Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism

Limited data are available about the diagnostic value of D-dimer testing in cancer patients with clinically suspected pulmonary embolism (PE). Therefore, we evaluated i) the safety and clinical usefulness of an ELISA D-dimer test to rule out PE in cancer patients compared with non-cancer patients and ii) whether adopting a higher D-dimer cut-off value might increase the usefulness of D-dimer in cancer patients. We analysed data from two outcome studies which enrolled 1,721 consecutive patients presenting in the emergency department with clinically suspected PE. Presence of an active malignancy was abstracted from the database. All patients underwent a sequential diagnostic work-up including an ELISA D-dimer test and a 3-month followup. Sensitivity and predictive value (NPV) were 100% in both cancer and non-cancer patients. PE was ruled out by a negative D-dimer test in 494/1,554 (32%) patients without cancer, and in 18/164 (11%) patients with a malignancy. At cut-off values varying from 500 to 900 microg/l, the sensitivity was unchanged (100%, 95% CI: 93% to 100%) and the specificity increased from 16% (95% CI: 11% to 24%) to 30% (95% CI: 22% to 39%). The 3-month thromboembolic risk was 0% (95% CI: 0% to 18%) in cancer patients with a negative D-dimer test. ELISA D-dimer appears safe to rule out pulmonary embolism in cancer patients but it is negative in only one of ten patients at the usual cut-off value. Increasing the cut-off value of D-dimer in cancer patients might increase the test's clinical usefulness.     

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.     

Incidence of chronic pulmonary hypertension in patients with previous pulmonary embolism

IntroductionThe true incidence of chronic thromboembolic pulmonary hypertension (CTPH) remains a matter of debate. Symptomatic CTPH is probably more common than previously reported, whereas the occurrence of asymptomatic CTPH has not been defined since very limited evidence on the incidence of asymptomatic CTPH diagnosed with echocardiography Doppler are currently available. We therefore carried out a prospective cohort study to assess the incidence of CTPH diagnosed with echocardiography Doppler in consecutive patients with a first episode of PE.MethodsConsecutive patients with a first episode of PE were evaluated with Doppler transthoracic echocardiography within 6 to 12 months after the index event. Pulmonary hypertension was defined as a systolic pulmonary artery pressure ≥ 40 mmHg at rest in the presence of residual perfusion defects at perfusion scintigraphy. Presence of symptoms related to pulmonary hypertension was evaluated with a standardized questionnaire.ResultsNinety-one patients (mean age 61.9 ± 15.7 years; range 22-89; 39 men) were enrolled. Eight patients (8.8%; 95% CI 4.5,16.4) had CTPH: of these, 4 (4.4%; 95% CI 2.0, 9.3) were symptomatic.ConclusionsAsymptomatic CTPH is not an uncommon finding after PE. Larger prospective trials with a longer follow up should assess the prognostic significance of asymptomatic CPTH.     

颅咽管瘤术后肺动脉栓塞的研究

目的研究颅咽管瘤术后肺动脉栓塞的发生情况及可能原因。方法回顾性分析185例颅咽管瘤病人的临床资料,其中发生肺动脉栓塞5例(2.7%),经CT肺动脉造影证实4例。对5例病人的血电解质水平、去氨加压素及地塞米松的使用进行研究。结果随访5例,时间6~30个月,死亡3例,痊愈2例。3例病人血钠持续高于正常值(145~170 mmol/L)。5例病人均至少使用1个月的去氨加压素及7 d的地塞米松。结论高钠血症、长期使用去氨加压素和地塞米松可能诱发血液高凝状态而增加病人术后发生肺动脉栓塞的风险。     

