Clinical probability and alveolar dead space measurement for suspected pulmonary embolism in patients with an abnormal D-dimer test result.

BACKGROUND: Most patients with suspected pulmonary embolism (PE) have a positive D-dimer test and undergo diagnostic imaging. Additional non-invasive bedside tests are required to reduce the need for further diagnostic tests. OBJECTIVES: We aimed to determine whether a combination of clinical probability assessment and alveolar dead space fraction measurement can confirm or exclude PE in patients with an abnormal D-dimer test. METHODS: We assessed clinical probability of PE and alveolar dead space fraction in 270 consecutive in- and outpatients with suspected PE and positive D-dimer. An alveolar dead space fraction < 0.15 was considered normal. PE was subsequently excluded or confirmed by venous compression ultrasonography, spiral computed tomography and a 3-month follow-up. Radiologists were unaware of the results of clinical probability and capnography. RESULTS: PE was confirmed in 108 patients (40%). Capnography had a sensitivity of 68.5% (95% confidence interval [CI]: 58.9-77.1%) and a specificity of 81.5% (95% CI: 74.6-87.1%) for PE. Forty-five patients (16.6%) had both a low clinical probability and normal capnography (sensitivity: 99.1%, 95% CI: 94.9-100%) and 34 patients (12.6%) had both a high clinical probability and abnormal capnography (specificity: 100%, 95% CI: 97.7-100%). CONCLUSION: Capnography alone does not exclude PE accurately. The combination of clinical probability and capnography accurately excludes or confirms PE and avoids further testing in up to 30% of patients.

[Treatment of venous thromboembolic disease]. / Traitement de la maladie thromboembolique veineuse.

Adequate initial anticoagulant treatment is required to prevent thrombus growth and recurrence. Intravenous unfractionated heparin is being replaced by low-molecular-weight heparin as the anticoagulant of choice for initial treatment of venous thromboembolism. Vitamin K antagonists remain the only oral anticoagulant available (target international normalized ratio: 2.5). The duration of therapy should be individualized according to the risk of recurrence and the risk of bleeding. Three months of treatment is usually adequate if thrombosis was provoked by a reversible risk factor such as surgery. For patients with unprovoked ("idiopathic") thrombosis, anticoagulant treatment for at least 6 months is indicated. For patients with a recurrence of venous thromboembolism or with an irreversible risk factor such as cancer, indefinite anticoagulant therapy is recommended. Long-term treatment with low-molecular-weight heparin is usually preferable for patients with active cancer. Systemic thrombolysis is indicated for patients with massive pulmonary embolism but controversy persists for those with isolated right ventricular dysfunction.

Factors V leiden and II 20210A in patients with symptomatic pulmonary embolism and deep vein thrombosis.

PURPOSE: Factor V Leiden and factor II 20210A are inherited disorders of the clotting system that occur frequently in patients with deep vein thrombosis. We conducted this study to determine whether these factors are also common in patients with pulmonary embolism. SUBJECTS AND METHODS: We determined the prevalence of factor V Leiden and factor II 20210A in 773 consecutive patients with objectively documented symptomatic deep vein thrombosis or symptomatic pulmonary embolism, or with a combination of these disorders. RESULTS: Isolated symptomatic deep vein thrombosis occurred in 345 patients; isolated symptomatic pulmonary embolism occurred in 236; and both anomalies occurred in 192. Factor V Leiden was present in 21 (9%) of the patients with isolated symptomatic pulmonary embolism, in 30 (16%) with both manifestations, and in 63 (18%) with isolated symptomatic deep vein thrombosis (P = 0.007). Factor V Leiden was more common among patients with deep vein thrombosis (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.2 to 3.7; P = 0.006) or both pulmonary embolism and deep vein thrombosis (OR = 1.8; 95% CI: 1.0 to 3.3; P = 0.07) than among patients with isolated pulmonary embolism. Factor V Leiden was less common in massive pulmonary embolism (5% [7 of 127]) than in submassive pulmonary embolism (13% [21 of 155], P = 0.03). We found no significant difference in the prevalence of factor II 20210A among the three groups. CONCLUSION: Factors V Leiden and II 20210A vary in prevalence among patients with pulmonary embolism and deep vein thrombosis, suggesting that the risk of pulmonary embolization may vary among patients who have different causes of venous thromboses.

