The coagulation and fibrinolytic systems in normal and abnormal pregnancy

The introductory section of the thesis presents a brief historical review of the development of knowledge of the effect of pregnancy on the haemostatic mechanism and gives an account of current concepts of the components and functions of the fibrinolytic enzyme system and the blood clotting mechanism. The effect of pregnancy and parturition on the components of the fibrinolytic enzyme system was investigated by serial studies of healthy women during normal pregnancy, labour and the puerperium. A marked deviation from the findings in normal non-pregnant subjects was found to develop during pregnancy. A substantial increase in the plasminogen level was found in the third trimester, the increase occurring pari-passu with a pronounced increase in the plasma fibrinogen concentation. In late pregnancy and during labour the level of plasminogen activator in the plasma was greatly decreased, whereas a normal level was present in the first week of the puerperium. A haemagglutination inhibition assay using sensi-tized sheep red cells was used to measure the level of fibrinogen/fibrin degradation products (F.D.P.) during normal pregnancy, labour and the puerperium. A sharp increase in the level of F.D.P. was found to occur during labour and in the puerperium, indicating that active fibrinolysis was taking place at these times. The effect of the process of childbirth and placental separation on the haemostatic mechanism was investigated by a detailed serial study of the coagulatioh and fibrinolytic systems during and after delivery. Shortening of clotting tests - recalcification time in plastic, kaolin-cephalin clotting time and partial thromboplastin time - a sharp increase of factors VIII and V, and a decrease of plasma firinogen were found as the placenta separated. Within one hour of normal delivery the levels of serum F.D.P. increased and plasma fibrinolytic activity returned to normal non-pregnant levels. The effect of placental separation was further investigated by simultaneous study of the changes in the uterine circulation and peripheral blood at caesarean section while the placenta was separating. A striking activation of the clotting mechanism was found in the uterine circulation during placental separation. The changes in the coagulation tests in the uterine circulation were largely a substantial amplification of those found in the peripheral blood at normal childbirth. The concurrent findings in the blood clotting and fibrinolytic systems suggest that during parturition the haemostatic mechanism plays an essential role in controlling uterine haemorrhage. In the early puerperium a secondary increase took place in the level of plasma fibrinogen, factor VIII remained elevated and the platelet count showed a pronounced rise. These changes are probably a response to the utilization of these factors during placental separation and are likely to predispose to thrombo-embolic complications. The coagulation and fibrinclytic systems in the newborn were studied in cord blood taken immediately the baby was delivered. The findings in the newborn were in sharp contrast to those in the mother. Low levels of Vitamin K dependent clotting factors were confirmed but raised levels of factors V and VIII were found and a highly significant correlation between the maternal and neonatal values. Pibrinolytic activity was greatly increased in the newborn contrasting with the diminished activity in the maternal blood. High levels of circulating inhibitor were also found in the cord blood. The findings in the cord blood suggest that during normal delivery an activation of the clotting mechanism takes place in the baby's blood as well as in the maternal blood, due apparently to the entry of thromboplastin into the foetal and maternal circulation during placental separation. Abruptio placentae is the complication of pregnancy most likely to be accompanied by defective haemostasis. Detailed studies of patients with abruptio placentae showed that low fibrinogen levels were accompanied by a decrease of plasminogen and depletion of coagulation factors II, V and VIII. Substantial levels of serum F.D.P. were found in the presence of diminished systemic fibrinolytic activity. As F.D.D. have a profound effect on the clotting mechanism and platelet function their presence in high levels is likely to be a major factor in the defective haemostasis of abruptio placentae. The findings suggest that the activation of the clotting mechanism which is confined to the uterine circulation during normal placental separation extends into the general circulation in patients with premature separation of the placenta. (Abstract shortened by ProQuest.)