Quantitative D-dimer Research Articles

The performance of quantitative D-dimer assays in Chinese clinical laboratories by analyzing data from National External quality Assessment Scheme

Background and aimsTo investigate performance of D-dimer assays in China and address analytical quality issues. Materials and methodsD-dimer assays data were collected from China National External Quality Assessment Scheme (China NEQAS) from 2014 to 2022. We analyzed reagents, assay results, reporting unit and cutoffs in 2022 China NEQAS. Interlaboratory coefficient variations (CVs) and influence of modified/unmodified test systems on CVs were investigated over 9 years. ResultsThere were 82 reagent brands in China NEQAS, but 55 reagent instructions did not indicate expression unit (DDU or FEU). Up to 7-fold of the ratio of max-to-min mean results was shown among different assays with same unit on the same sample. A prevalence of FEU (63.4%) over DDU (17.1%) was observed. Although 669 laboratories (37.9%) among 1766 laboratories used reagents without VTE exclusion claim, they also reported cutoffs. The CVs of only two assays were decreasing over years. CVs of modified test systems were higher than those of unmodified systems before improvement. ConclusionsExpression unit should be required to label in package inserts by regulatory authority. Laboratory professionals should follow instructions for use and prefer unmodified test systems for clinical safely application. Harmonization of reporting units through collaborative efforts is the promising step.

The Utility of Quantitative D-Dimer Assay as a Biomarker in the Diagnosis and Exclusion of Cerebral Venous Sinus Thrombosis.

The utility and sensitivity of quantitative D-Dimer assay to rule out the diagnosis of deep vein thrombosis is well established. We extrapolated this principle to evaluate the utility of D-Dimer assay in exclusion of cerebral venous sinus thrombosis (CVST). As advanced imaging modalities required for the diagnosis of CVST might not be available everywhere, it is important to have a sensitive biomarker and a clinical decision rule which can assist in the diagnosis. Patients undergoing CT/MR Venography of the brain with the suspicion of CVST were enrolled. Quantitative D-Dimer assay was performed in those who had CVST on CT/MR Venography and was compared with those who did not. A Clinical decision rule for the diagnosis of CVST was formulated using logistic regression analysis. Receiver operating characteristic analysis evaluating the diagnostic accuracy of D Dimer for patients with CVST as compared to those who did not revealed an AUROC of 0.694. D-Dimer levels of < 300ng/mL had a sensitivity of 90% for the exclusion of CVST. After logistic regression analysis, a clinical decision rule with a total score of 16 and individual components of Female gender (2 points), Headache (7 points), D-Dimer levels of ≥ 792ng/mL (7 points) was proposed. D-Dimer had a poor diagnostic accuracy for differentiation of patients who had CVST from those who did not, however, had a high sensitivity at values < 300ng/mL. The proposed clinical decision rule with a score of ≥ 9 had a good diagnostic accuracy in prediction of CVST (AUROC = 0.809).

DIAGNOSTIC UTILITY OF QUANTITATIVE D-DIMER TESTING IN CORRELATION WITH CT ANGIOGRAPHY IN RULING OUT THROMBOEMBOLISM- A PROSPECTIVE STUDY AT A TERTIARY CARE CENTRE

Background: Vascular Thromboembolism (VTE)- blockage of a blood vessel by the broken components of a blood clot, is commonly caused by Thromboembolism Deep venous thrombosis (DVT) and Pulmonary embolism (PE). It can also be caused by various other conditions, and have overlapping features. VTE's have signicant morbidity and mortality, treatment carries signicant side effects, hence, objective testing becomes must to establish or exclude the presence of thromboembolism. D-Dimer, a brin degradation product (FDP), appears in blood after degradation of blood clot by brinolysis. It is normally undetectable or detectable at a very low level, unless the body is forming and breaking down blood clots as in VTE. Materials and Methods: Quantitative D-Dimer test was performed using fully automated technique, on patient's serum. Latex particles coated with anti D-dimer monoclonal antibodies were mixed with the test plasma. In the presence of D-dimer, the latex particles agglutinate, the suspension claries and translates in low turbidimetric readings. All results were further correlated with their CT Angiography ndings.Results: Most patients had D-Dimer value in range of 1.0 to 2.0 µg/ml. High (96.77%) Sensitivity shows that the test can be used safely to detect Thromboembolism even in early stages, whereas, High Negative Predictive value (93.54%), suggests safe exclusion in suspected cases. Conclusion: D-Dimer is highly sensitive, accurate and rapid test, but alone cannot conclude diagnosis. It is advisable to correlate with combination of Radiological investigations (CT Angiography) and clinical probability- Revised Geneva score and to establish a nal diagnosis and plan an appropriate treatment.

