Evaluation of the Stratus CS Acute Care D-dimer assay (DDMR) using the Stratus CS STAT Fluorometric Analyzer: a prospective multisite study for exclusion of pulmonary embolism and deep vein thrombosis.

BACKGROUND: D-dimer testing is an integral part of the diagnostic algorithm in excluding patients with venous thromboembolism. In this study, we prospectively evaluated the Stratus DDMR D-dimer test in patients suspected of pulmonary embolism (PE) and deep vein thrombosis (DVT). METHODS: Patients suspected of venous thromboembolism were prospectively enrolled at four different clinical sites, with sodium citrate and lithium heparin plasma was tested using the DDMR D-dimer test on the Stratus CS analyzer. RESULTS: 1,012 patients were enrolled for analysis, with 85/603 (14.1%) patients with PE and 80/443 (18.1%) with DVT, and four of the patients (0.4%) with PE and DVT. For the samples collected in 3.2% sodium citrate, the DDMR method had a sensitivity, specificity, and negative predictive value for VTE of 98.0%, 38.1%, and 99.1%, respectively. For the samples collected in lithium heparin, the DDMR method had a sensitivity, specificity, and negative predictive value (NPV) for VTE of 98.9%, 28.8%, and 99.4%, respectively. In PE, DDMR testing on citrate plasma had a sensitivity, specificity, and NPV of 98.8%, 39.5%, and 99.6%, respectively, while heparin samples had a sensitivity, specificity, and NPV for PE of 98.0%, 28.4%, and 99.1%, respectively. In DVT, citrate plasma had a sensitivity, specificity, and NPV for DVT of 97.5%, 32.0%, and 98.3%, respectively, while heparin samples had a sensitivity, specificity, and NPV for DVT of 100%, 27.8%, and 100%, respectively. CONCLUSION: The Stratus CS DDMR D-dimer can be used in those patients with non-high clinical pre-test probability for the exclusion of PE.

Association of cyclooxygenase-1-dependent and -independent platelet function assays with adverse clinical outcomes in aspirin-treated patients presenting for cardiac catheterization.

BACKGROUND: Poor clinical outcome in aspirin-treated patients has been termed aspirin resistance and may result from inadequate inhibition of platelet cyclooxygenase-1 (COX-1) by aspirin. The objectives of this study were to determine prospectively whether COX-1-dependent and other platelet function assays correlate with clinical outcomes in aspirin-treated patients. METHODS AND RESULTS: Blood was collected before percutaneous coronary intervention from 700 consecutive aspirin-treated (81 or 325 mg for > or =3 days) patients. Platelet function was tested by (1) serum thromboxane B(2); (2) arachidonic acid-stimulated platelet surface P-selectin and activated glycoprotein IIb/IIIa and leukocyte-platelet aggregates; and (3) platelet function analyzer (PFA)-100 collagen-epinephrine and collagen-ADP closure time (CT). Adverse clinical outcomes of all-cause death, cardiovascular death, and major adverse cardiovascular events (cardiovascular death, myocardial infarction, hospitalization for revascularization, or acute coronary syndrome) were assessed by telephone interview and/or medical record review. Clinical outcomes information was obtained at 24.8+/-0.3 months after platelet function testing. By univariate analysis, COX-1-dependent assays, including serum thromboxane B(2) level, were not associated with adverse clinical outcomes, whereas the COX-1-independent assay, PFA-100 collagen-ADP CT <65 seconds, was associated with major adverse cardiovascular events (P=0.0149). After adjustment for covariables (including sex, aspirin dose, Thrombolysis in Myocardial Infarction risk score, clopidogrel use), both serum thromboxane B(2) >3.1 ng/mL and PFA-100 collagen-ADP CT <65 seconds were associated with major adverse cardiovascular events. In contrast, indirect measures of platelet COX-1 (arachidonic acid-stimulated platelet markers, shortened PFA-100 collagen-epinephrine CT) were not significantly associated with adverse clinical outcomes even after adjustment for covariables. CONCLUSIONS: In this prospective study of 700 aspirin-treated patients presenting for angiographic evaluation of coronary artery disease, residual platelet COX-1 function measured by serum thromboxane B(2) and COX-1-independent platelet function measured by PFA-100 collagen-ADP CT, but not indirect COX-1-dependent assays (arachidonic acid-stimulated platelet markers, shortened PFA-100 collagen-epinephrine CT), correlate with subsequent major adverse cardiovascular events. This study suggests that multiple mechanisms, including but not confined to inadequate inhibition of COX-1, are responsible for poor clinical outcomes in aspirin-treated patients, and therefore the term aspirin resistance is inappropriate.

Comparison of optical and mechanical clot detection for routine coagulation testing in a large volume clinical laboratory.

