Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Systematic Review and Meta-analysis.

BACKGROUND: The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. PURPOSE: To determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021. STUDY SELECTION: Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months after completing at least 3 months of initial anticoagulant treatment. DATA EXTRACTION: Two reviewers independently abstracted data and assessed study quality. Unpublished data required for analyses were obtained from authors of included studies. DATA SYNTHESIS: Among the 14 RCTs and 13 cohort studies included in the analysis, 9982 patients received a vitamin K antagonist (VKA) and 7220 received a direct oral anticoagulant (DOAC). The incidence of major bleeding per 100 person-years was 1.74 events (95% CI, 1.34 to 2.20 events) with VKAs and 1.12 events (CI, 0.72 to 1.62 events) with DOACs. The 5-year cumulative incidence of major bleeding with VKAs was 6.3% (CI, 3.6% to 10.0%). Among patients receiving either a VKA or a DOAC, the incidence of major bleeding was statistically significantly higher among those who were older than 65 years or had creatinine clearance less than 50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level less than 100 g/L. The case-fatality rate of major bleeding was 8.3% (CI, 5.1% to 12.2%) with VKAs and 9.7% (CI, 3.2% to 19.2%) with DOACs. LIMITATION: Data were insufficient to estimate incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs. CONCLUSION: In patients with a first unprovoked VTE, the long-term risks and consequences of anticoagulant-related major bleeding are considerable. This information will help inform patient prognosis and guide decision making about treatment duration for unprovoked VTE. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research. (PROSPERO: CRD42019128597).

Impact of residual pulmonary obstruction on the long-term outcome of patients with pulmonary embolism.

The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2-54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23-4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension.

Idiopathic interstitial pneumonias: do HRCT criteria established by ATS/ERS/JRS/ALAT in 2011 predict disease progression and prognosis?

PURPOSE: The objective of the study was to determine whether HRCT criteria for Usual Interstitial Pneumonia (UIP), possible UIP or no-UIP pattern recommended by ATS/ERS/JRS/ALAT guidelines 2011 are able to predict progression and prognosis of the disease in a group of patients with fibrotic idiopathic interstitial pneumonia (IIP). MATERIALS AND METHODS: This was a retrospective study conducted with the approval of the ethics committee. Two radiologists at baseline HRCT distributed 70 patients with fibrotic IIP into three groups on the basis of the 2011 guidelines: UIP pattern (group 1), possible UIP pattern (group 2), inconsistent with UIP pattern (group 3). The different abnormalities (honeycombing, reticulation, ground-glass and traction bronchiectasis), fibrotic score (reticulation + honeycombing) and overall CT score were visually scored at baseline and during the follow-up (total HRCT 178). The mortality rate of the three groups was compared. The baseline abnormalities were then correlated with the mortality rate in the UIP group. RESULTS: The inter-observer agreement in the classification of the abnormalities in the three groups was almost perfect (k = 0.92). After consensus, 44 patients were classified into group 1, 13 into group 2 and 13 into group 3. During a mean follow-up of 1386 days, overall CT score, fibrotic score, honeycombing and traction bronchiectasis showed a significant progression in group 1. The mortality rate was significantly higher in group 1 (18 deaths) versus group 2 and 3 (1 death each). In group 1, baseline honeycombing rate higher than 25 %, fibrotic score higher than 30, overall CT score greater than 45 and traction bronchiectasis in more than 4 lobes defined the worst prognosis. CONCLUSION: HRCT classification based on 2011 guidelines showed high accuracy in stratifying fibrotic changes because in our study UIP, possible UIP and inconsistent with UIP pattern seem to be correlated with different disease progression and mortality rate.

Advantages of real time three-dimensional echocardiography in the assessment of right ventricular volumes and function in patients with pulmonary hypertension compared with conventional two-dimensional echocardiography.

