Microsoft word - tmu2005issue#4 _2_.doc

TRANSFUSION MEDICINE UPDATE
Institute for Transfusion Medicine Issue #4 2005
Aspirin Resistance
Zella R. Zeigler, MD, Medical Director, Hemostasis & Thrombosis Outpatient Clinic
The Institute for Transfusion Medicine
___________________________________________________________________________ hereditary factors which influence platelet INTRODUCTION
responses. Bioavailability may be affected by The use of aspirin (in doses of 81-325 mg/day) non-compliance or concomitant use of non- for secondary prevention in cardiovascular steroidal anti-inflammatory agents. Increased disease reduces subsequent events by about platelet turnover and increased platelet COX-2 25%. Aspirin treatment failures may have expression have also been associated with multiple causes and aspirin resistance is aspirin resistance. In addition, platelet polymor- phisms, such as the PlA1A2 phenotype, appear Aspirin resistance is the inability of aspirin to to influence platelet responses to aspirin. produce the expected aspirin effect on in vitro tests of platelet function. Aspirin inhibits the TESTING:
cyclooxygenase (COX) pathway in the platelet, Different platelet function assays have been reducing the production of thromboxane A2 used to evaluate aspirin resistance. These (TxA2), a transient biologic product which include bleeding times, platelet aggregation in platelet rich plasma and in whole blood, vasoconstriction. Laboratory tests which have measurements of thromboxane synthesis, the been used to evaluate aspirin effects include the PFA-100 (Platelet Function Analyzer, Dade) and following: 1) inhibition of thromboxane (TxA2) rapid platelet function testing using an synthesis, 2) inhibition of TxA2 -dependent platelet aggregation (in platelet rich plasma or agglutination in whole blood in the Accumetrics whole blood), 3) prolongation of bleeding or closure times and 4) analysis of the propyl gallate (c-PG) effect (which activates platelets Accumetrics device) have the advantage of through the COX pathway) in the Ultegra Rapid being easily done in routine laboratories with Platelet Function Assay (Accumetrics VerifyNow real time results. The Accumetrics VerifyNow system is FDA approved for this purpose. In this With low aspirin doses, platelet TxA2 falls to assay system, aspirin resistance is defined as an < 95% after several days and this amount of aspirin resistance unit (ARU) > 550. Using the inhibition is necessary to influence platelet PFA-100, aspirin resistance has been defined variously as the lack of prolongation of the relationship between inhibition of TxA2 synthesis collagen/epinephrine closure time or as good and inhibition of second phase aggregation (collagen/epinephrine closure time >300 secs), response is not linear. Using various techniques, partial (prolonged collagen/epinephrine closure the incidence of aspirin resistance ranges from time but < 300 seconds) and no response (normal collagen/epinephrine closure time. MECHANISMS:
CLINICAL IMPACT:
Mechanisms for aspirin resistance include Retrospective and prospective studies in a lack of drug availability and acquired or techniques to evaluate aspirin resistance) have Shafer, AI. Genetic and acquired determinants of been performed with varying doses of aspirin. individual variability of response to antiplatelet These have included patients with cardiac disease, cerebral thrombosis, transient ischemic attacks and peripheral vascular disease. In Rozalski M, Boncler M, Luzak B, et al. Genetic general, aspirin resistance regardless of the factors underlying differential blood platelet laboratory test has been associated with a 1.8- sensitivity to inhibitors. Pharmacological Reports cardiovascular events. These results suggest that aspirin resistance is a real phenomenon Grotemeyer KH, et al. Two-year follow-up of aspirin responder and aspirin non responder. A pilot study including 180 post-stroke patients. TREATMENT OPTIONS:
management of aspirin resistance have not been Mueller MR et al. Variable platelet response to performed. There is no consensus regarding the low-dose ASA and the risk of limb deterioration management of aspirin resistance. However, if a in patients submitted to peripheral arterial patient has evidence for aspirin resistance, it angioplasty. Thromb Haemost 78: 1003-7; 1997. makes sense to a) educate the patient about substances. Additional considerations may thromboxane biosynthesis and the risk of include increasing the aspirin dose (some myocardial infarction, stroke, cardiovascular patients respond to a higher dose) or using death in patients at high risk for cardiovascular alternative antiplatelet therapy, with drugs such Grudmann et al. Aspirin non-responder status in REFERENCES
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Ultegra RPFA-ASA system. Point of Care 3 (2): Editor: Donald L. Kelley, MD, MBA: dkelley@itxm.org. For questions regarding this TMU, please contact Zella R. Zeigler, MD at: zzeigler@itxm.org or 412-209-7320. Copies of the Transfusion Medicine Update can be found on the ITxM web page at www.itxm.org.

Source: http://www.itxm.org/tmu/tmu2005/Issue4-05.pdf