State-of-the-Art Review : The Effect of Antiplatelet Drugs, Heparin, and Preanalytical Variables on Platelet Function Detected by the Platelet Function Analyzer (PFA-100®)

Abstract

The platelet function analyzer (PFA)-100 is a newly developed instrument that provides a rapid, in vitro, quantitative measurement of platelet adhesion and aggregation in whole blood flowing through a small aperture under high shear conditions. Thirty patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and ten normal individuals were included in this study. In vitro and in vivo studies were conducted to discern the effect of combinations of antiplatelet drugs (aspirin, ticlopidine, abciximab) and heparin on the performance of the device as well as the effects of preanalytical variables, such as method of sample collection and ex vivo anticoagulants. Studies were also conducted examining the effect of aperture size (standard 150 microns vs. smaller 120 microns) on the ability of the device to detect the effect of antiplatelet drugs. There was no difference in mean PFA-100 closure time with citrate versus PPACK anticoagulants or with venipuncture vs. sheath sampling. Closure times did not vary with heparin administration. Closure times were slightly longer for patients taking aspirin plus ticlopidine compared to aspirin alone (p = NS). In contrast adenosine disphosphate (ADP) induced platelet aggregation was significantly less in patients that took aspirin plus ticlopidine vs. aspirin alone (p = .0005). In vitro, there was a dose-dependent increase in closure time for both aperture sizes with increasing abciximab concentration. Although both cartridges showed infinite closure times at an abciximab concentration of 2.25 micrograms/mL, there was a slight benefit to using the 120 microns aperture cartridges at abciximab concentrations of 1.75 to 2.0 micrograms/mL. In ten patients who were followed during abciximab therapy to assess the effect of aperture size, the PFA-100 was able to detect in vivo platelet inhibition by abciximab, but detection of recovery from abciximab-induced platelet dysfunction was slightly better for the PFA-100 with the 120 microns aperture compared to the standard 150 microns aperture collagen/ADP cartridge.

Platelet Function Under Aspirin, Clopidogrel, and Both After Ischemic Stroke

“…Most interestingly, CADP-CT was longer under combined aspirin and clopidogrel than under either monotherapy. In patients undergoing percutaneous transluminal coronary angioplasty, the combination of ticlopidine and aspirin led to a nonsignificant increase in CADP-CT compared with aspirin alone 21 or was associated with normal CADP-CT 23 ; however, ticlopidine medication was shorter than in our study. The combination therapy was associated with a heterogenous response among our patients.…”

“…10 -12,20 -23 It is not sensitive to heparin or defects in coagulation proteins, eg, hemophilia A. 12,21 To the best of our knowledge, the PFA-100 has not been applied in clinical stroke. As expected, the CEPI-CT was strongly prolonged under treatment with aspirin compared with clopidogrel or the control group.…”

Effect of Therapeutic Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy on Platelet Function

“…Samples were drawn from a central line when available, otherwise by venipuncture. All central lines contained fluid with 0.5 units heparin per milliliter (heparin at this concentration does not affect PFA-100 time [10,11] ). Samples consisted of 1.8 ml drawn into the appropriate sodium citrate tubes, which were hand-carried to the laboratory.…”

Antiplatelet Drug Resistance and Drug-Drug Interactions: Role of Cytochrome P450 3A4

“…The ease of operation of the instrument makes it a useful tool to use in screening patients for selected plateletrelated homeostasis defects. A major limitation of the PFA-100 is that patients receiving intravenous GP IIb/IIIa inhibitors with profound GP IIb/IIIa inhibition will often have aperture closure times greater than 300 s, making interpretations difficult to delineate (27). The Rapid Platelet Function Assay (Accumetrics, San Diego, California, USA) is an automated tubidimetric whole blood assay designed to assess platelet function based on the ability to activated platelets to bind fibrinogen.…”