Prognostic value of D-dimer in patients with pulmonary embolism

D-dimer levels appear to be associated with the extent of the thromboembolic burden in patients with pulmonary embolism (PE). We therefore hypothesized that D-dimer levels at admission would be associated with prospective risk of mortality in patients with PE. We used data from 366 patients diagnosed with PE at four hospital emergency departments. A highly sensitive D-dimer test was prospectively performed at admission. The outcome was overall mortality within three months. We divided patients into quartiles on the basis of their D-dimer levels and compared mortality rates by quartile. We estimated sensitivity, specificity, and predictive values for mortality in the first and fourth quartile. Overall mortality was 5.2%. Patients who died had higher median D-dimer levels than patients who survived (4578 versus 2946 microg/l; p = 0.005). Mortality increased with increasing D-dimer levels, rising from 1.1% in the first quartile (<1500 microg/l) to 9.1% in the fourth quartile (>5500 microg/l) (P = 0.049). Sensitivity, specificity, and positive and negative predictive values of D-dimer levels <1500 microg/l to predict mortality were 95%, 26%, 7%, and 99%, respectively. Patients with PE who have D-dimer levels below 1500 microg/l have a very low mortality. Further studies must assess whether D-dimer, alone or combined with other prognostic instruments for PE, can be used to identify low-risk patients with PE who are potential candidates for outpatient treatment or an abbreviated hospital stay.     

Increased risk for pulmonary embolism in patients with bipolar disorder

OBJECTIVES: The purpose of this study was to investigate the increased risk for pulmonary embolism (PE) in patients with manic-depressive psychosis/bipolar disorder (BD). Affective patients show increased mortality compared with the background population. METHODS: A register study was carried out in which somatic and psychiatric information in 25,834 BD patients and 117,815 controls was extracted from The Danish Psychiatric Central Research Register, The National Register of Patients, The Danish Central Person Register and The Danish Register of Causes of Death, with similar information about patients with schizophrenia and anxiety for comparison. RESULTS: Patients with BD had a significantly increased occurrence of PE [increased incidence rate ratio (IRR)=1.61; 95% confidence interval (CI) (1.38, 1.88)]. An association was also found in schizophrenic patients [IRR=1.78; 95% CI (1.27, 2.51)] and in anxiety patients [IRR=1.49; 95% CI (1.10, 2.02)]. CONCLUSIONS: Increased occurrence of PE in patients with BD is one of the explanations of increased mortality in the affective patient group. A similar finding in females with schizophrenia and females with anxiety suggests 'mental disorder' as the risk factor for PE. The causes for the increased occurrence of PE in BD patients (and other diagnostic groups) need further investigation.     

Prognostic importance of anaemia in patients with acute pulmonary embolism

Although associated with adverse outcomes in other cardiopulmonary diseases, limited evidence exists on the prognostic value of anaemia in patients with acute pulmonary embolism (PE). We sought to examine the associations between anaemia and mortality and length of hospital stay in patients with PE. We evaluated 14,276 patients with a primary diagnosis of PE from 186 hospitals in Pennsylvania, USA. We used random-intercept logistic regression to assess the association between anaemia at the time of presentation and 30-day mortality and discrete-time logistic hazard models to assess the association between anaemia and time to hospital discharge, adjusting for patient (age, gender, race, insurance type, clinical and laboratory variables) and hospital (region, size, teaching status) factors. Anaemia was present in 38.7% of patients at admission. Patients with anaemia had a higher 30-day mortality (13.7% vs. 6.3%; p <0.001) and a longer length of stay (geometric mean, 6.9 vs. 6.6 days; p <0.001) compared to patients without anaemia. In multivariable analyses, anaemia remained associated with an increased odds of death (OR 1.82, 95% CI: 1.60-2.06) and a decreased odds of discharge (OR 0.85, 95% CI: 0.82-0.89). Anaemia is very common in patients presenting with PE and is independently associated with an increased short-term mortality and length of stay.     

Echocardiographic assessment of pulmonary arterial pressure in the follow-up of patients with pulmonary embolism

Background

Echocardiography remains a clinically useful screening test for chronic thromboembolic pulmonary hypertension (CTEPH) in patients with a history of pulmonary embolism (PE). To devise an effective screening strategy, the definition of a high-risk group is necessary.

Methods

We examined a total of 744 patients with acute symptomatic pulmonary embolism (PE) who were enrolled in a Spanish multicenter study. Patients were monitored every 6 months during the first two years, and then once a year thereafter. Transthoracic echocardiography was used to screen patients with a clinical suspicion of CTEPH during follow-up. Pulmonary arterial hypertension was defined as an estimated pulmonary artery systolic pressure (PAP) > 50 mm Hg. The index thromboembolic episode was considered severe if: (a) the patient was immobilized for medical reasons; or (b) systolic blood pressure was less than 90 mm Hg; or (c) troponin T values were above the reference range.

