Development of Blood Coagulation—A Fetal Lamb Model

Abstract

SummaryTo 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 from 10 fetuses were studied during the third trimester of pregnancy and 24 hr after birth. 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 Blood samples were withdrawn from the catheter three times each week for measurement of coagulation factor activities.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 t P < 0.05). The patterns of development for each of the coagulation factors were similar in all 10 animals studied. Fibrinogen, prothrombin, and factor VII show a decrease in activity early in the last trimester of pregnancy whereas other factors V, VIII, IX, X, XI, XII, and XI11 show a gradual increase in activity throughout the last trimester of pregnancy. Both factors VIII and IX show a significant increase in activity (23% factor VIII and 12% factor IX) associated with the process of delivery. The levels of coagulation factor activities at birth in the lamb relative to adult sheep normals are similar to those found in humans with the exception of factor XIII. Factor XIII is at normal levels in the newborn lamb and is reported to be at levels approximately 50% of the adult level in human infants. SpeculationThe development of a chronic fetal lamb preparation has allowed the construction of developmental patterns for coagulation factor activities throughout the last trimester of pregnancy. Further studies into the biology of the changes in coagulation factor activities observed and the influences of such stresses as hypoxemia and premature delivery should enhance our understanding of the bleeding neonate.

Development of Chemotactic Factor Inactivation–a Fetal Lamb Model

“…These levels decreased steadily to attain normal adult levels in term fetuses and were unaffected by labor and delivery. Age of the fetus, determined by the induced ovulation technique (1,7,8), correlated inversely with CFI activity in the fetus. This correlation accounted for 93.3% of the change in CFI activity, strongly suggesting that higher CFI activity is a function of fetal immaturity.…”

“…A heparinized catheter was plasma to induce neutro~hil chemotaxis (r = -0-%, P < 0.01), placed in the femoral artery of the fetuses at various gestational suggesting that CFI plays a major role in the regulation of ages under general anesthesia of the ewe (8). A group of eight leukocytes chemotaxis.…”

“…Complement activation in serum and plasma results in the to clear the catheter of saline, 9 rnl citrated blood was then generation of C5-derived chemotaxins (C5.fr) (2,20), which induce obtained as previously described (8). Following delivery, blood neutrophil (2), monocyte (3) and lymphocyte chemotaxis (4).…”

Effect of Hyperinsulinemia on the Development of Blood Coagulation in the Lamb Fetus

“…The gestational ages of the fctiiscs were known on the basis of induced ovulation technique (8). Before surgery the cwcs wcrc fastcd for 4 8 h. Anesthesia of the ewe and surgery on the fetus were perfornlcd as described previously (9).…”

Hyperglycemia-Induced Hyperinsulinemia Decreases Maternal and Fetal Plasma Protein C Concentration during Ovine Gestation

“…We chose the pregnant sheep because Kisker et al (8), Massicotte et al (9), and Moalic et al (10) previously showed that maturation of coagulation factors in the fetal lamb is similar to that of humans. In addition, one of the authors has observed increased catheter-related thromboses and occlusions in adult (maternal) and fetal sheep with chronic glucose and insulin infusions (W. W. Hay Jr, unpublished observations).…”