Transvenous catheter embolectomy.

Transvenous pulmonary embolectomy was first described in 1969 by Greenfield and associates who designed a special catheter for the aspiration of thrombi in the pulmonary circulatory system. This technique was applied in 64 patients with massive pulmonary embolism (PE) with a 70 to 72% survival rate. However, it is difficult to implement and has not gained widespread acceptance. More recently, several other catheter devices have been used in patients with PE. The total number of patients reported does not exceed 100. Relative angiographic improvement varies between 10 and 49%, but hemodynamic improvement is not observed or not measured in most patients and mortality varies between 9 and 30%. Fibrinolysis was associated with mechanical thrombectomy in 54% of the patients, making the results difficult to interpret. Transvenous pulmonary embolectomy remains an experimental procedure and should been attempted only in the very few patients with PE, uncontrolled cardiogenic shock, and absolute contraindication to fibrinolytic treatment. Animal models are required to compare the different devices available.

Markers of hemostatic system activation in pulmonary embolism. Changes during and after cessation of anticoagulant treatment.

Plasma levels of prothrombin fragment 1+2 (Fl+2), thrombin-antithrombin complexes (TAT) and D-dimers were measured in 15 patients with pulmonary embolism during heparin therapy, oral anticoagulation, and after cessation of warfarin therapy. Each patient had a favorable outcome during anticoagulant therapy (3 months), but late venous thromboembolism occurred in six cases. The mean levels of the three markers were significantly increased on day 4 after the thrombotic event, and normalized during warfarin therapy. Nine months after the initial pulmonary embolism, mean levels of the three markers, as compared with a control population, were significantly higher in the patients with late recurrences, whereas only TAT were slightly higher in patients without recurrences as compared with controls. Only TAT levels were significantly higher in the patients with late recurrences than in those without late recurrences. Thus, the levels of the three markers 9 months after pulmonary embolism seem to be interesting to identify patients with high risk of recurrence and who might require longer anticoagulant treatment.

Cardiorespiratory efficacy of thrombolytic therapy in acute massive pulmonary embolism: identification of predictive factors.

The aim of this study was to evaluate the contribution of clinical, angiographic and haemodynamic findings in predicting the cardiorespiratory efficacy of thrombolytic therapy in acute massive pulmonary embolism. Haemodynamic measurements and pulmonary angiography were performed before (H0) and 12 h after (H12) initiating thrombolytic therapy in 23 patients with acute massive pulmonary embolism (Miller index > or =20/34), and free of prior cardiopulmonary disease. Patients were divided into two groups according to the variation in oxygen delivery (deltaDO2) between H0 and H12: deltaDO2 >20% (responders, n=10) and deltaDO2 < or =20% (nonresponders, n=13). Before thrombolysis, clinical and angiographic findings were similar in both groups. Mean right atrial pressure (RAP) and total pulmonary (vascular) resistance (TPR) were higher, while cardiac index (CI), DO2 and mixed venous oxygen saturation (Sv,O2) were lower in responders. DO2 and Sv,O2 were more closely correlated with deltaDO2 than RAP, TPR and CI. Eight out of the 10 responders and two out of the 13 nonresponders had an Sv,O2 <55%, while nine of the responders and two of the nonresponders had a DO2 <350 mL x min(-1) x m(-2). In conclusion, the initial oxygen delivery and mixed venous oxygen saturation may predict the cardiorespiratory efficacy of thrombolytic therapy in acute massive pulmonary embolism. When pulmonary angiography is performed, measurement of mixed venous oxygen saturation may be a simple method by which to select patients for thrombolytic therapy.

Hemodynamic effects of fluid loading in acute massive pulmonary embolism.

