Unmet definitions in thromboprophylaxis for hospitalized medical patients: An appraisal for the need of recommendation.

Up to about 60% of venous thromboembolic events in a community are associated with hospitalization, and most can be prevented by appropriate thromboprophylaxis. Several randomized clinical trials and guidelines have addressed the issue of thromboprophylaxis in hospitalized patients and recommended strategies to assess patients' risk and thromboprophylaxis. Simple and validated risk assessment models are available to assist physicians in selecting patients who are at high risk for VTE, in whom thromboprophylaxis should be used. However, some concepts employed are imprecise or not appropriately defined. Indeed, there has been wide variation in the onset, duration, and adequacy of thromboprophylaxis, as well as in the definition of some risk factors. In this article, we highlight these issues and the unmet definitions in thromboprophylaxis in hospitalized patients mainly by addressing selected randomized clinical trials and guidelines.

Inter-observer reliability of a risk assessment model for venous thromboembolism in acutely-ill medical hospitalized patients: Results from a prospective cohort study.

OBJECTIVES: To analyze the inter-observer reliability of risk for venous thromboembolism (VTE) in a population of adult acutely-ill medical patients. METHODS: In this prospective cohort study, we collected risk factors and risk classification for VTE using RAM IMPROVE7. Kappa statistics was used to evaluate inter-observer reliability between lead clinicians and trained researchers. We evaluated occurrence of VTE in patients with mismatched classification. RESULTS: We included 2,380 patients, median age 70 years (interquartile range [IQR], 58-79), 56.2% female. Adjusted Kappa for VTE risk factors ranged from substantial (0.64, 95% confidence interval [CI], 0.61-0.67) for "immobilization", to almost perfect (0.98; 95% CI 0.97-0.99) for "thrombophilia"; risk classification was 0.64 (95% CI 0.60-0.67). Divergent risk classification occurred in 434 patients (18.2%) of whom seven (1.6%) developed VTE. CONCLUSION: Despite substantial to almost perfect reliability between observers for risk factors and risk classification, lead clinicians tended to underestimate the risk for VTE.

Derivation of a risk assessment model for hospital-acquired venous thrombosis: the NAVAL score.

Venous thrombosis (VT) is a preventable cause of death in hospitalized patients. The main strategy to decrease VT incidence is timely thromboprophylaxis in at-risk patients. We sought to evaluate the reliability of risk assessment model (RAM) data, the incremental usefulness of additional variables and the modelling of an adjusted score (the NAVAL score). We used the RAM proposed by Caprini for initial assessment. A 5 % systematic sample of data was independently reviewed for reliability. We evaluated the incremental usefulness of six variables for VT during the score modelling by logistic regression. We then assessed the NAVAL score for calibration, reclassification and discrimination performances. We observed 11,091 patients with 37 (0.3 %) VT events. Using the Caprini RAM, high-risk and moderate-risk patients were respectively associated with a 17.4 (95 % confidence interval [CI] 6.1-49.9) and 4.2 (95 % CI 1.6-11.0) increased VT risk compared with low-risk patients. Four independent variables were selected for the NAVAL score: "Age", "Admission clinic", "History of previous VT event" and "History of thrombophilia". The area under the receiver-operating-characteristic curve for the NAVAL score was 0.72 (95 % CI 0.63-0.81). The Net Reclassification Index (NRI) for the NAVAL score compared with the Caprini RAM was -0.1 (95 % CI -0.3 to 0.1; p = 0.28). We conclude that the NAVAL score is a simplified tool for the stratification of VT risk in hospitalized patients. With only four variables, it demonstrated good performance and discrimination, but requires external validation before clinical application. We also confirm that the Caprini RAM can effectively stratify VT risk in hospitalized patients in our population.

Combined oral contraceptives: venous thrombosis.

BACKGROUND: Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available. OBJECTIVES: To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. SEARCH METHODS: Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions. SELECTION CRITERIA: We selected studies including healthy women taking COC with VT as outcome. DATA COLLECTION AND ANALYSIS: The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies. MAIN RESULTS: 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 µg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk. AUTHORS' CONCLUSIONS: All combined oral contraceptives investigated in this analysis were associated with an increased risk of venous thrombosis. The effect size depended both on the progestogen used and the dose of ethinylestradiol. Risk of venous thrombosis for combined oral contraceptives with 30-35 µg ethinylestradiol and gestodene, desogestrel, cyproterone acetate and drospirenone were similar, and about 50-80% higher than with levonorgestrel. The combined oral contraceptive with the lowest possible dose of ethinylestradiol and good compliance should be prescribed-that is, 30 µg ethinylestradiol with levonorgestrel.

Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis.

OBJECTIVE: To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, Embase, Web of Science, Cochrane, Cumulative Index to Nursing and Allied Health Literature, Academic Search Premier, and ScienceDirect up to 22 April 2013. REVIEW METHODS: Observational studies that assessed the effect of combined oral contraceptives on venous thrombosis in healthy women. The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported. The requirement for crude numbers did not allow adjustment for potential confounding variables. RESULTS: 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 1.9 and 3.7 per 10,000 woman years, in line with previously reported incidences of 1-6 per 10,000 woman years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 µg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk. CONCLUSION: All combined oral contraceptives investigated in this analysis were associated with an increased risk of venous thrombosis. The effect size depended both on the progestogen used and the dose of ethinylestradiol.

Assessment of characteristics associated with pharmacologic thromboprophylaxis use in hospitalized patients: a cohort study of 10,016 patients.

The aim of the study was to evaluate patient characteristics associated with pharmacologic thromboprophylaxis (PTP) use/nonuse in a general tertiary hospital cohort. Eligible patients were classified according to venous thromboembolism (VTE) risk category by trained nurses. Either standard or low-molecular weight heparin was recommended to intermediate or high-risk VTE patients. Adopting the recommended PTP was at the physician's discretion. At discharge, PTP use was recorded. PTP was recommended to 10,016 patients, of whom 2165 (21.6%) received the recommended thromboprophylaxis. In the multivariate logistic regression, PTP use/nonuse remained independently associated with female sex [odds ratio (OR) 0.75; 95% confidence interval (CI) 0.68-0.84], age (OR 1.04; 95% CI 1.03-1.04), being admitted to the Gynecology-Obstetrics (OR 0.31; 95% CI 0.25-0.39) or surgery (OR 1.26; 95% CI 1.12-1.42), thrombophilia (OR 5.15; 95% CI 2.04-12.98), previous VTE event (OR 2.98; 95% CI 1.78-4.98), diabetes (OR 1.84; 95% CI 1.61-2.10), acute myocardial infarction (OR 5.87; 95% CI 4.81-7.17), and admission to a major orthopedic surgery (OR 3.03; 95% CI 1.98-4.64). PTP in this hospital population was grossly underused. Eight independent variables predicted use/nonuse of PTP. Targeting variables related to the use and nonuse of PTP is important to direct the application of thromboprophylaxis.

Prognostic value of computed tomographic pulmonary angiography and the pulmonary embolism severity index in patients with acute pulmonary embolism.

Pulmonary embolism is a serious and potentially fatal disorder. Pulmonary embolism risk stratification may allow early hospital discharge and outpatient treatment for low-risk patients. Also, it may prevent death by early medical intervention in high-risk groups. We evaluated objectively confirmed pulmonary embolism in 126 patients by multidetector computed tomographic pulmonary angiography at a single center from January 2008 to January 2010. The Pulmonary Severity Embolism Index (PESI), the right ventricle (RV) to left ventricle (LV) diameter (RV/LV) ratio and the vascular obstruction index (VOI) were derived from data extracted from electronic hospital records and image database. A total of six out of 96 patients (6.3%) died during follow-up. There was an association between PESI and mortality (P-value < 0.001 χ² test). PESI class I-II had a 100% negative predictive value for death in 90 days. No association was found between the RV/LV ratio, the VOI and mortality (P-value > 0.05 χ² test). Also, no association was found between the RV/LV ratio and the VOI and PESI (P-value > 0.05 χ² test). PESI is an accurate tool for pulmonary embolism prognostic stratification. It safely discriminates low-risk from high-risk patients regarding death outcome. We were unable to demonstrate an association between image scores and mortality.

Managing suspected venous thromboembolism in a mixed primary and secondary care setting using standard clinical assessment and D-dimer in a noninvasive diagnostic strategy.

