Platelet thrombus formation in patients with end-stage renal disease before and after hemodialysis as measured by the total thrombus-formation analysis system.

BACKGROUND: Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) often experience bleeding. However, mechanisms behind this bleeding tendency are incompletely understood but may involve platelet dysfunction. We, therefore, studied platelet-dependent thrombus formation in flowing whole blood inside a microchip coated with collagen, and its association with circulating von Willebrand factor (VWF). METHODS: Blood samples were obtained in 22 patients before and after HD. The area under the 10 min flow pressure curve in a microchip (AUC10) reflecting total platelet thrombogenicity was measured, using the Total Thrombus-formation Analysis System (T-TAS01). AUC10 < 260 indicates platelet dysfunction. VWF activity and antigen in plasma were also assayed. RESULTS: VWF levels were moderately elevated and increased further after HD (P < 0.01 or lower). In contrast, AUC10 before and after HD was < 260 in 17/22 patients and < 130 in 15/22 patients, with no statistically significant difference in pre- vs post-HD measurements, indicating reduced platelet thrombogenicity, but with some variability as 5/22 patients showed normal platelet responsiveness. AUC10 and VWF activity or antigen levels in plasma were not correlated, either before or after HD. CONCLUSIONS: Most ESRD patients display moderate-to-severe platelet dysfunction as assessed by shear-induced platelet-dependent thrombus formation with T-TAS01. HD does not influence platelet function despite HD-induced elevations in VWF. T-TAS01 should be further evaluated as a tool in the assessment of bleeding risk in patients on HD.

Clinical - pathological significance of leptin receptor (LEPR) expression in squamous cell carcinoma of the skin.

Adipokine leptin functions through its transmembrane receptors (LEPR). In many malignant tumors it stimulates the growth, migration and invasion of malignant cells. The aim of our work is to examine the effect of LEPR expression on the clinical-morphological properties of squamous cell carcinoma of the skin (cSCC). The biopsy material obtained by excision of squamous cell skin cancer was used. The test group consisted of excision biopsies of squamous cell carcinoma of the skin (n = 62), and the control group (n = 62) consisted of excision biopsies of non-tumor tissue of the skin (from the tumor environment) from an operative preparation delivered to the Pathohistology Department. After routine processing and paraffin molding, histochemical Hematoxylin-Eosin and immunohistochemical ABC method with anti LEPR and Ki67 antibodies were applied at 4 µm sections. The statistical software package SPSS for Windows (26.0) was used to analyze obtained results. Intracytoplasmic and intramembranous LEPR expression was found in 100 % of examined cSCCs. LEPR expression was statistically significantly associated with proliferation index and histologic grade of tumors. Pronounced LEPR expression was associated with a high proliferation index in 66.7 % of cases and with poorly differentiated cSCC in 94.4 %. Multivariate regression analysis showed that cSCCs with pronounced LEPR expression were seven times more often poorly differentiated than tumors with moderate or LEPR expression in trace. Our results indicate that LEPR expression is a predictor of the malignant potential of cSCC, so that based on LEPR expression, it is possible to identify an aggressive cSCC phenotype, which provides the possibility of individualizing anti-tumor treatment using LEPR antagonists.