BACKGROUND: In recent years, right ventricular (RV) function has acquired greater relevance as a clinical and prognostic marker in many physiopathological conditions. The study aims to point out the value of real time three-dimensional echocardiography (RT3DE) and tissue Doppler imaging (TDI) in the evaluation of patients affected by pulmonary hypertension (PH), compared with conventional two-dimensional (2D) echocardiography. METHODS: We enrolled 44 subjects affected by PH who underwent 2D and Doppler echocardiography, RT 3D Echocardiography and TDI evaluation of the RV, and a healthy control group. PH itself can induce severe functional and structural abnormalities of the RV, such as RV hypertrophy, RV dilation, and RV systolic and diastolic dysfunction. RESULTS: In this study, RV FAC, and TAPSE showed marked alterations in patients with PH compared to the control group (C): (RVFAC: [PH] 0.29 ± 0.07 vs. [C] 0.49 ± 0.05%, P < 0.0001; TAPSE: [PH] 15.3 ± 3.2 vs. [C] 21.1 ± 2.6 mm, P > 0.0001). The 3D RV end-diastolic volume was significantly higher in PH than in C (PH) (138.7 ± 25.3 vs. [C] 82.8 ± 12.5 mL, P < 0.0001] as well as 3D RV end-systolic volume (PH) (97.6 ± 21.5 vs. [C] 39.3 ± 9.5 mL, P < 0.0001). The 3D RV ejection fraction (EF) was significantly lower in the pulmonary hypertension group than in healthy subjects (31.8 ± 6.8 vs. [C] 52.5 ± 4.7%, P < 0.0001). CONCLUSIONS: In patients with PH, evaluation of the RV diastolic and systolic volume and EF by RT3DE has shown a higher discriminating power in comparison, respectively, with 2DRV diastolic area and the relative fractional area changes.

Long-term risk of recurrent venous thromboembolism among patients receiving extended oral anticoagulant therapy for first unprovoked venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: The long-term risk for recurrent venous thromboembolism (VTE) during extended anticoagulation for a first unprovoked VTE is uncertain. OBJECTIVES: To determine the incidence of recurrent VTE during extended anticoagulation of up to 5 years in patients with a first unprovoked VTE. METHODS: MEDLINE, EMBASE, and the Cochrane CENTRAL were searched to identify randomized trials and prospective cohort studies reporting recurrent VTE among patients with a first unprovoked VTE who were to receive anticoagulation for a minimum of six additional months after completing ≥3 months of initial treatment. Unpublished data on number of recurrent VTE and person-years, obtained from authors of included studies, were used to calculate study-level incidence rate, and random-effects meta-analysis was used to pool results. RESULTS: Twenty-six studies and 15 603 patients were included in the analysis. During 11 631 person-years of follow-up, the incidence of recurrent VTE and fatal pulmonary embolism per 100 person-years was 1.41 (95% CI, 1.03-1.84) and 0.09 (0.04-0.16), with 5-year cumulative incidences of 7.1% (3.0%-13.2%) and 1.2% (0.4%-4.6%), respectively. The incidence of recurrent VTE was 1.08 (95% CI, 0.77-1.44) with direct oral anticoagulants and 1.55 (1.01-2.20) with vitamin K antagonists. The case-fatality rate of recurrent VTE was 4.9% (95% CI, 2.2%-8.7%). CONCLUSIONS: In patients with a first unprovoked VTE, the long-term risk of recurrent VTE during extended anticoagulation is low but not negligible. Thus, clinicians and patients should be aware of this risk and take appropriate and timely action in case of suspicion of recurrent VTE. Estimates from this study can be used to advise patients on what to expect while receiving extended anticoagulation, and estimate the net clinical benefit of extended treatment to guide long-term management of unprovoked VTE.

Automated Computed Tomography analysis in the assessment of Idiopathic Pulmonary Fibrosis severity and progression.

PURPOSE: To investigate the role of a quantitative analysis software (CALIPER) in identifying HRCT thresholds predicting IPF patients' survival and lung function decline and its role in detecting changes of HRCT abnormalities related to treatment and their correlation with Forced Vital Capacity (FVC). METHODS: This retrospective study included 105 patients with a multidisciplinary diagnosis of IPF for whom one HRCT at baseline and concomitant FVC were available. HRCTs were evaluated with CALIPER and the correlation between FVC and radiological features were assessed. Radiological thresholds for survival prediction and functional decline were calculated for all patients. Fifty-nine patients with at least 2 serial HRCTs were classified into two groups based on treatment. For patients for whom a FVC within 3 months of the HRCT was available (n = 44), the correlation of radiological and clinical progression was evaluated. RESULTS: The correlation between FVC and CALIPER-derived features at baseline was significant and strong. A baseline CALIPER-derived interstitial lung disease (ILD%) extent higher than 20 % and pulmonary vascular related structures (PVRS%) score greater than 5 % defined a worse prognosis. A significant progression of CALIPER-derived features in all patients was found with a faster increase in untreated patients. ILD% and PVRS% changes during follow-up demonstrated strong correlations with FVC changes. CONCLUSIONS: CALIPER quantification of fibrosis and vascular involvement could distinguish disease progression in treated versus untreated patients and predict the survival. The changes in CALIPER-derived variables over time were significantly correlated to changes in FVC.

