Exclusion of pulmonary embolism using C-reactive protein and D-dimer

SummaryOur goal was to evaluate the diagnostic utility of C-reactive protein (CRP) alone or combined with clinical probability assessment in patients with suspected pulmonary embolism (PE), and to compare its performance to a D-dimer assay. We conducted a prospective study in which we performed a common immuno-turbidimetric CRP test and a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer test in 259 consecutive outpatients with suspected PE at the emergency department of a teaching hospital. We assessed clinical probability of PE by a validated prediction rule overridden by clinical judgment. Patients with D-dimer levels ≥ 500 µg/l underwent a work-up consisting of lower-limb venous ultrasound, spiral computer-ized tomography, ventilation-perfusion scan, or pulmonary angiography. Patients were followed up for three months. Seventy-seven (30%) of the patients had PE.The CRP alone had a sensitivity of 84% (95% confidence interval [CI).: 74 to 92%) and a negative predictive value (NPV) of 87% (95% CI: 78 to 93%) at a cutpoint of 5 mg/l. Overall, 61 (24%) patients with a low clinical probability of PE had a CRP < 5 mg/l. Due to the low prevalence of PE (9%) in this subgroup, the NPV increased to 97% (95% CI: 89 to 100%). The D-dimer (cutpoint 500 µg/l) showed a sensitivity of 100% (95% CI: 95 to 100%) and a NPV of 100% (95% CI: 94 to 100%) irrespective of clinical probability and accurately rule out PE in 56 (22%) patients. Standard CRP tests alone or combined with clinical probability assessment cannot safely exclude PE.

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C-reactive protein and D-dimer with clinical probability score in the exclusion of pulmonary embolism

British Journal of Haematology ◽

10.1111/j.1365-2141.2005.05652.x ◽

2005 ◽

Vol 130 (4) ◽

pp. 614-619 ◽

Cited By ~ 16

Author(s):

N. Steeghs ◽

R. J. Goekoop ◽

R. W. L. M. Niessen ◽

G. J. P. M. Jonkers ◽

H. Dik ◽

...

Keyword(s):

Pulmonary Embolism ◽

C Reactive Protein ◽

Probability Score ◽

Reactive Protein ◽

Clinical Probability ◽

D Dimer

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Relationship Between CRP, D-Dimer, D-Dimer/CRP with Clinical Probability and Diagnostic Value in Patients with Suspected Pulmonary Thoromboembolism

Journal of İzmir Chest Hospital ◽

10.5222/igh.2021.74745 ◽

2021 ◽

Author(s):

Yunus Günkan ◽

Cenk Babayiğit ◽

Nursel Dikmen

Keyword(s):

Pulmonary Embolism ◽

Sensitivity And Specificity ◽

Diagnostic Value ◽

Pulmonary Angiography ◽

Lung Scintigraphy ◽

Reactive Protein ◽

Clinical Probability ◽

Wells Score ◽

Diagnostic Values ◽

D Dimer

Objective: It was planned to investigate the diagnostic values for pulmonary thromboembolisym (PTE) by examining D-dimer, C-Reactive Protein (CRP), D-dimer/CRP ratio of patients who underwent computed tomography pulmonary angiography (CTPA) and/or lung scintigraphy with pre-diagnosis of pulmonary embolism. So it was thought that unnecessary computed tomograpy pulmonary Angiography could be reduced. Method: In our study, patients who were admitted to the chest diseases outpatient clinic and emergency department, who underwent CT pumonary Angiography and/or lung scintigraphy with a pre-diagnosis of pulmonary embolism, and who were simultaneously studied for D-dimer and CRP examinations were retrospectively evaluated. The efficiency and reliability of the Wells score and the combination of D-dimer, CRP and D-dimer/CRP ratio in the prediagnosis of pulmonary embolism were evaluated. Results: 46 of 79 patients with suspected pulmonary embolism included in our study were diagnosed with pulmonary thromboembolism with advanced tests. While the sensitivity and specificity of Wells score, D-dimer and CRP in diagnosing PTE were 41.3-100%, 91.3-27.3% and 84.7-42.4%, respectively, the cut off value of D-dimer/CRP ratio was 119.5. We found statistically significant higher D-dimer levels in patients with probable PTE according to Wells clinical scores. However, D-dimer/CRP ratio and CRP levels were statistically insignificant. Conclusion: In our study, D-dimer and CRP ratios were found to be significantly higher in patients with PTE, but D-dimer/CRP ratios were found to be less valuable in the diagnosis of PTE sensitivity and specificity.

