Clinical prediction of pulmonary embolism in respiratory emergencies

Introduction

The initial management of suspected pulmonary embolism (PE) is commonly done in respiratory departments, but is based on clinical prediction rules developed in other settings.

Objective

To determine the accuracy of established prediction rules for PE in patients with respiratory emergencies.

Design

A prospective study

Materials and Methods

Patients presenting to respiratory emergency department with acute symptoms and signs suggestive of PE (n = 183) and subsequently admitted to hospital were prospectively enrolled. Wells’ rule, original and revised Geneva scores, their components separately, and other common clinical parameters were recorded during admission. PE was diagnosed by perfusion lung scanning, computed tomographic pulmonary angiography, lower limb venous ultrasonography, magnetic resonance pulmonary angiography, and/or pulmonary angiography.

Results

PE was confirmed in 52 and ruled out in 131 patients. Tachycardia, atelectasis, elevated hemidiaphragm, clinical signs of deep-venous thrombosis, physician perception that PE is the likeliest diagnosis, previous thromboembolism, chest pain, and absence of chronic obstructive pulmonary disease or cough were associated with the presence of PE. These significant parameters could be combined for accurate pre-test PE prediction, with a newly devised combinatorial tool exhibiting the highest area under curve [0.92 (95% CI: 0.87-0.97)], followed by Wells’ rule [0.86 (95% CI 0.79-0.92)], the revised Geneva score [0.83 (95% CI 0.77-0.90)], and the original Geneva score [0.75 (95% CI 0.68-0.83)].

Conclusion

Wells’ rule and the revised Geneva score are more useful in diagnosing PE in respiratory emergencies. A newly devised prediction tool can be of even greater accuracy in this patient population.     

Hospital mortality due to pulmonary embolism and an evaluation of the usefulness of preventative interventions

Background

Mortality rates due to pulmonary embolism (PE) are difficult to estimate often due to the presence of comorbid disease.

Objectives

To determine the accuracy of hospital records in identifying PE cases, PE-related mortality, and the number of PE-related deaths which are potentially preventable.

Methods

Retrospective chart review of PE cases hospitalized at The Ottawa Hospital over an 8 year period. Cases were reviewed to determine accuracy of coding, as well as the certainty with which PE was the cause of death. In PE-related deaths, a determination was made as to whether any interventions may have been life-saving.

Results

498 cases of 612 (81%) cases coded as PE were correctly coded. 111 (22%) died during hospitalization, 63% of deaths were attributed to PE. The presence of a cardiorespiratory comorbidity or cancer was independently associated with an increased rate of death due to PE. 54% of PE-related deaths were determined to be potentially preventable, most commonly by appropriate DVT prophylaxis. A significantly higher number of cancer patients as compared to non-cancer patients may have potentially had their death due to PE prevented by an inferior vena cava filter (IVCF). Systemic thrombolysis was deemed to be potentially life-saving in 1/38 PE-related deaths.

Conclusion

Hospital mortality due to clinically recognized PE can be determined by chart review of PE cases identified using the ICD coding system. Death due to PE is often potentially preventable; in the subgroup with cancer and DVT/PE, an IVCF may be a potentially useful intervention to prevent death due to PE. Prospective studies are needed to confirm these results.     

Comparison of the clinical usefulness of two quantitative D-Dimer tests in patients with a low clinical probability of pulmonary embolism

Background

Quantitative D-Dimer tests are established methods in the non-invasive diagnostic management to rule out venous thromboembolism (VTE). The diagnostic performance and the clinical efficiency different D-Dimer assays in the exclusion of pulmonary embolism (PE) have not yet been compared in a clinical outcome study.

Objective

Evaluation of the efficiency and safety of excluding the diagnosis of PE with two different quantitative D-Dimer assays in consecutive patients with clinically suspected PE.

Patients and Methods

We studied the VTE-failure rate of 2206 consecutive patients with an unlikely clinical probability in whom VIDAS or Tinaquant D-Dimer tests were performed.

