Clinical, Pharmacokinetic, and Pharmacogenetic Determinants of Clopidogrel Resistance in Korean Patients with Acute Coronary Syndrome / 대한진단검사의학회지

BACKGROUND: Clopidogrel has been widely used to prevent recurrent ischemia in patients with acute coronary syndrome (ACS). However, inter-individual variability in response to clopidogrel has been a problem in the clinical setting. The aim of the present study was to investigate the frequency of clopidogrel resistance and to determine the clinical, pharmacokinetic, and pharmacogenetic factors for clopidogrel resistance in Korean patients with ACS. METHODS: Clinical information, such as the underlying diseases and concurrent medications, of 114 patients with ACS who received clopidogrel therapy was studied. The degree of inhibition of platelets was assessed using the VerifyNow assay (Accumetrics, USA). The patients who showed less than 20% inhibition of platelets were defined as non-responders to clopidogrel treatment. Steady state plasma concentrations of clopidogrel were measured using HPLC/tandem mass spectrometry. CYP2C19 genotyping was also performed. RESULTS: A wide inter-individual variability was observed in platelet inhibition (0-76%); 56 patients (49%) showed less than 20% inhibition. There were no differences between the patients' history of diabetes mellitus and concurrent medications as well as the plasma concentrations of clopidogrel of the responders and non-responders. CYP2C19 variants, including CYP2C19*2 and CYP2C19*3, were more commonly observed in the non-responders than in the responders (P value<0.0001). CONCLUSIONS: The response to clopidogrel was highly variable in Korean patients with ACS. The results of the present study confirmed that the genetic polymorphism of CYP2C19 could be important in clopidogrel response. However, further studies are required to investigate other likely factors involved in clopidogrel resistance.

insight on serum levels of hepatocyte growth factor and anti-platelet antibodies in various hepatic insults and their correlation with concomitant thrombocytopenia

Many recent studies have shown that hepatocyte growth factor [HGF] is a potent mitogen in vivo. HGF play an important role in liver regeneration because it is increased after liver injury and higher levels are maintained in serum during liver regeneration. This study was designed to evaluate serum levels of hepatocyte growth factor [HGF] and blood positivity for anti-platelet antibodies [APA] in children with acute and chronic liver diseases [CLD] of varied etiology and to correlate their levels with concomitant thrombocytopenia. The study included 50 patients and 20 control children. There were 20 patients with acute viral hepatitis [AVH] and 30 patients with CLD [10 chronic viral hepatitis, 10 metabolic liver diseases, and 10 autoimmune liver diseases]. Venous blood sample was collected for complete blood count, liver function tests and for ELISA estimation of serum HGF and detection of blood positivity for APA. All liver function tests were significantly [p<0.05] increased in patients compared to control Platelet count was significantly [p<0.05] decreased in patients with chronic viral hepatitis [CVH] and autoimmune LD compared to both control and AVH groups. Serum HGF level was significantly elevated in all patients [PI =0.006] compared to control levels and in patients with autoimmune LD compared to patients with AVH [P2=0.013], CVH [P3=0.02] and metabolic LD [P4=0.03]. There was a positive significant correlation between serum levels of HGF and serum total bilirubin, ALT and blood positivity for APA. The APA was detected in 25 patients' blood samples with a significantly higher frequency in patients with autoimmune LD. Using the receiver operating characteristic [ROC] curve analysis revealed that blood positivity for APA is a specific, while thrombocytopenia is sensitive indicators for liability of occurrence of bleeding episodes. It could be concluded that serum levels of HGF were elevated in all forms of hepatic insults and correlate with the extent of hepatic derangement as judged by serum levels of total bilirubin and serum ALT. Moreover, 50% of patients with chronic liver diseases were found positive for APA that correlate with serum levels of HGF and the extent of concomitant thrombocytopenia and could be considered as a specific predictor for the occurrence of bleeding episodes in these patients

Determinación de anticuerpos antiplaquetarios, mediante la técnica de inumnofluorescencia indirecta en población infantil aparentemente sana / Determination of antibodies antiplaquetarios by means of the technical of inmunofluorecenica indirect in population childlike apparently healthy

La Púrpura Trombocitopénica (PTI), es una enfermedad frecuente en la infancia, pudiendo presentarse asociada a otras patologías. Esta puede tener etiología autoinmunitaria, en la que se observa destrucción excesiva de plaquetas mediada por autoanticuerpos contra antígenos presentes en la superficie plaquetaria, induciendo así su eliminación por los macrófagos del hígado y del bazo, contribuyendo así a la trombocitopenia. Por otro lado, se ha descrito la presencia de estos anticuerpos en personas normales, por lo que se planteó la inmunofluorescencia indirecta (IFI) en un grupo de once niños aparentemente sanos, tanto en suero como en eluido de plaquetas. En la mayoría de ellos no se detectaron anticuerpos antiplaquetarios séricos, ni tampoco en eluido. Sin embargo, el 18 por ciento presentó reacción positiva para estos anticuerpos, solo en la primera dilución (1:5). Así fue posible establecer este título como dentro de los rangos de normalidad para las posteriores determinaciones. De igual manera, se procesaron muestras de nueve niños con diagnóstico clínico PTI, en los que fue posible detectar a estos anticuerpos en diferentes diluciones de suero y eluido de plaquetas, indicando así la existencia de un fenómeno autoinmunitario. Los títulos encontrados en estos pacientes fueron superiores o iguales 1:10, lo que diferenció significativamente del grupo normal, en relación a la magnitud de la presencia de anticuerpos antiplaquetarios (p<0,005). Los hallazgos de anticuerpos antiplaquetarios en el eluido obtenido de las plaquetas de estos pacientes también corresponden a diferentes títulos, aunque estos no se detectaron en todos los casos. Sería necesario complementar la caracterización de anticuerpos antiplaquetarios en mayor número de individuos con PTI y establecer una posible una posible relación con otros parámetros

Terapia antiplaquetaria despues de cirugia coronaria / Antiplatelet therapy after coronary surgery

El tratamiento post-operatorio con drogas antiplaquetarias ha demostrado ser benefico para prevenir la obstruccion de injertos venosos utlizados en cirugia coronaria. Este estudio analiza 2 grupos de pacientes, uno (212) si terapia antiplaquetaria y el otro (205) con antiplaquetarios. Se encontro una diferencia importante en la recurrencia clinica de la angina post-operatoria. Se discute la fisiopatologia en la oclusion post-operatoria temprana y tardia de los injertos y el efecto de los medicamentos antiplaquetarios en la prevencion de ese fenomeno