Soluble P-Selectin and Age Adjusted D-Dimer As Predictive Biomarkers of Venous Thrombosis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2863-2863
Author(s):  
Dana E Angelini ◽  
Cathy Stabler ◽  
Angela E. Hawley ◽  
Kenneth E. Guire ◽  
Daniel Durant Myers ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Predictive Value ◽  
Duplex Ultrasound ◽  
The Elderly ◽  
Probability Score ◽  
Clinical Probability ◽  
Wells Score ◽  
History Of ◽  
D Dimer ◽  
Rule Out

Abstract Introduction: Accurate and rapid diagnosis is essential in acute venous thromboembolism (VTE) to help prevent significant morbidity and mortality. Soluble P-selectin (sP-sel) is a cell surface ligand that aids in cell adhesion. It is released from activated platelets and damaged endothelial cells resulting in release of procoagulant molecules from leukocytes and aiding in thrombus generation. Our lab has previously shown elevated sP-sel is highly predictive of VTE in combination with clinical probability (Wells score). Current standards for ruling out VTE include combining Wells Score and plasma D-dimer; however, D-dimer increases with age and is less useful in the elderly. Age adjusted D-dimer, defined as 10*age in patients ≥50 years old, has been described as being more sensitive, which could rule out more clots in the elderly, sparing them from other diagnostic tests. Methods: We performed a prospective cohort study of patients ≥18 years old who presented with symptoms of deep venous thrombosis (DVT) in upper or lower extremities from December 2008 to July 2013. Exclusion criteria included isolated calf DVT, superficial thrombosis, indeterminate duplex scans, pregnancy or nursing mothers, therapeutic anticoagulation, and symptoms of simultaneous upper and lower extremity (LE) clot. After informed consent was obtained, biomarkers were drawn and duplex ultrasound was used to confirm or deny presence of acute clot. Our objective was to examine the accuracy of biomarker combinations and clinical probability score to rule in or rule out acute venous thrombus. Results: We recruited 461 patients to the study. Patients with positive lower extremity DVT were significantly more likely to be male, have a prior history of DVT, have active cancer or history of cancer, and be inpatient. Table 1: Biomarkers and Clinical Probability Score of Patients Presenting with Symptoms of LE DVT Table 1:. Biomarkers and Clinical Probability Score of Patients Presenting with Symptoms of LE DVT There were no significant differences in biomarkers between upper and lower extremity VTE aside from non-significance of sP-sel in upper extremity clots. We calculated the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of several combinations of biomarkers and clinical probability assessment. Table 2: Specificity and PPV Table 2:. Specificity and PPV Table 3: Sensitivity and NPV Table 3:. Sensitivity and NPV Using the age adjusted D-dimer did not improve the overall sensitivity when compared to the traditional cut off. However, sub-analysis demonstrated using D-dimer <500 ng/mL in those ≥ 50 ruled out 35 patients while the age adjusted D-dimer ruled out an additional 17 patients (12% increase). An additional 10% of patients ≥60 years were ruled out using the age adjusted D-dimer alone; this benefit rose to 15% in patients ≥70 years old. Use of the age adjusted D-dimer did not increase false negative results. Conclusions: We found Wells ≥ 2 and sP-sel ≥ 90 ng/mL had the highest specificity of any combination of biomarkers, highlighting its clinical utility as a predictive biomarker of thrombosis. Using this combination would allow clinicians to accurately rule in venous thrombus without need for further imaging. In this study, we would have successfully identified 48 (25%) patients with acute thrombus without duplex ultrasound. Compared to the traditional cut off value, age adjusted D-dimer did not increase sensitivity in those >age 50, but its utility increased with age, making it a promising biomarker to safely rule out thrombosis in the elderly. Disclosures No relevant conflicts of interest to declare.

Performance of five D-dimer assays for the exclusion of symptomatic distal leg vein thrombosis

2012 ◽  
Vol 107 (02) ◽  
pp. 369-378 ◽  
Author(s):  
Jan Schwonberg ◽  
Carola Hecking ◽  
Marc Schindewolf ◽  
Dimitrios Zgouras ◽  
Susanne Lehmeyer ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Diagnostic Value ◽  
Vein Thrombosis ◽  
Clinical Probability ◽  
Wells Score ◽  
Deep Vein ◽  
Test Result ◽  
D Dimer ◽  
Rule Out ◽  
Compression Ultrasonography