Results

The prevalence of PE in 1238 patients whose D-Dimer level was analyzed with Tinaquant assay was 11%. The VIDAS assay group consisted of 968 patients with a PE prevalence of 13%. The VIDAS assay had a sensitivity of 99.2% (95%CI; 96- > 99.9%), the Tinaquant assay of 97.3% (95%CI; 93 -99%). The negative predictive value (NPV) in the Tinaquant assay group was 99.4% (95%CI 98-99.8%) in comparison to 99.7% (95%CI 99-> 99.9%) in the VIDAS assay group. During 3 month of follow-up, there were no fatal cases of PE among patients with normal D-Dimer and unlikely clinical probability in both D-Dimer assay groups. In addition, the test efficiency of Tinaquant assay was significantly higher in comparison to VIDAS assay (52% vs 42%, p < 0.001).

Conclusion

Both Tinaquant and VIDAS D-Dimer tests perform equally well in combination with an unlikely clinical probability in excluding PE. The Tinaquant test was shown to be more efficient.     

Clinical relevance of pulmonary infarction in patients with pulmonary embolism

Introduction

Data regarding the clinical relevance of pulmonary infarction (PI) in patients with pulmonary embolism (PE) are lacking. The aim of this study was to investigate the clinical features of PE patients with PI and the prognostic role of PI for PE patients.

Materials and Methods

Based on computed tomography scan, 509 patients with PE were divided into two groups, the infarction group (n = 45) and the non-infarction group (n = 464). A variety of clinical parameters were compared between the two groups.

Results

In the infarction group, the largest pulmonary arteries involved by emboli were central rather than peripheral and more proximal as compared to the non-infarction group (p = 0.01 and p < 0.03, respectively). Thrombolytic agents tended to be more frequently administered in the infarction group (13.3% [n = 6] versus 6.3% [n = 29], p = 0.07). In-hospital mortality, PE-related deaths, and the recurrence rate of PE did not differ between the two groups.

Conclusions

The present study did not demonstrate that PI is a prognostic indicator of recurrence and mortality in PE patients. We suggest the possibility that blood clot burden is greater in PE patients with PI, although PI by itself occurs in small pulmonary arteries.     

Outpatient treatment of symptomatic pulmonary embolism: A systematic review and meta-analysis

Background

Patients with acute deep vein thrombus (DVT) can safely be treated as outpatients. However the role of outpatient treatment in patients diagnosed with a pulmonary embolism (PE) is controversial. We sought to determine the safety of outpatient management of patients with acute symptomatic PE.

Materials and Methods

A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Pooled proportions for the different outcomes were calculated.

Results

A total of 1258 patients were included in the systematic review. The rate of recurrent venous thromboembolism (VTE) in patients with PE managed as outpatients was 1.47% (95% CI: 0.47 to 3.0%; I²: 65.4%) during the 3 month follow-up period. The rate of fatal PE was 0.47% (95% CI: 0.16 to 1.0%; I²: 0%). The rates of major bleeding and fatal intracranial hemorrhage were 0.81% (95% CI: 0.37 to 1.42%; I²: 0%) and 0.29% (95% CI: 0.06 to 0.68%; I²: 0%), respectively. The overall 3 month mortality rate was 1.58% (95% CI: 0.71 to 2.80%; I²: 45%). The event rates were similar if employing risk stratification models versus using clinical gestalt to select appropriate patients for outpatient management.

Conclusions

Independent of the risk stratification methods used, the rate of adverse events associated with outpatient PE treatment seems low. Based on our systematic review and pooled meta-analysis, low-risk patients with acute PE can safely be treated as outpatients if home circumstances are adequate.     

Comparison of the Wells score with the simplified revised Geneva score for assessing pretest probability of pulmonary embolism

Introduction

The Wells score is widely used in the assessment of pretest probability of pulmonary embolism (PE). The revised Geneva score is a fully standardized clinical decision rule that was recently validated and further simplified. We compared the predictive accuracy of these two scores.

Methods

Data from 339 patients clinically suspected of PE from two prospective management studies were used and combined. Pretest probability of PE was assessed prospectively by the Wells score. The simplified revised (SR) Geneva score was calculated retrospectively. The predictive accuracy of both scores was compared by area under the curve (AUC) of receiver operating characteristic (ROC) curves.

Results

The overall prevalence of PE was 19%. Prevalence of PE in the low, moderate and high pretest probability groups assessed by the Wells score and by the simplified revised Geneva score was respectively 2%(95% CI (CI) 1-6) and 4% (CI 2-10), 28% (CI 22-35) and 25% (CI 20-32), 93% (CI 70-99) and 56% (CI 27-81). The Wells score performed better than the simplified revised Geneva score in patients with a high suspicion of PE (p < 0.05). The AUC for the Wells score and the simplified revised Geneva score was 0.85 (CI: 0.81 to 0.89) and 0.76 (CI: 0.71 to 0.80) respectively. The difference between the AUCs was statistically significant (p = 0.005).

