Abstract
Physiologic and pathologic changes of coagulation and fibrinolysis activities during pregnancy were studied with particular emphasis on α2-plasmin inhibitor (α2PI). The results are as follows:
1) The value of α2PI, following transient increase, decreased slightly during the 16 th through 19th weeks of gestation, and it again rose during the 28 th through 35 th weeks. It showed a marked, statistically significant decrease after the 38 th week until immediately prior to delivery. After the 38th week of gestation, antithrombin III (AT III) decreased as well, showing a correlation with α2PI. Plasminogen (plg) also decreased, while α2 macroglobulin (α2M) remained unchanged after the 38th week. These findings are in accordance with other investigators' findings that fibrinopeptides A and B and soluble fibrin monomer complex increased markedly. The decreased α2PI value returned to the pre-pregnancy value on the fifth or sixth day of puerperium.
2) Analysis of the maternal venous blood immediately after delivery and the fetal umbilical venous blood revealed that values of α2PI, plg, and APTT decreased significantly in the fetal blood (p<0.01), which suggested reduced production of these proteins because of incomplete growth of the liver. The value of AT III also tended to decrease, but there were no differences in PT and α2M between the maternal and fetal blood.
3) Findings of bleeding tendency are important for early recognition of DIC, but our study showed that α2PI decreased at the very beginning of DIC because of increased consumption, and that reduction of plg and AT III and prolongation of PT preceded the appearance of abnormal activities of other factors related to coagulation and fibrinolysis.
4) When the dead fetus was retained in the uterus, the value of α2PI was extremely low. This finding may suggest that in some cases increased activities of coagulation and fibrinolysis occur even prior to the death of the fetus.
5) In cases of advanced toxemia of the pregnancy in which severe fetal injuries such as fetal death occurred, α2PI was markedly low. However, cases of toxemia of the pregnancy in which α2PI becomes lower than the lower limit of the physiologic fluctuation during pregnancy seem few in number.
In some cases of eclampsia, marked reduction of α2PI, lowered AT III and plg, and increased ma on the TEG were noted prior to the attack of eclampsia. In another case, although other coagulation and fibrinolysis factors were not abnormal, marked bradycardia was noted in a nonstress test. In this case, an elective cesarean section was performed on the 1 st day of the 34 th week as a life-saving procedure. In one other case, aZPI remarkably decreased following delivery eclampsia. Therefore, not only hypertension and severe proteinuria but abnormalities in coagulation and fibrinolysis factors should be looked for.
Administration of urokinase in the amount of 24, 000 to 48, 000 as a treatment for toxemia of the pregnancy particularly for its after effects, showed no significant changes.
6) When coagulation and fibrinolysis activities are abnormally increased, the value of aZPI changes closely reflecting these abnormalities from the very beginning. In stead of the one dimensional method of Laurell which requires 72 hours for measuring aZPI, a new, very quick method employing synthesized substrate method is now being developed. It is hoped that this new method will make it possible to measure aZPI as a useful clinical practice, for increased activities of coagulation and the fibrinolysis system can be recognized very early by the measurement of aZPI.
