scholarly journals Biomarkers for the diagnosis of venous thromboembolism: D-dimer, thrombin generation, procoagulant phospholipid and soluble P-selectin

2018 ◽  
Vol 71 (11) ◽  
pp. 1015-1022 ◽  
Author(s):  
Nicoletta Riva ◽  
Kevin Vella ◽  
Kieron Hickey ◽  
Lorenza Bertù ◽  
Daniel Zammit ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Thrombin Generation ◽  
Diagnostic Algorithm ◽  
Pulmonary Angiography ◽  
Forest Plot ◽  
Clotting Time ◽  
Lung Scan ◽  
Soluble P ◽  
The Impact ◽  
D Dimer

BackgroundThe diagnostic algorithm for venous thromboembolism (VTE) currently involves a composite of pre-test probability, D-dimer and imaging. Other laboratory tests, however, may assist in the identification of patients with VTE.AimTo assess the accuracy of different coagulation tests (D-dimer, thrombin generation, phospholipid-dependent (PPL) clotting time, soluble P-selectin (sP-selectin)) as biomarkers of acute VTE.MethodsRandom samples arriving at the Coagulation Laboratory at Mater Dei Hospital (Msida, Malta) from the Accident and Emergency Department with a request for D-dimer measurement were collected between August 2015 and February 2016. The following tests were performed: Innovance D-dimer (Siemens Healthcare Diagnostics), HemosIL D-dimer HS (Instrumentation Laboratory), thrombin generation (using the calibrated automated thrombogram), STA Procoag PPL (Diagnostica Stago) and sP-selectin (Affymetrix; eBioscience). VTE was objectively confirmed by compression ultrasonography, CT pulmonary angiography or ventilation/perfusion lung scan.Results100 samples were collected (33 with VTE). A strong positive linear correlation was found between the two D-dimer tests (r=0.97, p<0.001). Patients with VTE showed significantly higher sP-selectin concentrations compared with patients without VTE (75.7 ng/mL vs 53.0 ng/mL, p<0.001). In the random forest plot, the two D-dimer assays showed the highest variable importance, followed by sP-selectin. A sP-selectin cut-off of 74.8 ng/mL was associated with 72.7% sensitivity and 78.2% specificity for acute VTE in our cohort.ConclusionOur results confirmed D-dimer as the main biomarker of VTE and speculated a role for sP-selectin. The impact of thrombin generation was limited and no role emerged for the PPL clotting time. These observations need to be confirmed in large management studies.

scholarly journals Advances in the Diagnosis of Venous Thromboembolism: A Literature Review

Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 365 ◽  
Author(s):  
Harish Patel ◽  
Haozhe Sun ◽  
Ali N. Hussain ◽  
Trupti Vakde
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Valsalva Maneuver ◽  
Imaging Modality ◽  
Diagnostic Algorithm ◽  
Pulmonary Angiography ◽  
Vein Thrombosis ◽  
Compression Ultrasound ◽  
Test Probability ◽  
D Dimer

The incidence of venous thromboembolism (VTE), including lower extremity deep vein thrombosis (DVT) and pulmonary embolism (PE) is increasing. The increase in suspicion for VTE has lowered the threshold for performing imaging studies to confirm diagnosis of VTE. However, only 20% of suspected cases have a confirmed diagnosis of VTE. Development of pulmonary embolism rule-out criteria (PERC) and update in pre-test probability have changed the paradigm of ruling-out patient with low index of suspicion. The D-dimer test in conjunction to the pre-test probability has been utilized in VTE diagnosis. The age appropriate D-dimer cutoff and inclusion of YEARS algorithm (signs of the DVT, hemoptysis and whether PE is the likely diagnosis) for the D-dimer cutoff have been recent updates in the evaluation of suspected PE. Multi-detector computed tomography pulmonary angiography (CTPA) and compression ultrasound (CUS) are the preferred imaging modality to diagnose PE and DVT respectively. The VTE diagnostic algorithm do differ in pregnant individuals. The prerequisite of avoiding excessive radiation has recruited planar ventilation-perfusion (V/Q) scan as preferred in pregnant patients to evaluate for PE. The modification of CUS protocol with addition of the Valsalva maneuver should be performed while evaluating DVT in pregnant individual.

