Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility : a randomized trial

Q1Q18-18BACKGROUND: Extended-duration low-molecular-weight heparin has been shown to prevent venous thromboembolism (VTE) in high-risk surgical patients. OBJECTIVE: To evaluate the efficacy and safety of extended-duration enoxaparin thromboprophylaxis in acutely ill medical patients. DESIGN: Randomized, parallel, placebo-controlled trial. Randomization was computer-generated. Allocation was centralized. Patients, caregivers, and outcome assessors were blinded to group assignment. (ClinicalTrials.gov registration number: NCT00077753) SETTING: 370 sites in 20 countries across North and South America, Europe, and Asia. PATIENTS: Acutely ill medical patients 40 years or older with recently reduced mobility (bed rest or sedentary without [level 1] or with [level 2] bathroom privileges). Eligibility criteria for patients with level 2 immobility were amended to include only those who had additional VTE risk factors (age >75 years, history of VTE, or active or previous cancer) after interim analyses suggested lower-than-expected VTE rates. INTERVENTION: Enoxaparin, 40 mg/d subcutaneously (2975 patients), or placebo (2988 patients), for 28 +/- 4 days after receiving open-label enoxaparin for an initial 10 +/- 4 days. MEASUREMENTS: Incidence of VTE up to day 28 and of major bleeding events up to 48 hours after the last study treatment dose. RESULTS: Extended-duration enoxaparin reduced VTE incidence compared with placebo (2.5% vs. 4%; absolute risk difference favoring enoxaparin, -1.53% [95.8% CI, -2.54% to -0.52%]). Enoxaparin increased major bleeding events (0.8% vs. 0.3%; absolute risk difference favoring placebo, 0.51% [95% CI, 0.12% to 0.89%]). The benefits of extended-duration enoxaparin seemed to be restricted to women, patients older than 75 years, and those with level 1 immobility. LIMITATION: Estimates of efficacy and safety for the overall trial population are difficult to interpret because of the change in eligibility criteria during the trial. CONCLUSION: Use of extended-duration enoxaparin reduces VTE more than it increases major bleeding events in acutely ill medical patients with level 1 immobility, those older than 75 years, and women. PRIMARY FUNDING SOURCE: Sanofi-aventis

Determination of rivaroxaban by different factor Xa specific chromogenic substrate assays: reduction of interassay variability

Rivaroxaban and other oral direct factor Xa inhibitors (ODiXa) are currently developed for prophylaxis and treatment of thromboembolic diseases using fixed doses. Although routine monitoring is not required, assessing the intensity of anticoagulation may be useful under certain clinical conditions. ODiXa prolong coagulation times of several clotting assays and, thus, their concentration may be determined in factor Xa specific chromogenic substrate assays. So far, no standardized and validated assay is commercially available. Here, five methods (A through E) are studied and optimized to reduce interassay variability. Human pooled plasma was spiked by a serial dilution of rivaroxaban (25–900 ng/ml). The release of para-nitroaniline from the chromogenic substrates was measured by the optical density (OD) at 405 nm. Method B was identified to yield the lowest sum of deviations from the mean value of the OD concentration curve calculated from all assays. Spline functions were developed for OD versus concentration curves for all methods. The calculated OD versus concentration curves overlapped for all methods. The coefficient of variation for all assays and concentrations of rivaroxaban decreased from 25.3 ± 11.4% using the original data to 3.8 ± 2.2% using the calculated data (P < 0.0001). The robustness of the chromogenic assay (method B) remains to be corroborated in interlaboratory comparisons

Association between long travel and venous thromboembolic disease: a systematic review and meta-analysis of case-control studies

The term “economy-class syndrome” defines an infrequent episode of venous thromboembolism (VTED) related to a long travel, namely by plane. However, this relation has not clearly been demonstrated by investigators. We carried out a systematic review and a meta-analysis of cases-control studies that had studied this topic. We realised a systematic review of the literature and selected all the case-control studies published. Two authors carried out a methodological evaluation according to the Scottish Intercollegiate Guidelines Network items (concordance was analysed by weighted kappa index), and a systematic analysis of the potential biases of each study was assessed. We carried out the meta-analysis with the data extracted from the studies. We recovered eight cases-control studies. The relation between the antecedent of a long travel and subsequent VTED varied from OR = 1.1 to OR = 4.0 and was found to be significant in four studies. The studies were highly heterogeneous in methodology and so the results obtained about the relation between the long travel and the VTED and the score at SIGN50. Two meta-analysis were carried out: only with travels by plane in which the relation was not significant (OR = 1.21; CI 95%, 0.95–1.55) and with all types of transport, with a slightly significant relation (OR = 1.46; CI95%, 1.24–1.72). We may deduce from this systematic review that there does exist a weak association between episodes of VTED and a long travel, but not by plane specifically. The heterogeneity and the methodological quality of the studies published preclude of more robust conclusions

Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes

Lenalidomide, an oral immunomodulatory agent, has received approval in the USA from the Food and Drug Administration (FDA) for the management of myelodysplastic syndromes (MDS) classified by the International Prognostic Scoring System (IPSS) as low risk or intermediate-1 risk and with a deletion 5q (del(5q)) cytogenetic abnormality. Although some patients with del(5q) have a relatively good prognosis, all del(5q) patients will become transfusion-dependent at some point during the course of their disease. The results of two clinical trials in more than 160 patients with MDS have demonstrated clear therapeutic benefits of lenalidomide, with >60% of patients achieving independence from transfusion during therapy, irrespective of age, prior therapy, sex, or disease-risk assessment. The recommendations presented in this review will aid the safe administration of lenalidomide for the treatment of patients with low-risk or intermediate-1-risk MDS and a del(5q) cytogenetic abnormality, and they will help physicians avoid unnecessary dose reduction or interruption, thus assuring the best efficacy for patients

The association between air travel and deep vein thrombosis: Systematic review & meta-analysis

BACKGROUND: Air travel has been linked with the development of deep vein thrombosis (DVT) since the 1950s with a number of plausible explanations put forward for causation. No systematic review of the literature exploring this association has previously been published. METHODS: A comprehensive search was undertaken (Data bases searched were: MEDLINE, EMBASE, Cochrane Library) for studies that estimated both the incidence and the risk of DVT in air travellers relative to non-air travellers. RESULTS: In total 254 studies were identified but only six incidence studies and four risk studies met inclusion criteria justifying their use in a systematic review. Incidence of symptomatic DVT ranged from (0%) in one study to (0.28%) which was reported in pilots over ten years. The incidence of asymptomatic DVT ranged from (0%) to (10.34%). Pooled odds ratios for the two case control studies examining the risk of DVT following air travel were 1.11 (95% CI: 0.64–1.94). Pooled odds ratios for all models of travel including two studies of prolonged air travel (more than three hours) were 1.70 (95% CI: 0.89–3.22). CONCLUSION: We found no definitive evidence that prolonged (more than 3-hours) travel including air travel, increases the risk of DVT. There is evidence to suggest that flights of eight hours or more increase the risk of DVT if additional risk factors exist

Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY

<p>Abstract</p> <p>Background</p> <p>Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.</p> <p>Methods</p> <p>Acutely-ill, non-surgical patients ≥70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days.</p> <p>Results</p> <p>1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81).</p> <p>Conclusions</p> <p>Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation.</p> <p>Trial Registration</p> <p>clinicaltrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00451412">NCT00451412</a></p