A study on diagnostic and prognostic significance of laboratory parameters and its correlation with HRCT of lung in Covid-19 patients

Coronaviruses had a wide range of symptoms from asymptomatic to severe illness and has caused significant morbidity and death among large population infected with this virus. To correlate CT severity score with each blood parameter like (TLC counts, Absolute neutrophil count, Absolute lymphocyte count, neutrophilic/lymphocytic ratio, quantitative D-dimer, ferritin, CRP, IL-6 and LDH). To assess diagnostic and prognostic significance of each parameter in predicting severity of disease.The present study was a 1-year prospective, a hospital-based study from 1 August 2020 to 31 July 2021 and included 100, COVID-19 confirmed cases. The clinical, radiological and laboratory reports were collected. The CT score were compared with different blood parameters. The results were analyzed statistically using correlation coefficient(r).27 patients having a CT severity score 1-10 were graded in mild category. 27 patients having CT severity score 11-15 were graded in moderate category.34 patients having CT severity score 16- 20 were graded as severe.12 patients having CT severity score 21-25 were graded as very severe. The present study showed raised TLC count &amp;#62; 11000 / µl in 35% patients suffering from COVID -19. Absolute neutrophil count &amp;#62; 7000/µl was seen in 50 % patients. 65% patients showed Absolute lymphocyte count &amp;#60;1000&amp;#62; 3.5 was seen in 83% patients. Raised D-Dimer &amp;#62;500 ng/ml was observed in 74 % patients. 92 % subjects showed raised Serum ferritin &amp;#62;150ng/ml. IL-6 &amp;#62;10pg/ml was seen in 92 % patients. Q-CRP &amp;#62;10 mg/l was seen in 97 % patients.HRCT chest severity score of patients with COVID-19 has positive correlation with various laboratory parameters and hence can be used as an indicator of disease severity. It can play a vital role in the management of COVID-19 and should be used for comprehensive evaluation.

Markers of hypercoagulability in children with newly diagnosed acute lymphoblastic leukemia.

Venous thromboembolism (VTE) is a known complication for children with acute lymphoblastic leukemia (ALL). The aim of this study was to identify laboratory biomarkers that predict which children with ALL are at risk for VTE during induction chemotherapy. Newly diagnosed ALL patients admitted to Children's Hospital Los Angeles with a central venous catheter (CVC) were eligible to participate. Participants' blood samples (complete blood count [CBC], quantitative D-dimer, prothrombin fragment 1.2 [PTF 1.2], and thrombin-antithrombin complexes [TAT]) were collected at day 0 (baseline/prior to induction), day 7 (±2days), day 14 (±2days), day 21 (±2days), and day 28 (±2days) of induction chemotherapy or until participants presented with a symptomatic VTE. Seventy-five participants aged 1-21years were enrolled and included in the final analysis. Twenty-six (35%) of the 75 participants were diagnosed with a CVC-associated VTE (22 asymptomatic and four symptomatic). There was a statistically significant difference between VTE and non-VTE participants for D-dimer (odds ratio [OR] 1.61, 95% confidence interval [CI]: 1.59-1.64), TAT (OR 1.34, 95% CI: 1.32-1.38), and PTF 1.2 (OR 1.31, 95% CI: 1.25-1.37) at all time points. Participants >10years had a significantly higher risk of developing a VTE compared to participants <4years (p=.007). Older children with ALL as well as those with an elevated TAT, PTF 1.2, or D-dimer showed an increased risk of VTE, which may hold potential for predicting VTE in future studies.

D-dimer as a safe, convenient and easily available biomarker, when combined with conventional sentinel node biopsy in clinically node negative breast cancer to assess metastatic disease in axilla and reduce false negative results

Background: Breast cancer is frequently associated with activation of the hemostatic system and the extent of this activation correlates with a more advanced tumor stage. D-dimer is a biomarker that indicates the activation of hemostasis and fibrinolysis.Methods: This is a prospective, observational, analytical study in which we compare plasma D-dimer levels among three groups’ i.e., healthy subjects, benign patients and breast cancer patients. We have also evaluated plasma D-dimer levels in patients with lymphadenopathy and in those patients who did not have palpable lymph nodes. Plasma D-dimer levels were further characterized based on TNM classification in breast cancer patients where quantitative D-dimer levels were correlated with clinical stage grouping.Results: Through our study we have observed that D-dimer level is inexpensive and a convenient method for diagnosis and prognosis of breast cancer. We have used a control group so as to evaluate a more accurate result. Comparison between benign and malignant lesions was made and we have achieved a significant p value, which proved our study positive for raised D-dimer levels in cancer breast.Conclusions: D-dimer proves to be a safe, convenient and easily available biomarker which can be combined with conventional sentinel node biopsy in clinically node negative breast cancer to assess metastatic disease in axilla and reduce false negative results. Plasma D-dimer level was positively correlated with clinical stage of solid cancers.

