No abstract

Introduction Venous thromboembolism may recur in up to 30% of patients with a spontaneous venous thromboembolism after a standard course of anticoagulation. Identification of patients at risk for recurrent venous thromboembolism would facilitate decisions concerning the duration of anticoagulant therapy. Objectives In this exploratory study, we investigated whether whole blood gene expression data could distinguish subjects with single venous thromboembolism from subjects with recurrent venous thromboembolism. Methods 40 adults with venous thromboembolism (23 with single event and 17 with recurrent events) on warfarin were recruited. Individuals with antiphospholipid syndrome or cancer were excluded. Plasma and serum samples were collected for biomarker testing, and PAXgene tubes were used to collect whole blood RNA samples. Results D-dimer levels were significantly higher in patients with recurrent venous thromboembolism, but P-selectin and thrombin-antithrombin complex levels were similar in the two groups. Comparison of gene expression data from the two groups provided us with a 50 gene probe model that distinguished these two groups with good receiver operating curve characteristics (AUC 0.75). This model includes genes involved in mRNA splicing and platelet aggregation. Pathway analysis between subjects with single and recurrent venous thromboembolism revealed that the Akt pathway was up-regulated in the recurrent venous thromboembolism group compared to the single venous thromboembolism group. Conclusions In this exploratory study, gene expression profiles of whole blood appear to be a useful strategy to distinguish subjects with single venous thromboembolism from those with recurrent venous thromboembolism. Prospective studies with additional patients are needed to validate these results.

Venous thromboembolism is a major cause of morbidity and mortality affecting over 2 million people in the United States each year. The American College of Chest Physicians (ACCP) published their first consensus statement on antithrombotic therapy in 1986, and the most recent guidelines from the ACCP on this topic were released in 2008. We aim to summarize the most recent ACCP guidelines on therapy for venous thromboembolism with practical application and interpretation for the practicing physician. We will briefly review the rating system used in the guidelines for the level of evidence and the strength of the recommendation. We will then discuss the recommendations for initial anticoagulant therapies including low molecular weight heparin, unfractionated heparin, and fondaparinux for patients with both deep vein thrombosis (DVT) and pulmonary embolism (PE). A discussion of the guidelines on duration of anticoagulant therapy with a vitamin K antagonist is also included. In addition, we will address the use of thrombolytic therapy and inferior vena cava filter placement for DVT and PE. Prevention of postphlebitic syndrome is discussed as well. We will conclude with a brief discussion of future directions including several novel therapeutic anticoagulants.

The majority of fatal cases of pulmonary embolism in hospitalized patients occur in acutely ill, medically treated patients. Current guidelines, based on a large number of prospective, randomized, controlled trials evaluating the safety and efficacy of pharmacologic venous thromboembolism (VTE) prophylaxis in medical patients, now recommend using VTE prophylaxis in this population. Unfortunately, prophylaxis rates in medical patients are unacceptably low, despite efforts to develop strategies for improving implementation of prophylaxis regimens. Studies indicate that a substantial proportion of patients with VTE present after hospital discharge, but no clinical trials evaluating VTE prophylaxis for medical outpatients have yet been published. In this Review, we examine the literature on VTE prophylaxis in hospitalized medical patients, and evaluate the available data for the outpatient setting.