Q: How do Sonoclot, PFA-100, and Accumetrics compare in assessing platelet function? Does each have an application to assess aspirin, Plavix, and Integrilin?
A. The Sonoclot, PFA-100, and Accumetrics instruments measure the effect of aspirin, Plavix, and other antiplatelet medications but with different parameters and different information.
The PFA-100, manufactured by Dade Behring, has, for the most part, replaced the bleeding time and is widely used in most hospitals to measure platelet function. The PFA-100 system has two cartridges. The collagen-ADP cartridge detects aspirin effects or aspirin-like effects. The collagen-epinephrine cartridge detects von Willebrand disease, intrinsic platelet defects, and other platelet-inhibiting agents. This is the instrument of choice for general platelet-function screening.
Accumetrics manufactures the Ultegra instrument, which measures aspirin and Plavix resistance. The aspirin-resistance test uses the reagent cationic propyl gallate, which activates the platelet COX-1 pathway and quantifies platelet aggregation as aspirin reaction units, or ARU. Aspirin nonresponsiveness is defined as 550 ARU or greater.
The Plavix-resistance test measures P2Y12 receptor blockade. The system is a turbidimetric-based, optical detection aggregation. Fibrinogen-coated microparticles aggregate in whole blood in proportion to the number of expressed platelet GPIIb/GPIIIa receptors. The results are reported as a percentage of platelets inhibited. The normal average is between 40 and 60 percent.
The Sonoclot, manufactured by Sienco, is a global measurement of the hemostatic system. It produces a graph or signature induced by the activated clotting time and measures the rate of fibrin polymerization and clot retraction. However, it has a large coefficient of variation (9.2 to 41.7 percent). It is generally used as a bedside analyzer during operative procedures. It is not widely used in most hospitals as a general measure of platelet function. I would not recommend it as an instrument for routine platelet-function screening.
Feuring M, Haseroth K, Janson CP, et al. Inhibition of platelet aggregation after intake of acetylsalicylic acid detected by a platelet function analyzer (PFA-100). Int J Clin Pharmacol Ther. 1999;37:584–588.
LaForce WR, Brudno DS, Kanto WP, et al. Evaluation of the Sonoclot analyzer for the measurement of platelet function in whole blood. Ann Clin Lab Sci. 1992;22:30–33.
Wang JC, Aucoin-Barry D, Manuelian D, et al. Incidence of aspirin nonresponsiveness using the Ultegra Rapid Platelet Function Assay-ASA. Am J Cardiol. 2003;92:1492–1494.
William E. Luper, MD
Hemostasis Thrombosis Laboratory Ltd.
Q. Why is graft-versus-host disease more prevalent among recipients of blood from related donors than among recipients of blood from unrelated donors?
A. The pathogenesis of graft-versus-host disease, or GVHD, requires immunocompetent cells from the donor to engraft and multiply in an immunologically recognizable recipient. Most often, this occurs in the setting of allogeneic hematopoietic stem cell transplantation (where its occurrence is predictable), but it may also occur after transfusion if a sufficient number of viable lymphocytes are transfused. At greatest risk is a recipient whose disease or (chemo)therapy, or both, has reduced the immune system’s capability to respond to the transfused cells. However, any donor-recipient pairing could potentially lead to post-transfusion GVHD if the donor were to have an “unrejectable” phenotype: If the blood donor is homozygous for a human leukocyte antigen haplotype for which the recipient is heterozygous, the transfused and engrafted cells would be able to recognize and attack an antigen expressed by host cells, but the host cells would not “see” an immunogenic target on their attackers.
This may happen approximately once in every 22,000 transfusions in the United States but would be expected to occur more frequently when the donor and recipient were related genetically and in societies with a population whose human leukocyte antigen alleles were less diverse.
CAP transfusion medicine checklist question TRM.45270, phase II, asks, “Is there a process to ensure that all directed donations between blood relatives are irradiated?” Some facilities opt not to disentangle family relationships and instead irradiate all directed donations. In Japan, where the population is less genetically diverse, all cellular components are irradiated in response to the higher frequency of post-transfusion GVHD in immunocompetent recipients. Storage time (during which leukocyte viability decreases) and leukoreduction may also reduce the likelihood that a sufficient dose of viable cells capable of causing GVHD is transfused.
In the future, pathogen-inactivation treatments may cross-link or disrupt, or both, the DNA of leukocytes at a frequency even higher than that achieved by gamma irradiation and may be effective at preventing post-transfusion GVHD.
James P. AuBuchon, MD
E. Elizabeth French Professor and Chair of Pathology
Dartmouth-Hitchcock Medical Center
Chair, CAP Transfusion Medicine Resource Committee