Conclusions

In our population the Wells score appeared to be more accurate than the simplified revised Geneva score. The impact of this finding in terms of patient outcomes should be investigated in a prospective study.     

Prospective diagnostic accuracy assessment of the HemosIL HS D-dimer to exclude pulmonary embolism in emergency department patients

Introduction

Chest pain and shortness of breath are among the most common symptoms requiring immediate evaluation. Testing for pulmonary embolism (PE) has become easier and widespread due to D-dimer blood tests. Safe use of these tests is only possible if sensitivity is high and they are used in non-high probability patients. We evaluated diagnostic performance of the HemosIL HS D-dimer, which despite FDA approval in 2005, has been minimally reported in prospective standard clinical care.

Materials and methods

We used a prospective observational study design to follow patients in a single center with the HemosIL HS ordered for symptoms of possible PE with positive test result if > 243 ng/ml. The outcome was PE or deep venous thrombosis (DVT) at the time of presentation or subsequent 45 days determined by structured evaluation of imaging tests, phone, or medical record follow-up in all patients.

Results

529 patients received a D-dimer and 4.7% were ultimately diagnosed with PE or DVT. The sensitivity of the HemosIL HS was 96.0% (95% CI; 79.6 to 99.9%) specificity was 65.7% (95% CI; 61.4 to 69.8%) and likelihood ratio negative was 0.06 (95% CI; 0.01 to 0.42). The probability of PE in patients with a negative D-dimer was 1/332 or 0.3% (95% CI; 0.01% to 1.67%). The receiver operator curve had an area under the curve of 0.87 and supported the current cut-point as optimal.

Conclusions

The HemosIL HS D-dimer had high sensitivity, very low negative post-test probability and is useful in excluding PE in the acute care setting.     

A simple non-invasive diagnostic algorithm for ruling out chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism

Background

Our aim was to construct a diagnostic model for ruling out chronic thromboembolic pulmonary hypertension (CTEPH) in symptomatic patients after acute pulmonary embolism (PE) that is based on simple, non-invasive tests.

Methods

Plasma levels of various CTEPH associated biomarkers and conventional ECG criteria for right ventricular pressure overload were assessed in 82 consecutive patients with confirmed CTEPH and 160 consecutive patients with a history of PE who were suspected to have CTEPH, but in whom this disease was ruled out.

Results

ECG criteria of right ventricular hypertrophy were detected more frequently in patients with CTEPH (77%) than in the patients without CTEPH (11%, Odds ratio 26, 95% confidence interval [CI] 13-53). Also, clotting factor FVIII activity and the levels of N-terminal-pro-brain-type natriuretic peptide (NT-pro-BNP), Growth Differentiation Factor-15, C-reactive protein and urate, but not D-dimer level, were higher in patients with CTEPH. A diagnostic model including ECG criteria and NT-pro-BNP levels had a sensitivity of 94% (95% CI 86-98%) and a specificity of 65% (95% CI 56-72%). The area under the receiver-operator-characteristic curve was 0.80 (95% CI 0.74-0.85) for the diagnosis of CTEPH. Even with high disease prevalences of up to 10%, the negative predictive value of this model proved to be very high (99%, 95% CI 97-100%).

Conclusions

Ruling out CTEPH in patients after acute PE seems to be safe without additional diagnostic testing in absence of ECG criteria indicative of right ventricular hypertrophy and a normal NT-pro-BNP level.     

Home treatment in pulmonary embolism

Background

Limited data exist on the feasibility of providing outpatient care to patients with acute pulmonary embolism (PE).

Methods

We conducted a multicenter randomized clinical trial in acute symptomatic PE to compare the efficacy and safety of early discharge versus standard hospitalization. A clinical prediction rule was used to identify low-risk patients. All patients were followed for three months. The primary outcomes were venous thromboembolic recurrences, major and minor bleeding, and overall mortality.