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Tissue Plasminogen Activator Plasma Levels as a Potential Diagnostic Aid in Acute Pulmonary Embolism

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-0310-tpapla ◽

2003 ◽

Vol 127 (3) ◽

pp. 310-315

Author(s):

Julio Flores ◽

Angel García-Avello ◽

Victor M. Flores ◽

JoséL. Navarro ◽

Felipe Canseco ◽

...

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Lower Limb ◽

Pulmonary Angiography ◽

Enzyme Linked Immunosorbent Assay ◽

Clinical Probability ◽

Tissue Plasminogen ◽

Lung Scan ◽

Pai 1 ◽

D Dimer

Abstract Context.—Pulmonary embolism (PE) is a potentially fatal and frequent complication of deep venous thrombosis, and the most reliable techniques for the diagnosis of PE are not universally available and have other limitations. Objective.—To determine the efficacy of 4 different fibrinolysis system parameters, namely, tissue plasminogen activator (tPA), tissue plasminogen activator inhibitor type 1 (PAI-1), plasmin-antiplasmin complexes (PAP), and D-dimer, in the diagnosis of acute PE. Setting.—A 350-bed university hospital serving an area with 280 000 inhabitants. Patients.—Sixty-six consecutive outpatients with clinically suspected PE. The diagnosis of PE was based on ventilation-perfusion (V/Q) lung scan in combination with clinical assessment, lower limb study, and (when required) pulmonary angiography. Main Outcome Measures.—At the moment of clinical suspicion, a sample of venous blood was obtained to measure levels of tPA, PAI-1, PAP, and D-dimer using an enzyme-linked immunosorbent assay method. Results.—Twenty-seven patients (41%) were classified as PE positive (high clinical probability and V/Q lung scan [n = 12], nondiagnostic V/Q lung scan and high clinical probability [n = 1], inconclusive V/Q lung scan and positive lower limb examination for deep venous thrombosis [n = 11], and positive pulmonary angiography [n = 3]), and 39 patients (59%) were classified PE negative. The sensitivity/negative predictive value for tPA, using a cutoff of 8.5 ng/mL, and PAI-1, using a cutoff of 15 ng/mL, were 100%/100% and 100%/100%, respectively. A tPA level lower than 8.5 ng/mL occurred in 13 (19.7%; all PE negative) of 66 patients with suspected PE, and PAI-1 levels were lower than 15 ng/mL in 9 (13.6%; all PE negative) of 66 patients with suspected PE. The D-dimer, using a cutoff of 500 ng/mL, showed a sensitivity and negative predictive value of 92.6% and 87.5%, respectively. Conclusions.—Our data indicate that tPA and PAI-1 levels are potentially useful in ruling out PE, although tPA seems to be the better parameter. The sensitivity levels and negative predictive values for the rapid enzyme-linked immunosorbent assay for D-dimer used in this investigation were low compared with previous studies using the same test.

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The Value of D-Dimer in Patients with Increased C-Reactive Protein Suspected of Pulmonary Embolism.

Blood ◽

10.1182/blood.v114.22.5056.5056 ◽

2009 ◽

Vol 114 (22) ◽

pp. 5056-5056

Author(s):

Claire Siemes ◽

Paul Berendes ◽

Frans van der Straaten ◽

Ton Cleophas ◽

Mark-David Levin

Keyword(s):

