Comparison of four D-dimer assays in the context of venous thromboembolism in the emergency department.

INTRODUCTION: This observational study conducted across seven emergency care units compares the efficacy of four D-dimer detection methods, namely HemosIL D-dimer HS (HS), HemosIL D-dimer HS-500 (HS-500), VIDAS D-dimer (VIDAS), and HemosIL AcuStar D-dimer (ACUSTAR). The primary focus is on patients with a clinical suspicion of deep venous thrombosis (DVT) or pulmonary embolism (PE). METHODS: A total of 149 samples were collected from patients with suspected DVT or PE. The confirmation of DVT/PE was based on calf ultrasound or computed tomography-Angiography. Direct comparisons were made between the different detection methods, considering both their analytical performance and clinical utility. Additionally, the impact of an age-adjusted cut-off on the diagnostic accuracy of each method was assessed. RESULTS: The results revealed comparable negative predictive value, sensitivity, and specificity across the methods, with a notable exception of increased specificity for HS compared with HS-500 (50.8% vs. 41.5%, p = 0.03). Further analysis incorporating an age-adjusted cut-off demonstrated a significant improvement in specificity for HS. When using the age-adjusted cut-off, HS exhibited a substantial increase in specificity compared with HS-500 (63.1% vs. 49.2%, p = 0.004) and demonstrated significantly higher specificity compared with VIDAS (63.1% vs. 53.8%, p = 0.04). CONCLUSION: The study emphasizes the nonuniversal effect of an age-adjusted cut-off and discusses the potential necessity for different cut-off values, particularly in the case of HS-500. These findings contribute to the understanding of D-dimer detection methods in the context of DVT and PE, providing insights into their relative performances and the potential optimization through age-adjusted cut-offs.

A collaborative study by the Working Group on Hemostasis and Thrombosis of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) on the interference of haemolysis on five routine blood coagulation tests by evaluation of 269 paired haemolysed/non-haemolysed samples.

INTRODUCTION: Haemolysis is the leading cause of sample rejection in laboratory haemostasis. Most studies focused on artificially haemolysed samples. The aim of this study was a prospective assessment of spontaneous haemolysis on haemostasis tests, by comparing results of haemolysed (H) versus new, non-haemolysed (NH) specimens, collected within 4hrs. As new coagulometers can identify interfering substances, visual assessment of haemolysis was also compared with instrumental haemolysis index and stratified in subclasses. MATERIALS AND METHODS: Two hundred and sixty nine paired samples were collected and analysed using ACL TOP750-CTS (Instrumentation Laboratory, Bedford, USA), for prothrombin time (PT), activated partial thromboplastin time (aPTT), D-Dimer (DD), fibrinogen (Fib) and antithrombin (AT). Bias between H and NH was calculated and compared with the respective critical difference (CD). RESULTS: Mean bias was - 0.1 s for PT (P = 0.057), - 1.1 s for aPTT (P < 0.001), 1025 ng/mL for DD (P < 0.001), - 0.04 g/L for Fib (P = 0.258) and 1.4% for AT (P = 0.013). Bias exceeding the CD varied according to the method, with larger differences for aPTT (36.1%) and DD (17.1%) and < 8% for PT, Fib and AT. No correlation emerged between free haemoglobin values and difference in haemostasis tests in H and NH samples for any tests. Moderate/severe haemolysis involved > 95% of samples. The agreement between visual assessment and instrumental evaluation of haemolysis was 0.62. CONCLUSION: Spurious haemolysis deeply influences aPTT and DD, and to a lesser extent AT and Fib. Prothrombin time seems only slightly influenced, suggesting that PT can be accepted also in haemolysed samples. Although a good inter-observer correlation of haemolysis evaluation was found, the instrumental assessment of haemolysis seems recommendable.

Position Paper on laboratory testing for patients on direct oral anticoagulants. A Consensus Document from the SISET, FCSA, SIBioC and SIPMeL.

Although direct oral anticoagulants (DOAC) do not require dose-adjustment on the basis of laboratory test results, the measurement of their anticoagulant effect is useful in special situations. This position paper issued by the Italian Scientific Societies that are mainly involved in the management of patients on DOAC is aimed at providing guidance to care-givers on which tests should be used and the situations in which testing is useful. The guidance is based on the data from the literature so far available and/or on consensus among experts.

