Development Of Blood Coagulation-A Fetal Lamb Model

Abstract

To study the normal development of blood coagulation factor activities in a growing fetus while avoiding the effects of labor and delivery, a chronic fetal lamb model was developed in which serial blood samples were obtained from 10 chronically catheterized fetuses during the third trimester of pregnancy and 24 hours following spontaneous delivery of live-born lambs. Under operating room conditions with sterile technique, a polyethylene catheter to which heparin had been bound to both internal and external surfaces, was inserted into the femoral artery of the fetus. The catheter was brought out through a skin pouch to the side of the ewe, and enclosed in a zip lock bag. Blood samples were withdrawn from the catheter three times each week for measurement of coagulation factor activities. Levels of coagulation factor activities at birth in noncatheterized animals were not different from those found in catheterized animals except for factor IX activity which was 12% higher in the catheterized animals (0.02<p<0.05). Fibrin/fibrinogen degradation products and fibrin monomer levels were not increased during gestation and the shape of the changes in activity of individual clotting factors over time in the different fetuses was remarkably constant for each of the factors measured. Fibrinogen, prothrombin, and factor VII showed a decrease in activity early in the third trimester of pregnancy, whereas factors V, VIII, IX, X, XI, XII, and XIII showed a gradual increase in activity throughout the last trimester of pregnancy. Both factors VIII and IX showed a significant increase in activity (23% factor VIII and 12% factor IX) associated with the process of delivery. Changes in blood coagulation in the fetal lamb were similar to those thought to occur in humans. Similarities included fibrinogen, factors V and VIII which reached or exceeded adult levels at birth and the vitamin-K dependent factors II, VII, IX and X which remained below adult levels at term.