OBJECTIVE: To assess the hemodynamic effects of fluid loading in patients with acute circulatory failure caused by acute massive pulmonary embolism (AMPE). DESIGN: Prospective study. SETTING: Respiratory critical care unit of a university hospital. PATIENTS: Thirteen patients free of previous cardiopulmonary disease with angiographically proven AMPE (Miller index = 24 +/- 1), with acute circulatory failure defined by a cardiac index (CI) lower than 2.5 L/min/m2. INTERVENTION: Infusion of 500 mL of dextran 40 over 20 mins. MEASUREMENTS AND MAIN RESULTS: Fluid loading induced a substantial increase in right atrial pressure from 9 +/- 1 mm Hg to 17 +/- 1 mm Hg and in right ventricular end-diastolic volume index from 123 +/- 14 mL/m2 to 150 +/- 11 mL/m2 (p < .05 for both comparisons). The increase in right ventricular preload was associated with an increase in Cl from 1.6 +/- 0.1 to 2.0 +/- 0.1 L/min/m2 (p < .05), whereas right ventricular ejection fraction (15 +/- 3% at baseline vs. 16 +/- 3% after fluid loading) and total pulmonary vascular resistance index (1689 +/- 187 dyne x sec/cm5 x m2 at baseline vs. 1492 +/- 166 dyne x sec/ cm5 x m2 after fluid loading) remained unchanged. The increase in Cl induced by fluid loading was inversely correlated to baseline right ventricular end-diastolic volume index (r = -.89 ; p< .05). CONCLUSIONS: These results suggest that fluid loading can improve hemodynamic status in patients with acute circulatory failure caused by AMPE.

Diagnostic value of two rapid and individual D-dimer assays in patients with clinically suspected pulmonary embolism: comparison with microplate enzyme-linked immunosorbent assay.

A semiquantitative enzyme-linked immunosorbent assay (ELISA) test (Instant IA D-dimer) and a new quantitative rapid and individual test (STA-Liatest DDi) were compared with the reference microplate ELISA (Asserachrom D-Di) for D-dimer testing in 142 patients clinically suspected of pulmonary embolism, on the basis of clinical symptoms and signs, electrocardiogram, blood gases and chest X-Ray abnormalities. The cut-off value for the quantitative tests was 500 ng/ml and Instant IA was interpreted by three readers. Pulmonary embolism was confirmed by lung scan or angiography in 60 patients (42%). The sensitivities of ELISA and STA-Liatest DDi were 92% [95% confidence interval (CI) 82-97%] and 93% (95% CI 84-98%), respectively. The three readings of Instant IA D-dimer disagreed in 27 (19%) of the patients and sensitivity varied from 83 to 93% according to the readers. In the 115 patients with concordant readings, sensitivity was 92% (95% CI 82-98%). These results suggest that STA Liatest DDi may be used instead of microplate ELISA for the exclusion of pulmonary embolism, whereas the use of Instant IA D-dimer for this purpose is limited by the number of discordant results.

Incidence and predictors of major hemorrhagic complications from thrombolytic therapy in patients with massive pulmonary embolism.

PURPOSE: The risk factors for bleeding in patients receiving recombinant tissue-type plasminogen activator for massive pulmonary embolism are not known. PATIENTS AND METHODS: The hospital records of 132 consecutive patients who received recombinant tissue-type plasminogen activator for massive pulmonary embolism were retrospectively reviewed. Bleeding was estimated by using the bleeding severity index, a method previously validated in patients receiving anticoagulants. Multivariate stepwise logistic regression was used to identify independent risk factors for bleeding. Four other definitions of bleeding in large pulmonary embolism thrombolytic trials were also used, and the agreement among these criteria was assessed. RESULTS: According to the bleeding severity index, 33 patients (25%) had one or more major bleeding complications. Hemorrhage at the venous puncture site for angiography was the most frequent complication (15 patients, 11%). Major bleeding at the catheterization site was more common at the femoral site (14 of 63 patients = 22%) than at the brachial site (1 of 63 patients = 2%; P = 0.0004). The use of the five different bleeding definitions resulted in a variation in the major bleeding rate from 3% to 43%. The kappa coefficient varied from 0.07 to 0.84, indicating poor agreement between most of the classifications. CONCLUSION: The use of the femoral vein for pulmonary angiography was the only variable significantly associated with major bleeding. Most of the differences observed in the pulmonary embolism thrombolytic trials are likely related to the differences in the definition of bleeding rather than to the thrombolytic regimen.

[Role of spiral CT in the emergency diagnosis of pulmonary embolism]. / Place de l'angioscanner dans le diagnostic des embolies pulmonaires en urgence.

