Platelet and neutrophil cross-talk-mediating cancer growth and metastasis in patients with urinary bladder cancer

The initial selectin-dependent events that mediate tumor cell tethering to platelets, leukocytes, and vascular endothelium can regulate the extravasation and colonization of metastatic cells into distant tissues. We aimed to clarify the role of selectin-selectin ligand interactions in tumor growth and progression in patients with bladder cancer. Thirty patients with bladder cancer were the participants in this study classified as follows: locally invasive group [n = 10], urinary bladder cancer group with regional lymph node involvement [n = 10], and urinary bladder cancer group with regional lymph nodes and distant metastasis [n = 10]. Flow cytometry was used to determine both the platelet surface expression of P-selectin [CD62P] and the neutrophil surface expression of PSGL-1 [CD162], whereas enzyme-linked immunosorbent assay was used for the assay of soluble P-selectin. Neutrophil PSGL-1 expression among the different groups studied was not statistically significant. However, there was enhanced platelet activation as evidenced by increased platelet surface expression of P-selectin together with an increase in its soluble form, which was more prominent with advancement of the disease, especially in patients with distant metastasis. Also, a strong positive correlation was found between platelet P-selectin and its soluble form with the tumor grading. In addition, stepwise multiple regression analysis showed that both P-selectin and platelet count are significant independent determinants for the stage of bladder cancer, suggesting augmentation of P-selectin-ligand interaction. These data preclude that disease progression in patients with bladder cancer is dependent on the complex interaction between P-selectin and its ligand. Targeting of these molecules may represent a unique approach to tumor therapy and prevention of metastasis

Impact of neutrophil apoptosis on haemostatic activation in chronic liver disease patients

Recent studies suggest the impact of apoptosis on the mechanisms leading to hypercoagulability. We aimed to clarify the potential role of neutrophil apoptosis in neutropenia and hypercoagulable state encountered in chronic liver disease patients. This study was conducted on fifteen normal controls and fourty five patients with chronic liver disease classified according to modified Child Pugh classification into, Child A, B and C groups [15 cases each]. Studied Haemostatic parameters include, prothrombin time, partial thromboplastin time, tissue factor, protein C antigen, protein S antigen, and markers of haemostatic activation [prothrombin fragment 1+2, thrombus precursor protein and D-dimer]. Flowcytometric study was done for quantitative assay of neutrophil apoptotic subpopulations to detect the percentage of early and late apoptotic, and necrotic neutrophils using AnnexinV-FITC/Propidium iodide dye. Semiquantitative assay of apoptotic neutrophils showing DNA fragmentation was performed on neutrophil culture using terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling [TUNEL] test. In addition to enzyme linked immunosorbent assay for soluble Fas [APO-1/CD95] in culture supernatant. The results revealed a rise in the neutrophil apoptotic and necrotic markers with progression of the disease, and they were inversely correlated with the absolute neutrophil count. The apoptotic neutrophil cells showed a significant positive correlation with several haemostatic parameters [tissue factor, prothrombin fragment 1+2, thrombus precursor protein and Ddimer], which further incriminate the apoptotic mechanisms in the hypercoagulable state encountered in this clinical setting. Enhanced neutrophil apoptosis and necrosis in patients with chronic liver disease may explain in part the mechanism of neutropenia in these patients and may be one of the important factors which drive the haemostatic balance towards the hypercoagulable state

Relation between thrombin activatable fibrinolysis inhibitor and haemostatic alterations in patients with chronic liver disease and portal vein thrombosis

Recently, a new inhibitor of fibrinolysis was discovered which down regulates fibrinolysis after its activation by thrombin and was therefore named thrombin activatable fibrinolysis inhibitor [TAFI]. We aimed at evaluating TAFI level in chronic liver disease [CLD] and its relationship to important haemostatic parameters namely: tissue factor [TF], prothrombin fragment 1+2 [Fl+2], thrombomodulin [TM], protein C [PC], protein S [PS], thrombus precursor protein [TpP] and D-dimer [D-di] in a trial to clarify the role of TAFI in haemostatic alterations frequently encountered in CLD. The study included 35 CLD patients [Chid B or C], 15 [out of them] were complicated by portal vein thrombosis [PVT], in addition to 15 healthy controls. Significant reduction in TAFI level was detected in CLD patient with and without PVT in comparison to controls, however a significantly higher values were noticed in patients complicated by PVT when compared to those without thrombosis. Correlation analysis demonstrated a strong correlation between TAFI level and other measured parameters namely PT, PTT, PC, PS and D-dimer in PVT group. It could be concluded that TAFI plays a crucial role in regulation of coagulation and fibrinolysis. Reduced TAFI level in patients with CLD could result in up regulation of fibrinolysis. High TF level, associated with decreased natural anticoagulants namely PC and PS accompanied by a higher TAFI level and its increased activation could play a role in the development of PVT as a complication of CLD