Pulmonary Embolism ◽

Conflicts Of Interest ◽

Area Under The Curve ◽

Roc Curves ◽

Serum Levels ◽

C Reactive Protein ◽

Reactive Protein ◽

Interaction Term ◽

Pulmonary Embolisms ◽

D Dimer

Abstract Abstract 5056 OBJECTIVE To investigate the relation between elevated levels of C-reactive protein (CRP) and D-dimer, and to study whether D-dimer levels can be interpreted in relation to elevated levels of CRP in the prediction of a pulmonary embolism in order to increase its specificity without decline in sensitivity. METHODS Between august 2004 and april 2007 (33 months) serum levels of C-reactive protein (mmol/L) and D-dimer (mmol/L) were cross-sectionally collected and pulmonary embolisms on CT-angiograms were scored within 48 hours. The study was devided into three parts. First, characteristics of excluded persons were studied. Second, the correlation between CRP and D-dimer level was considered in those with a defined (i.e. values with < and > symbols excluded) biomarker level. Finally, the effect of CRP level on the sensitivity of D-dimer for pulmonary embolisms was examined. RESULTS CRP and D-dimer levels were positively correlated ( r = 0.37; p < 0.001), and both were increased in persons with a pulmonary embolism (CRP: p = 0.02; D-dimer: p < 0.001). 14 % of variability in D-dimer level was explained by CRP level. Median D-dimer levels were increased in the pulmonary embolism (PE) group, however, the increase in D-dimer level by CRP quartile as was found in the non-PE was not seen in de PE-group. Adding the interaction term of CRP and D-dimer to the statistical model showed some influence on the area under the curve (AUC). Nevertheless, this was not significantly different from the model with only D-dimer levels. However, when stratified for CRP quartile, ROC-curves of the predictive effect of D-dimer on pulmonary embolisms showed a decrease in AUC by increment of CRP quartile. CONCLUSION CRP and D-dimer are positively correlated, and both predictive of PE. The predictive value of D-dimer for PE declines by increment of CRP, although this seems to be safely for a broader range of accompanied CRP levels. Disclosures No relevant conflicts of interest to declare.

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THE RELIABILITY OF CLINICAL PROBABILITY SCORE IN (WELLS SCORE) THE DIAGNOSIS OF PULMONARY EMBOLISM (PE) IN COVID-19 PATIENTS

International Journal of Advanced Research ◽

10.21474/ijar01/13417 ◽

2021 ◽

Vol 9 (09) ◽

pp. 345-349

Author(s):

Saleh Alkhubaizi ◽

◽

Ahmad Al. ALalwi ◽

Mamdoh Mahboob ◽

Mohammed Al. Thubity ◽

...

Keyword(s):

Pulmonary Embolism ◽

Medical Records ◽

Healthcare Professionals ◽

Medical Center ◽

Pulmonary Angiography ◽

Clinical Probability ◽

Study Results ◽

Significant Difference ◽

Wells Score ◽

D Dimer

Background: The risk of developing pulmonary embolism (PE) is high in patients infected with COVID-19, and its diagnosis is a severe challenge for healthcare professionals duringthe COVID-19 pandemic. Physicians are frequently usingcomputed tomography pulmonary angiography(CTPA), d-dimer, and well score for the diagnosis of PE. Methods: A retrospective study was used in which we investigated the reliability of clinical well scores by collecting data, such as medical records in registered form (serum D-dimer level and Wells scores) of every patient for whom physicians have requested whose CTPA with suspicion of PE at King Faisal Medical Center (KFMC) from the period from 1st of April to the 1st of October. Results: The study results showed significantly higher values of d-dimer in patients with positive PEcompared to those with negative values. In addition wells score is not a reliable preclinical score in diagnosis PE in COVID 19 patient. Conclusions: As per the results of the well score, there is no significant difference between vulnerable people with PE +ve and -ve.

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Widespread Parenchymal Abnormalities and Pulmonary Embolism on Contrast-Enhanced CT Predict Disease Severity and Mortality in Hospitalized COVID-19 Patients

Frontiers in Medicine ◽

10.3389/fmed.2021.666723 ◽

2021 ◽

Vol 8 ◽

Author(s):

Francesca Campoccia Jalde ◽

Mats O. Beckman ◽

Ann Mari Svensson ◽

Max Bell ◽

Magnus Sköld ◽

...

Keyword(s):