Results

One hundred and thirty two low-risk patients with acute symptomatic PE were randomized to early discharge (n = 72) or standard hospitalization (n = 60). Overall mortality was 4.2% (95% CI, 0.5-8.9) in the early discharge group and 8.3% (95% CI, 1.1-15) in the standard hospitalization group (Relative Risk (RR) 0.5; 95% confidence interval [CI], 0.12-2.01). Non-fatal recurrences were 2.8% (95% CI, 1.1-6.6) in the early discharge group and 3.3% (95% CI, 1.3-8%) in the standard hospitalization group (RR 0.8; 95% CI, 0.12-5.74). The rates of clinically relevant bleeding were 5.5% in the early discharge group and 5% in the standard hospitalization group (P = 0.60). Short-term mortality was 2.8% (95% CI, 0.8-9.6%) in the early discharge group as compared with 0% in the standard hospitalization group. Based on the rate of short-term death in a carefully selected population, the study was suspended.

Conclusions

In spite of the number of complications in patients with acute symptomatic PE randomized to standard hospitalization or early discharge did not differ significantly. The rate of short-term mortality was unexpectedly high in a (a priori) low-risk group of patients with acute PE. The accuracy of clinical prediction scores needs to be validated in well designed clinical trials. (ClinicalTrials.gov number, NCT00214929.)     

Active search for chronic thromboembolic pulmonary hypertension does not appear indicated after acute pulmonary embolism

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life threatening but often, by pulmonary endarterectomy, curable disease. The incidence of CTEPH after an acute pulmonary embolism (PE) appears to be much higher than previously thought. Systematic follow-up of patients after PE might increase the number of diagnosed CTEPH patients.

Aim

To study whether, compared to current clinical practice, a systematic search for CTEPH in patients after acute PE would increase the number of patients diagnosed with symptomatic, potentially treatable CTEPH.

Methods

Consecutive patients with a prior diagnosis of acute PE were presented with a questionnaire, designed to establish the presence of either new or worsened dyspnea after the acute PE episode. If so, patients were evaluated for the presence of CTEPH.

Results

PE patients (n = 110; 56 ± 18 years) were included after a median follow-up of three years. Overall mortality was 34% (37 patients); 1 patient had died due to CTEPH.In total 62 out of 69 questionnaires were returned; 23 patients reported new or worsened dyspnea related to the PE episode, and qualified for additional testing. In 2 patients, CTEPH was already diagnosed prior to this study. None of the remaining patients met the criteria for the diagnosis of CTEPH. The overall incidence of 2.7% (3/110; 95%CI 0.6-7.8%) is in agreement with earlier reported incidences.

Conclusion

Our findings do not point to a role for a systematic search and pro-active approach towards patients with a recent history of pulmonary embolism to increase the number of patients diagnosed with potentially treatable CTEPH.     

The impact of co-morbid conditions on family history of venous thromboembolism in Whites and Blacks

Introduction

Our objectives were to compare the magnitude of family history as a risk factor for venous thromboembolism (VTE) risk between Blacks and Whites, and to assess the impact of co-morbid conditions on familial risk for VTE.

Materials and methods

We used data from the Genetic Attributes Thrombosis Epidemiology (GATE) study, a matched case-control study which enrolled Blacks and Whites aged 18-70 years in Atlanta, Georgia. A total of 1,094 case patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE) and 1,264 control patients were interviewed about their family history.

Results

Family history of VTE was a statistically significant risk factor for VTE among Blacks (odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.0-4.1; P value < 0.0001) and among Whites (OR = 2.7, 95% CI 1.9-3.7; P value < 0.0001); among Blacks and Whites who were obese or had hypertension; among Blacks who had diabetes mellitus or cancer; as well as among males and females, and across all age categories. Family history of VTE increased the risk of VTE among Blacks with cancer by about 6-fold, whereas among Blacks without cancer the increased risk due to a positive family history was about 3-fold; a 2-fold relative difference. In addition, family history was a risk factor for VTE among case patients with DVT only or with PE only. The effect of family history generally was stronger among those with recurrent episodes of VTE compared with a first episode of VTE. For example, family history of any VTE was a strong risk factor among Black females with recurrent VTE compared with Black females with first VTE (OR = 3.9, 95% CI 2.0-7.5; P value < 0.0001).

Conclusion

Our study indicated that the adjusted attributable fraction for VTE was 16.9% among Blacks vs. 18.3% among Whites, and certain co-morbid conditions could further increase the risk of VTE associated with a positive family history of VTE.     

Sex-specific risk factors for recurrent venous thromboembolism

Background

Men have higher risk of recurrent venous thromboembolism (VTE) than women but this sex difference remains unexplained. In addition, whether men and women share same risk factors for recurrent VTE is unclear.