Performance Evaluation of the Quantitative Point-of-Care LumiraDx D-Dimer Test.

IntroductionFibrin degradation product d-dimer can be a valuable indicator for venous thromboembolism (VTE). The use of d-dimer testing in primary care settings can be limited by restricted access to laboratory services. This performance evaluation compares a quantitative, point-of-care (POC) d-dimer assay (LumiraDx d-Dimer Test) with a reference laboratory-based d-dimer assay.MethodsPlasma samples from patients presenting to secondary care in the UK, USA, and Germany were analyzed centrally using the LumiraDx d-Dimer Test and the reference test (bioMérieux VIDAS d-Dimer Exclusion II immunoassay). Method comparison used Passing–Bablok regression analysis with pre-specified equivalence criteria of r ≥ 0.9 and slope of 0.9–1.1. The NOVEL-3 study (NCT04375982) compared equivalency of fingerstick, venous blood (VB), and plasma samples from the same patient, tested at US primary care clinics next to the patient using the POC LumiraDx d-Dimer device. Measurements obtained from fingerstick and VB samples were compared with results from plasma samples, using Deming regression. The healthy reference range was determined using plasma samples of healthy volunteers, collected by commercial suppliers in Germany and the USA, which were analyzed centrally using the LumiraDx d-Dimer Test and the reference test.ResultsThe LumiraDx d-Dimer Test demonstrated agreement with the bioMérieux VIDAS d-Dimer Exclusion II immunoassay for plasma samples (r = 0.923, slope of 1.016, n = 1767). There was good agreement between fingerstick/VB samples and plasma samples (r = 0.980–0.986, n = 93) measured using the LumiraDx d-Dimer Test. Overall error rates were 1.8%. The healthy reference range 90% percentile for d-dimer was calculated as 533 µg/l fibrinogen equivalent units (FEU).ConclusionsThe quantitative LumiraDx d-Dimer Test is easy to use and can accurately measure d-dimer levels in a range of blood sample types, including fingerstick samples, which could improve assessment of VTE cases in community and hospital near-patient settings.

COVID and venous thrombosis: systematic review of literature.

We aimed to review the prevalence, the risk factors and the outcomes of venous thrombosis (VT) in patients hospitalized for COronaVirus Disease 19 (COVID-19). Electronic bibliographic databases were searched using the words "COVID venous thrombosis". The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. The search of the literature retrieved 877 results. After assessment of full texts, 69 papers were included in the qualitative analysis and 23 of them in the quantitative evaluation. The analyzed studies included a total of 106,838 patients hospitalized for COVID-19 from January to December 2020. The pooled reported prevalence rate of VT was in median 16.7% (IQR 5.8-30%), being higher in ICU patients (60.8-85.4%). VT events were reported in about 75% of cases in the popliteal and calf veins. Signs and symptoms were present in 6.1% of cases. At quantitative evaluation, older age, D-dimer and obesity increased the odds to experience a VT (OR=3.54, 95% CI 0.65-6.43, P=0.01; OR=956.86, 95% CI 225.67-1668.05, P=0.01; OR=1.42, 95% CI 1.01-1.99, P=0.03 respectively). Female sex seemed to be protective against the odds of VT (OR=0.77, 95% CI 0.63-0.93, P=0.007). Among patients hospitalized for COVID-19, VT is a relatively common finding, with higher prevalence rates in ICU patients. VT occurs mostly in the distal regions of the lower limb and is asymptomatic in most cases. Older age, obesity and higher D-dimer values on admission increased the odds of VT, while female sex was protective against the odds of VT.

