Raúl Izaguirre-Ávila

Background/Objectives: There is wide variability in the individual response to clopidogrel, which depends on CYP2C19 polymorphisms as well as on intrinsic and extrinsic platelet factors. Clopidogrel resistance has been related to an adverse evolution in patients with coronary artery disease. The aim of this study is to analyze the prevalence of CYP2C19 polymorphisms in Mexican mestizo patients and their relationship with clopidogrel platelet response by means of platelet aggregation. Methods: Patients who experienced coronary artery disease (CAD) (N = 160) or stroke (N = 11) and received treatment with clopidogrel were analyzed for CYP2C19 alleles *1, *2, *3, and *17. In total, 81 patients were tested for clopidogrel resistance by ADP-induced aggregation in platelet-rich plasma. CYP2C19 polymorphism was expressed as ultrarapid-, normal-, rapid-, normal/intermediate, intermediate, and poor metabolizers, and the clopidogrel response was assessed by platelet aggregation. Results: The allelic frequencies were 9.6%, 0%, and 11.7% for CYP2C19*2, *3, and *17, respectively. The frequencies of CYP2C19 genotypes were as follows: CYP2C19*1/*1 (62.6%); CYP2C19*1/*17 (19.9%); CYP2C19*1/*2 (12.3%); CYP2C19*2/*17 (2.3%); CYP2C19*2/*2 (2.3%); and CYP2C19*17/*17 (0.6%). Of 81 patients with platelet aggregation, 55.6% were responsive, and 44.4% were resistant to clopidogrel. Clopidogrel resistance had a non-significant trend of association with unfavorable genotypes for metabolism (CYP2C19 *1/*2, *2/*17, and *2/*2) vs. favorable genotypes (CYP2C19 *1/*1, *1/*17, and *17/*17), 64.7% vs. 39.1%, respectively (p = 0.059). Conclusions: The prevalence of CYP2C19 polymorphisms in Mexican mestizo patients is similar to that of the general population. Clopidogrel resistance is a complex in vitro phenomenon that is not explained by CYP2C19 polymorphisms alone.

In 1936, Ignacio Chávez submitted a proposal to the Mexican government for the creation of a cardiology institute. He had studied in Paris, Berlin, an...

En 1936 Ignacio Chávez presentó al gobierno mexicano un proyecto para la creación de un instituto de cardiología. Había es...

Coagulopathy and thrombosis associated with coronavirus disease 2019 (COVID-19) represent a major issue in the management of this disease. In the past months, clinical studies have demonstrated that COVID-19 patients present with a particular hypercoagulable state, in which a markedly increased D-dimer concomitant with increased levels of fibrinogen are observed. This hypercoagulable state leads to an increased risk of thrombosis, which seems to be higher among those patients with critical symptoms of COVID-19. The best therapeutic approach to prevent thrombotic events in COVID-19 has not been determined yet and several questions regarding thromboprophylaxis therapy, such as the time to initiate anticoagulation, type of anticoagulant and dose regimen, have emerged among physicians. To address these concerns, several medical societies have published position papers to provide the opinion of thrombosis experts on the management of coagulopathy and thrombosis associated with COVID-19. In line with this, the Latin America Cooperative Group of Hemostasis and Thrombosis (Grupo CLAHT) has constituted a panel of experts in thrombosis and hemostasis to discuss the available data on this topic. The aim of this review is to summarize the current evidence regarding hemostatic impairment and thrombotic risk in COVID-19 and to provide a carefully revised opinion of Latin American experts on the thromboprophylaxis and management of thrombotic events and coagulopathy in patients with suspected COVID-19.

For centuries, the mystery surrounding blood coagulation stimulated the curiosity of researchers. The knowledge about this function has increased notably in the last century and has permitted to understand numerous physiopatho logical phenomena in several hemorrhagic and thrombotic diseases, and has made it possible to develop diverse drugs of proved efficacy for prevention and therapy. All this was initiated in 1905, when Paul Morawitz published an extensive monograph on the four factors of blood coagulation known until then (fibrinogen, thrombin, thrombokinase, and calcium). In that work, he proposed a blood coagulation model in two stages: thrombin generation and fibrinogen coagulation. In the 1940s a true golden age in coagulation was started with the results of Quick's prothrombin time test, described in 1936, and since then the most employed coagulation test. Besides numerous factors involved in this function were discovered and classified. The discovery and introduction of heparin and coumarin in the anticoagulant therapeutics opened a measureless panorama for the arrival of new antithrombotic drugs. By the middle of the XX century, the mechanism of coagulation had been practically deciphered and diverse models based on sequential enzymatic function were proposed, called first chain reactions and in cascade reactions later. In the second half of the XX century, numerous regulatory mechanisms of coagulation were identified and diverse laboratory tests appeared that have allowed highly precise diagnoses of a variety of diseases. Blood separation techniques have permitted to produce factor concentrates for clinical use. With the identification of the genes that encode the synthesis of coagulation factors, it has been possible to produce them by means of molecular biology techniques, being the most significant the production of factors VIII, IX, and VII. The present model of coagulation is based on tissular factor activation and the participation of cells, concepts that were already implicit in the classical theory of Morawitz.

Acetylsalicylic acid inhibits thromboxane A2 production and reduces the risk of vascular occlusive events by 20% to 25%. Ticlopidine inhibits ADP-dependent platelet aggregation and reduces the same risk by 30% to 35%, but produces some adverse effects. Clopidogrel is a ticlopidin-related antiplatelet drug, with the same mechanism of action; it reduces the expression of the glycoprotein Ilb/Illa, the fibrinogen receptor on the platelet surface. Clopidogrel has the same clinical efficacy of ticlopidin and has a decreased incidence of adverse effects. The effect of one daily dose of 75 mg of clopidogrel on platelet function in 90 subjects was evaluated; 41 with coronary artery disease and 49 with cerebral vascular disease. Before treatment and after 6 and 12 weeks, bleeding time and fibrinogen plasma concentration were also evaluated. There was a reduction in 5-μM ADP-induced platelet aggregation of 38% ± 27% at 6 weeks and 44% ± 29% at 12 weeks in patients with coronary artery disease; 35% ± 41%, 29% ± 59% in the cerebral vascular disease group; and 36% ± 36% and 35% ± 49% in the total group. Reduction of 20,ug/mL collagen-induced platelet aggregation was not significant in any group. Plasma fibrinogen levels did not vary during treatment. Bleeding time was significantly prolonged in all studied groups. There were no hemorrhagic complications; only digestive discomfort in less than 3% of patients. Clopidogrel efficiently reduces ADP-induced platelet aggregation and prolongs bleeding time and is a safe and efficacious antiplatelet drug.