Comparative hemostatic protein alterations accompanying pregnancy and parturition

Abstract

Pregnancy and parturition represent adaptive, physiological stress situations that elicit both blood coagulation protein changes and endocrine alterations. This paper briefly reviews the interrelationship of these responses by comparing the available data in several mammalian species including man, dog, cow, and pig. Hemostasis is an enzymatically controlled cascade process involving platelets and specific coagulation proteins that results in the formation of insoluble strands of fibrin. Although qualitatively similar in most mammals, quantitative differences exist in the circulating levels of individual coagulation proteins which may contribute towards the different rates of clot formation. In the late gestation stage of human pregnancy, significant increases are observed in the circulating biological activities of the coagulation factors VII, VIII:C, IX, and X. In the dog, the activities of factors VII and IX reach peak values in midpregnancy, while in the cow little or no changes are observed except for factor VII values which show a significant increase only around the time of parturition. These coagulation changes appear to be associated with fluctuations in circulating hormone values, particularly plasma estrogen. In human pregnancy, the circulating levels of fibrinogen, the precursor of fibrin, increase during the gestation period reaching maximum values during and immediately following parturition. In the dog and the cow two distinct increases in fibrinogen values are observed, the first in the midgestation period and the second in the immediate postparturition period. In the pig, fibrinogen values also rise significantly at parturition. Oral contraceptive studies in the human female have indicated that changes in circulating activities of coagulation proteins are hormonally influenced. Results from injection of various steroid hormones in the dog, pig, and rabbit have shown this to also hold true for these species. In both the dog and the pig, progesterone and the prostaglandin, PGF2α, induce marked increases in fibrinogen values, while estrogen alone has apparently no effect on this protein. These results emphasize the lack of a clear understanding of the relationship between the coagulation proteins and reproductive hormone changes. In all species examined, fibrinogen values rise at parturition when progesterone values are falling. Although in the human female the effect of pregnancy and ingestion of oral contraceptives on fibrinolysis has been examined, this aspect of the hemostatic process has not been evaluated in domestic animals. The paucity of information and the diversity of the response of the coagulation proteins in different species to hormonal manipulation reflect the limited understanding that exists pertaining to the interrelationships between circulating hormones, coagulation proteins, and hemostasis.