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Biomedical subjects

Marian A Packham

Publications and source records attributed to Marian A Packham.

3 recordsLinked to original sources
PubMed2003

Platelet function assays.

The roles of platelets in hemostasis and arterial thrombosis involve their adherence to sites of vessel injury or ruptured atherosclerotic plaques, aggregation to form hemostatic plugs or thrombi, and acceleration of the coagulation cascade leading to the formation of thrombin. These roles of platelets are described in this review, hereditary platelet defects and other abnormalities associated with bleeding disorders are listed, and the various aggregating agents are discussed. A number of tests of platelet function are reviewed, including a description of their advantages and disadvantages: bleeding time determination; measurement of platelet aggregation in citrated platelet-rich plasma by recording changes in light transmission; measurement of platelet aggregation in citrated whole blood by impedance aggregometry; measurement of platelet-related hemostasis with the high shear Platelet Function Analyzer (PFA-100) system and the Ultegra Rapid Platelet Function Assay; use of the Cone and Plate(let) Analyzer to measure platelet adherence and aggregation under conditions of high shear; measurement of secretion of granule contents (ATP, 14C-serotonin, platelet factor 4, beta-thromboglobulin) and the formation of thromboxane B(2); and use of flow cytometry to assess the state of platelet activation (including conformational changes in membrane glycoproteins and surface expression of P-selectin and phosphatidylserine) ex vivo and in vitro following addition of agonists, and to measure levels of platelet membrane glycoproteins in the detection of inherited deficiencies.

Blood Platelet Disorders↗
PubMed2002

Ethanol enhances the inhibitory effect of an oral GPIIb/IIIa antagonist on human platelet function.

Ethanol is a commonly used substance that can significantly influence platelet responses when combined with therapeutic drugs. In in vitro studies, we combined ethanol with LY309562, a novel 2,6-disubstituted isoquinolone RGD mimic that competes for fibrinogen binding to GPIIb/IIIa. Ethanol inhibits aggregation and secretion, partly by inhibiting thromboxane A(2) formation. We measured aggregation and secretion of dense granule contents by platelets labeled with [(14)C] serotonin in plasma from blood anticoagulated with FPRCH(2)Cl (PPACK). Alone, LY309562 dose-dependently inhibited aggregation induced by 10 micromol/L adenosine diphosphate, 1 microg/mL collagen, 2 micromol/L U46619 (a thromboxane A(2) mimetic), or 15 micromol/L SFLLRN (protease-activated receptor-1-activating peptide); inhibition was complete at 1 micromol/L LY309562 and partial at 0.1 micromol/L (50% inhibitory concentration [IC(50)] 0.19-0.33 micromol/L). Secretion induced by collagen, U46619, and SFLLRN was also inhibited by LY309562 (IC(50) 0.08-0.31 micromol/L). At inhibitory concentrations of LY309562, ethanol (2 or 4 mg/mL) further inhibited responses to collagen, U46619, and SFLLRN (IC(50) for aggregation 0.12-0.16 micromol/L; for secretion 0.04-0.12 micromol/L). Responses of aspirin-treated platelets to U46619 were also inhibited, indicating that ethanol was not acting solely by inhibiting thromboxane A(2) formation. Because it is likely that our results with LY309562 are representative of results with other GPIIb/IIIa antagonists, our in vitro data suggest that the concomitant use of GPIIb/IIIa antagonists and consumption of alcoholic beverages may result in further impairment of platelet participation in hemostasis and thrombosis.

Amino Acid Chloromethyl Ketones↗