Mutações gênicas das glicoproteínas plaquetárias e resposta ao tirofiban na síndrome coronariana aguda
Palavras-chave:
Glicoproteínas, Complexo glicoproteico GPIIb-IIIa de plaquetas, Polimorfismo genético, Síndrome coronariana aguda, Angina instável, Infarto do miocárdioResumo
CONTEXTO E OBJETIVOS: Inibidores da glicoproteína (abciximab, eptifibatide, tirofiban) são utilizados em pacientes com angina instável e infarto do miocárdio sem elevação do segmento ST (IAMSSST) antes da intervenção coronária percutânea. Dentre eles, o tirofiban é o menos eficaz. Nossa hipótese é que a resposta ao tirofiban possa estar associada a mutações no gene da glicoproteína. DESENHO E LOCAL: Estudo prospectivo na Unidade de Emergência do Instituto do Coração (InCor), Universidade de São Paulo (USP). MÉTODOS: Foram analisadas a evolução intra-hospitalar e agregabilidade plaquetária em resposta ao tirofiban de 4 mutações da glicoproteína em 50 pacientes com indicação para intervenção coronária percutânea, 17 (34%) com angina instável e 33 (66%) com IAMSSST. A agregação plaquetária foi analisada pelo método de Born. Amostras de sangue foram obtidas antes e uma hora após infusão do tirofiban. As glicoproteínas Ia (807C/T), Ib (Thr/Met), IIb (Ile/Ser) e IIIa (PIA) foram as mutações selecionadas. RESULTADOS: Hipertensão, dislipidemia, diabetes, tabagismo, doença coronariana e acidente vascular cerebral prévios foram semelhantes entre os grupos. Observou-se menor agregabilidade plaquetária dos genótipos mutantes da glicoproteína IIIa antes da administração de tirofiban do genótipo selvagem (41% ± 22% versus 56% ± 21%; P = 0,035). Genótipos mutantes da glicoproteína IIIa correlacionaram-se moderadamente com menor inibição plaquetária (r = -0,31; P = 0,030). Após a administração tirofiban, as mutações das glicoproteínas Ia, Ib, IIb, e IIIa não influenciaram o grau de inibição da agregação plaquetária e mortalidade intra-hospitalar. CONCLUSÕES: Mutações das glicoproteínas Ia, Ib, IIb e IIIa não influenciaram a agregação plaquetária em resposta ao tirofiban nos pacientes com angina instável e IAMSSST.
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Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med. 1995;332(23):1553-9.
Kleiman NS. Pharmacokinetics and pharmacodynamics of glycoprotein IIb-IIIa inhibitors. Am Heart J. 1999;138(4 Pt 2):263-75.
Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. N Engl J Med. 1998;338(21):1488-97.
Zhao XQ, Théroux P, Snapinn SM, Sax FL. Intracoronary thrombus and platelet glycoprotein IIb/IIIa receptor blockade with tirofiban in unstable angina or non-Q-wave myocardial infarction. Angiographic results from the PRISM-PLUS trial (Platelet receptor inhibition for ischemic syndrome management in patients limited by unstable signs and symptoms). PRISM-PLUS Investigators. Circulation. 1999;100(15):1609-15.
Topol EJ, Moliterno DJ, Herrmann HC, et al. Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med. 2001;344(25):1888-94.
Batchelor WB, Tolleson TR, Huang Y, et al. Randomized COMparison of platelet inhibition with abciximab, tiRofiban and eptifibatide during percutaneous coronary intervention in acute coronary syndromes: the COMPARE trial. Comparison Of Measurements of Platelet aggregation with Aggrastat, Reopro, and Eptifibatide. Circulation. 2002;106(12):1470-6.
Cox D, Smith R, Quinn M, et al. Evidence of platelet activation during treatment with a GPIIb/IIIa antagonist in patients presenting with acute coronary syndromes. J Am Coll Cardiol. 2000;36(5):1514-9.
Quinn MJ, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa inhibitors: recognition of a two-edged sword? Circulation. 2002;106(3):379-85.
Jallu V, Poulain P, Fuchs PF, Kaplan C, de Brevern AG. Modeling and molecular dynamics of HPA-1a and -1b polymorphisms: effects on the structure of the β3 subunit of the αIIb β3 integrin. PLoS One. 2012;7(11):e47304.
Andrioli G, Minuz P, Solero P, et al. Defective platelet response to arachidonic acid and thromboxane A(2) in subjects with Pl(A2) polymorphism of beta(3) subunit (glycoprotein IIIa). Br J Haematol. 2000;110(4):911-8.