The Use of a Rapid D-dimer Blood Test in the Diagnostic Workup for Pulmonary Embolism: A Management Study

1999 ◽  
Vol 82 (12) ◽  
pp. 1588-1592 ◽  
Author(s):  
Marinus van Marwijk Kooy ◽  
Jos Pouwels ◽  
Anneke Engelage ◽  
Bart Kuipers ◽  
Harry Büller ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Diagnostic Algorithm ◽  
Venous Thromboembolic Event ◽  
Pulmonary Angiography ◽  
Normal Lung ◽  
Management Study ◽  
Clinical Probability ◽  
Lung Scan ◽  
Test Result ◽  
D Dimer

Summary Background. D-dimer assays have a potential to rule out pulmonary embolism in case of a normal test result. We studied the clinical utility of incorporating the SimpliRED D-dimer test result and clinical probability in the routine diagnostic work-up of patients with suspected acute pulmonary embolism. Methods. In a prospective management study 245 consecutive patients, hospitalised as well as outpatients, were included. A SimpliRED D-dimer test and perfusion/(ventilation) scintigraphy were obtained in all patients, whereas clinical probability was determined in the subgroup of patients with a non-diagnostic scan and normal D-dimer result. A diagnostic algorithm determined the necessity for further testing and decisions about treatment. All patients were followed up for 3 months. Results. In 54 patients (22%) with a normal lung scan and 50 patients (21%) with a high probability lung scan, antithrombotic therapy was withheld or started respectively, irrespective of the D-dimer result. A non-diagnostic lung scan was found in 137 (56%) patients, of whom 70 patients had an abnormal D-dimer test, in whom further testing was ordered. Of the remaining 67 patients with a non-diagnostic lung scan and normal D-dimer test 8 patients had a high clinical probability, and the subsequent ultrasonography and pulmonary angiography yielded pulmonary emboli in 1 patient. In the remaining 66 patients, pulmonary embolism was considered to be absent and antithrombotic treatment was stopped/withheld. During follow-up of these patients only one patient experienced a possible venous thromboembolic event (failure rate 1,5% ; 95% CI 0-8%). The SimpliRED D-dimer was normal in 6 of 61 patients with proven pulmonary embolism (sensitivity 90% ; 95% CI 80-96%). Conclusion. Our findings suggest that it is safe to withhold anticoagulant therapy in those patients with a non-diagnostic lung scan, a normal SimpliRED D-dimer test result, and without a high clinical probability. This results in a substantial decreased need for ultrasonography and pulmonary angiography. The SimpliRED should not be used in isolation to exclude pulmonary embolism.

D-Dimer and Thrombin-Antithrombin III Complexes in Patients with Clinically Suspected Pulmonary Embolism

1992 ◽  
Vol 67 (04) ◽  
pp. 408-412 ◽  
Author(s):  
Christine Demers ◽  
Jeffrey S Ginsberg ◽  
Marilyn Johnston ◽  
Patrick Brill-Edwards ◽  
Akbar Panju
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
High Probability ◽  
Pulmonary Angiography ◽  
Normal Lung ◽  
Suspected Pulmonary Embolism ◽  
Predictive Values ◽  
Lung Scan ◽  
D Dimer

