The thrombotic risk in Cushing's syndrome-questions, answers, and the algorithm to consider in its assessment: part I-thrombotic risk not related to surgery.

Introduction: Recently, it has been reported that there is a great diversity in strategies used for thromboprophylaxis in patients with Cushing's syndrome (CS). An aim of this review was to discuss these practices in light of the existing data on the thrombotic risk in patients with CS and guidelines for medically ill patients. Methods: The four relevant topics and questions on thrombotic risk in CS were identified. The current guidelines on prevention and diagnosis of venous thromboembolism (VTE) were reviewed for the answers. An algorithm to consider in the assessment of the thrombotic risk in patients with CS was proposed. Results: To address both generic and CS-specific risk factors for VTE, the algorithm includes the stepwise approach consisting of Padua Score, urine free cortisol, and CS-VTE score, with no indication for routine thrombophilia testing in the prediction of an index VTE episode. Having confirmed VTE, selected patients require thrombophilia testing to aid the duration of anticoagulant treatment. The separate part of the algorithm is devoted to patients with ectopic adrenocorticotropic hormone syndrome in whom exclusion of VTE precedes introducing routine thromboprophylaxis to prevent VTE. The cancer-related VTE also prompts thromboprophylaxis, with the possible vessel invasion. The algorithm presents a unifactorial and multifactorial approach to exclude high-bleeding risks and safely introduce thromboprophylaxis with low-molecular-weight heparin. Summary: Our article is the first to present an algorithm to consider in the thrombotic risk assessment among patients with Cushing's syndrome as a starting point for a broader discussion in the environment. A plethora of factors affect the VTE risk in patients with CS, but no studies have conclusively evaluated the best thromboprophylaxis strategy so far. Future studies are needed to set standards of care.

Caprini VTE computerized risk assessment improves the use of thromboprophylaxis in hospitalized patients with pulmonary disorders.

BACKGROUND: Adequate thromboprophylaxis reduces the risk of venous thromboembolism (VTE) by half in hospitalized patients. A single scoring system is recommended to improve thromboprophylaxis. OBJECTIVES: We investigated the impact of implementing a computerized system to prevent VTE in inpatients with pulmonary diseases and identified predictors of the overuse and underuse of pharmacological thromboprophylaxis. MATERIAL AND METHODS: We compared the use of thromboprophylaxis with enoxaparin in all patients hospitalized for pulmonary disorders in a tertiary hospital in Kraków, Poland, in 2014 and 2017, before and after introducing a computerized thromboprophylaxis system. Using the Caprini risk assessment, the overuse and underuse of thromboprophylaxis were defined as the use in patients with <5 points and ≥5 points, respectively. RESULTS: Both cohorts (n = 2007 in 2014 and n = 1570 in 2017) were similar with regard to age and sex. The most frequent causes of hospitalization were intestinal lung disease (39.0%) and lung cancer (20.4%) in 2017, and pneumonia (38.8%) and lung cancer (27.5%) in 2014. Although the use of thromboprophylaxis was comparable in both cohorts, it was used more frequently in high VTE risk patients in 2017 compared with 2014 (96.98% compared to 29.17%, respectively, p < 0.001), with a concomitant reduction in its overuse (2.26% compared to 6.26%, respectively, p < 0.001). In 2017, no predictors of thromboprophylaxis underuse were identified. The overuse was mainly predicted by the diagnosis of airway diseases (odds ratio (OR) = 0.16, 95% confidence interval (95% CI) = 0.02-1.17, p = 0.015). CONCLUSIONS: Our findings indicate the benefits of using a computerized system to manage pharmacological thromboprophylaxis in pulmonary inpatients.

The comparison between Caprini and Padua VTE risk assessment models for hospitalised cancer patients undergoing chemotherapy at the tertiary oncology department in Poland: is pharmacological thromboprophylaxis overused?

AIM OF THE STUDY: Thromboprophylaxis in cancer patients during hospitalization reduces the risk of venous thromboembolism (VTE). MATERIAL AND METHODS: To assess the underuse and the overuse of thromboprophylaxis in cancer patients at a tertiary oncology department, we retrospectively analyzed 1983 consecutive hospitalizations of 498 cancer patients who received chemotherapy from October 2016 to May 2017. The Padua prediction score (≥ 4 points) and Caprini risk assessment (≥ 5 points) were used to identify patients at high risk of VTE. RESULTS: The majority of individuals (n = 363, 72.9%) suffered from advanced lung cancer. We found that 419 (84.14%) patients received thromboprophylaxis with enoxaparin 40 mg qd,including 181 (43.2%) individuals using concomitant mechanical thromboprophylaxis. As few as 44 (8.8%) and 11 (2.2%) patients did not receive thromboprophylaxis despite high VTE risk based on the Caprini risk assessment and Padua prediction score, respectively (p < 0.001). The number of patients without high risk of VTE, who received pharmacological thromboprophylaxis, was higher when the Padua prediction score was used compared with the Caprini risk assessment (n = 391 [78.5%] vs. n = 210 [42.2%], respectively; p < 0.001). Three patients (0.6%) experienced vascular events during hospital stay, including one symptomatic deep vein thrombosis. No major bleeding was observed. Predictors of thromboprophylaxis overuse were as follows: previous VTE and abnormal pulmonary function for both scales. CONCLUSIONS: This study shows that thromboprophylaxis in cancer in patients undergoing chemotherapy is suboptimal in Poland in part due to the use of various VTE risk scores yielding discrepant results in everyday practice.

