The PFA-100 system is a platelet function analyzer designed to measure platelet-related primary hemostasis. The instrument uses two disposable cartridges: a collagen/epinephrine (CEPI) and a collagen/ADP (CADP) cartridge. Previous experience has shown that CEPI cartridges detect qualitative platelet defects, including acetylsalicylic acid (ASA)-induced abnormalities, while CADP cartridges detect only thrombocytopathies and not ASA use. In this seven-center trial, 206 healthy subjects and 176 persons with various platelet-related defects, including 127 ASA users, were studied. The platelet function status was determined by a platelet function test panel. Comparisons were made as to how well the defects were identified by the PFA-100 system and by platelet aggregometry. The reference intervals for both cartridges, testing the 206 healthy subjects, were similar to values described in smaller studies in the literature [mean closure time (CT) 132 s for CEPI and 93 s for CADP]. The use of different lot numbers of cartridges or duplicate versus singleton testing revealed no differences. Compared with the platelet function status, the PFA-100 system had a clinical sensitivity of 94.9% and a specificity of 88.8%. For aggregometry, a sensitivity of 94.3% and a specificity of 88.3% were obtained. These values are based on all 382 specimens. A separate analysis of sensitivity by type of platelet defect, ASA use versus congenital thrombocytopathies, revealed for the PFA-100 system a 94.5% sensitivity in identifying ASA users and a 95.9% sensitivity in identifying the other defects. For aggregometry, the values were 100% for ASA users and 79.6% for congenital defects. Analysis of concordance between the PFA-100 system and aggregometry revealed no difference in clinical sensitivity and specificity between the systems (p > 0.9999). The overall agreement was 87.5%, with a Kappa index of 0.751. The two tests are thus equivalent in their ability to identify normal and abnormal platelet defects. Testing 126 subjects who took 325 mg ASA revealed that the PFA-100 system (CEPI) was able to detect 71.7% of ASA-induced defects with a positive predictive value of 97.8%. The overall clinical accuracy of the system, calculated from the area under the ROC curve, was 0.977. The data suggest that the PFA-100 system is highly accurate in discriminating normal from abnormal platelet function. The ease of operation of the instrument makes it a useful tool to use in screening patients for platelet-related hemostasis defects.

The PFA-l()O'!!!l system* (Oade International [ne., Miami, FL) is a platelet function anaIyzer, the design of which is based on the technology of the Thrombostat 4000 VDG, Seton, Germany.t It was developed to measure primary, platelet dependent hemostasis in citrated whole blood in vitro. A first pilot study was conducted with the instrument to assess performance characteristics. Healthy subjects (normals) who had not ingested any medications, and patients (abnormals) with primary, platelet-related hemostasis defects, which included users of aspirin, were studied with two test cartridges; collagen/ADP and collagen/epinephrine. Before the study certain variables were tested that ascertained that blood drawn into either 3.8% or 3.2% sodium citrate containing vacutainers (rather than syringes) could be used for testing. Tests must be performed within a five-hour time span from drawing to testing, and blood must be kept at room temperature. Normal reference nlues were 77-133 seconds closure limes for collagen/ADP and 98-185 seconds for collagen! epinephrine. Precision testing revealed a CV of <10% for within-day and between-day (five days) analyses on collagen/ADP cartridges and a CV of 5-14% for both runs on the collagen/epinephrine cartridges. No clinically important differences were found between measurements in the two positions of the instrument, although one follows the other. Tests on 99 normals and 70 abnormals were performed and data expressed as receiver/operator characteristics (ROC) curves that assess the combined sensitivity and specificity of a procedure. An area under the curve of 1.0 means that all samples (normals + abnormals) were accurately identified; a value of 0.5 indicates that the test is noninformative. Using collagen/ADP cartridges a value of 0.76 was found when testing 99 normals and 52 abnormals. All aspirin users had been omitted from the abnormals. With the cOllagenl epinephrine cartridges, evaluating 99 normals and 70 abnormais, a value of 0.89 was obtained. This analysis entailed also aspirin users. Of 24 known aspirin users the collagen!epinephrine cartridges identified 20 that had normal closure times with the collagen! ADP cartridges. Three aspirin users had abnormal values with both cartridges, one subject was normal with both. When the traditional Ivy bleeding times were plotted as an ROC curve, an area under the curve of 0.698 was found. The data suggest that the PFA-I()OtSl system identifies normals and abnormals (subjects with primary, platelet related hemostasis derects) with greater sensitivity and specificity than the present widely used bleeding time. The instrument is easy to use and could be adapted 10 routine laboratory use. The data presented are preliminary and need to be confirmed by additional testing.

No abstract

Assays which detect the release of platelet-specific proteins and of peptides during thrombogenesis and are considered markers of activation of platelets and the coagulation system have recently been developed. This study was designed to utilize these haemostasis-related markers to test the hypothesis that a prethrombotic state is related to the presence, aetiology and severity of heart failure. Seventy patients with heart failure were evaluated and data were compared with 36 normal volunteers and 41 patients with coronary artery disease without heart failure (CAD). Thrombogenesis was documented using assays which measure platelet function, thrombin activity and fibrinolysis. Platelet function was measured by determining plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (BTG). Thrombin-antithrombin III complexes (TAT) and fibrinopeptide A (FPA) were determined to evaluate thrombin activity. Fibrinolytic activity was assessed by measuring D-Dimer levels. Patients with heart failure, when compared to normals, had increased plasma levels of BTG (89 +/- 62 IU.ml-1 vs 50 +/- 59 IU.ml-1, P < 0.01), TAT (4.6 +/- 4.3 micrograms.l-1 vs 2.3 +/- 0.64 micrograms.l-1, P < 0.005), and D-Dimer levels (506 +/- 444 IU.ml-1 vs 191 +/- 144 IU.ml-1, P < 0.0001). Patients with heart failure, when compared to the CAD group, had increased plasma levels of D-Dimer (506 +/- 444 ng.ml-1 vs 191 +/- 144 ng.ml-1, P < 0.05). Aetiology of heart failure did not affect these measurements. Patients with severe heart failure, as determined by high plasma norepinephrine concentration or low ejection fraction, were more likely to have activation of platelets and the coagulation system.(ABSTRACT TRUNCATED AT 250 WORDS)

The sticky platelet syndrome (SPS) is an autosomal dominant platelet disorder associated with arterial and venous thromboembolic events. It is characterized by hyperaggregability of platelets in platelet-rich plasma with adenosine diphosphate (ADP) and epinephrine (type I), epinephrine alone (type II), or ADP alone (type III). Clinically, patients may present with angina pectoris, acute myocardial infarction (MI), transient cerebral ischemic attacks, stroke, retinal thrombosis, peripheral arterial thrombosis, and venous thrombosis, frequently recurrent under oral anticoagulant therapy. Clinical symptoms, especially arterial, often present following emotional stress. Combinations of SPS with other congenital thrombophilic defects have been described. Low-dose aspirin treatment (80 to 100 mg) ameliorates the clinical symptoms and normalizes hyperaggregability. The precise etiology of this defect is at present not known, but receptors on the platelet surface may be involved. Normal levels of platelet factor 4 (PF4) and p-thromboglobulin in plasma suggest that the platelets are not activated at all times; they appear to become hyperactive upon ADP or adrenaline release. In vivo clumping could temporarily or permanently occlude a vessel, leading to the described clinical manifestations. The syndrome appears to be prominent especially in patients with unexplained arterial vascular occlusions.