Recurrent Epistaxis and Diffuse Hepatic and Splenic Vascular Malformations

Question: A 48-year-old man was admitted to emergency department because of left upper abdominal pain for 3 weeks and yellow urine for 1 week. The patient was diagnosed with splenic hemangioma for 3 years and recurrent epistaxis for 5 years, without further treatment. Physical examination showed tenderness and rebound pain in the left upper abdomen, no muscle tension, with shifting dullness. Laboratory studies showed a neutrophil count of 8990/mm3 (reference range, 1900–8000/mm3), a hemoglobin level of 66 g/L (reference range, 131–172 g/L), a total bilirubin level of 57.23 μmol/L (reference range, 5.1–20 μmol/L), a serum alanine aminotransferase level of 302.9 U/L (reference range, 9–50 U/L), a serum aspartate aminotransferase level of 117.5 U/L (reference range, 15–40 U/L), an activated partial prothrombin time of 34.6 (reference range, 25–34), and a quantitative D-dimer level of 361.23 (reference range, 0–0.55). Emergency abdominal computed tomography scan showed diffuse hepatic and splenic vascular malformations (Figure A), and a ruptured splenic tumor (Figure B, arrow). It is worth noting that the patient's father had the same disease during his lifetime after asking about the family history. What is the most likely diagnosis? Look on page 808 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and images in GI. After consultation with the patient, he underwent emergency splenectomy and liver biopsy. Histopathology demonstrated the dilatation of hepatic capillaries, showing hemangioma-like changes (Figure C). The ruptured splenic tumor was confirmed pathologically as hemangioendothelioma. After a multidisciplinary consultation, the patient was diagnosed with hereditary hemorrhagic telangiectasia (HHT) according to the Curaçao criteria.1Faughnan M.E. Palda V.A. Garcia-Tsao G. et al.International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia.J Med Genet. 2011; 48: 73-87Crossref PubMed Scopus (745) Google Scholar HHT, also called Osler–Weber–Rendu disease, is an autosomal-dominant disease. Up to one-third of patients have hepatic involvement and manifest as vascular malformations,2Chung D.Y. Federle M.P. Barrett J.P. et al.Hepatic hereditary hemorrhagic telangiectasia.Clin Gastroenterol Hepatol. 2006; 4 (xx)Abstract Full Text Full Text PDF Scopus (1) Google Scholar such as hepatic arteriovenous fistula (Figure D, rectangle). Martini3Martini G.A. The liver in hereditary haemorrhagic teleangiectasia: an inborn error of vascular structure with multiple manifestations: a reappraisal.Gut. 1978; 19: 531-537Crossref PubMed Scopus (95) Google Scholar classified patients with hepatic disease due to HHT into 3 subgroups: patients who had telangiectases with fibrosis or cirrhosis (as in our case), those who had cirrhosis without telangiectases, and those who had telangiectases without fibrosis or cirrhosis. Treatment is mostly supportive, but severe patients may require hepatic artery embolization or liver transplantation.2Chung D.Y. Federle M.P. Barrett J.P. et al.Hepatic hereditary hemorrhagic telangiectasia.Clin Gastroenterol Hepatol. 2006; 4 (xx)Abstract Full Text Full Text PDF Scopus (1) Google Scholar During the period of waiting for liver transplantation, the patient developed hepatic and renal insufficiency and respiratory failure. On day 11 of hospitalization, the patient's family asked to be transferred back to the local hospital for treatment. The patient died of multiple organ failure on the third day after transfer.

