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 15 normal controls and 45 patients with chronic liver disease classified according to modified Child Pugh classification into, Child A, B and C groups (15 cases each). Haemostatic parameters studied include, prothrombin time, partial thromboplastin time, tissue factor, protein C antigen, protein S antigen, and markers of haemostatic activation [prothrombin fragment 1+2 (F1+2), thrombus precursor protein (TpP) 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 Annexin V-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 labelling 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 D-dimer). Regression analysis proved that apoptotic parameters are independent determinants of prothrombotic markers, which further incriminate the apoptotic mechanisms in the hypercoagulable state encountered in this clinical setting.
Essawy
Faiza M
FM
Haematology Department, Theodor Bilharz Research Institute, Ministry of Scientific Research, Imbaba, Giza, Egypt.
Bekheet
Iman W
IW
Saleh
Abeya F
AF
Madkour
Mona E
ME
Bayoumi
Emad El-Din A
Eel-D
D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000032:analysis; D001780:Blood Coagulation Tests; D002908:Chronic Disease; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006509:Hepatitis B / Q000097:blood / Q000150:complications; D006526:Hepatitis C / Q000097:blood / Q000150:complications; D006801:Humans; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009503:Neutropenia / Q000209:etiology; D009504:Neutrophils / Q000473:pathology*; D017293:Protein S / Q000032:analysis; D012555:Schistosomiasis mansoni / Q000097:blood / Q000150:complications; D019851:Thrombophilia / Q000097:blood / Q000209:etiology*; D019014:fas Receptor / Q000097:blood
D017304:Annexin A5; D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D017293:Protein S; D019014:fas Receptor; C036309:fibrin fragment D