Computed Tomography ◽

Pulmonary Embolism ◽

Pulmonary Artery ◽

Troponin T ◽

Main Pulmonary Artery ◽

C Reactive Protein ◽

Reactive Protein ◽

Parenchymal Abnormalities ◽

Pulmonary Artery Diameter ◽

D Dimer

Purpose: Severe COVID-19 is associated with inflammation, thromboembolic disease, and high mortality. We studied factors associated with fatal outcomes in consecutive COVID-19 patients examined by computed tomography pulmonary angiogram (CTPA).Methods: This retrospective, single-center cohort analysis included 130 PCR-positive patients hospitalized for COVID-19 [35 women and 95 men, median age 57 years (interquartile range 51–64)] with suspected pulmonary embolism based on clinical suspicion. The presence and extent of embolism and parenchymal abnormalities on CTPA were recorded. The severity of pulmonary parenchymal involvement was stratified by two experienced radiologists into two groups: lesions affecting ≤50% or >50% of the parenchyma. Patient characteristics, radiological aspects, laboratory parameters, and 60-day mortality data were collected.Results: Pulmonary embolism was present in 26% of the patients. Most emboli were small and peripheral. Patients with widespread parenchymal abnormalities, with or without pulmonary embolism, had increased main pulmonary artery diameter (p < 0.05) and higher C-reactive protein (p < 0.01), D-dimer (p < 0.01), and troponin T (p < 0.001) and lower hemoglobin (p < 0.001). A wider main pulmonary artery diameter correlated positively with C-reactive protein (r = 0.28, p = 0.001, and n = 130) and procalcitonin. In a multivariant analysis, D-dimer >7.2 mg/L [odds ratio (±95% confidence interval) 4.1 (1.4–12.0)] and ICU stay were significantly associated with embolism (p < 0.001). The highest 60-day mortality was found in patients with widespread parenchymal abnormalities combined with pulmonary embolism (36%), followed by patients with widespread parenchymal abnormalities without pulmonary embolism (26%). In multivariate analysis, high troponin T, D-dimer, and plasma creatinine and widespread parenchymal abnormalities on CT were associated with 60-day mortality.Conclusions: Pulmonary embolism combined with widespread parenchymal abnormalities contributed to mortality risk in COVID-19. Elevated C-reactive protein, D-dimer, troponin-T, P-creatinine, and enlarged pulmonary artery were associated with a worse outcome and may mirror a more severe systemic disease. A liberal approach to radiological investigation should be recommended at clinical deterioration, when the situation allows it. Computed tomography imaging, even without intravenous contrast to assess the severity of pulmonary infiltrates, are of value to predict outcome in COVID-19. Better radiological techniques with higher resolution could potentially improve the detection of microthromboses. This could influence anticoagulant treatment strategies, preventing clinical detoriation.

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From dyspnea to pulmonary embolism

Therapeutische Umschau ◽

10.1024/0040-5930.66.9.643 ◽

2009 ◽

Vol 66 (9) ◽

pp. 643-647 ◽

Cited By ~ 1

Author(s):

Arnaud Perrier

Keyword(s):

Pulmonary Embolism ◽

Large Body ◽

Prediction Rule ◽

Clinical Suspicion ◽

First Episode ◽

Left Heart Failure ◽

Coronary Syndrome ◽

Clinical Probability ◽

D Dimer ◽

Rule Out

Pulmonary embolism (PE) is often evoked in patients with new-onset or worsening dyspnea, especially when it is associated with pleuritic chest pain. However, the prevalence of PE in patients with a clinical suspicion ranges from 20 % to as low as 5 %. Unfortunately, what exactly constitutes a clinical suspicion of PE in a patient with dyspnea can not be accurately standardized. The presence of risk factors for venous thromboembolism should prompt the search for PE. However, their absence does not rule out PE as the cause of the patient’s symptoms, since around 30 % of patients with a first episode of PE have no risk or precipitating factors. Once PE is suspected, the diagnostic workup can be standardized and based on a large body of evidence, combining clinical assessment by a prediction rule, D-dimer measurement and CT angiography in patients with an elevated D-dimer level or a high clinical probability of PE. Patients with obvious alternative diagnoses such as acute left heart failure, pneumonia or acute coronary syndrome should not be investigated for PE.

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Age-Adjusted D-Dimer Cut-off Levels to Rule out Pulmonary Embolism: A Prospective Outcome Study

Blood ◽

10.1182/blood.v122.21.lba-4.lba-4 ◽

2013 ◽

Vol 122 (21) ◽

pp. LBA-4-LBA-4

Author(s):

Marc Righini ◽

Paul den Exter ◽

Josien van ES ◽

Franck Verschuren ◽

Alexandre Ghuisen ◽

...

Keyword(s):