D-dimer testing for suspected venous thromboembolism in the emergency department. Consensus document of AcEMC, CISMEL, SIBioC, and SIMeL.

D-dimer testing is currently considered a cornerstone in the diagnostic approach of patients with suspected venous thromboembolism (VTE) across different health-care settings, including the emergency department (ED). Nevertheless, inappropriate or incorrect activities developing throughout the total testing process may substantially impair the clinical usefulness of this test and delay or even challenge the fast rule out or diagnosis of VTE. The leading problem of D-dimer is represented by the poor specificity for diagnosing VTE, wherein a minority of patients with a positive D-dimer are finally diagnosed with VTE, and even more importantly, the specificity further decreases with ageing, thus contributing to increase the overcrowding in short stay units such as the ED. Due to the large heterogeneity that characterizes the use of D-dimer in the emergency room, three Italian societies of laboratory medicine (Italian Committee for Standardization of Hematology and Laboratory Methods, Italian Society of Clinical Biochemistry and Molecular Biology, and Italian Society of Laboratory Medicine), along with the Academy of Emergency Medicine and Care, have developed a consensus document about the use of D-dimer testing for diagnostics of patients with suspected VTE in this health-care setting. The evidence-based indications contained in this document will cover the leading preanalytical, analytical, and postanalytical issues that may impair the clinical efficacy of D-dimer testing in the ED.

Reticulocyte count, mean reticulocyte volume, immature reticulocyte fraction, and mean sphered cell volume in elite athletes: reference values and comparison with the general population.

BACKGROUND: The role of measurement of reticulocytes and their parameters is growing in sports medicine. The use of reticulocyte counts in protocols for evaluating and screening for the suspected abuse of hormones that stimulate the bone marrow is an example. Reticulocytes are also important for evaluation of the performance and general health status of athletes, especially for monitoring therapies and diets. The current availability of fully automated haematological systems that can measure reticulocyte numbers and characteristics (volume, density) increases the potential use of these parameters in laboratory and sports medicine. Few studies have considered the application of these parameters in athletes and a lack of specific reference ranges means that their valid clinical use is difficult. METHODS: Using a Coulter LH700 instrument, we measured reticulocyte count (Retics), mean reticulocyte volume (MRV), immature reticulocyte fraction (IRF), and mean sphered cell volume (MSCV) in 106 male professional elite athletes (football and rugby players and skiers). Reference intervals for the athletes were compared with the intervals found for a control group of 73 age-matched males. RESULTS: We calculated the following reference intervals: 0.30-1.54% for Retics, 93.1-114.8 fL for MRV, 0.18-0.39% for IRF, and 76.8-94.5 fL for MSCV. CONCLUSIONS: No statistically significant differences were observed for Retics, MRV, IRF, and MSCV between elite athletes and controls. Significant differences were observed for haemoglobin (Hb), erythrocytes, haematocrit (Ht), and mean corpuscular volume. Moreover, no statistical differences were observed among different sports, whereas differences were remarked in football and rugby players between the samples drawn before the start of competitive season and the samples drawn during the season, demonstrating that reticulocyte counts and parameters are useful for monitoring sportsmen.

Effect of a short antibiotic treatment with roxithromycin on circulating adhesion molecules after coronary stenting: a single-center pilot trial.

BACKGROUND: The aim of this study was to assess the effect of periprocedural antibiotic treatment with roxithromycin on circulating cell adhesion molecules and restenosis after coronary stent implantation. METHODS: Case-control study enrolling 25 consecutive patients submitted to coronary stenting for stable, single-vessel coronary artery disease, treated with 300 mg roxithromycin once daily for 5 days, starting 2 days before the procedure (group R). Twenty-five patients, matched for lesion site, length and diameter, as control group (group C). The serological status for Chlamydia pneumoniae (CP) infection (IgG, ELISA) was assessed in all patients. The plasma concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), E-selectin and C-reactive protein at 1 month after coronary stenting were compared with baseline values. Binary restenosis (> or = 50%) was also evaluated at 6 months. RESULTS: sICAM-1 significantly decreased at 1 month in group R vs group C (371 +/- 181 vs 573 +/- 273 ng/ml, p = 0.005). This decrease was more evident in patients with a positive serology for CP (CP+) (group R 373 +/- 131 vs group C 597 +/- 255 ng/ml, p = 0.014). Antibiotic treatment had no effects on circulating E-selectin levels at 1 month (56.7 +/- 97 vs 49.8 +/- 62 ng/ml, p = 0.54). The restenosis rate (9/50, 18%) was similar in the two groups (group R 5/25 [20%], group C 4/25 [16%]). The restenosis rate was similar in the CP+ vs CP- group (6/35 [17%] vs 3/15 [20%]). CONCLUSIONS: A short course of treatment with roxithromycin at the time of coronary stenting induces a significant reduction in the sICAM-1 levels at 1 month but apparently does not influence the restenosis rate.