Sleep apnea in morbidly obese patients: prevalence and clinical predictivity.

BACKGROUND: Little is known about the prevalence of obstructive sleep apnea-hypopnea syndrome (OSAHS) in morbidly obese patients and whether such patients show peculiar clinical findings that may make it easier to suspect and diagnose OSAHS. OBJECTIVES: To investigate prevalence of OSAHS in patients with morbid obesity and find a simple structured model for predicting the results of polysomnography. METHODS: The study enrolled a group of 101 consecutive inpatients (33 males, age range 20-80 years) with a body mass index > or =40, whose symptoms of OSAHS were not known, and a validation group of 45 patients. RESULTS: Habitual snoring, nocturnal apneas or awakening as well as diurnal sleepiness were frequent findings (90.1, 40.6, 50.5 and 61.4%, respectively). Chronic obstructive pulmonary disease, hypertension, diabetes and myocardial ischemia were also frequently associated (22.8, 56.4, 30.7 and 6.9%, respectively). OSAHS was found in 61 (60.4%) patients, in 33.7% it was of severe degree. A multivariate logistic regression model allowed to select the independent predictors of OSAHS: age, male sex, diurnal sleepiness and the value of minimum nocturnal saturation. Sensitivity of 97%, specificity of 77% as well as positive and negative predictive values of 87% and 95%, respectively, were obtained; similar results were found in the validation group. When the best obtainable cutoff on the receiver operating characteristic curve is below 40%, the instrumental diagnosis might be excluded in as many as 33% of cases, since they are not affected by OSAHS or have OSAHS of mild degree. CONCLUSIONS: OSAHS is present in almost two thirds of morbidly obese patients. By applying the prediction model we propose, one may calculate the probability of a morbidly obese patient of being affected by OSAHS.

Should Perfusion Scintigraphy Be Performed to Follow Patients with Acute Pulmonary Embolism? If So, When?

This investigation evaluated the changes of pulmonary perfusion at 4 different points of follow-up within 1 y in patients with pulmonary embolism (PE) and the factors predictive of complete or incomplete recovery of pulmonary perfusion. Methods: Patients with symptomatic PE underwent perfusion lung scintigraphy and blood gas analysis within 48 h from clinical presentation, after 1 wk, and after 1, 6, and 12 mo; echocardiography was performed at baseline and after 6 and 12 mo. All perfusion lung scintigraphy scans were examined by 2 expert nuclear medicine physicians with a scoring method that attributed a score of 0, 0.5, or 1 for extension (maximum score, 18) to the presence of perfusion defects (PD), both at baseline and on each follow-up scan. Results: Among 183 patients who completed 1 y of follow-up, the median baseline PD score was 8.2; it decreased significantly at each follow-up time point until 6 mo (P < 0.001). Median baseline alveolar-arterial difference in oxygen partial pressure (PA-aO2) was 50.9 and decreased significantly up to 1 mo (P < 0.001); median pulmonary artery systolic pressure (PAsP) was 45.9 mm Hg and decreased significantly until 12 mo (P < 0.001). A correlation was found between PD and both PA-aO2 (P < 0.05) and PAsP (P < 0.05). We found a correlation between PD ≠ 0 and PAsP ≥ 40 mm Hg at 12 mo (P < 0.05); in 6 (3.3%) of these patients such a correlation was still present after 24 mo, suggesting they could develop chronic thromboembolic pulmonary hypertension. Low baseline PD (odds ratio, 0.80; P < 0.0001) and high 1-wk percent recovery (odds ratio, 1.04; P < 0.0001) were predictive factors of complete 6-mo recovery. Conclusion: Perfusion scintigraphy may be useful to follow patients with PE. The follow-up should consist of 3 steps: the baseline examination, which reflects the severity of PE; the scan at 1 wk, which indicates the early amount of reperfusion; and the scan at 6 mo, which demonstrates the maximum attainable recovery. Patients with incomplete recovery and persistence of pulmonary hypertension on the 24-mo control should be further studied for possible development of chronic thromboembolic pulmonary hypertension.