SummaryOne hundred and fifty-six consecutive patients with clinically suspected pulmonary embolism (PE) had blood drawn to measure levels of D-dimer and thrombin-antithrombin (TAT) complexes and underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance plethysmography (IPG); pulmonary angiography was performed in 10 patients. Patients were classified as: PE-positive (positive pulmonary angiography or high probability lung scan or non-high probability lung scan and abnormal IPG) or, PE-negative (normal lung scan or normal pulmonary angiography) or PE-unlikely (non-high probability lung scan and normal serial IPG and absence of venous thromboembolism in follow-up). Thirty patients were classified as PE-positive, 64 as PE-negative and 62 patients as PE-unlikely. PE-positive patients were treated with anticoagulants, whereas PE-negative and PE-unlikely patients were not. PE-unlikely patients were followed for 3 months with repeat IPG and clinical evaluation for the occurrence of venous thromboembolism. The sensitivities, specificities, positive predictive values and negative predictive values of the D-dimer and TAT complex assays were calculated for patients classified as PE-positive and PE-negative. In addition, the prevalences of normal D-dimer and TAT complex assays were calculated for PE-unlikely patients.Cutoffs of 300 ng/ml for D-dimer and 3.5 μg/ml for TAT complexes provided sensitivities of 96% for both assays, negative predictive values of 97% for D-dimer and 96% for TAT complexes and specificities of 52% for D-dimer and 51% for TAT complexes. The specificities of the assays were higher in patients without comorbid conditions and in outpatients. Among PE-unlikely patients, 14 had normal D-dimer levels and 5 had normal levels of TAT complexes. None of these patients developed venous thromboembolism in follow-up.Our study indicates that: 1) PE is highly unlikely in patients who have D-dimer levels of less than 300 ng/ml and/or levels of TAT complexes below 3.5 μg/ml, and 2), because of their relatively low positive predictive values, further investigation is required if levels of D-dimer and/or TAT complexes are above these cutoffs. These results should be confirmed in future clinical management trials.

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

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.

Risk factors for venous thromboembolism in patients with diabetes undergoing joint arthroplasty

2020 ◽  
Author(s):  
Wei Deng ◽  
Lili Huo ◽  
Qiang Yuan ◽  
Deyong Huang ◽  
Quan Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Protective Role ◽  
Pulmonary Angiography ◽  
Joint Arthroplasty ◽  
Multivariate Logistic Regression Model ◽  
Mechanical Prophylaxis ◽  
Patients With Diabetes ◽  
High Level ◽  
D Dimer

Abstract Background: Venous thromboembolism (VTE) is a significant complication after joint arthroplasty. Diabetes is related to a few changes in coagulation and fibrinolysis that may lead to thrombophilia. We aim to investigate the incidence of and risk factors for VTEs in patients with diabetes undergoing total hip (THA) or total knee anthroplasty (TKA) in a single centre in China. Methods: Patients with diabetes who underwent THA or TKA from January 2016 to December 2018 (n=400) at Beijing Jishuitan Hospital were recruited in this study. Lower limb venous Doppler ultrasound was performed before and after surgery to confirm deep venous thrombosis (DVT). Computer tomography pulmonary angiography was done to confirm pulmonary embolism (PE) for those with new postoperative DVT and typical symptoms of PE. A multivariate logistic regression model was conducted to examine factors associated with the development of postoperative VTE. Results: The overall incidence of postoperative VTE in patients with diabetes after THA or TKA was 46.8% (187 of 400). Female patients and patients undergoing TKA had higher incidence of postoperative VTE. Patients who developed postoperative VTE were older, and had higher levels of preoperative D-Dimer level and Caprini score. Increased VTE risks were associated with high level of preoperative D-Dimer (OR=2.11, 95%CI=1.35-3.30) and TKA (OR=2.29, 95%CI=1.29-4.01). Postoperative initiation of concomitant mechanical prophylaxis and low molecular weight heparin (LMWH) was protective for postoperative DVT (OR=0.56, 95%CI=0.37-0.86). Conclusions: VTE is common in patients with diabetes undergoing joint arthroplasty. Patients undergoing TKA or with a high level of preoperative D-Dimer are at a considerable risk of developing postoperative VTE. There may be a protective role of postoperative initiation of concomitant mechanical prophylaxis and LMWH for VTE.

scholarly journals Validation and impact of a simplified clinical decision rule for diagnosing pulmonary embolism in primary care: design of the PECAN prospective diagnostic cohort management study

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e031639 ◽  
Author(s):  
Rosanne van Maanen ◽  
Frans H Rutten ◽  
Frederikus A Klok ◽  
Menno V Huisman ◽  
Jeanet W Blom ◽  
...  
Keyword(s):  
Primary Care ◽  
Pulmonary Embolism ◽  
False Negative ◽  
Diagnostic Algorithm ◽  
Clinical Decision ◽  
Final Diagnosis ◽  
Hospital Environment ◽  
Diagnostic Study ◽  
The Impact ◽  
D Dimer