SummaryThe diagnostic value of D-dimer (DD) in the exclusion of proximal deep-vein thrombosis (DVT) is well-established but is less well-known in the exclusion of distal (infrapopliteal) DVT. Therefore, we evaluated the diagnostic abilities of five DD assays (Vidas-DD, Liatest-DD, HemosIL-DD, HemosIL-DDHS, Innovance-DD) for excluding symptomatic proximal and distal leg DVT. A total of 243 outpatients whose symptoms were suggestive of DVT received complete compression ultrasonography (cCUS) of the symptomatic leg(s). The clinical probability of DVT (PTP) was assessed by Wells score. Thirty-eight proximal and 31 distal DVTs (17 tibial/fibular DVTs, 14 muscle DVTs) were diagnosed by cCUS. Although all assays showed high sensitivity for proximal DVT (range 97–100%), the sensitivity was poor for distal DVT (range 78–93%). None of the assays were individually able to rule out all DVTs as a stand-alone test (negative predictive value [NPV] 91–96%). However, a negative DD test result combined with a low PTP exhibited a NPV of 100% for all DVTs (including proximal, tibial/fibular, and muscle DVTs) with the HemosIL-DDHS and Innovance-DD. All proximal and tibial/fibular DVTs, but not all muscle DVTs, could be ruled out with this strategy using the Liatest-DD and Vidas-DD. The HemosIL-DD could not exclude distal leg DVT, even in combination with a low PTP. The combination of a negative DD with a low PTP showed a specificity of 32–35% for all DVTs. In conclusion, our study shows that when used in conjunction with a low PTP some DD assays are useful tools for the exclusion of distal leg DVT.

scholarly journals Prediction of cerebral venous thrombosis with a new clinical score and D-dimer levels

Neurology ◽  
2020 ◽  
Vol 95 (7) ◽  
pp. e898-e909
Author(s):  
Mirjam R. Heldner ◽  
Susanna M. Zuurbier ◽  
Bojun Li ◽  
Rascha Von Martial ◽  
Joost C.M. Meijers ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Predictive Value ◽  
Cerebral Venous Thrombosis ◽  
Area Under The Curve ◽  
Clinical Score ◽  
Duration Of Symptoms ◽  
Clinical Variables ◽  
Probability Score ◽  
Clinical Probability ◽  
D Dimer

ObjectiveTo investigate prediction of cerebral venous thrombosis (CVT) by clinical variables and D-dimer levels.MethodsThis prospective multicenter study included consecutive patients with clinically possible CVT. On admission, patients underwent clinical examination, blood sampling for D-dimers measuring (ELISA test), and magnetic resonance/CT venography. Predictive value of clinical variables and D-dimers for CVT was calculated. A clinical score to stratify patients into groups with low, moderate, or high CVT risk was established with multivariate logistic regression.ResultsCVT was confirmed in 26.2% (94 of 359) of patients by neuroimaging. The optimal estimate of clinical probability was based on 6 variables: seizure(s) at presentation (4 points), known thrombophilia (4 points), oral contraception (2 points), duration of symptoms >6 days (2 points), worst headache ever (1 point), and focal neurologic deficit at presentation (1 point) (area under the curve [AUC] 0.889). We defined 0 to 2 points as low CVT probability (negative predictive value [NPV] 94.1%). Of the 186 (51.8%) patients who had a low probability score, 11 (5.9%) had CVT. The frequency of CVT was 28.3% (34 of 120) in patients with a moderate (3–5 points) and 92.5% (49 of 53) in patients with a high (6–12 points) probability score. All low CVT probability patients with CVT had D-dimers >500 μg/L. Predictive value of D-dimers for CVT for >675 μg/L (best cutoff) vs >500 μg/L was as follows: sensitivity 77.7%, specificity, 77%, NPV 90.7%, and accuracy 77.2% vs sensitivity 89.4%, specificity 66.4%, NPV 94.6%, and accuracy 72.4%, respectively. Adding the clinical score to D-dimers >500 μg/L resulted in the best CVT prediction score explored (at the cutoff ≥6 points: sensitivity 83%/specificity 86.8%/NPV 93.5%/accuracy 84.4%/AUC 0.937).ConclusionThe proposed new clinical score in combination with D-dimers may be helpful for predicting CVT as a pretest score; none of the patients with CVT showed low clinical probability for CVT and D-dimers <500 μg/L.ClinicalTrials.gov identifierNCT00924859.

scholarly journals Wells’ Score in Diagnosis of Pulmonary Embolism in Patient with Thrombocytopenia: A Case Report