The pulmonary arteries can be visualized with spiral CT after injection of iodinated contrast material. Its contribution to emergency diagnosis of pulmonary embolism has been recently evaluated. Sensitivity for the detection of segmentary or more proximal thrombi is nearly 100% with a specificity estimated at 96%. These figure are much lower for subsegmentary emboli, varying from 63% to 83% for sensitivity and from 85% to 100% for specificity. The requirement for treatment in these minor forms remains however a topic of debate. Due to its noninvasive character and the diagnostic performance, spiral CT is well adapted for cases of suspected massive embolism. Inversely, for minimal embolism, spiral CT cannot eliminate the diagnosis before the results of other explorations are known.

A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: Evaluations dans l'Embolie Pulmonaire.

BACKGROUND: Low-molecular-weight heparin appears to be at least as effective and safe as standard, unfractionated heparin for the treatment of deep-vein thrombosis, but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism. METHODS: We randomly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin (tinzaparin) given once daily in a fixed dose or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months. We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism, major bleeding, and death. RESULTS: In the first eight days of treatment, 9 of 308 patients assigned to receive unfractionated heparin (2.9 percent) reached at least one of the end points, as compared,with 9 of 304 patients assigned to low-molecular-weight heparin (3.0 percent; absolute difference, 0.1 percentage point; 95 percent confidence interval, -2.7 to 2.6). By day 90, 22 patients assigned to unfractionated heparin (7.1 percent) and 18 patients assigned to low-molecular-weight heparin (5.9 percent) had reached at least one end point (P=0.54; absolute difference, 1.2 percentage points; 95 percent confidence interval, -2.7 to 5.1). The risk of major bleeding was similar in the two treatment groups throughout the study. CONCLUSIONS: Under the conditions of this study, initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism.

[Comparison of efficacy and tolerability of a thrombolytic treatment with rt-PA in acute massive pulmonary embolism in the elderly and patients under 75 years of age]. / Comparaison de l'efficacité et de la tolérance d'un traitement thrombolytique par rt-PA dans l'embolie pulmonaire aiguë massive chez le sujet âgé et chez les moins de 75 ans.

BACKGROUND: Pulmonary embolism often occurs in elderly patients. However, clinical presentation and treatment of massive pulmonary embolism (PE) in the elderly have not been extensively investigated. We report the results of rt-PA bolus infusion in patients aged 75 years or more suffering from massive PE. METHODS: Fifty-four adult patients referred to our institution with symptoms suggestive of massive PE were included in a therapeutic trial of single-chain rt-PA. Patients with a Miller angiographic score of at least 20/34 were considered for entry into the study. Patients were divided into two groups according to their age. Clinical presentation at admission, resolution of scintigraphic vascular obstruction, death rate, hemorrhagic complications, recurrent pulmonary embolism and long-term follow-up were compared between both groups. RESULTS: Twenty-eight patients were less than 75 years old and 26 patients were aged 75 years or more. Clinical symptoms at admission were similar in both groups. The mean absolute improvement in the lung scan perfusion defect, the rate of major bleeding, and the long-term evolution were not statistically different between older and younger patients. CONCLUSION: Clinical presentation and tolerance of massive PE did not differ between elderly and non-elderly patients. Old age should not preclude thrombolytic therapy in massive PE, provided there are no other contraindications for thrombolytic treatment.

Lung perfusion scans and hemodynamics in acute and chronic pulmonary embolism.

