Summary. Background: Prophylaxis of venous thromboembolism (VTE) in hospitalized medical patients is largely underused. We sought to assess the value of a simple risk assessment model (RAM) for the identification of patients at risk of VTE. Methods: In a prospective cohort study, 1180 consecutive patients admitted to a department of internal medicine in a 2-year period were classified as having a high or low risk of VTE according to a predefined RAM. They were followed-up for up to 90 days to assess the occurrence of symptomatic VTE complications. The primary study outcome was to assess the adjusted hazard ratio (HR) of VTE in high-risk patients who had adequate in-hospital thromboprophylaxis in comparison with those who did not, and that of VTE in the latter group in comparison with low-risk patients. Results: Four hundred and sixty-nine patients (39.7%) were labelled as having a high risk of thrombosis. VTE developed in four of the 186 (2.2%) who received thromboprophylaxis, and in 31 of the 283 (11.0%) who did not (HR of VTE, 0.13; 95% CI, 0.04-0.40). VTE developed also in two of the 711 (0.3%) low-risk patients (HR of VTE in high-risk patients without prophylaxis as compared with lowrisk patients, 32.0; 95% CI, 4.1-251.0). Bleeding occurred in three of the 186 (1.6%) high-risk patients who had thromboprophylaxis. Conclusions: Our RAM can help discriminate between medical patients at high and low risk of VTE. The adoption of adequate thromboprophylaxis in high-risk patients during hospitalization leads to longstanding protection against thromboembolic events with a low risk of bleeding.

While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence. Design and MethodsWe followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion. ResultsAfter a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5-12.5) after 1 year, 19.6% (17.5-21.7) after 3 years, 29.1% (26.3-31.9) after 5 years, and 39.9% (35.4-44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82-2.90) in patients whose first VTE was unprovoked, 2.02 (1.52-2.69) in those with thrombophilia, 1.44 (1.03-2.03) in those presenting with primary DVT, 1.39 (1.08-1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06-1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change. Interpretation and ConclusionsBesides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age. 1-6 While it is generally accepted that patients with thromboembolic events of unknown origin have a more than two-fold higher rate of recurrent VTE in comparison to patients whose thrombosis is associated with acquired, transient risk factors, 1-6 whether other of the patients' baseline features can help to identify those subjects who might benefit from prolonged anticoagulation is unclear. For example, it is virtually unknown whether aging, an important risk factor for VTE, 4 is also associated with an increased risk of recurrence. The role of thrombophilic abnormalities, especially those that are highly prevalent in western countries (i.e., factor V Leiden and prothrombin G20210A mutation), is controversial.5-14 Although recent data suggest that clinical presentation with primary PE 15 and male sex 16-18 increase the risk of recurrent VTE, these findings still await confirmation. Finally, whether the duration of anticoagulation following the initial thrombotic episode has any influence on the subsequent rate of recurrent VTE is uncertain. 2,19-22Here we report on the prospective long-term followup of a large series of patients with proximal DVT and...

Post-thrombotic sequelae develop in almost half of patients with proximal DVT. Below-knee compression elastic stockings reduce this rate by approximately 50%.

IntroductionPlatelet plug formation at the site of vascular injury is initiated by von Willebrand factor (VWF) interacting with the subendothelial matrix, followed by its binding to platelet glycoprotein (GP) Ib 1,2 and subsequent platelet activation and aggregation. VWF is synthesized by endothelial cells and megakaryocytes, 3,4 and one of its main particular features is a polymer structure ranging in size from 500 000 to more than 20 million Dalton, 5 the largest forms being hemostatically the most efficient. 6 A broad range of values characterizes plasma VWF levels, which average around 10 g/mL. Acquired and inherited factors both modulate plasma VWF levels, and twin studies have demonstrated that 66% of all variations in plasma VWF are genetically determined, while 30% of them depend on ABO blood group, 7 O blood group individuals having plasma VWF levels 25% lower than non-O subjects. 8 ABO group genotyping shows that O 1 O 1 subjects have the lowest VWF levels, and non-O group individuals heterozygous for the O 1 allele have significantly lower VWF levels than AA, AB, or BB subjects. 9,10 Glycosylation accounts for 19% of VWF by weight, and ABO determinants identified on the N-linked oligosaccharide chains are part of this glycosylation process. 11,12 ABO groups are added to the N-linked glycan chains of VWF in the post-Golgi compartment of endothelial cells before VWF secretion, albeit with the variable contribution of the endothelial cells from different vascular beds. 13 The carbohydrate moiety plays an important part in VWF polymerization and function, 14 and also affects the liver-mediated clearance of VWF. In animal models, the removal of sialic acid has been shown to induce an increase in VWF clearance, 15 and the half-life of VWF is halved in mice characterized by an aberrantly glycosylated VWF (due to the absence of the enzyme ST3Gal-IV). 16 Moreover, recombinant VWF, lacking in carbohydrate, is cleared from the circulation faster than its glycosylated counterpart, 16 and posttranslational changes in VWF induced by Galgt2, aberrantly expressed in endothelial cells, lead to a 20-fold increase in VWF clearance. 17 ABO group determinants may also regulate the susceptibility of VWF to the proteolytic action of ADAMTS13, proteolysis being faster in the case of the O blood group. 18 A different susceptibility to cleavage by ADAMTS13 may thus be one of the ways in which ABO group affects VWF removal from the circulation and consequent VWF levels.Although the mechanisms behind ABO blood group and VWF levels have yet to be fully clarified, it has been clearly demonstrated that the effects are mediated by the ABO antigen structures on the N-linked oligosaccharide chains of circulating VWF, and particularly by H antigen expression. 19 Understanding these mechanisms is of clinical relevance: non-O individuals have been shown to carry a significantly greater risk of venous thromboembolism, ischemic heart disease, and peripheral vascular disease, 21-23 while the O blood group is much more common in von Willebra...