RESUMO
BACKGROUND: The pathophysiologic mechanisms leading to residual platelet reactivity (RPR) on antiplatelet therapy, a condition high prevalent in patients with acute coronary syndrome, are not yet elucidated. In the acute phase of coronary artery disease large amounts of ultra large VWF multimers (ULVWF) are released and cleaved by the activity of ADAMTS-13. OBJECTIVE: Aim of this study was to evaluate the relationships between VWF antigen (VWF:Ag) levels, collagen binding activity of VWF (VWF:CB), ADAMTS-13 and interleukin-6 (IL-6) levels in affecting platelet response to dual antiplatelet treatment. METHODS: In 159 acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions we measured platelet function by platelet aggregation with two agonists [1 mM arachidonic acid (AA) and 10 microM ADP]. We defined patients with RPR those with platelet aggregation by AA >20% and/or ADP (10 micromol) >70%. RESULTS: We found significantly lower ADAMTS-13 activity, elevated IL-6, VWF:Ag and VWF:CB levels in patients with RPR. A lower ADAMTS-13 activity was present in patients with VWF:Ag and VWF:CB in the upper tertile. At the multivariate analysis ADAMTS-13 activity and IL-6 were independent risk factors for RPR. CONCLUSION: Our results indicate that ADAMTS-13 activity and IL-6 levels independently affect RPR and suggest that, by different pathways, both are involved in the variable response to antiplatelet therapy.
Assuntos
Proteínas ADAM/metabolismo , Síndrome Coronariana Aguda/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Fator de von Willebrand/análise , Proteína ADAMTS13 , Síndrome Coronariana Aguda/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Gaseous mediators such as nitric oxide (NO) play a major regulatory role in the cardiovascular system homeostasis, including platelet aggregation. Here, we investigated whether hydrogen sulfide (H(2)S), a newly recognized endogenous mediator, can affects aggregation of human platelets, using sodium hydrogen sulfide (NaHS) as H(2)S-donor. NaHS inhibited platelet aggregation induced by ADP, collagen, epinephrine, arachidonic acid, thromboxane mimetic, U46619, and thrombin. H(2)S effect was not dependent by cAMP/cGMP generation, NO production or potassium-channels opening. NaHS concentrations (up to 10 mM) did not exert toxic effects on platelet viability. The possible protective role of endogenous H(2)S in cardiovascular system is discussed.