Methods

In a prospective cohort study, 583 patients (234 men and 349 women) aged 18 to 90, with a first idiopathic VTE, were followed for an average of 28 months. We assessed the association between baseline characteristics and VTE recurrence by gender.

Results

Recurrent VTE occurred in 38 women and 36 men (incidence = 4.6% and 7.5% per year respectively; HR = 1.6; 95% CI, 1.0-2.6). This relation between sex and recurrent VTE was more pronounced in patients younger than 50 years and in the presence of factor V Leiden (FVL) mutation. Multivariate analyses showed that obesity (HR, 2.8 (95% CI, 1.3-6.0)) and aging (HR, 1.3 (95% CI, 1.1-1.4) per 10 years increase) were related to an increased risk of recurrent VTE in women while FVL mutation (HR, 3.5 (95% CI, 1.5-8.1)) was a risk factor of recurrent VTE among men.

Conclusion

Men and women do not share the same risk factors for recurrent VTE. Consequently, gender has to be taken into account to improve the risk stratification and prevention of VTE recurrence.     

Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: A meta-analysis

Introduction

The Wells clinical decision rule (CDR) and D-dimer tests can be used to exclude pulmonary embolism (PE). We performed a meta-analysis to determine the negative predictive value (NPV) of an “unlikely” CDR (≤ 4 points) combined with a normal D-dimer test and the safety of withholding anti-coagulants based on these criteria.

Methods

Prospective studies that withheld anti-coagulant treatment from patients with clinically suspected PE and an “unlikely” CDR in combination with a normal D-dimer concentration without performing further tests were searched for in Medline, Cochrane and Embase. Primary endpoints were the recurrence rate of venous thromboembolism (VTE) and PE-related mortality during 3-months follow-up.

Results

Four studies including 1660 consecutive patients were identified. The pooled incidence of VTE after initial exclusion of acute PE based on an “unlikely” CDR and normal D-dimer was 0.34% (95%CI 0.036-0.96%), resulting in a NPV of 99.7% (95%CI: 99.0-99.9%, random effects-model). The risk for PE related mortality was very low: 1/1660 patients had fatal PE (0.06%, 95%CI 0.0017-0.46%).

Conclusion

Acute PE can be safely excluded in patients with clinically suspected acute PE who have an “unlikely” probability and a negative D-dimer test and anticoagulant treatment can be withheld. There is no need for additional radiological tests in these patients to rule out PE.     

Performance of the Wells score in patients with suspected pulmonary embolism during hospitalization: A delayed-type cross sectional study in a community hospital

Introduction

The role of the Wells score for patients who develop signs and symptoms of pulmonary embolism (PE) during hospitalization has not been sufficiently validated. The aim of this study is to evaluate the performance of the Wells score for inpatients with suspected PE and to evaluate the prevalence of pulmonary embolism.

Materials and Methods

We conducted a cross sectional study nested in the prospective Institutional Registry of Thromboembolic Disease at Hospital Italiano de Buenos Aires from June 2006 to March 2011. We included patients who developed symptoms of pulmonary embolism during hospitalization. Patients were stratified based on the Wells score as PE likely (> 4 points) or PE unlikely (≤ 4 points). The presence of pulmonary embolism was defined by pre-specified criteria.

Results

Six hundred and thirteen patients met the inclusion criteria, with an overall prevalence of PE of 36%. Two hundred and nineteen (34%) were classified as PE likely and 394 (66%) as PE unlikely with a prevalence of PE of 66% and 20%, respectively. The Wells score showed a sensitivity of 65 (95% CI 59-72), specificity 81 (95% CI 77-85), positive predictive value 66 (95% CI 60-72) and negative predictive value 80 (95% CI 77-84).

Conclusions

The Wells Score is accurate to predict the probability of PE in hospitalized patients and this population had a higher prevalence of PE than other cohorts. However, the score is not sufficiently predictive to rule out a potentially fatal disorder.     

Testing for occult cancer in patients with pulmonary embolism: Results from a screening program and a two-year follow-up survey

Introduction

An association between pulmonary embolism (PE) and a subsequent diagnosis of cancer has been repeatedly reported. Although screening and early detection might play a pivotal part in reducing mortality from cancer, there are currently no definite data to suggest that cancer screening may improve survival rates in patients with PE. We hereby present the results of a screening program and a two-year follow-up survey for detecting occult cancer in this patient population.

