THE ROLE OF PROTEIN KINASE A AND C IN PLATELET DYSFUNCTION AMONG PATIENTS WITH ACUTE GASTRODUODENAL ULCER BLEEDING

Abstract

In order to establish signaling mechanisms of platelet dysfunction among patients with acute gastroduodenal ulcer bleeding the assessment of agonist-induced platelet aggregation was performed by means of the spectrophotometric method and inhibitory method at the time of hospitalization of patients and the third day after. It has been shown that on the first day of hospitalization the level of collagen- and ADP- induced platelet aggregation was decreased among patients with acute gastroduodenal ulcer bleeding in comparison with the controlgroup. In cases of medium/high level of platelet aggregation, the reverse aggregation graph was recorded that was associated with the risk of recurrent bleeding. On the third day after hospitalization, the rise of ADP-induced platelet aggregation was found on account of PKA becomes a positive regulator of platelet intracellular signaling system. The assessment of induced platelet aggregation among patients with acute gastroduodenal ulcer bleeding compared with the control group allowed to discover a double decreased platelet aggregation to ADP (p=0.004) and 4.5-times decreased platelet aggregation to collagen (p=0.0001). The characteristics of aggregation graphs to ADP have shown partially inverse and inverse platelet aggregation, that was widely spread among patients with medium/high level of platelet aggregation. The previous issue has been associated with reverse and partially reverse aggregation graphs to collagen. Moreover, the highest rate of recurrent bleeding was found among patients with medium/high level of platelet aggregation to collagen (p=0.02) which was featured by a long latency period. The scrutiny also has revealed the correlation between ADP and collagen-induced platelet aggregation (r=0.28; p=0.01), which indicates that platelet disfunction takes place in the intracellular signaling system. On the first day of hospitalization no effect of PK A inhibitor on ADP-induced platelet aggregation was detected (p=0.71). The examination of effect of PK C inhibitor on ADP-induced platelet aggregation also has revealed no effect (p=0.57). In addition to the level of platelet aggregation inhibitors did not influence the characteristics of aggregation graphs. The comparison of ADP- and collagen-induced platelet aggregation in dynamics (on the first and the third days of hospitalization) has shown 2-times growth of platelet aggregation to ADP (p<0.05) and no changes of collageninduced platelet aggregation (p=0.59). On the third day of hospitalization the increase in the effect of PK A inhibitor on ADP-induced was recorded (p<0.05). The study of the effects of PK C inhibitor on ADP-induced platelet aggregation has revealed no differences (p=0.69).

Keywords

• gastroduodenal ulcer
• acute bleeding
• hemostasis
• platelets
• platelet signaling system
• protein kinases (a and c).