The effect of liver disease on the vitamin K dependent factors in haemostasis.

This thesis deals with the effect of liver disease on the vitamin K dependent clotting factors II, VII, IX, X. Chapter I is a review of the literature and gives a background to the biological importance of vitamin K and the mechanism of its action. In Chapter II the effect of liver disease on the synthesis of the vitamin K dependent clotting factors is described, in particular the effect on factor VII. It was concluded that there is a relationship between the synthetic ability of the liver and circulating levels of the vitamin K dependent clotting factors. This synthetic ability is disturbed in liver disease. The study of serial changes in the vitamin K dependent clotting factors following the infusion of vitamin K is described in Chapter III. The study was concerned with assessing the effect of treatment on clotting factor levels as well as th pathways involved in the adsorption and utilisation of the vitamin K. In addition the study indicated that during the initial treatment with vitamin K the four vitamin K dependent clotting factors were synthesized at the same rate. The rate of synthesis during the 24 hour period of analysis appeared to be biphasic, indicating possible feed back mechanism on the synthesis pathway. Principal component analysis of the data derived during the 24 hour response indicated that an analysis at 16 - 18 hours may provide adequate information on the ultimate response to vitamin K. Proteins induced by vitamin K absence (PIVKA) in liver disease were investigated in Chapter IV, using the modified thrombotest as well as immunological techniques. The presence of PIVKA and PIVKA II was demonstrated in some forms of liver disease. Following the administration of vitamin K normal factor II appeared within one hour and a for PIVKA II of 17 hours was established. Furthermore, the appearance and disappearance of normal factor II and PIVKA II are identical. It was concluded that such a finding was related to a conformational change in the intracellular PIVKA II and this finding is discussed in the context of its effect on the haemostatic mechanisms.