Delii V. The mechanisms of platelets dysfunction among patients with acute gastroduodenal ulcers bleeding

The thesis is devoted to the platelet dysfunction among patients with acute gastroduodenal ulcers bleeding in consequence of receptors and signaling system disorders. Typical kinds of failure of the platelet response to adhesion and aggregation factors were decreased response, prolonged activation and reversible aggregation. In patients with prolonged activation increased frequency of rebleedings were observed even in case of the middle and high platelets response (р<0.05). Humoral factors acted as modulators when adhesion and aggregation factors had induced low platelets response. During the first 6 hours from the manifestation of bleeding the lowest level of the platelets response to collagen (11.5±5.6%) and ADP (23.3±9.9 %) was recorded. However, after 24-48 hours, the platelets response to collagen (45.8±12.0%) and ADP (53.7±10.1%) increased (p<0.05). The platelets response to humorous factors remained unchanged in time. It was not significant change in the platelets response to adhesion/aggregation factors while using inhibitors of PKA and PKC, which is associated with the variety of vector and amplitude changes. An exception was collagen-induced platelet aggregation while using an inhibitor of PKC (р<0.05). Negative role of PKA in the platelets response is associated with rebleeding (p<0.05). Leukocyte-leukocyte aggregates were observed in peripheral blood in the absence of platelets among them. In vitro analysis of leukocyte effect on the platelets response showed negative influence on collagen-induced platelet aggregation (p<0.01) and bimodal effect on aggregation induced by ADP (decrease - p<0.01; increase - p<0.05). The significant increase of the number of macrophages was found in the biopsy of the ulcer edge of patients with bleeding recurrence compared with patients with effective hemostasis. The number of macrophages correlated with the number of neutrophils (r=0,702; p<0,001). Important predictors of bleeding recurrence were the increased number of macrophages (p<0.001) and increased neutrophil infiltration (p<0.05). Negative influence of leukocytes on collagen-induced platelet aggregation (р<0.01) and a bimodal effect on ADP-induced aggregation were found (reduced aggregation p<0.01, increased aggregation p<0.05). It has been found that on the third day after admission the level of ADP-induced platelets aggregation exceeded the first day level of platelets response in 2 times (p<0.05). Statistically significant differences between the platelets response to collagen on the first and third days were not established. Despite this, the median increased in 2 times. On the third day after admission, PKA possessed the role of a positive regulator of the intracellular signaling system, while the functional role of PKC remained unchanged.