Different patterns of interleukin-6 and von Willebrand factor antigen changes after coronary stenting in unstable versus stable angina.

BACKGROUND: Inflammation plays an important role in the pathogenesis of acute coronary syndromes. The purpose of our study was to evaluate the time course and the clinical relevance of inflammatory markers in patients with unstable angina undergoing successful coronary stent implantation. METHODS: Fifty-six patients (33 with unstable and 23 with stable angina) scheduled for single vessel coronary angioplasty followed by successful stent implantation were studied. Blood samples for measurements of interleukin-6 (IL-6) and von Willebrand factor antigen (vWf) were taken immediately before coronary angioplasty and 24 hours and 1 month after the procedure. Patients were clinically examined 1 month after the procedure. RESULTS: The mean levels of IL-6 before stenting were significaNtly higher in unstable than in stable angina patients (p = 0.002), whereas baseline values of vWf showed no difference between the two groups. In unstable angina, serum levels of IL-6 and of vWf did not change 24 hours after stent implantation, but significantly decreased 1 month after the procedure (p = 0.005 and p = 0.0015 respectively). In stable patients, serum levels of IL-6, but not of vWf, increased 24 hours after the procedure and returned to baseline levels 1 month after stent implantation (p = 0.046). CONCLUSIONS: In unstable angina, successful treatment of the culprit lesion by coronary stenting results in a significant decrease in the serum levels of IL-6 and of vWf 1 month after the procedure, suggesting that, in this clinical condition, elevated levels of these parameters correlate with the instability of the atheromatous plaque and that their decrease after successful stent implantation is the result of plaque stabilization.

Comparative short-term prognostic value of hemostatic and inflammatory markers in patients with non-ST elevation acute coronary syndromes.

BACKGROUND: Recent data show that markers of inflammation, endothelial perturbation as well as activation of the coagulation and fibrinolytic systems are altered in unstable angina. The purpose of this study was to compare the 30-day prognostic value of the indexes of inflammation [interleukin-6 (IL-6)], endothelial activation [von Willebrand factor antigen (vWf)], fibrinolysis [plasminogen activator inhibitor-1 (PAI-1)] and coagulation (F1 + 2), in a consecutive series of patients with non-ST elevation acute coronary syndromes. METHODS: Eighty-eight patients consecutively admitted to the coronary care unit because of chest pain occurring within the previous 24 hours were included in the study. Blood was drawn on admission to the coronary care unit and 72 hours thereafter for the assessment of plasma levels of IL-6, vWf, F1 + 2 and PAI-1. Troponin I serum levels were measured 6 to 12 hours after admission. All patients underwent coronary arteriography. RESULTS: Patients were divided into two groups according to their 30-day outcome: 57 patients (group 1) had an uneventful outcome, whereas 31 patients had an adverse clinical event (4 died, 1 had a Q wave myocardial infarction and 26 had refractory angina). The baseline biochemical variables were similar between group 1 and group 2 patients. Seventy-two hours following admission, an increase in the serum levels of IL-6 was observed in 71% of group 2 patients and in 28% of group 1 patients (p = 0.0001). The other measured variables showed significant changes at 72 hours versus entry only in group 1 patients, and no significant difference between the two groups. The areas under the ROC curves were higher for IL-6 (0.72) than for the other variables (0.58 for F1 + 2, 0.52 for vWf and 0.54 for PAI-1). In a multivariate model, including clinical, angiographic, and biochemical variables, only the change in IL-6 over 72 hours was significantly associated with a worse 30-day outcome (odds ratio 8.472, 95% confidence interval 1.030-69.671). CONCLUSIONS: This study shows that a mounting inflammatory process, as indicated by increasing levels of IL-6 over the first 72 hours after admission, is the most powerful predictor of the 30-day prognosis in patients with non-ST elevation acute coronary syndromes.