[The role of coagulation and fibrinolysis system in pathogenesis of toxemia of pregnancy].
It is well known that many pathophysiological findings in toxemia of pregnancy are explained by imbalance of coagulation and fibrinolysis system. The purpose of this study is to elucidate a precise role of coagulation and fibrinolysis system in pathogenesis of toxemia of pregnancy.


METHODS
1) Classification of toxemia of pregnancy. Three hundred and thirty seven of toxemia of pregnancy are classified based on the onset period, and incidence of severity of disease and IUGR, rate of genetic factor of hypertension are compared in each group. 2) Platelet factor 4 (pf4) and beta-thromboglobulin (beta-TG), Fibrinopeptide A (FPA), thrombin-ATIII complex, ATIII fibrinopeptide B beta 15-42, D dimer FDP and plasmin-alpha 2 PI complex are assayed. The levels of PGI2, tissue plasminogen activator (tPA) and thrombomodulin (TM) are measured after venous occlusion. Immunoreactivity and biological activity of TM in urine are analyzed. 3) Aminoacid sequence of TM from normal and toxemia of pregnancy are determined by analyzing cDNA for TM. Moreover, TM are synthesized from recombined DNA and enzymological properties of TM obtained from normal and toxemia of pregnancy are compared. 4) Release of PGI2, tPA and TM by addition of thrombin are observed using monolayer culture of endothelial cells from cord. Enzymological properties of purified placental TM are analyzed.


RESULTS
1) The incidence of severe type, IUGR and the rate of patients who possess genetic factors for hypertension are higher in early onset type, suggesting that hypertension is the predominant characteristics in early onset type and that genetic factors for hypertension are tightly involved. 2) All parameters such as platelets, coagulation and fibrinolysis system are elevated in toxemia of pregnancy compared to those in normal pregnancy. Coagulation index that consists of above parameters is well correlated with clinical index that consists of clinical findings (r = 0.7006, p less than 0.0001). The net increase of PGI2, tPA and TM by venous occlusion are decreased along with severity of toxemia of pregnancy. The potency of production of PGI2 from endothelial cells in maternal omentum is impaired in the severe toxemia of pregnancy. Purified TM in urine from normal pregnancy and toxemia of pregnancy has 63K dalton of single band on SDS-PAGE. However, bioactivity/immunoreactivity ratio of TM in early onset type is lower than those in late onset type, and affinity of TM for thrombin and protein C is decreased in early onset type.(ABSTRACT TRUNCATED AT 400 WORDS)
Nakabayashi
M
M
Maternal and Perinatal Center, Tokyo Women's Medical College.
D000596:Amino Acids / Q000032:analysis; D001777:Blood Coagulation; D001798:Blood Proteins / Q000378:metabolism; D002824:Chorionic Villi / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis / Q000097:blood; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D006973:Hypertension / Q000150:complications; D007564:Japan; D015337:Multicenter Studies as Topic; D009154:Mutation; D010976:Platelet Count; D011225:Pre-Eclampsia / Q000097:blood / Q000209:etiology* / Q000235:genetics; D011247:Pregnancy / Q000097:blood; D011249:Pregnancy Complications, Cardiovascular; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D018179:Receptors, Thrombin; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000097:blood; D014470:Umbilical Cord / Q000098:blood supply
D000596:Amino Acids; D001798:Blood Proteins; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator