Portal vein thrombosis and haematemesis in chronic liver disease. Are P-selectin and PSGL-1 clues?

Bleeding and thrombotic complications are common problems in patients with chronic liver disease [CLD]. The aim of the present study was to evaluate the level of soluble P [sP]-selectin, and P-selectin glycoprotein ligand-1 [PSGL-1] [CD162] expression on neutrophils among patients with CLD and to clarify the role of their interaction, by measuring the platelet leucocyte aggregates, on the clinical outcome of the haemostatic balance in those patients. We also investigated the hypothesis that the balance between platelet activation and endothelial biological function is impaired. sP-selectin and thrombomodulin [TM] levels were measured by enzyme-linked immunosorbent assay [ELISA] and flowcytometric detection of CD162 was performed. Platelet-leucocyte aggregation [PLA] in whole blood was measured as positive for CD41a and CD45 in 66 CLD patients divided into the portal vein thrombosis group [PVT] [n = 25], the haematemesis group [n = 21] and the haemostatically stable group [n = 20]. sP-selectin was significantly elevated in all patient groups. Decreased surface expression of CD162 on neutrophils was detected in all patients' groups. PLA was statistically significantly increased in the PVT group. TM was statistically significantly increased in the PVT, haematemesis and haemostatically stable groups. PLA may play a role in the unique PVT outcome of the haemostatic balance in a group of patients whose credentials of hyperdynamic portal circulation predispose them to bleeding rather than thrombosis. Consequently, P-selectin-targeted therapy may be used to prevent this complication

Expression of leukocyte adhesion molecular MAC-1 [CD11B/CD18] and L-selectin[CD62L] in patients with chronic renal failure undergoing regular hemodialysis

Mac1 and L-selectin expressed on leukocytes are critical for leukocyte adhesion to inflammed endothelium. Degranulation of polymorphnuclear leukocytes [PMN] during hemodialysis [HD] is usually assessed by measuring degranulation products. Our aim was to evaluate the effect of HD on leukocyte activation and degranulation. Fifteen normal controls and fifteen patients under chronic renal dialysis treatment were studied for Mac 1 and L-selectin expression on granulocytes by flowcytometry. PMN degranulation products; myeloperoxidase[MPO] and lactoferrin[LF] were determined in serum by ELISA method. The results of Mac 1 expression on granulocytes demonstrated a statistical significant increase in post HD compared to both pre HD [P<0.05] and control groups [P<0.05]. A statistical significant increase was also noted between Pre HD and the control group [P<0.05]. Post HD results showed a statistical significant decreased L-selectin granulocyte expression when compared to Pre HD group [P<0.05]. Post HD group showed a statistically significant increase of both MPO and LF when compared to predialysis and control group [P<0.05]. There was also a statistically significant increase in Pre HD group compared to control group in both MPO and LF levels [P<0.05].In post hemodialysis group there was a negative correlation between MAC1 and L-selectin [r=0.41]. Our finding showed that HD might influence the expression of leukocyte adhesion molecules and subsequently degranulation of PMN. Their measurement might be an indicator of PMN disturbed functions

Released platelet and granule contents: implication of thrombospondin in haemorrhagic diathesis in hepatosplenic schistosomiasis

This work was carried out on 75 subjects, 60 patients suffering from hepatosplenic schistosomiasis in different stages of the disease; in addition to 15 nonbilharzial normal controls. Thrombospondin and other platelet alpha granule contents including firbronectin, platelet factor 4, Beta-thromboglobulin, alpha 2-antiplasmin, plasminogen activator inhibitor, C1 inactivator, histidine rich glycoprotein, fibrinogen and plasminogen were studied. They were estimated in all groups in a trial to clarify the impact of thrombospondin and other alpha-granule contents on the alteration or haemostasis and haematemesis in hepatosplenic schistosomiasis. Specific investigations for platelets were estimated including bleeding time, platelet count and platelet aggregation. The data obtained revealed significant progressive decrease of the platelet alpha-granule contents studied [except thrombospondin] with the advancement of the disease especially in advanced fibrotic and haematemesis groups. Thrombospondin [TSP] showed significant progressive increase parallel to the progress of the disease. This may be explained by its longer life span and by its extraplatelet sources mainly the vascular endothelium. The data confirm that high level of TSP may serve as a templet whereupon the cofactors for the initiation or enhancement of fibrinolysis occur. These data confirm that the platelets play an important role in haemorrhagic diathesis in late stages of hepatosplenic schistosomiasis; this is through thrombocytopenia, decrease platelet function and its alpha-granule contents including antiproteases in addition to the important role played by TSP