MO385THE IMPACT OF SARS-COV-2 INFECTION ON MORTALITY IN CKD PATIENTS – A SINGLE-CENTER PILOT STUDY

Background and AimsSince the beginning of 2019, once COVID-19 pandemic was declared, there is a keen interest in understanding the impact of SARS-CoV-2 infection on chronic kidney disease (CKD) patients, regarding the influence on CKD progression and the suitable therapy options, as most of the indicated medications are contraindicated for a glomerular filtration rate (GFR) below 30 ml/min, and, in addition, there is a little experience in dialyzed patients. The aim of our single-center pilot study is to determine the influence of SARS-CoV-2 infection on CKD patients’ (dialyzed or not) outcome and hospitalization rate.MethodWe evaluated the patients diagnosed with COVID-19, admitted in our Department between October and December 2020. The inclusion criteria were: age > 18 years old, diagnosis of CKD – predialysis and hemodialyzed patients. The exclusion criteria were: patients without pre-existing CKD. All included subjects signed the patients’ consent. To all included patients we performed the following tests: total blood count, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, ferritin, serum free iron, serum creatinine, urea, uric acid, calcemia, total proteins, electrolytes and acid-base balance, urinary exams (including urine culture), coagulation and lipid profile, quantitative D-dimer, IL-6, procalcitonin, and imaging tests (CT, pulmonary Rx, abdominal ultrasonography). The patients were monitored by the infectious disease medical team that adjusted the therapy according to the patients’ lab and imagistic results. The specific treatment for SARS-CoV-2 infection included primary anti-interleukin receptor monoclonal antibody drugs (such as Anakinra, Tocilizumab), corticotherapy (dexamethasone), anti-retroviral therapy (remdesivir, favipiravir) only in hemodialyzed patients or in those presenting an eGFR > 30 mL/min, antibiotics, antifungal drugs, and oxygen-therapy. Usually, anti-interleukin receptor monoclonal antibody consisted in 7 doses, administrated every 48 hours. The dose of all other recommended drugs was adapted according to the patients’ eGFR.ResultsA total of 63 patients were admitted in our Department and were under our care, presenting medium or severe forms of SARS-CoV-2 infection. After applying the inclusion and exclusion criteria, only 38 patients were considered eligible: 21 male patients (mean age 63.52 ± 13.82 years), and 17 female patients (mean age 67.24 ± 12.83 years). 31.57% represented the percentage of death during the hospitalization (due to the severity of the disease, 4 patients died within 24 hours) in patients presenting heterogenous comorbidities, such as diabetes mellitus, hypertension, pre-existing glomerulonephritis and/or oncological pathologies; we also noticed that female gender represented 58.33% of the deceased patients. The mean hospitalization period in the deceased patients was 6.42 ± 5.38 days – 4 ± 3.21 days in female gender, and 9.8 ± 6.30 days in male gender.ConclusionMost of our patients, although diagnosed with medium and severe forms of SARS-CoV-2 infection, presented a favorable evolution, and an adequate response to the specific medication. We observed that most of the deceased cases were female patients, and compared to the male deceased subject, female deceased patients presented a lower period of hospitalization. Therefore, probably female CKD patients with comorbidities and diagnosed with COVID-19 are more predisposed to an unfavorable prognosis. Further and larger clinical trials are necessary to validate the impact of SARS-CoV-2 infection on mortality in CKD patients.

Using Quantitative D-Dimer to Determine the Need for Pulmonary CT Angiography in COVID-19 Patients.

INTRODUCTION:COVID-19 has been frequently cited as a condition causing a pro-inflammatory state leading to hypercoagulopathy and increased risk for venous thromboembolism. This condition has thus prompted prior studies and screening models that utilize D-dimer for pulmonary embolism (PE) into question. The limited research to date has failed to provide tools or guidance regarding what COVID-19 positive patients should receive pulmonary CT angiography screening. This knowledge gap has led to missed diagnoses, CT overutilization, and increased morbidity and mortality.OBJECTIVE:The purpose of this study was to examine the utility of the quantitative D-dimer lab marker in a convenience sample of 426 COVID-19 positive patients to assist providers in determining the utility of pulmonary CT angiography.METHODS:The authors conducted a retrospective analysis on all COVID-19 positive patients within the Henry Ford Medical System between March 1st, 2020 through April 30th, 2020 who received pulmonary CT angiography and had a quantitative D-dimer lab drawn within 24 hours of CT imaging.RESULTS:Our sampling criteria yielded a total of n = 426 patients, of whom 347 (81.5%) were negative for PE and 79 (18.5%) were positive for PE. The average D-dimer in the negative PE group was 2.95 μg./mL. (SD 4.26), significantly different than the 9.15 μg./mL. (SD 6.80) positive PE group (P < 0.05; 95% CI -7.8, -4.6). Theoretically, applying the traditional ≤ 0.5 μg./mL. D-dimer cut-off to our data would yield a sensitivity of 100% and specificity of 7.49% for exclusion of PE. Based on these results, the authors would be able to increase the D-dimer threshold to < 0.89 μg./mL. to maintain their sensitivity to 100% and raise the specificity to 27.95%. Observing a D-dimer cut-off value of ≤ 1.28 μg./mL. would reduce sensitivity to 97.47% but increase the specificity to 57.93%.CONCLUSIONS:These study results support the utilization of alternative D-dimer thresholds to exclude PE in COVID-19 patients. Based on these findings, providers may be able to observe increased D-dimer cut-off values to reduce unnecessary pulmonary CT angiography scans.