Role of perfusion defects at follow-up lung scan in predicting recurrences after a first episode of symptomatic pulmonary embolism: a retrospective analysis.

: The optimal duration of anticoagulant therapy after a first episode of unprovoked pulmonary thromboembolism is not fully defined. The identification of patients more prone to recurrence would be useful in this context but is currently relatively unreliable. Perfusion lung scan (PLS) is an established approach for the follow-up of patients with pulmonary embolism to identify recurrences and to help in the diagnosis of chronic thromboembolic pulmonary hypertension. The aim of the study was to investigate the potential role of residual perfusion defects at follow-up perfusion scans in predicting pulmonary embolism recurrences. We retrospectively analyzed PLSs of 252 patients with a first episode of unprovoked, symptomatic pulmonary embolism. The agreement between two experienced readers, as assessed by the kappa test, was good, with kappa indices ranging from 0.84 (baseline scan) to 0.98 (last prerecurrence available scan). Sixteen patients developed a late (at least 1 month from the index episode) recurrence identified through the appearance of (a) new perfusion defect(s) not matching radiograph alterations. When patients were divided based on the presence or absence of at least two unperfused segments at the 6-month follow-up lung scan, the probability of recurrence was significantly higher in the latter (P = 0.03 by log-rank test). The use of persistent perfusion defects at follow-up PLS as a guide to determine optimal duration of anticoagulant therapy after a first, unprovoked episode of acute pulmonary thromboembolism is a viable strategy that should be further investigated.

Liver Enlargement Predicts Obstructive Sleep Apnea-Hypopnea Syndrome in Morbidly Obese Women.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is frequently present in patients with severe obesity, but its prevalence especially in women is not well defined. OSAHS and non-alcoholic fatty liver disease are common conditions, frequently associated in patients with central obesity and metabolic syndrome and are both the result of the accumulation of ectopic fat mass. Identifying predictors of risk of OSAHS may be useful to select the subjects requiring instrumental sleep evaluation. In this cross-sectional study, we have investigated the potential role of hepatic left lobe volume (HLLV) in predicting the presence of OSAHS. OSAHS was quantified by the apnea/hypopnea index (AHI) and oxygen desaturation index in a cardiorespiratory inpatient sleep study of 97 obese women [age: 47 ± 11 years body mass index (BMI): 50 ± 8 kg/m2]. OSAHS was diagnosed when AHI was ≥5. HLLV, subcutaneous and intra-abdominal fat were measured by ultrasound. After adjustment for age and BMI, both HLLV and neck circumference (NC) were independent predictors of AHI. OSAHS was found in 72% of patients; HLLV ≥ 370 cm3 was a predictor of OSAHS with a sensitivity of 66%, a specificity of 70%, a positive and negative predictive values of 85 and 44%, respectively (AUC = 0.67, p < 0.005). A multivariate logistic model was used including age, BMI, NC, and HLLV (the only independent predictors of AHI in a multiple linear regression analyses), and a cut off value for the predicted probability of OSAHS equal to 0.7 provided the best diagnostic results (AUC = 0.79, p < 0.005) in terms of sensitivity (76%), specificity (89%), negative and positive predictive values (59 and 95%, respectively). All patients with severe OSAHS were identified by this prediction model. In conclusion, HLLV, an established index of visceral adiposity, represents an anthropometric parameter closely associated with OSAHS in severely obese women.

Five-year follow-up of pulmonary embolism under anticoaugulation: The PISA-PEET (Pulmonary Embolism Extension Therapy) study.

Benefits and harms of long-term anticoagulant therapy (AT) after acute pulmonary embolism (PE) are poorly known. The aim of this study was to investigate the outcome of patients with PE treated with AT for 5 years according to American College of Chest Physicians (ACCP) guidelines.Patients with both unprovoked and secondary PE were consecutively enrolled in a "real life" study. After a 12-month AT, they continued or stopped the treatment according to ACCP guidelines, and were followed-up for 5 years. Outcomes were all-cause mortality, recurrence, and fatal recurrence under AT.Of the original consecutive 585 patients, 471 were included (83 dead, 31 lost during the 1st year). Of these, 361 (76.6%) continued AT. During 5 years, death occurred in 109 (30.2%) patients, with a mortality rate of 8.00 events/100 person-years of follow-up; recurrence in 34 (9.4%), with an incidence rate of 2.58 events/person-years; fatal recurrence in 13 (3.6%), with an incidence rate of 0.95 events/person-years. The case fatality rate for recurrence was 38.2%. In the subgroup of patients with unprovoked PE, the chance of dying was significantly lower (RR 0.35; 95% confidence interval 0.24-0.53) and the tendency to fatal recurrence (not significantly) greater (0.11 events/100 person-years vs 0.07 events/100 person-years) than in the remaining patients. Major bleeding occurred in 5 (1.3%) patients. The case fatality rate for bleeding was 14.3%.During 5-year AT, 30% of patients dies, 10% experiences recurrences, and 5% has fatal recurrences. According to guidelines, most patients need to continue AT; the case fatality rate for bleeding is lower than that for recurrence.

Application of a pharmacokinetic/pharmacogenetic approach to assess the nicotine metabolic profile of smokers in the real-life setting.

The nicotine metabolite ratio, i.e., the ratio 3-hydroxycotinine/cotinine, is used to assess the nicotine metabolic status and has been proven to predict the response to smoking cessation treatments in randomized clinical trials. In the current study, a pharmacokinetic-pharmacogenetic integrated approach is described, based on the development of a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for nicotine metabolite ratio assay in plasma and a real-time PCR analysis for fast genotyping of CYP2A6. The pharmacokinetic-pharmacogenetic approach was validated in 66 subjects with different smoking status. The LC/MS/MS assay was rapid and sensitive enough to detect plasma cotinine levels also in second-hand exposed abstainers. In the cohort of patients of the present study the following results were obtained: (i) the frequencies of CYP2A6 genetic variants were comparable with those from clinical trials carried out in Caucasian populations; (ii) all the subjects carrying the CYP2A6 deficient allele also had a slow metabolizer phenotype; (iii) slow metabolizers had mean nicotine metabolite ratio approximately 50% of that of the normal/fast metabolizers; (iv) women had higher nicotine metabolite ratio than men; and (v) salivary nicotine metabolite ratio measures were comparable to plasma levels. Overall, the findings of the current study demonstrate that the simultaneous assessment of nicotine metabolite ratio and CYP2A6 genotype from human blood samples is feasible and accurate and could be used in a smoking cessation program to optimize treatments and identify those smokers who inherit metabolically deficient CYP2A6 alleles.

Elective surgery for giant bullous emphysema: a 5-year clinical and functional follow-up.

BACKGROUND: So far, very few studies in the literature have reported data on the long-term follow-up of patients who have undergone surgery for giant bullous emphysema (GBE), and much still needs to be known on the late fate of these patients. AIMS: To evaluate patients who have undergone elective surgery due to GBE, early and late mortality following surgery, the early and late reappearance of bullae, and the early and late modifications of clinical and functional data. SUBJECTS AND METHODS: Forty-one consecutive patients (36 men; mean [+/- SD] age, 48.4 +/- 14.8 years) who underwent elective surgery for GBE were enrolled in a prospective study, and were studied both before and after undergoing bullectomy for a 5-year-follow-up period. Analyses were performed on the whole population and on two subgroups of patients who were divided on the basis of the absence of underlying diffuse emphysema (group A; n = 23) or the presence of underlying diffuse emphysema (group B; n = 18). RESULTS: The early mortality rate was 7.3% (within the first year), and the late mortality rate was 4.9% (overall mortality rate at 5 years, 12.2%; mortality rate in group B, 27.8%). Bullae did not reappear and residual bullae did not become enlarged in any patients at the site of the bullectomy. During the follow-up, the dyspnea score was reduced significantly soon after bullectomy and up to the fourth year of follow-up; intrathoracic gas volume also was reduced significantly (average, 0.7 L). The same was true for the FEV1 percent predicted and the FEV1/vital capacity ratio, which kept increasing until the second year; then, from the third year of follow-up these values were reduced, yet remained above the prebullectomy values until the fifth year of follow-up. When considered separately, the patients in group B appeared to be the most impaired, clinically and functionally (eg, FEV1 showed a similar significant increase up to the second year in both groups after surgery, while a different mean annual decrease was appreciable from the second to the fifth year of follow-up: group A, 25 mL/year; group B, 83 mL/year. Furthermore, patients in group B were the only ones who contributed to the mortality rate, on the whole showing a behavior similar to that of patients who had undergone lung volume reduction surgery. CONCLUSIONS: In patients with GBE who were enrolled in the study prospectively and were investigated yearly during a 5-year-follow-up period, elective surgery appears to have been fairly safe, and allowed clinical and functional improvement for at least 5 years. Better results may be expected in patients without underlying diffuse emphysema.

