Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA189

Poster Communications

Platelet dysfunction is associated with lack of repair in patients with gastroduodenal ulcer bleeding

O. Sulaieva1, V. Delii1, S. Zharikov2, P. Kondratenko2

1. Histology, Zaporozhye State Medical University, Zaporozhye, Ukraine. 2. Surgery, M. Gorky Donetsk National Medical University, Kramatorsk, Ukraine.


Background. There is a growing body of data describing molecular mechanisms of healing of peptic ulcers [1, 2]. However mechanisms of recurrent ulcer bleeding (UB) development are still unclear. It was shown that ulcer bleeding is associated with platelet dysfunction and inflammatory reaction affecting thrombogenesis [3, 4]. Despite the fact that platelets are considered as an important moderator of ulcer healing [5], there is no data on relationship between platelets and ulcer healing after bleeding. Aim of this study was to assess platelets' activity and peptic ulcer healing among patients with bleeding. Methods. 32 patients (males, 56±3 year-old) with gastric and duodenal peptic ulcers complicated with acute bleeding (Forrest II class) were enrolled in the investigation. According to the outcome of UB all patients were subdivided into two groups - with sustained hemostasis (1st group, n=18) and rebleeding (2nd group, n=14). All the recruited patients provided informed consent. Platelet aggregation induced by adenosine diphosphate (ADP, 5 μM) and collagen (1 μM) was measured alone and after co-incubation with inhibitors of protein kinase A and C (PKA and PKC; tolbutamide and neomycin respectively, 200 µM). To assess healing we counted α-SMA, СD31 and Ki-67 positive cells in biopsies of ulcer margin, taken within 24 hours of UB symptoms onset. RESULTS. There were no relationships between platelet aggregation and such factors as gender, age, comorbidity and severity of hemorrhage. Collagen- and ADP-induced aggregation of platelets among patients with UB was significantly lower comparing with control (p=0,01). We fixed the predominance of reversible pattern of the platelet aggregation in 2nd group. Both control group and 1st group demonstrated the decrease of platelet aggregation after inhibition of PkA. However in 2nd group tolbutamide did not change aggregation induced by ADP. Non-selective Inhibitor of PkC significantly declined ADP-induced platelet aggregation in 1st group and increased platelets aggregation in 2nd group (p=0,02). However, this did not provide stabilization of ADP-induced platelet aggregation. These changes were accompanied with different repair pattern in 1st and 2nd groups. We found the decline of myofibroblasts number (p<0,001) and angiogenesis (p<0,01) among rebleeders, but there were no differences in Ki-67 positive cells with regard to outcome. Conclusion. Abnormal signalling in platelets among patients with UB was associated with decrease of platelets aggregation and lack of its stabilization. These changes could be caused by alteration of degranulation and lead to un-sustained hemostasis, violation of ulcer healing and rebleeding development.

Where applicable, experiments conform with Society ethical requirements