Results

The incidence of PAP > 50 mm Hg at 36 months was 8.3% (95% confidence interval = 4.6%-14.5%). Statistical analysis showed a highly significant association between a severe index thromboembolic episode and the subsequent detection of PAP > 50 mm Hg on echocardiography, with high positive likelihood ratio (2.40) and negative predictive value (> 0.97).

Conclusions

Patients with a severe index thromboembolic episode would constitute a high-risk group for the development of CTEPH. This group of patients should be subjected to a strict follow-up protocol.     

Right ventricular dysfunction in hemodynamically stable patients with acute pulmonary embolism

Background

Echocardiography for risk stratification in hemodynamically stable patients with pulmonary embolism (PE) is well-established. Right ventricular dysfunction (RVD) is associated with an elevated mortality and adverse outcome. The aim of our study was to compare RVD criteria and investigate the role of elevated systolic pulmonary artery pressure (sPAP) in the diagnosis of RVD.

Methods

We retrospectively analyzed the echocardiographic and laboratory data of all hemodynamically stable patients with confirmed PE (2006-2011). The data were compared with three different definitions of RVD: Definition 1: RV dilatation, abnormal motion of interventricular septum, RV hypokinesis or tricuspid regurgitation. Definition 2: as with definition 1 but including elevated sPAP (> 30 mmHg). Definition 3: elevated sPAP (> 30 mmHg) as single RVD criterion.

Results

A total number of 129 patients (59.7% women, age 70.0 years (60.7/81.0)) were included in this study. Median Troponin I level was measured as 0.02 ng/ml (0/0.14); mean sPAP 33.9 ± 18.5 mmHg. The troponin cut-off levels for predicting a RVD of the 3 RVD definitions were in definition 1-3: > 0.01 ng/ml, > 0.01 ng/ml and > 0.00 ng/ml. Analysis of the ROC curve showed an AUC for RVD definitions 1-3: 0.790, 0.796 and 0.635.

Conclusions

The combination of commonly used RVD criteria with added elevated sPAP improves the diagnosis of RVD in acute PE. Troponin I values of > 0.01 ng/ml in acute PE point to an RVD.     

Risk factors for adverse short-term outcome in patients with pulmonary embolism

Pulmonary embolism (PE) is a common and potentially fatal disease. Death usually occurs before hospital admission or in the initial in-hospital phase. A number of clinical and instrumental findings have been associated with a high risk of adverse short-term clinical outcomes in patients with PE. Advanced age, concomitant cardiopulmonary disease, and haemodynamic instability, as well as large perfusion defects at lung scanning and acute right heart dysfunction as assessed by echocardiography, are associated with adverse in-hospital outcome. Elevated serum levels of troponin I have been recently demonstrated to be associated with severe right ventricular dysfunction and adverse in-hospital outcome in patients with PE. Early recurrence of PE is associated with a high mortality rate. Right heart dysfunction, as assessed by echocardiography and an acute fall in platelet count, have been suggested as risk factors for recurrence of PE. A reduction in mortality in the subgroup of patients with a poor prognosis might be achieved by using more aggressive treatments such as thrombolysis and surgical or interventional procedures. However, such treatments are invariably associated with bleeding and other procedural complications.     

Prognostic value of the Geneva prediction rule in patients with pulmonary embolism

Background

Assessment of pre-test probability of pulmonary embolism (PE) and prognostic stratification are two widely recommended steps in the management of patients with suspected PE. Some items of the Geneva prediction rule may have a prognostic value.We analyzed whether the initial probability assessed by the Geneva rule was associated with the outcome of patients with PE.

Methods

In a post-hoc analysis of a multicenter trial including 1,693 patients with suspected PE, the all-cause death or readmission rates during the 3-month follow-up of patients with confirmed PE were analyzed. PE probability group was prospectively assessed by the revised Geneva score (RGS). Similar analyses were made with the a posteriori-calculated simplified Geneva score (SGS).

Results

PE was confirmed in 357 patients and 21 (5.9%) died during the 3-month follow-up. The mortality rate differed significantly with the initial RGS group, as with the SGS group. For the RGS, the mortality increased from 0% (95% Confidence Interval: [0–5.4%]) in the low-probability group to 14.3% (95% CI: [6.3-28.2%]) in the high-probability group, and for the SGS, from 0% (95% CI: [0–5.4%] to 17.9% (95% CI: [7.4-36%]). Readmission occurred in 58 out of the 352 patients with complete information on readmission (16.5%). No significant change of readmission rate was found among the RGS or SGS groups.

