembolism (VTE) in patients with cancer has a high rate of recurrence and bleeding complications. Guidelines recommend low-molecular-weight heparin (LMWH) for at least 3–6 months and possibly indefinitely for patients with active malignancy. There are few data supporting treatment with LMWH beyond 6 months. The primary aim of the study was to determine the safety of tinzaparin between 6 and 12 months in cancer-associated VTE. Methods: Patients with active cancer and newly diagnosed VTE were enrolled in a prospective study and received subcutaneous tinzaparin for all duration of study. The rates of bleeding and recurrent VTE were evaluated at months 1, 2–6 and 7–12. Findings: Of 246 patients enrolled, 141 and 89 completed 6 and 12 months of therapy; 52% had deep vein thrombosis (DVT); 30% had pulmonary embolism (PE); and 18% both. The overall frequency of major bleeding was 4.1% (10/246). Major bleeding occurred in 1.6% (4/246) in the first month, and 0.005% (1/689.87), 0.6% (4/650) and 0.07% (1/1305) per patient-month during months 2–6, 7–12 and beyond 12, respectively. Recurrent VTE in patients with tinzaparin was 6.9% (17/246). The incidence rate was 2.4% (6/246) for month 1, 2.9% (6/204) during months 2–6 and 1.4% (2/141) during months 7–12. Fifty-seven patients died, 42% in the first 6 months after VTE. One patient died due to recurrent VTE and two due to bleeding. Conclusion: Long-term treatment with Tinzaparin in cancer-associated VTE is effective and safe, with a low rate of bleeding and recurrences. The risk of developing complications (severe bleeding or recurrence) was higher in the first month and lower over the subsequent months.