Lopes NH, Pereira AC, Hueb W, et al. Effect of glycoprotein IIIa PlA2 polymorphism on outcome of patients with stable coronary artery disease and effect of smoking. Am J Cardiol. 2004;93(12):1469-72.
Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation. 2002;106(14):1893-900.
Born GV, Cross MJ. The aggregation of blood platelets. J Physiol. 1963;168:178-95.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215.
Reiner AP, Aramaki KM, Teramura G, Gaur L. Analysis of platelet glycoprotein Ia (alpha2 integrin) allele frequencies in three North American populations reveals genetic association between nucleotide 807C/T and amino acid 505 Glu/Lys (HPA-5) dimorphisms. Thromb Haemost. 1998;80(3):449-56.
Unkelbach K, Kalb R, Santoso S, et al. Genomic RFLP typing of human platelet alloantigens Zw(PIA), Ko, Bak and Br (HPA-1, 2, 3, 5). Br J Haematol. 1995;89(1):169-76.
Wagner KR, Giles WH, Johnson CJ, et al. Platelet glycoprotein receptor IIIa polymorphism P1A2 and ischemic stroke risk: the Stroke Prevention in Young Women Study. Stroke. 1998;29(3):581-5.
Cook GE, Bray PF, Hamlington JD, et al. PlA2 polymorphism and efficacy of aspirin. Lancet. 1998;351(9111):1253.
Szczeklik A, Undas A, Sanak M, Frolow M, Wegrzyn W. Relationship between bleeding time, aspirin and the PlA1/A2 polymorphism of platelet glycoprotein IIIa. Br J Haematol. 2000;110(4):965-7.
Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Variability in platelet aggregation following sustained aspirin and clopidogrel treatment in patients with coronary heart disease and influence of the 807 C/T polymorphism of the glycoprotein Ia gene. Am J Cardiol. 2005;96(8):1095-9.
Gonzalez-Conejero R, Rivera J, Corral J, et al. Biological assessment of aspirin efficacy on healthy individuals: heterogeneous response or aspirin failure? Stroke. 2005;36(2):276-80.
Floyd CN, Ellis BH, Ferro A. The PlA1/A2 polymorphism of glycoprotein IIIa as a risk factor for stroke: a systematic review and meta-analysis. PLoS One. 2014;9(7):e100239.
Floyd CN, Mustafa A, Ferro A. The PlA1/A2 polymorphism of glycoprotein IIIa as a risk factor for myocardial infarction: a meta- analysis. PLoS One. 2014;9(7):e101518.
Kereiakes DJ, Broderick TM, Roth EM, et al. Time course, magnitude, and consistency of platelet inhibition by abciximab, tirofiban, or eptifibatide in patients with unstable angina pectoris undergoing percutaneous coronary intervention. Am J Cardiol. 1999;84(4):391-5.
O’Connor FF, Shields DC, Fitzgerald A, et al. Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes. Blood. 2001;98(12):3256-60.
Wheeler GL, Braden GA, Bray PF, et al. Reduced inhibition by abciximab in platelets with the PlA2 polymorphism. Am Heart J. 2002;143(1):76-82.
Weber AA, Jacobs C, Meila D, et al. No evidence for an influence of the human platelet antigen-1 polymorphism on the antiplatelet effects of glycoprotein IIb/IIIa inhibitors. Pharmacogenetics. 2002;12(7):581-3.
Verdoia M, Pergolini P, Camaro C, et al. PlA(1)/PlA(2) polymorphism does not influence response to Gp IIb-IIIa inhibitors in patients undergoing coronary angioplasty. Blood Coagul Fibrinolysis. 2013;24(4):411-8.
Khaspekova SG, Zyuryaev IT, Yakushkin W, et al. Relationships of glycoproteins IIb-IIIa and Ib content with mean platelet volume and their genetic polymorphisms. Blood Coagul Fibrinolysis. 2014;25(2):128-34.
Schneider DJ, Herrmann HC, Lakkis N, et al. Enhanced early inhibition of platelet aggregation with an increased bolus of tirofiban. Am J Cardiol. 2002;90(12):1421-3.
Sethi A, Bahekar A, Doshi H, et al. Tirofiban use with clopidogrel and aspirin decreases adverse cardiovascular events after percutaneous coronary intervention for ST-elevation myocardial infarction: a meta-analysis of randomized trials. Can J Cardiol. 2011;27(5):548-54.
Dormandy J, Ernst E, Matrai A, Flute PT. Hemorrheologic changes following acute myocardial infarction. Am Heart J. 1982;104(6):1364-7.
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