D-dimer and C-reactive Protein Blood Levels Over Time Used to Predict Pulmonary Embolism in Two COVID-19 Patients

The diagnosis of pulmonary embolism is challenging in symptomatic COVID-19 patients since shortness of breath, chest pain, tachycardia, tachypnoea, fever, oxygen desaturation and high D-dimer blood levels might be features of both diseases. We present two COVID-19 patients in whom pulmonary embolism was suspected (and diagnosed) due to a discrepancy between an increase in D-dimer blood levels and a decrease in C-reactive protein blood levels over time. We believe that an opposite change in the blood levels of both biomarkers over time may be used as a novel method to predict pulmonary embolism in COVID-19 patients.

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

Thrombosis and Haemostasis ◽

10.1160/th03-03-0175 ◽

2003 ◽

Vol 90 (12) ◽

pp. 1198-1203 ◽

Cited By ~ 10

Author(s):

Daniel Hayoz ◽

Bertrand Yersin ◽

Arnaud Perrier ◽

Ghassan Barghouth ◽

Pierre Schnyder ◽

...

Keyword(s):

Pulmonary Embolism ◽

Clinical Judgment ◽

Prediction Rule ◽

Pulmonary Angiography ◽

Enzyme Linked Immunosorbent Assay ◽

Probability Assessment ◽

C Reactive Protein ◽

Reactive Protein ◽

Clinical Probability ◽

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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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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Cerebrovascular comorbidity, high blood levels of C - reactive protein and D-dimer are associated with disease outcomes in COVID-19 patients

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-201002 ◽

2020 ◽

pp. 1-12

Author(s):

Foad Alzoughool ◽

Lo’ai Alanagreh ◽

Suhad Abumweis ◽

Manar Atoum

Keyword(s):

Case Reports ◽

Meta Analysis ◽

Serum Levels ◽

Blood Levels ◽

C Reactive Protein ◽

Reactive Protein ◽

Cerebrovascular Complications ◽

Increased Risk ◽

Risk Of Disease ◽

D Dimer

The emerging coronavirus disease (COVID-19) swept the world, affecting more than 200 countries and territories. As of August 22, 2020, the pandemic infected more than 23,329,752 including 807,054 patients who have died. Although the main clinical features of the pandemic disease are respiratory, cerebrovascular comorbidities emerged as one of the leading causes of death associated with COVID-19. Different case reports have indicated that C-reactive protein (CRP) and D-dimer (pro-inflammatory biomarkers) were elevated in COVID-19 patients, which can significantly increase the risk of ischemic stroke. Available data on cerebrovascular complications in COVID-19 patients were collected and a meta-analysis was designed and carried out to evaluate the risk of severity and mortality associated with high levels of CRP and D-dimer levels in COVID-19 patients. In addition, we aimed to describe the overall event rate of pre-existing cerebrovascular disease in COVID-19 patients. In our analysis, 5,614 cases have been studied, out of these patients 164 cases have developed cerebrovascular comorbities. Cerebrovascular comorbidity increased the risk of disease severity (odd ratio = 4.4; 95% CI: 1.48 to 12.84) and mortality (odd ratio = 7.0; 95% CI: 2.56 to 18.99). Statistical analyses showed that CRP and D-dimer serum levels were elevated by six-folds in the severe cases of COVID-19 patients. This significant increase in these two proteins levels can serve as a vital indicator for COVID-19 patients who are at increased risk of severe COVID-19 cerebrovascular complications, such as stroke.

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Risk stratification of emergency department patients with chest pain using d-dimer and high-sensivity C-reactive protein

Annals of Emergency Medicine ◽

10.1016/j.annemergmed.2004.07.147 ◽

2004 ◽

Vol 44 (4) ◽

pp. S45

Author(s):

C.L. Chong ◽

M. Mahadevan

Keyword(s):

Emergency Department ◽

Chest Pain ◽

Risk Stratification ◽

C Reactive Protein ◽

Reactive Protein ◽

Emergency Department Patients ◽

D Dimer

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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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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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Challenges of Diagnosing Viral Myocarditis in Adolescents in the Era of COVID-19 and MIS-C

Case Reports in Pediatrics ◽

10.1155/2021/4797498 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Hemali P. Shah ◽

Richard Frye ◽

Sunny Chang ◽

Erin Faherty ◽

Jeremy Steele ◽

...

Keyword(s):

Myocardial Injury ◽

Viral Myocarditis ◽

Shortness Of Breath ◽

Chest Tightness ◽

C Reactive Protein ◽

Reactive Protein ◽

Erythrocyte Sedimentation ◽

Clinical Presentations ◽

Inflammatory Syndrome ◽

D Dimer

Myocarditis has a wide array of clinical presentations ranging from asymptomatic to sudden cardiac death. Pediatric myocarditis is a rare disease, with an estimated annual incidence of 1 to 2 per 100,000 children though its true prevalence remains unknown due to its variable and often subclinical presentation. The diagnosis of myocarditis is challenging in the era of COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C), which can have overlapping clinical conundrum. Here, we present a case of a 17-year-old male presenting with chest tightness, shortness of breath, and electrocardiogram (EKG) findings concerning for myocardial injury along with elevated inflammatory markers such as D-dimer, ESR (Erythrocyte Sedimentation Rate), and CRP (C-Reactive Protein). We discuss the key elements of our clinical experience with this case and review the literature for pediatric myocarditis, with a focus on differentiating it from MIS-C in the current COVID-19 pandemic era.

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