2019 ◽  
Vol 20 (3) ◽  
pp. 281-285
Author(s):  
Dragan Panic ◽  
Andreja Todorovic ◽  
Milica Stanojevic ◽  
Violeta Iric Cupic
Keyword(s):  
Pulmonary Embolism ◽  
Chest Pain ◽  
Acute Pulmonary Embolism ◽  
Pretest Probability ◽  
Clinical Prediction ◽  
Clinical Prediction Rules ◽  
Prediction Rules ◽  
Clinical Probability ◽  
Wells Score ◽  
D Dimer

Abstract Current diagnostic workup of patients with suspected acute pulmonary embolism (PE) usually starts with the assessment of clinical pretest probability, using clinical prediction rules and plasma D-dimer measurement. Although an accurate diagnosis of acute pulmonary embolism (PE) in patients is thus of crucial importance, the diagnostic management of suspected PE is still challenging. A 60-year-old man with chest pain and expectoration of blood was admitted to the Department of Cardiology, General Hospital in Cuprija, Serbia. After physical examination and laboratory analyses, the diagnosis of Right side pleuropne monia and acute pulmonary embolism was established. Clinically, patient was hemodynamically stable, auscultative slightly weaker respiratory sound right basal, without pretibial edema. Laboratory: C-reactive protein (CRP) 132.9 mg/L, Leukocytes (Le) 18.9x109/L, Erythrocytes (Er) 3.23x1012/L, Haemoglobin (Hgb) 113 g/L, Platelets (Plt) 79x109/L, D-dimer 35.2. On the third day after admission, D-dimer was increased and platelet count was decreased (Plt up to 62x109/L). According to Wells’ rules, score was 2.5 (without symptoms on admission), a normal clinical finding with clinical manifestation of hemoptysis and chest pain, which represents the intermediate level of clinical probability of PE. After the recidive of PE, Wells’ score was 6.5. In summary, this study suggests that Wells’ score, based on a patient’s risk for pulmonary embolism, is a valuable guidance for decision-making in combination with knowledge and experience of clinicians. Clinicians should use validated clinical prediction rules to estimate pretest probability in patients in whom acute PE is being consiered.

Repeat duplex ultrasound scanning in suspected Deep Vein Thrombosis (DVT): putting the onus back on the referring clinician

2016 ◽  
Vol 15 (2) ◽  
pp. 63-67
Author(s):  
Bryan Renton ◽  
S Thiru ◽  
CP Griffin
Keyword(s):  
Deep Vein Thrombosis ◽  
Duplex Ultrasound ◽  
Ultrasound Scanning ◽  
Nice Guideline ◽  
Vein Thrombosis ◽  
Dramatic Rise ◽  
Wells Score ◽  
Deep Vein ◽  
Repeat Scanning ◽  
D Dimer

Duplex scanning is utilised by many departments in the investigation of suspected Deep Vein Thrombosis (DVT). NICE Guideline CG144 recommended repeat scanning for patients in whom the initial Wells score was ‘likely’ in the presence of a raised D-Dimer, following a normal first scan. Following implementation of this recommendation in our department there was a dramatic rise in the number of repeat scans being undertaken, all of which were negative for DVT. Introduction of an electronic message to the report, placing the onus back on the referring clinician to arrange repeat scan if deemed appropriate resulted in a fall in the number of scans being undertaken without impacting on patient outcome.

Pulmonary embolism in Bujumbura

2021 ◽  
Vol 25 (4) ◽  
pp. 298-305
Author(s):  
Eugène Ndirahisha ◽  
Thierry Sibomana ◽  
Joseph Nyandwi ◽  
Ramadhan Nyandwi ◽  
Sébastien Manirakiza ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Past History ◽  
Personal Data ◽  
Minor Bleeding ◽  
Short Term ◽  
Clinical Probability ◽  
Medical Associations ◽  
Venous Thromboembolic ◽  
Wells Score ◽  
History Of