Materials and methods

A total of 107 patients with PE were consecutively enrolled. All subjects underwent an initial screening program followed by a two-year follow-up survey. We calculated the sensitivity of our screening program, and identified risk factors associated with occult cancer by means of logistic regression.

Results

The initial screening program yielded positive results in five patients (4.7%), and four additional cases were identified during the 2-year follow-up. The overall sensitivity of our screening program in idiopathic PE was 55.5%. In the entire study cohort, the number necessary for screening was 12.1 (6.1 in idiopathic PE, and 58 in secondary PE). Logistic regression analysis revealed that a shock index ≥ 1 (odds ratio: 5.467; p = 0.007) and idiopathic PE (odds ratio: 12.82; p = 0.03) were independent risk factors for occult cancer in our PE patients.

Conclusions

A simple and noninvasive screening program yields an acceptable sensitivity for detecting occult cancer in idiopathic PE patients. These results highlight the importance of screening for occult cancer in patients diagnosed with PE, especially in idiopathic forms.     

The G534E-polymorphism of the gene encoding the Factor VII-activating protease is a risk factor for venous thrombosis and recurrent events

Introduction

A single nucleotide polymorphism of the factor VII activating protease (FSAP), FSAP Marburg I (rs7080536) has been identified as a risk factor for venous thrombosis, but its clinical role has so far been controversial in part due to small cohort sizes. The aim of the present case-control study was to elucidate the impact of the FSAP Marburg I polymorphism (FSAP-MI) on the development of venous thromboembolic disease (VTE) with other known sequence variations, including Factor V Leiden (rs6025) and Factor II G20210A (rs1799963).

Materials and Methods

The study included 891 patients (312 male and 579 female) with a history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and 1283 healthy blood donors with no history of venous thromboembolic disease.

Results

We found that besides to the well-established aforementioned sequence variations of FV and Prothrombin, the FSAP Marburg I (FSAP-MI) polymorphism was significantly associated with the development of DVTs (1.65 (1.16-2.34) OR (95% CI)) and recurrent thromboembolic events (DVT and PE) (2.13 (1.35-3.36) OR (95% CI)). Comparing patients displaying one or more events FSAP-MI was still associated with the development of recurrent thromboembolic events (1.64 (1- 2.69) OR (95% CI)).

Conclusions

We conclude that FSAP Marburg-I genotyping may be used to determine the risk for thromboembolic disorders in patients with suspected thrombophilia and known DVT or PE.     

Derivation and validation of a multivariate model to predict mortality from pulmonary embolism with cancer: The POMPE-C tool

Background

Clinical guidelines recommend risk stratification of patients with acute pulmonary embolism (PE). Active cancer increases risk of PE and worsens prognosis, but also causes incidental PE that may be discovered during cancer staging. No quantitative decision instrument has been derived specifically for patients with active cancer and PE.

Methods

Classification and regression technique was used to reduce 25 variables prospectively collected from 408 patients with AC and PE. Selected variables were transformed into a logistic regression model, termed POMPE-C, and compared with the pulmonary embolism severity index (PESI) score to predict the outcome variable of death within 30 days. Validation was performed in an independent sample of 182 patients with active cancer and PE.

Results

POMPE-C included eight predictors: body mass, heart rate > 100, respiratory rate, SaO2%, respiratory distress, altered mental status, do not resuscitate status, and unilateral limb swelling. In the derivation set, the area under the ROC curve for POMPE-C was 0.84 (95% CI: 0.82-0.87), significantly greater than PESI (0.68, 0.60-0.76). In the validation sample, POMPE-C had an AUC of 0.86 (0.78-0.93). No patient with POMPE-C estimate ≤ 5% died within 30 days (0/50, 0-7%), whereas 10/13 (77%, 46-95%) with POMPE-C estimate > 50% died within 30 days.

Conclusion

In patients with active cancer and PE, POMPE-C demonstrated good prognostic accuracy for 30 day mortality and better performance than PESI. If validated in a large sample, POMPE-C may provide a quantitative basis to decide treatment options for PE discovered during cancer staging and with advanced cancer.     