Conclusions

Returning to the initial PE probability evaluation may help clinicians predict 3-month mortality in patients with confirmed PE.(ClinicalTrials.gov: NCT00117169)     

Thrombolysis in hemodynamically stable patients with acute pulmonary embolism: A meta-analysis

Introduction

The role of thrombolysis in hemodynamically stable patients with acute pulmonary embolism (PE) remains controversial. We performed a meta-analysis of randomized trials to assess the effect of thrombolysis in these patients.

Materials and Methods

We searched MEDLINE and EMBASE for randomized studies comparing thrombolysis and heparin for the initial treatment of hemodynamically stable PE patients. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated. NNH to cause a major bleeding (MB) or an intracranial hemorrhage (ICH) and NNT to avoid one death were also calculated.

Results

Eleven studies (1833 patients) were included seven with rt-PA, three with tenecteplase and one with urokinase. Patients randomized to thrombolysis had a significant increased risk for MB (5.9% vs 1.9%; OR 2.83, 95% CI 1.68-4.76, I² 18.7%) and an increased risk for ICH (1.74% versus 0.6%; OR 2.36, 95% CI 0.98-5.71, I² 0%) and for fatal bleeding (1.3% versus 0.54%; OR 1.84, 95% CI 0.73-4.61, I² 0%). A not-significant reduction for all-cause death (1.74% vs 2.51%; OR 0.68, 95% CI 0.37-1.26, I² 0%) and a significant reduction for recurrent PE (1.1% vs 2.5%; OR 0.44, 95% CI 0.21-0.92, I² 0%) in favor of thrombolysis compared with heparin was found. NNH to cause a MB or an ICH were 27 and 91 patients, respectively. NNT to avoid one death was 125 patients.

Conclusions

Due to increased risk for MB and ICH with no evidence of reduction in mortality, thrombolysis should not be used for most normotensive PE patients.     

Evaluation of perioperative fatal pulmonary embolism and death in cancer surgical patients: the MC-4 cancer substudy

Cancer patients undergoing surgery are at a high risk of venous thromboembolism, but few studies have described the rate of autopsy-confirmed fatal pulmonary embolism after heparin thromboprophylaxis. In a post hoc analysis of a randomized study (MC-4), which compared the efficacy and safety of certoparin (3000 anti-Xa IU, subcutaneously, once-daily) with unfractionated heparin (5000 IU, subcutaneously, three-times daily) in 23078 patients undergoing surgery lasting more than 30 min, the incidence of autopsy-confirmed fatal pulmonary embolism, death and bleeding in the cancer patients (n=6124) was compared with non-cancer patients (n=16954). Fatal pulmonary embolism was significantly more frequent in cancer patients (0.33% [20/6124]) than in non-cancer patients (0.09% [15/16954], relative risk (RR), 3.7 [95% confidence intervals (CI), 1.80, 7.77], p=0.0001) at 14 days post-prophylaxis. Perioperative mortality was also significantly higher in cancer patients than in noncancer patients (3.14% [192/6124] vs. 0.71% [120/16954], RR, 4.54 [95% CI, 3.59, 5.76], p=0.0001), as were blood loss (p<0.0001), and transfusion requirements (p<0.0001). Prevention of venous thromboembolism in cancer surgical patients remains a clinical challenge.     

Silent pulmonary embolism in patients with distal deep venous thrombosis: Systematic review

Purpose

The purpose of this investigation was to determine the prevalence of silent pulmonary embolism (PE) in patients with deep venous thrombosis (DVT) limited to the calf veins.

Methods

This is a systematic review. We attempted to identify all published investigations that reported the prevalence of silent PE in patients with infrapopliteal DVT. Studies were identified by searching PubMed through January 2014. The search was augmented by manually reviewing the references in all original articles and in reviews.

Results

The prevalence of silent PE in patients with DVT limited to the calf veins was described in 6 investigations. Pooled data showed a prevalence of 24 of 183 (13.1%) (95% CI 8.9-18.8%).

Conclusion

Silent PE in patients with DVT limited to the calf veins is not rare. Imaging at the time of diagnosis of calf vein DVT, typically with a perfusion scan alone, may be useful, but there is an economic cost and exposure to radiation.