Performance of the Quantitative Latex Immunoturbidimetric D-dimer Assay for the Diagnosis of Acute Pulmonary Embolism at Rafik Hariri University Hospital

Background and aims: The diagnostic workup for pulmonary embolism (PE) includes D-dimer assay and computed tomographic angiography. Several D-dimer assays have been approved for PE diagnosis with different sensitivity and specificity. We aimed to study the sensitivity and specificity of the quantitative latex agglutination D-dimer assay used in a referral teaching hospital in Lebanon for the diagnosis of acute PE. Methods: Using a retrospective chart review, we studied 300 patients who had D-dimer test at Rafik Hariri University Hospital in the period between January 1, 2012 and December 31, 2013. Accordingly, 93 patients had a CT angiography after being suspected to have acute PE. A statistical table 2*2 was used to compare the results of CT angiography and D-dimer test. Results: Thirteen patients (13.97%) had PE and 60 patients (64.51%) had positive D-dimer test. Quantitative latex agglutination D-dimer assay had a sensitivity of 69%, specificity of 36%, and negative predictive value of 88%. False positive ratio was also 64%. Moreover, the receiver operating characteristic (ROC) curve was obtained with an area under the curve measuring 0.527. Conclusion: Quantitative latex agglutination D-dimer assay has a high negative predictive value; thus, it can exclude a PE diagnosis if it is associated with low clinical pretest probability.

Role of D-dimer in patients of operable breast cancer with lymph node metastases: A matched cross-sectional study

Introduction: Breast cancer is the most common malignancy amongst women worldwide. Presence of axillary lymph nodes metastases is an important predictor of survival in patients with infiltrative breast cancer. D-dimer levels are elevated in the plasma of various solid tumor patients. There still exists a gap in our knowledge regarding the relationship between quantitative D-dimer levels and extent of disease in primary breast cancer. Aim: To study the fibrinolytic pathway by assaying D-dimer in breast cancer cases and to calculate a suggestive cutoff value for D-dimer for its use a specific marker of lymph node metastasis preoperatively in the cases of breast cancer. Materials and Methods: In this matched cross-sectional hospital-based study, 50 diagnosed cases of operable breast carcinoma not taking any treatment for the cancer and 50 healthy women both in the 25–65 years age group were selected as cases and controls, respectively. Peripheral venous blood was collected and analyzed for prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), D-dimer, platelet count, and mean platelet volume. Results: D-dimer was significantly increased in cases compared to healthy controls. It was markedly increased in patients with lymph node involvement irrespective with the number of nodes involved, while PT, aPTT, and TT did not show significant difference. Receiver operating characteristic curve gave a sensitivity of 56% and specificity of 91%, for cutoff value of 0.765 for D-dimer, in order to predict the chances of lymph node metastases preoperatively. Conclusions: D-dimer is a simple, noninvasive, quick, and nonexpensive laboratory investigation which can be used as a predictor of depicting lymph node metastasis.

P5017Factors associated with a negative D-dimer test in patients diagnosed with acute symptomatic pulmonary embolism

Abstract Background The recommended diagnostic strategy for suspected acute pulmonary embolism (PE) combines the assessment of pre-test probability, D-dimer level, and -if indicated- computed tomography pulmonary angiography. Purpose To evaluate the frequency and potential explanations for negative D-dimer tests in patients diagnosed with acute PE. Methods The multicentre Follow-up of Acute Pulmonary Embolism (FOCUS) cohort study prospectively enrolled 1,100 consecutive patients diagnosed with acute symptomatic PE; two-year follow-up is ongoing. The items of the Simplified revised Geneva Score and the D-dimer levels at diagnosis have been prospectively collected, but they did not necessarily guide management decisions. Quantitative D-dimer was measured on admission either by quantitative latex-based assays or enzyme-linked immunosorbent assays. A negative D-dimer was defined by fixed (0.50 μg/mL) or age-adjusted (age*0.01 μg/mL if age&gt;50) cut-off. Results Using the fixed cut-off, a negative D-Dimer was detected in 17 of 773 patients with ultimately diagnosed PE (miss rate 2.2% [95% CI 1.4–3.5]); using the age-adjusted cut-off, the test was discordant with the PE diagnosis in 24 patients (3.1% [2.1–4.6]). In Figure 1, red dots indicate negative D-dimer test by fixed cut-off and blue dots indicate additional negative D-dimer tests by age-adjusted cut-off. In 448 (59%) patients post-hoc classified as PE-unlikely, 11 (2.5% [1.4–4.3]) and 14 (3.1% [1.9–5.2]) patients had a negative D-dimer using the two different cut-offs, respectively. Haemoptysis on admission, V/Q scan-based diagnosis, and chronic lung disease were associated with a discordant D-dimer, while an inverse association existed for concomitant DVT. In 7 (29%) PE cases with normal D-dimer, PE was verified to be subsegmental also in a post-hoc evaluation. Another seven (29%) patients were receiving anticoagulation at the time of D-dimer assessment. Figure 1 Conclusions Our results show that the frequency of discordance between a normal D-dimer test and the diagnosis of acute PE is low, but not negligible. One third of discordant findings were related to subsegmental PE. Physicians should be aware that the risk of obtaining a false-negative D-dimer might be higher in specific subgroups of patients. Acknowledgement/Funding The sponsor (University Medical Center of the Johannes Gutenberg University, Mainz) has obtained grants from Bayer Vital GmbH and Bayer Pharma AG