IntroductionCombined with patient history and physical examination, a negative D-dimer can safely rule-out pulmonary embolism (PE). However, the D-dimer test is frequently false positive, leading to many (with hindsight) ‘unneeded’ referrals to secondary care. Recently, the novel YEARS algorithm, incorporating flexible D-dimer thresholds depending on pretest risk, was developed and validated, showing its ability to safely exclude PE in the hospital environment. Importantly, this was accompanied with 14% fewer computed tomographic pulmonary angiography than the standard, fixed D-dimer threshold. Although promising, in primary care this algorithm has not been validated yet.Methods and analysisThe PECAN (DiagnosingPulmonaryEmbolism in the context ofCommonAlternative diagNoses in primary care) study is a prospective diagnostic study performed in Dutch primary care. Included patients with suspected acute PE will be managed by their general practitioner according to the YEARS diagnostic algorithm and followed up in primary care for 3 months to establish the final diagnosis. To study the impact of the use of the YEARS algorithm, the primary endpoints are the safety and efficiency of the YEARS algorithm in primary care. Safety is defined as the proportion of false-negative test results in those not referred. Efficiency denotes the proportion of patients classified in this non-referred category. Additionally, we quantify whether C reactive protein measurement has added diagnostic value to the YEARS algorithm, using multivariable logistic and polytomous regression modelling. Furthermore, we will investigate which factors contribute to the subjective YEARS item ‘PE most likely diagnosis’.Ethics and disseminationThe study protocol was approved by the Medical Ethical Committee Utrecht, the Netherlands. Patients eligible for inclusion will be asked for their consent. Results will be disseminated by publication in peer-reviewed journals and presented at (inter)national meetings and congresses.Trial registrationNTR 7431.

Prothrombotic State Induced by Middle-Distance Endurance Exercise in Middle-Aged Athletes

2018 ◽  
Vol 44 (08) ◽  
pp. 747-755 ◽  
Author(s):  
Gian Salvagno ◽  
Cantor Tarperi ◽  
Matteo Gelati ◽  
Martina Montagnana ◽  
Elisa Danese ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Blood Group ◽  
Thrombin Generation ◽  
Area Under The Curve ◽  
Abo Blood Group ◽  
Middle Aged ◽  
Endurance Running ◽  
Von Willebrand ◽  
The Impact ◽  
D Dimer

AbstractSince the impact of possible prothrombotic factors on blood coagulation resulting from exercise remains elusive, this study investigated the acute effects of middle-distance endurance running on blood coagulation parameters in middle-aged athletes. The study population consisted of 33 male endurance runners who were engaged in a 21.1 km run under competitive conditions. Blood samples were collected before the run, immediately after the run, and 3 hours after run completion. Samples were assessed for activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, D-dimer, factor VIII (FVIII), von Willebrand factor antigen (VWF:Ag), endogenous thrombin potential (area under the curve of thrombin generation [TGA-AUC]), and peak thrombin generation (TGA-PK). Post-run variations were expressed as delta (Δ). At baseline, APTT was found to be significantly associated with ABO blood group, VWF:Ag, and FVIII; fibrinogen with age; VWF:Ag with BMI, training regimen, and ABO blood group; APTT with FVIII; FVIII with VWF:Ag and ABO blood group; APTT with VWF:Ag; and TGA-PK with ABO blood group, PT, and TGA-AUC. Immediately after the run, statistically significant increases were observed for PT, D-dimer, VWF:Ag, and FVIII, while statistically significant reductions could be observed for APTT, TGA-AUC, and TGA-PK. Fibrinogen values remained unchanged. Significant correlations were observed between Δ VWF:Ag and Δ FVIII, Δ APTT and Δ VWF:Ag, Δ APTT and Δ FVIII, Δ TGA-AUC and Δ TGA-PK, and between Δ D-dimer and Δ TGA-AUC and Δ TGA-PK. No Δ variation was associated with running time. The results of this study seemingly suggest that middle-distance competitive running may evoke several prothrombotic changes in blood coagulation.

scholarly journals Highly Elevated Quantitative D-Dimer Assay Values Increase the Likelihood of Venous Thromboembolism