Relevance . Pulmonary embolism constitutes a diagnostic and therapeutic emergency. In Africa, data are still difficult to obtain. Thus, the objectives of this work is to describe epidemiological, clinical, therapeutic aspects and short-term outcomes of pulmonary embolism confirmed by thoracic angioscan at Kira hospital in Bujumbura, the biggest city of Burundi with population about 375 000. Patients and Methods . This was a descriptive study of 18 patients who had a pulmonary embolism confirmed by thoracic angioscan in Bujumbura from January 1st, 2015 to December 31st, 2018. We included in our study any patient with pulmonary embolism consenting to participate and processing personal data after some clarified explanations in accordance with the World Medical Associations Declaration of Helsinki. For each registered patient, we collected socio-demographic, past history of cardiac disease and factors risk, clinical, echocardiographic and scannographic findings with Wells score. Variables were presented as means and percentages. Results and Discussion. The average age was 53.5 12.3 years with a sex ratio of 1.25 in favor of women. The modal class was the 50 to 59 age group (33.3%). The clinical probability pre-test by simplified Wells score was high in 66.6% and medium in 33.3% of cases. A history of venous thromboembolic disease was the most common risk factor. Dyspnea was the most reason of consultation with 94.4% of cases. One patient died (5.6%) during hospitalization. Six months after discharge from the hospital, we recorded 3 cases (16.7%) of death, 6 cases (33.3%) of pulmonary heart, 3 cases (16.7%) of recurrent pulmonary embolism and one case of vitamin K antagonist overdose with minor bleeding. Conclusion. Pulmonary embolism is common in relatively young population with a predominance of females and chronic no communicable diseases as risk factors. Examination of a patient with an angioscanner is a sensitive and specific clinical study of pulmonary embolism. The outcome is favorable under appropriate treatment in short term.

scholarly journals Serum D-dimer should not be used in the diagnosis of venous thromboembolism within 28 days of total knee replacement surgery

2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Ethan Toner ◽  
Tobenna Oputa ◽  
Heather Robinson ◽  
Olivia McCabe-Robinson ◽  
Andrew Sloan
Keyword(s):  
Venous Thromboembolism ◽  
Total Knee Replacement ◽  
Positive Predictive Value ◽  
Positive Result ◽  
Knee Replacement ◽  
Predictive Value ◽  
Replacement Surgery ◽  
Total Knee ◽  
D Dimer ◽  
Rule Out

Abstract Background Serum D-dimer is frequently used to rule out a diagnosis of venous thromboembolism (VTE), a recognised complication following total knee replacement (TKR). TKR is known to cause a rise in D-dimer levels, reducing its specificity. Previous studies have demonstrated that D-dimer remains elevated within 10 days of TKR and therefore should be avoided. The aim of this study was to determine whether serum D-dimer tests are clinically appropriate in identifying VTE when performed within 28 days of TKR. Methods Case notes for patients who had a serum D-dimer test performed for clinically suspected VTE at ≥ 28 days following TKR were retrospectively reviewed for a 6-year period. Demographics, D-dimer result, time after surgery and further radiological investigations were recorded. Results Fifty patients underwent D-dimer tests at ≥ 28 days following surgery (median 60 days, range 29–266); 48 of these patients had a positive result. Of these, five had confirmed VTE on radiological investigations. Serum D-dimer was raised in 96% of the patients. Only 10.42% of these patients had confirmed VTE. No patients with negative D-dimers had confirmed VTE. Conclusions These findings suggest that serum D-dimer remains raised for at least 28 days and possibly considerably longer following TKR. Serum D-dimer should not be used in patients with clinically suspected VTE within this period because of its unacceptably low specificity of 4.44% and positive predictive value of 10.42%, which can lead to a delay in necessary further radiological investigations, waste of resources and unnecessary exposure to harm.

scholarly journals P001: Age-adjusted D-dimer and two-site compression point of care ultrasonography to rule out acute deep vein thrombosis - a pilot study

CJEM ◽  
2018 ◽  
Vol 20 (S1) ◽  
pp. S57-S57
Author(s):  
K. Alqaydi ◽  
J. Turner ◽  
L. Robichaud ◽  
D. Hamad ◽  
X. Xue ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Point Of Care ◽  
Screening Tools ◽  
Duplex Scan ◽  
Vein Thrombosis ◽  
Wells Score ◽  
Deep Vein ◽  
D Dimer ◽  
Rule Out