Activated protein C resistance in patients following venous thromboembolism receiving rivaroxaban versus vitamin K antagonists: assessment using Russell viper venom time-based assay.

: Activated protein C resistance (APC-R) is assessed as part of thrombophilia screening, preferably in patients not taking oral anticoagulants. Rivaroxaban is known to alter some APC-R assays. To our knowledge, there have been no reports on the effect of rivaroxaban on the Russell viper venom time (RVVT)-based APC-R assay in real-life patients. In 168 consecutive outpatients suspected of having venous thromboembolism because of thrombophilia, APC-R was determined using the RVVT-based ProC Ac R assay (Siemens, Marburg, Germany). Patients receiving rivaroxaban or vitamin K antagonists were eligible. We measured rivaroxaban concentrations using the anti-Xa Biophen DiXal assay (Hyphen Biomed, Neuville-Sur-Oise, France) and factor V Leiden using the real-time PCR. APC-R was detected in 23 (28%) patients on rivaroxaban (n = 81) administrated 2-48 h since the blood draw, 15 (28%) patients on vitamin K antagonists (n = 54), and in four (12%) patients off anticoagulation (n = 33). Compared with nonanticoagulated patients, APC-R ratios were similar in patients on rivaroxaban, without any correlation with rivaroxaban concentrations (from 0 to 303 µg/l). None of the patients on rivaroxaban were found to have false-negative or false-positive APC-R ratios. Rivaroxaban concentrations up to 300 µg/l do not affect results of the ProC Ac R RVVT-based assay, which could be recommended in patients referred to a clinic for thrombophilia screening in whom the time since the last dose of rivaroxaban is uncertain.

An automated method for fibrin clot permeability assessment.

The fibrin clot permeability coefficient (Ks) is a useful measure of porosity of the fibrin network, which is determined by a number of genetic and environmental factors. Currently available methods to evaluate Ks are time-consuming, require constant supervision and provide only one parameter. We present an automated method in which drops are weighed individually, buffer is dosed by the pump and well defined clot washing is controlled by the software. The presence of a straight association between drop mass and their dripping time allows to shorten the measurement time twice. In 40 healthy individuals, Ks, the number of drops required to reach the plateau (DTP), the time to achieve the plateau (TTP) and the DTP/TTP ratio (DTR) were calculated. There was a positive association between Ks (r = 0.69, P < 0.0001) evaluated by using the manual [median of 4.17 (3.60-5.18) ·10⁻9 cm²) and the automated method [median of 4.35 (3.74-5.38) ·10⁻9 cm²]. The correlation was stronger (r = 0.85, P < 0.001) in clots with DTP of 7 or less (n = 12). DTP was associated with total homocysteine (tHcy) (r = 0.35, P < 0.05) and activated partial thromboplastin time (APTT) (r = -0.34, P < 0.05), TTP with Ks (r = -0.55, P < 0.01 for the manual method and r = -0.44, P < 0.01 for the automated method) and DTP (r = 0.75, P < 0.0001), and DTR with Ks (r = 0.70, P < 0.0001 for the manual method and r = 0.76, P < 0.0001 for the automated method), fibrinogen (r = -0.58, P < 0.0001) and C-reactive protein (CRP) (r = -0.47, P < 0.01). The automated method might be a suitable tool for research and clinical use and may offer more additional parameters describing fibrin clot structure.

2009 evidence-based clinical practice guidelines for diagnosing a first episode of lower extremities deep vein thrombosis in ambulatory outpatients.

INTRODUCTION: The GRADE working group has recently suggested a rigorous framework for clinical practice guidelines (CPG) addressing diagnostic tests and test strategies based on the impact of alternative approaches on patient-important outcomes. The framework mandates explicit evidence summaries, ratings of the quality of evidence, and specifying recommendations as strong or weak. OBJECTIVES: To test the feasibility and performance of the GRADE approach, we applied this framework to well-researched issues in the diagnoses of deep venous thrombosis (DVT). METHODS: A 16-member panel with interest in thromboembolism and CPG development identified pertinent clinical questions. Our search for relevant studies included existing CPG and systematic reviews. We summarized the data in form of evidence tables and developed recommendations including, when needed, a formal consensus process. RESULTS AND CONCLUSIONS: We provide three groups of recommendations for clinicians practicing in settings with access to different types of D-dimer tests -- highly sensitive, moderately sensitive, and no availability of D-dimer. We consider the use of clinical prediction rules in guiding the diagnostic process, the potential for negative D-dimer or venous ultrasound (US) to rule out disease, and the role of follow-up testing (US following positive D-dimer result, D-dimer following negative US, and serial US) depending on the probability of DVT at the start of diagnostic process. We recommend the following: that clinicians without access to a highly or moderately sensitive D-dimer test rely on US to guide DVT diagnosis; that those with access use the highly sensitive D-dimer to determine, in patients with low or moderate probability of DVT (by the Wells rule) whether US is needed; that in patients with low pre-test probability (pre-TP) and a negative D-dimer (either highly or moderately sensitive) they follow patients without further testing; that in patients with high pre-test probability they perform a compression ultrasound without D-dimer testing.