TH Open ◽  
2019 ◽  
Vol 03 (01) ◽  
pp. e2-e9 ◽  
Author(s):  
Samuel Francis ◽  
Alexander Limkakeng ◽  
Hui Zheng ◽  
Judd Hollander ◽  
Gregory Fermann ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Prospective Observational Study ◽  
Secondary Analysis ◽  
Pulmonary Angiography ◽  
Ct Pulmonary Angiography ◽  
Vein Thrombosis ◽  
Ultrasound Computed Tomography ◽  
Deep Vein ◽  
Work Up ◽  
D Dimer

Objectives In patients with suspected venous thromboembolism (VTE), the D-dimer assay is commonly utilized as part of the workup. The assay is primarily used to determine whether to proceed with radiographic imaging. We compared D-dimer levels in patients suspected of having VTE. We hypothesized that higher D-dimer values predict a higher likelihood of subsequent VTE diagnosis. Methods We conducted a secondary analysis of a multinational, prospective observational study of low- to intermediate-risk adult patients presenting to the emergency department with suspicion of VTE. Demographic and clinical data were collected in a structured manner. Advanced imaging including ultrasound, computed tomography (CT) pulmonary angiography, and ventilation/perfusion scanning was obtained at the discretion of the treating physicians. Imaging was evaluated by board-certified radiologists in real time. D-dimer values' bins were evaluated using a logistic regression model. Results We evaluated 1,752 patients for suspected deep vein thrombosis (DVT), with 191 (10.4%) DVT positive. We evaluated 1,834 patients for suspected pulmonary embolism (PE), with 108 (5.9%) PE positive. Higher D-dimer values in both groups were associated with higher likelihood of subsequent VTE diagnosis, with D-dimer values > 3,999 ng/mL in both groups having the highest incidence of VTE. More than 50% of those patients were VTE positive. Conclusions Increasing D-dimer values predict increased likelihood of being found VTE positive in this patient population. Among those in the highest D-dimer category, > 3,999 ng/mL, over half of patients were VTE positive. Further research could determine additional nuance in D-dimer as a tool to work up suspected VTE.

Performance of a diagnostic algorithm based on a prediction rule, D-dimer and CT-scan for pulmonary embolism in patients with previous venous thromboembolism

2015 ◽  
Vol 113 (02) ◽  
pp. 406-413 ◽  
Author(s):  
Paul L. den Exter ◽  
Inge C. M. Mos ◽  
Menno V. Huisman ◽  
Frederikus A. Klok ◽  
Maria José Fabiá Valls ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Random Effect ◽  
Prediction Rule ◽  
Diagnostic Algorithm ◽  
Clinical Prediction Rule ◽  
Incidence Rates ◽  
Specific Patient ◽  
History Of ◽  
D Dimer

SummaryDiagnostic management of suspected pulmonary embolism (PE) in patients with a history of venous thromboembolism (VTE) is complicateddue to persistent abnormal D-dimer levels, residual embolic obstruction and higher clinical prediction rule (CPR) scores. We aimed to evaluate the safety and efficiency of the standard diagnostic algorithm consisting of a CPR, D-dimer test and computed tomography pulmonary angiography (CTPA) in this specific patient category. We performed a systematic literature search for prospective studies evaluating a diagnostic algorithm in consecutive patients with clinically suspected PE and a history of VTE. The VTE incidence rates during three-month follow-up and the number of indicated CTPAs were pooled using random effect models. Four studies concerning 1,286 patients were included with a pooled baseline PE prevalence of 36 % (95 % confidence interval [CI] 30–42). In only 217 patients (15 %; 95 %CI 11–20) PE could be excluded without CTPA. The three-month VTE incidence rate was 0.8 % (95 %CI 0.06–2.4) in patients managed without CTPA, 1.6 % (95 %CI 0.3–4.0) in patients in whom PE was excluded by CTPA and 1.4 % (95 %CI 0.6–2.7) overall. In the pooled studies, PE was safely excluded in patients with a history of VTE based on a CPR followed by a D-dimer test and/or CTPA, although the efficiency of the algorithm is relatively low compared to patients without a history of VTE.

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