Introduction: Deep vein thrombosis (DVT) can lead to significant morbidity and mortality if not diagnosed and treated promptly. Currently, few methods aside from venous duplex scanning can rule out DVT in patients presenting to the Emergency Department (ED). Current screening tools, including the use of the subjective Wells score, frequently leads to unnecessary investigations and anticoagulation. In this study, we sought to determine whether two-site compression point-of-care ultrasound (POCUS) combined with a negative age-adjusted D-dimer test can accurately rule out DVT in ED patients irrespective of the modified Wells score. Methods: This is a single-center, prospective observational study in the ED of the Jewish General Hospital in Montreal. We are recruiting a convenience sample of patients presenting to the ED with symptoms suggestive of DVT. All enrolled patients are risk-stratified using the modified Wells criteria for DVT, then undergo two-site compression POCUS, and testing for age-adjusted D-dimer. Patients with DVT unlikely according to modified Wells score, negative POCUS and negative age-adjusted D-dimer are discharged home and receive a three-month phone follow-up. Patients with DVT likely according to modified Wells score, a positive POCUS or a positive age-adjusted D-dimer, will undergo a venous duplex scan. A true negative DVT is defined as either a negative venous duplex scan or a negative follow-up phone questionnaire for patients who were sent home without a venous duplex scan. Results: Of the 42 patients recruited thus far, the mean age is 56 years old and 42.8% are male. Twelve (28.6%) patients had DVT unlikely as per modified Wells score, negative POCUS and negative age-adjusted D-dimer and were discharged home. None of these patients developed a DVT on three-month follow-up. Thirty patients (71.4%) had either a DVT likely as per modified Wells score, a positive POCUS or a positive age-adjusted D-dimer and underwent a venous duplex scan. Of those, six patients had a confirmed DVT (3 proximal & 3 distal). POCUS detected all proximal DVTs, while combined POCUS and age-adjusted D-dimer detected all proximal and distal DVTs. None of the patients with a negative POCUS and age-adjusted D-dimer were found to have a DVT. Conclusion: Two-site compression POCUS combined with a negative age-adjusted D-dimer test appears to accurately rule out DVT in ED patients without the need for follow-up duplex venous scan. Using this approach would alleviate the need to calculate the Wells score, and also reduce the need for radiology-performed duplex venous scan for many patients.

scholarly journals LO55: Comparison of the age-adjusted D-dimer, clinical probability-adjusted D-dimer, and Wells rule with D-dimer for diagnosing deep vein thrombosis in the emergency department.

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S27-S27
Author(s):  
S. Sharif ◽  
C. Kearon ◽  
M. Eventov ◽  
P. Sneath ◽  
M. Li ◽  
...  
Keyword(s):  
False Negative ◽  
False Negative Rate ◽  
Duplex Ultrasonography ◽  
Vein Thrombosis ◽  
Clinical Probability ◽  
Negative Rate ◽  
Wells Score ◽  
Wells Rule ◽  
Deep Vein ◽  
D Dimer

Introduction: Diagnosing deep vein thrombosis (DVT) is of critical importance because of its associated morbidity and mortality. Diagnosing DVT can be challenging in the Emergency Department (ED) due to inconsistent adherence to, and utilization of the Wells rule. Both the age-adjusted and clinical probability adjusted D-dimer have been shown to decrease ultrasound (US) utilization rates. We aimed to compare the safety and efficacy of the Wells score with D-dimer to the age-adjusted and clinical probability-adjusted D-dimer in Canadian ED patients tested for DVT. Methods: This was a health records review of ED patients investigated for DVT at two EDs over a two-year period. Inclusion criteria were ED physician ordered duplex ultrasonography or D-dimer for investigation of lower limb DVT. Patients under the age of 18 were excluded. DVT was considered to be present during the ED visit if DVT was diagnosed on duplex ultrasonography and was treated for acute DVT, or if the patient was subsequently diagnosed with pulmonary embolism (PE) or DVT during the next 30 days. Trained researchers extracted anonymized data. The Wells D-dimer, age-adjusted D-dimer, and the clinical probability-adjusted D-dimer rules were applied retrospectively. The rate of duplex ultrasonography imaging and the false negative rate was calculated for each rule. Results: Between April 1st 2013 and March 31st 2015, there were 1,198 patients tested for DVT. Of the low and moderate clinical pretest probability patients (Wells score ≤ 2), only 436 had a D-Dimer test and were eligible for our analysis. The average age of the patients was 59, 56% were female, and 4% had a malignancy. 207/436 patients (47.4%, 95%CI 42.8-52.2%) would have had US imaging for DVT if the age-adjusted D-dimer rule was used. 214/436 patients (49.1%, 95%CI 44.4-53.8%) would have had imaging for DVT if the clinical probability-adjusted D-dimer was used. If the Wells rule was used with the standard D-dimer cutoff of 500, 241/436 patients (55.2%, 95%CI 50.6-59.9%) would have had imaging for DVT. The false-negative rate for the Wells rule was 1.5% (95%CI 0.5-4.4%). The false-negative rate for the age-adjusted D-dimer rule was 1.3% (95%CI 0.4-3.8%). The false-negative rate for the clinical-probability adjusted D-Dimer was 1.8% (95%CI 0.7-4.5%). Conclusion: In comparison with the approach of the Wells score and D-dimer, both the age-adjusted and clinical probability-adjusted D-dimer diagnostic strategies could reduce the proportion of patients who require US imaging.

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