Pulmonary Embolism ◽

Clinical Practice ◽

Emergency Room ◽

Pulmonary Angiography ◽

Outcome Study ◽

Clinical Probability ◽

Imaging Test ◽

D Dimer ◽

Rule Out

Abstract Introduction D-dimer testing allows to safely rule out pulmonary embolism (PE) without imaging test in approximately one third of outpatients. However, D-Dimer test is less useful as age increases because of a lower specificity. We recently derived an age-adjusted D-dimer cut-off value (age-adjusted cut-off = patient’s age x 10 in patients aged > 50 years, in μg/L), which allowed to significantly increase the proportion of patients in whom PE could be non-invasively excluded, without compromising safety. However, before being implemented in clinical practice, the safety of the age-adjusted cut-off should be verified in a management outcome study. Methods We designed a multicentre multinational prospective management outcome study. All consecutive outpatients seen in the emergency room of 22 centres in 4 countries with clinically suspected PE were assessed by a sequential diagnostic strategy based on the assessment of clinical probability, D-dimer measurement and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the usual threshold of 500 μg/L and their age-adjusted cut-off did not undergo CTPA and were left untreated and formally followed for a three-month period. Results Between January 1, 2010 and February 28, 2013, we included 3,377 patients. Mean age was 62 years, and 57% were females. Overall, the proportion of confirmed PE was 18%. Among the 2,927 patients with a non-high clinical probability, 832 (28.4%) had a D-Dimer < 500 μg/L, and 345 additional patients (11.8%) had a D-Dimer comprised between 500 μg/L and their age-adjusted cut-off. During the 3-month follow-up period, out of the 345 patients with a D-Dimer between 500 μg/L and their age-adjusted cut-off, 18 patients received anticoagulation for another indication than PE. Of the remaining 327 patients, 7 died, and 7 underwent testing for suspected venous thromboembolism (VTE), of which one was confirmed. Therefore, the failure rate of the age-adjusted cut-off was 1/327: 0.3%, (95% CI 0.1 to 1.7%). Overall, 789 patients were aged 75 years or more, of them 697 had a non-high clinical probability. The proportion of patients with D-Dimer < 500 μg/L was 50/697 (7.2%). Another 161 patients had a D-Dimer above 500 μg/L and under their age-adjusted cut-off. Therefore, the proportion of patients > 75 with a negative D-Dimer using the age-adjusted cut-off was 211/697 (30.3%), of them none had a confirmed VTE during follow-up: 0.0%, (95%CI: 0.0 to 1.9%). Conclusions Our study demonstrates that the age-adjusted D-Dimer cut-off may now be used in clinical practice in emergency room patients with suspected PE. Combined with clinical probability, it increases the number of patients in whom PE can be excluded without imaging test, and this is particularly true among elderly patients, with a four-fold increased yield of D-dimer. A D-Dimer above 500 μg/L but under the age-adjusted cut-off safely excludes the diagnosis of PE, with a 3-month risk of VTE in line with that observed in patients with a D-Dimer under 500 μg/L or after a negative pulmonary angiography, the gold-standard test for PE. Disclosures: No relevant conflicts of interest to declare.

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Venous Thromboembolism in Patients Discharged after COVID-19 Hospitalization

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0041-1727284 ◽

2021 ◽

Author(s):

Matthias M. Engelen ◽

Christophe Vandenbriele ◽

Tim Balthazar ◽

Eveline Claeys ◽

Jan Gunst ◽

...

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

C Reactive Protein ◽

Systematic Screening ◽

Vein Thrombosis ◽

Reactive Protein ◽

Risk Patients ◽

Deep Vein ◽

D Dimer

Abstract Background Venous thromboembolism (VTE) is a frequent complication of COVID-19, so that the importance of adequate in-hospital thromboprophylaxis in patients hospitalized with COVID-19 is well established. However, the incidence of VTE after discharge and whether postdischarge thromboprophylaxis is beneficial and safe are unclear. In this prospective observational single-center study, we report the incidence of VTE 6 weeks after hospitalization and the use of postdischarge thromboprophylaxis. Methods Patients hospitalized with confirmed COVID-19 were invited to a multidisciplinary follow-up clinic 6 weeks after discharge. D-dimer and C-reactive protein were measured, and all patients were screened for deep vein thrombosis with venous duplex-ultrasound. Additionally, selected high-risk patients received computed tomography pulmonary angiogram or ventilation–perfusion (V/Q) scan to screen for incidental pulmonary embolism. Results Of 485 consecutive patients hospitalized from March through June 2020, 146 patients were analyzed, of which 39% had been admitted to the intensive care unit (ICU). Postdischarge thromboprophylaxis was prescribed in 28% of patients, but was used more frequently after ICU stay (61%) and in patients with higher maximal D-dimer and C-reactive protein levels during hospitalization. Six weeks after discharge, elevated D-dimer values were present in 32% of ward and 42% of ICU patients. Only one asymptomatic deep vein thrombosis (0.7%) and one symptomatic pulmonary embolism (0.7%) were diagnosed with systematic screening. No bleedings were reported. Conclusion In patients who had been hospitalized with COVID-19, systematic screening for VTE 6 weeks after discharge revealed a low incidence of VTE. A strategy of selectively providing postdischarge thromboprophylaxis in high-risk patients seems safe and potentially effective.

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