Quantitative d-dimer level and anticoagulant therapy in idiopathic intracranial hypertension

BackgroundIdiopathic intracranial hypertension (IIH) is a syndrome characterized by elevated intracranial pressure (ICP) of unknown etiologyAim of the workThe aim of this research is to study the quantitative d-dimer level and the role of anticoagulant therapy in absence of occlusive sinus thrombosis in patients with IIH.MethodologyTwenty-four patients with IIH according to the modified Dandy criteria were enrolled. Headache impact test (HIT6), ophthalmological assessment including Frisen classification for papilledema, visual acuity, visual field, and visual evoked potentials were performed to the patients. Serum quantitative d-dimer level was measured using the enzyme-linked immunosorbent assay (ELISA) technique for the patients and for 24 healthy matched controls. Patients were divided into two groups: group (1) received acetazolamide and low molecular weight heparin (LMWH) in a prophylactic dose for 2 weeks while group (2) received acetazolamide only. Both groups continued on acetazolamide for 6 months. We followed the patients after 1 and 6 months later through the HIT6 test and the ophthalmological assessment.Resultsd-dimer level was statistically higher among the cases compared to the controls. Also, a statistically significant improvement was recorded in the ophthalmological assessment after 6 months among both groups; more evident in group (1).ConclusionThe elevated d-dimer level and the visual improvement in IIH patients receiving LMWH added to acetazolamide suggest the presence of an underlying unrecognized non-occlusive venous cerebral microthrombi impeding the cerebrospinal fluid (CSF) drainage.Trial registrationClinicalTrials,gov on 22/5/2019, NCT03963336.

Quantitative D-dimer Level and Anticoagulant Therapy in Idiopathic Intracranial Hypertension

Quantitative D-dimer Level and Anticoagulant Therapy in Idiopathic Intracranial Hypertension

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

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.

The DAGMAR Score: D-dimer assay-guided moderation of adjusted risk. Improving specificity of the D-dimer for pulmonary embolism

We generated a novel scoring system to improve the test characteristics of D-dimer in patients with suspected PE (pulmonary emboli).Electronic Medical Record data were retrospectively reviewed on Emergency Department (ED) patients 18 years or older for whom a D-dimer and imaging were ordered between June 4, 2012 and March 30, 2016. Symptoms (dyspnea, unilateral leg swelling, hemoptysis), age, vital signs, medical history (cancer, recent surgery, medications, history of deep vein thrombosis or PE, COPD, smoking), laboratory values (quantitative D-dimer, platelets, and mean platelet volume (MPV)), and imaging results (CT, VQ) were collected.Points were designated to factors that were significant in two multiple regression analyses, for PE or positive D-dimer. Points predictive of PE were designated positive values and points predictive of positive D-dimer, irrespective of presence of PE, were designated negative values.The DAGMAR (D-dimer Assay-Guided Moderation of Adjusted Risk) score was developed using age and platelet adjustment and points for factors associated with PE and elevated D-dimer.Of 8486 visits reviewed, 3523 were unique visits with imaging, yielding 2253 (26.5%) positive D-dimers. 3501 CT scans and 156 VQ scans were completed, detecting 198 PE.In our cohort, a DAGMAR Score < 2 equated to overall PE risk < 1.2%. Specificity improved (38% to 59%) without compromising sensitivity (94% to 96%). Use of the DAGMAR Score would have reduced CT scans from 2253 to 1556 and lead to fewer false negative results.By considering factors that affect D-dimer and also PE, we improved specificity without compromising sensitivity.

“HERDOO2” clinical decision rule to guide duration of anticoagulation in women with unprovoked venous thromboembolism. Can I use any d-Dimer?