Hemostasis instrumentation has rapidly advanced and laboratories are demanding fully automated coagulation systems. Two distinct technological families exist based on optical and mechanical clot detection methodologies. Until now, there have been no comprehensive studies to determine whether one methodology is superior to the other. In order to answer this question, we conducted a large clinical study performing standard coagulation testing on more than 2,000 clinical samples randomly chosen from a high-volume laboratory in a tertiary care hospital. Results demonstrated that photo-optical clot detection and electro-mechanical detection systems were highly correlated (r-squared values >or= 0.96 for all assays) Correlation between the two clot detection systems was maintained even when measuring turbid samples (r-squared values >or= 0.98 for all assays).

Hypersensitivity of platelets to adenosine diphosphate in patients with stable cardiovascular disease predicts major adverse events despite antiplatelet therapy.

Enhanced platelet activity correlates with early markers of myocardial damage in patients with cardiovascular disease. However, the extent to which enhanced platelet function signals subsequent adverse clinical outcomes in patients with cardiovascular disease is unknown. Blood from patients with stable cardiovascular disease receiving aspirin (325 mg/day) as the only antiplatelet therapy was tested for closure time (CT) with the Dade PFA-100 Platelet Function Analyzer system collagen/adenosine diphosphate (ADP) [CADP] cartridge and platelet aggregometry using 10 microM ADP. This study intentionally focused on those patients defined as aspirin sensitive by previously established criteria of arachidonic acid- and ADP-induced platelet aggregometry, and separately by collagen/epinephrine (CEPI) CT using the PFA-100. Follow up averaged 22 months for the adverse clinical events of death, myocardial infarction or cerebrovascular accident. For aspirin sensitivity determined by aggregometry, patients with CADP CT < 90 seconds (125/296 = 42.2%) had a composite endpoint rate of 19.2% (24/125), while those with CADP CT 90 seconds (171/296 = 57.8%) had an endpoint rate of 5.3% (9/171). Patients with CADP CT <90 seconds had a relative risk (RR) of 3.65 (95% CI.: 1.76-7.57) for recurrent events and 6.56 (95% CI.: 1.93-22.35) for death compared to patients with CADP CT 90s. Nearly identical results were obtained when patients were categorized as aspirin sensitive by CEPI CT. Platelet aggregometry with 10 microM ADP yielded no significant RR for the selected outcomes. Platelet function testing using the PFA-100 system appears to identify a subgroup of stable cardiovascular disease patients with increased risk of major adverse events that is associated with hypersensitivity to ADP, regardless of apparently effective aspirin therapy.

Determination of platelet aggregation inhibition during percutaneous coronary intervention with the platelet function analyzer PFA-100.

BACKGROUND: A simple device to rapidly evaluate platelet function may aid in optimizing glycoprotein IIb/IIIa inhibition during percutaneous coronary intervention (PCI). We prospectively studied platelet function in 250 patients receiving abciximab or eptifibatide during PCI. METHODS AND RESULTS: The platelet function analyzer PFA-100 (Dade-Behring, Deerfield, Ill) measures platelet function by determining the time to occlusion of an aperture in a biochemically active membrane as whole blood flows under high shear conditions. Platelet aggregation causes aperture occlusion, and results are reported as a closure time (CT). All patients received either abciximab or eptifibatide, along with aspirin and heparin; patients undergoing stent implantation received aspirin and a thienopyridine postprocedure. The CT was measured at baseline and 10 minutes, 4 hours, 12 hours (abciximab-only), and 24 hours after the bolus. Profound inhibition was exhibited in most patients shortly after the platelet inhibitor bolus and during the course of therapy. We observed recovery of platelet function 12 hours after discontinuation of abciximab, with a high degree of interpatient variability, and ongoing profound platelet inhibition 4 to 6 hours after the discontinuation of eptifibatide. Among patients treated with abciximab, patients who were obese recovered from platelet inhibition sooner than patients who were not obese, whereas patients who were elderly had delayed recovery compared with patients who were not elderly. Failure to achieve maximal platelet inhibition (nonclosure) at 10 minutes indicated a possible association with adverse clinical events at the 6-month follow-up examination (60% vs 20%). CONCLUSIONS: PFA-100 is a rapid simple assay used as a means of assessing inhibition of platelet aggregation during PCI performed with glycoprotein IIb/IIIa inhibition. Failure to achieve nonclosure early after the initiation of abciximab therapy warrants further investigation because there may be an association with adverse cardiac events at 6-month follow-up.

Assessment of thrombocytopenic disorders using the Platelet Function Analyzer (PFA-100).

The Platelet Function Analyzer (PFA-100) was used to measure platelet function in paediatric patients with destructive versus underproduction thrombocytopenia. Closure time (CT) and total volume (TV) measurements with standard 150 microm apertures discriminated between patients with similar platelet counts from 30 to 150 x 10(9)/l. However, at platelet counts < 30 x 10(9)/l, a 100-microm aperture (experimental) gave the best assessment of platelet function. TV results could be analysed even when CTs were indeterminate. Further investigations are warranted to more fully understand the relationships among platelet function as measured by the PFA-100 in standard/experimental modes, bleeding and transfusion outcome in thrombocytopenia.