Pulmonary embolism: lung scan and computed tomography.

The diagnosis of pulmonary embolism may be confounded by a clinical presentation that is often subtle or atypical. Therefore pulmonary angiography, although invasive, has been widely used to prove pulmonary embolism. The aim of this review is to discuss the value of non-invasive techniques, such as lung scan and chest computed tomography scan, in the diagnosis of pulmonary embolism. Ventilation-perfusion scan has demonstrated a very high specificity (97%) but a quite low sensitivity (41%) in the diagnosis of pulmonary embolism, while perfusion lung scan not associated with ventilation scan has shown a specificity of 92% and a considerably high sensitivity (87%). The chest computed tomography scan has not yet shown a definite degree of specificity and sensitivity in the diagnosis of pulmonary embolism, although we suppose that this technique will become widely used. However, we emphasize that the diagnosis of pulmonary embolism is not a mere technical problem.

Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H2O2 was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons). Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r²â€Š= .27 and .31, respectively; p<.05 for both correlations). Exposure of lung epithelial cells to H2O2 caused an increase in microparticle-bound tissue factor without affecting tissue factor mRNA. Procoagulant microparticles are increased in interstitial lung diseases and correlate with functional impairment. These structures might contribute to the activation of factor X and to the factor Xa-mediated fibrotic response in lung injury.

Diagnosis and treatment of pulmonary embolism: a multidisciplinary approach.

The diagnosis of pulmonary embolism (PE) is frequently considered in patients presenting to the emergency department or when hospitalized. Although early treatment is highly effective, PE is underdiagnosed and, therefore, the disease remains a major health problem. Since symptoms and signs are non specific and the consequences of anticoagulant treatment are considerable, objective tests to either establish or refute the diagnosis have become a standard of care. Diagnostic strategy should be based on clinical evaluation of the probability of PE. The accuracy of diagnostic tests for PE are high when the results are concordant with the clinical assessment. Additional testing is necessary when the test results are inconsistent with clinical probability. The present review article represents the consensus-based recommendations of the Interdisciplinary Association for Research in Lung Disease (AIMAR) multidisciplinary Task Force for diagnosis and treatment of PE. The aim of this review is to provide clinicians a practical diagnostic and therapeutic management approach using evidence from the literature.

Diagnosis of pulmonary embolism.

Conventional pulmonary arteriography for the diagnosis of pulmonary embolism (PE) bears several limitations in clinical practice, basically due to its invasiveness. On the other hand, no single noninvasive test is both sensitive and specific for the diagnosis of PE. Therefore, the choice of available noninvasive diagnostic tests guided by the clinical probability of PE is a good compromise at present. The first necessary step toward the diagnosis of PE is to raise the clinical suspicion, given that no diagnosis can be made if PE is not considered in the differential diagnosis of patients with acute cardiorespiratory symptoms. Second, empirical or standardized rules for predicting clinical probability may be combined with one or more noninvasive tests with the aim of increasing the accuracy of the noninvasive diagnosis. The strategy for the noninvasive diagnosis of PE varies among different centers according to the availability of each single technique that may be integrated with another and according to the characteristics of the population that refers to each single center. Therefore, spiral CT should not be used as a primary tool for the diagnosis of PE; its role needs to be re-evaluated in light of its sensitivity, feasibility, and radiation burden on the patients. In patients in whom the diagnosis of PE cannot be made at the end of the noninvasive pathway, the use of the invasive techniques must be taken into consideration. In our experience, however, such cases should not exceed 15 to 20% of the total patient population.