Unprovoked proximal venous thrombosis is associated with an increased risk of asymptomatic pulmonary embolism

Introduction

Pulmonary embolism (PE) is common in patients with deep venous thrombosis (DVT). The outcome of DVT with concomitant symptomatic PE is worse than the outcome of isolated DVT. The risk factors for DVT and simultaneous asymptomatic PE have not been systematically studied yet.

Aim

To evaluate the frequency and risk factors for asymptomatic PE in patients with DVT.

Patients/methods

In 155 consecutive patients with a first episode of DVT and no PE symptoms, a ventilation-perfusion lung scan was performed. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated and concentrations of D-dimer, high-sensitivity CRP (hsCRP), tissue plasminogen activator (t-PA) and troponin were measured. Laboratory tests for thrombophilia were performed.

Results

Asymptomatic PE was present in 36% of patients. No differences in gender, age, BMI and WHR were found between the patients with and without PE. PE was more common in patients with proximal DVT than in those with distal DVT (42% vs. 17%, p < 0.01), and in patients with unprovoked DVT compared to patients with provoked DVT (51% vs. 28%, p < 0.01). The risk of silent PE was the highest in patients with unprovoked proximal DVT (OR, 6.9; 95% CI, 2.3–21.0). Patients with asymptomatic PE had significantly higher values of D-dimer, hsCRP, t-PA and troponin than patients with isolated DVT.

Conclusions

Asymptomatic PE affected more than one third of patients with a first DVT. Unprovoked proximal DVT is the most important risk factor for the occurrence of silent PE.     

Trends in mortality of pulmonary embolism - an international comparison

Background

Evidence from several clinical and epidemiological studies suggests a decreasing incidence and mortality of pulmonary embolism (PE), but results are still controversial. We analysed time trends of fatal pulmonary embolism in several countries across Europe and North America.

Methods

We extracted age-, sex-, and country-specific number of deaths due to PE (415.1 ICD-9; I26 ICD-10) from 1980 to 2004 as available from the WHO mortality database, which comprises mortality data and population density in 5-year age groups based on national vital statistics. Yearly age- and sex-standardised mortality rates and their 95% confidence intervals for PE were calculated. We compared overall and sex-specific age-standardised mortality rates across different European countries and the USA over time.

Results

Age- and sex-standardised PE-specific mortality in 1990 varied between 2.7/100,000 (2.5-3.0/100,000) in The Netherlands and 12.8/100,000 (12.0-13.5/100,000) in Austria. While in most countries PE mortality decreased over time, PE mortality increased distinctly in Poland from 4.0/100,000 (3.75-4.27/100,000) to 7.7/100,000 (7.45-8.03/100,000) in 2003. In Germany, we observed a continuous slight increase and in The Netherlands no clear change of PE mortality was seen.

Discussion

While comparison of cause of death data over time and across countries should be undertaken with caution due to inaccuracies in assigning the cause of death and national conventions in coding, the general trend of a decline in PE mortality could not be shown in several European countries.     

A porcine model of massive, totally occlusive, pulmonary embolism

Background

A reliable, animal model of massive, totally occlusive, pulmonary embolism (PE) is lacking.

Objectives

To design an animal model of totally occlusive PE and to challenge the model by a plasminogen activator.

Methods

In eight anaesthetized pigs (~ 90 kg) a massive preformed autologous thrombus was injected into the caval vein. One animal was autopsied to assess the extent of injected clot, whereas in the other animals extracorporeal life support (ECLS) was initiated and continued for three hours. These animals received 100 mg rt-PA. Blood gases, coagulation tests, creatine kinase (CK), lactate dehydrogenase (LDH), end-tidal CO2, systemic and pulmonary artery blood pressures and flow were registered.

Results

All animals went into circulatory arrest within 2 minutes after injection of the thrombus. In the animal where ECLS was not started, autopsy relieved a totally occlusive embolus of the pulmonary artery. The ECLS maintained a systemic blood flow of 6-8 L/min with adequate oxygenation and CO2-removal. However, lactate increased and base-excess became negative. Ddimer increased, fibrinogen decreased, and CK and LDH increased. All seven animals were weaned from ECLS. Despite the rt-PA treatment, the animals had at that time low end tidal CO2/PaCO2 ratio and increased mean pulmonary arterial pressure, suggesting a significant amount of embolic material remaining in the pulmonary artery.

Conclusion

This model of massive, totally occlusive, pulmonary embolism mimics well fatal PE seen in the clinic, and has the potential for use in testing of new therapeutic interventions.