Venous thromboembolism is a potentially lethal disease if not properly treated. Noninvasive strategies have become an attractive clinical option for effective diagnosis. There has been controversy, however, regarding the use of standard clinical rules in a primary care setting. The objective of the present study was to validate a noninvasive diagnostic strategy in an emergency unit giving assistance to patients with primary and secondary care needs. A total of 291 outpatients (primary and secondary care needs) with suspected venous thromboembolism attending the emergency unit of a general hospital from August 2002 to 2004 were retrospectively evaluated. The diagnostic strategy included assessment of risk for venous thromboembolism and a rapid quantitative enzyme-linked immunosorbent assay D-dimer test. Venous thromboembolism was ruled out in patients with a low-probability or intermediate-probability risk (or an unlikely diagnosis) and a negative D-dimer. The prevalence of venous thromboembolism was 8.2%. Patients with an unlikely diagnosis comprised 93.8% of the evaluations for deep venous thrombosis, and those with a low probability for pulmonary embolism comprised 81.4%. Proportions of patients with venous thromboembolic events observed were 7.2% in patients with an unlikely diagnosis of deep venous thrombosis and 3.0% in those with low probability for pulmonary embolism. The percentage of patients with a thrombotic event excluded using this strategy was 37% (positive predictive value 13%, negative predictive value 100%). In conclusion, this noninvasive clinical strategy is safe for ruling out venous thromboembolism, and excludes the need for imaging tests in about one-third of the patients in the population studied.

Monocytes and plasma tissue factor levels in normal individuals and patients with deep venous thrombosis of the lower limbs: potential diagnostic tools?

INTRODUCTION: Tissue factor (TF) is the main physiological initiator of blood coagulation; it is membrane-bound on monocytes (mTF) and free in plasma (pTF). Abnormal expression of TF by monocytes has been implicated in various diseases. We therefore quantified monocytes expressing TF and pTF levels in patients with lower-limb deep venous thrombosis (DVT). MATERIALS AND METHODS: DVT was confirmed by Duplex Scan. Blood mTF levels under resting condition (baseline), after incubation without (unstimulated) and with (stimulated) lipopolysaccharide (LPS), and total mTF levels were determined by flow cytometry using two analytical methods (Histogram and Quadrant-Statistics). Plasma TF levels were measured using an enzyme-linked immunoabsorbent assay (ELISA). Results were compared with age-matched controls. RESULTS: Histogram analysis in patients with DVT showed significantly elevated mTF levels for baseline, unstimulated and total mTF over controls. For Quadrant-Statistics, DVT patients also showed significantly raised baseline, unstimulated, stimulated and total mTF. Similarly, pTF levels were significantly raised in subjects with DVT compared to controls. Baseline mTF levels correlated with pTF levels by Histogram and Quadrant-Statistics analysis. Using the relative operating characteristic (ROC) curve, baseline mTF and pTF assays displayed sensitivity and specificity in detecting DVT. Quadrant-Statistics baseline mTF and pTF gave the best discrimination. CONCLUSIONS: The TF assays used in this study showed acceptable sensitivity and specificity and are cost-effective and practical. Therefore, they should be considered in patients with, or at risk of, DVT.

Hypercoagulability markers in young asymptomatic heterozygous carriers of factor V Leiden (G1691A) or prothrombin (G20210A) variant.

BACKGROUND: Mutations in factor V (factor V Leiden-G1691A) and prothrombin (G20210A) genes are important risk factors for thrombophilia due to their high incidence in patients with thromboembolic events, especially among the young. However, it is not clear if levels of hypercoagulability markers are significantly altered in asymptomatic young carriers of factor V Leiden or prothrombin G20210A. METHODS: Hemostatic status of 32 asymptomatic young individuals carrying these mutations and of 18 normal control individuals was investigated through the determination of plasma thrombomodulin (TM), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and D-dimer. RESULTS: No significant differences were observed in these hemostatic markers when comparing groups of individuals carrying mutations and the control group. CONCLUSION: Analysis of these results leads to the conclusion that the presence of these mutations, in the absence of acquired risk factors, does not constantly predispose these young carriers to a state of hypercoagulability.

Managing venous thromboembolism in Latin American patients: emerging results from the Brazilian Registry.

A Brazilian National Registry was established in 1999 to investigate the incidence of risk factors for venous thromboembolism (VTE) in hospitalized medical and surgical patients and to investigate the use of thromboprophylaxis in these populations. A 4-year pilot study confirmed the feasibility and value of a registry project in this region, showing a dramatic increase in the use of low-molecular-weight heparin (LMWH) over the study period, associated with a sixfold reduction in the incidence of symptomatic VTE. Data on more than 27,000 patients from the Brazilian Registry have revealed that almost 25% of high-risk patients and 45% of those at moderate risk currently receive no thromboprophylaxis. Among the high-risk patients-in whom general measures alone are not considered appropriate prophylaxis-42% of patients did not receive pharmacological prophylaxis with either LMWH or unfractionated heparin. The Brazilian Registry highlights the need to raise awareness of VTE risk factors and recommended prophylactic regimens in Latin America.