UNLABELLED: To assess the relationship between pulmonary vascular obstruction and hemodynamic status in acute pulmonary embolism (APE) and in chronic thromboembolic pulmonary hypertension (CTEPH), perfusion lung scan and hemodynamic measurements were obtained in 31 consecutive patients with APE and in 45 with CTEPH. METHODS: Lung scans were scored independently by two experience observers who determined the percentage of vascular obstruction (PVOs). Mean pulmonary artery pressure (PAP) and total pulmonary resistance (TPR) were obtained during right heart catheterization. In patients with APE, measurements were recorded within a 1-hr interval before and 12 hours after thrombolysis. This yielded 62 paired PVOs values with concomitant PAP and TPR measurements. In patients with CTEPH, data were recorded within a 3-day interval. RESULTS: Mean PVOs (%) values were similar in APE and CTEPH patients (59 +/- 13 vs. 58 +/- 15), whereas PAP and TPR were significantly higher in CTEPH patients (51 +/- 17 mmHg and 23 +/- 11 U/m2, respectively) than in APE patients (23 +/- 8 mmHg and 9 +/- 5 U/m2, respectively, p < 0.001). In APE patients, significant hyperbolic correlations were found linking PVOs with PAP and TPR (r = 0.75, p < 0.01 for PAP; r = 0.71, p < 0.01 for TPR). In CTEPH, there were no significant correlations between PVOs and PAP or TPR. For the same level of PVOs, patients with CTEPH had higher PAP and TPR value than patients with APE. CONCLUSION: In APE without prior cardiopulmonary disease, increases in PAP and TPR are correlated in a nonlinear fashion with the degree of pulmonary vascular obstruction as assessed by lung scanning. In CTEPH patients, the higher PAP and TPR values as compared to APE patients with comparable degrees of PVOs are consistent with previous reports that pulmonary hypertension in CTEPH is due not only to the obstruction of proximal pulmonary arteries but also to remodeling of small distal arteries in nonoccluded areas.

Bronchiolitis obliterans organizing pneumonia associated with chlamydial infection.

A 70 year old man presented with symptoms and laboratory findings suggestive of chlamydial pneumonia. Despite adequate antibiotic therapy, his condition did not improve and transbronchial biopsies disclosed a typical feature of bronchiolitis obliterans organizing pneumonia (BOOP). After initiation of corticosteroid therapy, there were marked clinical and radiographic improvements. This report demonstrates that chlamydial infection may be associated with BOOP.

Clinical presentation and results of thrombolytic therapy in older patients with massive pulmonary embolism: a comparison with non-elderly patients.

OBJECTIVE: To assess the clinical presentation and effectiveness of thrombolytic therapy in older patients suffering from massive pulmonary embolism. DESIGN: Analysis of a previously reported study of patients with massive pulmonary embolism using a dichotomous classification of age. SETTING: A medical intensive care unit in one hospital center. PARTICIPANTS: All subjects had massive pulmonary embolism as evidenced by scintigraphic and/or angiographic assessment. The 54 patients included in this study were divided into two groups according to age: 28 patients were less than 75 years old and 26 patients were 75 years old or older. INTERVENTION: All patients received a bolus regimen of single-chain recombinant tissue-type plasminogen and were subsequently treated by heparin and warfarin. MEASUREMENTS: Clinical symptoms at admission, resolution of scintigraphic vascular obstruction, death rate, hemorrhagic complications, recurrent pulmonary embolism, and long-term follow-up were compared between both groups. RESULTS: Clinical symptoms at admission were similar in both groups. The mean absolute improvement in the lung scan perfusion defect, the rate of major bleeding, and the long-term evolution were not statistically different between older and younger patients. CONCLUSION: Clinical symptoms, including hemodynamic condition, did not differ between elderly and nonelderly patients suffering from massive pulmonary embolism. Old age should not preclude thrombolytic therapy in massive pulmonary embolism, provided there is no other contraindication for thrombolytic treatment.

Subcutaneous low-molecular-weight heparin fragmin versus intravenous unfractionated heparin in the treatment of acute non massive pulmonary embolism: an open randomized pilot study.

Low-molecular-weight heparins have been extensively investigated in the treatment of deep venous thrombosis but limited data are available concerning their use in pulmonary embolism. In an open, pilot, randomized study, we compare the safety and efficacy of Fragmin, a low-molecular-weight heparin with those of unfractionated heparin in 60 patients with non massive pulmonary embolism (Miller Index < 20). Thirty one patients received unfractionated heparin intravenously and 29 received a fixed dose of 120 Anti-Xa IU/kg of Fragmin administered subcutaneously twice a day for 10 days. There was no pulmonary embolism recurrence nor major bleeding in either group during the treatment period. The decrease in pulmonary vascular obstruction on perfusion lung scan between day 0 and day 10 was 17 +/- 13% in the Fragmin group and 16 +/- 13% in the heparin group (NS). These results indicate that Fragmin may be a safe and effective treatment of submassive pulmonary embolism.