BackgroundThe “HERDOO2 rule” is a prospectively validated clinical decision rule used to identify low-risk women who can safely discontinue anticoagulants after completing 5–12 months of anticoagulant treatment for unprovoked venous thromboembolism. The VIDAS®d-Dimer (DD) assay, a component of the rule, was used in the derivation and validation of the rule at half the usual diagnostic cut-point for exclusion of venous thrombosis. It is unknown if other commercial DD assays used at a corresponding cut-point will categorize patients at high concordance with the VIDAS® DD. ObjectiveTo determine if other available automated quantitative DD assays have high enough concordance with the VIDAS® DD assay to allow their use within the “HERDOO2” clinical decision rule. MethodsFrozen plasma samples from a sub-set (n = 248) of female participants in the “HERDOO2” validation study were tested using five DD assays: VIDAS®, Innovance®, HemosIL®, Tina-quant® and Liatest®, with duplicate testing for 50 samples. First, using the mean DD for 50 samples with duplicate results, we determined the optimal cut-point values for each test that corresponded with a VIDAS® DD result of 250 μg/L using linear regression analysis. Next, kappa analysis was conducted on the DD results of the remaining 198 samples to determine concordance between each tested DD at the respective optimal cut-point and the VIDAS® DD at 250 μg/L. In a separate analysis we determined the concordance at half the usual venous thrombosis exclusion cut-point. ResultsRegression analysis of the DD results in 50 samples identified the optimal cut-point for each DD assay to match a VIDAS® DD cut-point of 250 μg/L: Innovance® 177 μg/L, Liatest® 233 μg/L, Tina-quant® 48 μg/L and HemosIL® 56 μg/L. Next, in 198 different samples, the concordance of VIDAS® DD (≥250 μg/L or <250 μg/L) was explored at the optimal cut-point of the other DD assays. The concordance was poor for all DD assays: Innovance® (kappa 0.38 (95% CI, 0.26–0.51)), Liatest® (kappa 0.38 (95% CI, 0.25–0.50)), HemosIL® (kappa 0.36 (95% CI, 0.23–0.49)) and Tina-quant® (kappa 0.30 (95% CI, 0.16–0.43)). Similar poor concordance was identified using half of the diagnostic DD cut-point for each tested assay: Innovance® (kappa 0.44 (95% CI, 0.32–0.56)), Liatest® (kappa 0.38 (95% CI, 0.25–0.51)), HemosIL® (kappa 0.04 (95% CI, −0.01—0.08)) and Tina-quant® (kappa 0.04 (95% CI, −0.004–0.07)). ConclusionThe “HERDOO2 rule” is the only prospectively validated clinical decision rule that can be used to identify low-risk women with unprovoked venous thrombosis who can safely discontinue anticoagulants. An important implementation issue is whether any commercial DD assay can be used in the HERDOO2 rule, and at what cut-point. Our analysis shows that the HemosIL®, Innovance®, Liatest® and Tina-quant® DD assays should not be used in the “HERDOO2” rule due to poor concordance with the VIDAS® DD assay and unacceptable misclassification of women at high and low risk of recurrent venous thrombosis.

Ruling out pulmonary embolism across different subgroups of patients and healthcare settings: protocol for a systematic review and individual patient data meta-analysis (IPDMA)

BackgroundDiagnosing pulmonary embolism in suspected patients is notoriously difficult as signs and symptoms are non-specific. Different diagnostic strategies have been developed, usually combining clinical probability assessment with D-dimer testing. However, their predictive performance differs across different healthcare settings, patient subgroups, and clinical presentation, which are currently not accounted for in the available diagnostic approaches.MethodsThis is a protocol for a large diagnostic individual patient data meta-analysis (IPDMA) of currently available diagnostic studies in the field of pulmonary embolism. We searched MEDLINE (search date January 1, 1995, till August 25, 2016) to retrieve all primary diagnostic studies that had evaluated diagnostic strategies for pulmonary embolism. Two authors independently screened titles, abstracts, and subsequently full-text articles for eligibility from 3145 individual studies. A total of 40 studies were deemed eligible for inclusion into our IPDMA set, and principal investigators from these studies were invited to participate in a meeting at the 2017 conference from the International Society on Thrombosis and Haemostasis. All authors agreed on data sharing and participation into this project. The process of data collection of available datasets as well as potential identification of additional new datasets based upon personal contacts and an updated search will be finalized early 2018. The aim is to evaluate diagnostic strategies across three research domains: (i) the optimal diagnostic approach for different healthcare settings, (ii) influence of comorbidity on the predictive performance of each diagnostic strategy, and (iii) optimize and tailor the efficiency and safety of ruling out PE across a broad spectrum of patients with a new, patient-tailored clinical decision model that combines clinical items with quantitative D-dimer testing.DiscussionThis pre-planned individual patient data meta-analysis aims to contribute in resolving remaining diagnostic challenges of time-efficient diagnosis of pulmonary embolism by tailoring available diagnostic strategies for different healthcare settings and comorbidity.Systematic review registrationProspero trial registration: ID 89366.