Coagulation and fibrinolysis changes in normal pregnancy. Increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis.

OBJECTIVE

To establish the physiologic changes in the coagulation and fibrinolytic systems during normal pregnancy and puerperium.

STUDY DESIGN

One hundred and seventeen normal pregnant women were investigated in a longitudinal study involving five measurements: blood samples were collected at 10, 20, 30, 36 weeks and on the second day puerperium and were assayed for prothrombin time (PT expressed in INR), activated partial thromboplastin time (PTT), fibrinogen (FBG), antithrombin III activity (AT III), protein C activity (PC), protein S activity (PS), prothrombin fragments 1+2 (F1+2), type 1 plasminogen activator inhibitor activity (PAI) and tissue-plasminogen activator antigen (t-PA). Student t-test, One Way Analysis of Variance (ANOVA) and Bonferroni test were used for statistical analysis. P<0.05 (two tails) was assumed to indicate a significant difference.

RESULTS

Fibrinogen concentrations were always increased with respect to controls (P<0.001), while protein S was always decreased, with values averaging 60% of those of controls from the 10th week of pregnancy onwards (P<0.001). Variance analysis showed a statistically significant increase with gestational age for procoagulant factors (INR: P<0.001; FBG: P<0.001), a reduction for anticoagulants (PC: P<0.0001; PS: P<0.0001), and a rise for F1+2 (P<0.0001). With regard to fibrinolysis, there was an increase both for t-PA (P<0.0001) and PAI-1 (P<0.0001) during pregnancy. The t-PA values were always comprised in the normal range. PAI-1 were increased with respect to control values starting from 31st week. The most significant variations in the procoagulants (expressed by PT and FBG) were recorded up to the 20th week (P<0.001); from the 30th week onwards, they remained stable until after the delivery. The same was true for protein S levels (P<0.001), except that the difference between the 10th and the 20th weeks was not statistically significant. The level of F1+2 gradually increased throughout pregnancy (P<0.001), and then fell in the puerperium (P<0.001).

CONCLUSIONS

The parameters showing the greatest variation during pregnancy were PT, FBG, PS, F1+2 and PAI-1. The existence of a hypercoagulable state in pregnancy was suggested by the increased levels of F1+2.