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Many studies have linked smoking with cardiovascular disease, but the components and the mechanisms responsible are unclear. Smoking has been reported to enhance platelet aggregation and adhesiveness, probably via nicotine. The study is aimed at ascertaining which coagulation pathway is mostly affected in chronic smokers in Enugu, South-east Nigeria. The study comprised of 200 subjects (100 chronic smokers and 100 non-smokers as controls). The chronic smokers had mean age of 40±19 years, whereas the control had mean age of 41±20 years. Exactly 4.5mls of blood was drawn and gently mixed with 0.5ml of sodium citrate anticoagulant in a ratio of 9 parts of blood to 1 part of the anticoagulant and used for the assay. Prothrombin time (PT) and activated partial thromboplastin time with kaolin (APTTK) were analyzed using standard operating procedures with Plasmascann® kit reagent and Hemoscann® test kit from Quimica Clinica Aplicada S.A (QCA) respectively. The statistical analysis was done using Graph pad prism software of Statmate. The result showed statistical significant decrease (P<0.05) in PT and APTTK in the smokers compared to the age-matched controls. A linear regression was used to show that chronic smoking affects the intrinsic pathway more than the extrinsic pathway (p<0.05). The study showed that chronic smoking affects coagulation pathways generally, most especially the intrinsic pathway.