Haemostatic changes and acquired activated protein C resistance in normal pregnancy.
Influence of changes in levels of coagulation factors and anticoagulants on acquired activated protein C (APC) resistance were studied in 40 healthy women during normal pregnancy. Factor VIII (FVIII), von Willebrand factor antigen (VWF:Ag), free protein S (FPS) and protein C were determined at 5-13, 14-26 and 27-40 weeks gestation and more than 6 weeks postpartum. APC anticoagulant activity was determined by measuring the activated partial thromboplastin time before and after adding human APC, expressed as the APC-sensitivity ratio (APC-SR). During the second and third gestation trimesters a significant increase (P < 0.05) in FVIII and VWF:Ag levels and a decrease in FPS levels were seen compared with the first trimester. Postpartum FVIII and VWF:Ag levels significantly decreased and FPS levels increased compared with the third trimester. Protein C levels remained unchanged during pregnancy and postpartum. Between increased FVIII and lowered APC-SR a trend of inverse correlation (r = -0.329; P = 0.076) occurred in the second trimester. No correlation was found between APC-SR and FPS or VWF:Ag levels. A remarkable finding is the strong inverse relationship between APC-SR and protein C levels (r <or= -0.392; P < 0.05) during pregnancy and postpartum. This may indicate that anticoagulant activity of added human APC measured by activated partial thromboplastin time is diminished in the presence of high endogenous protein C levels. A possible hypothesis is steric hindrance by sample protein C of APC binding sites on target activated factor V and/or cofactor protein S. The clinical significance of this finding should be determined because it complicates the interpretation of lowered APC-SR.
Mahieu
Boris
B
Laboratory of Haemostasis and Haematology, Antwerp University Hospital, Edegem, Belgium.
Jacobs
Nadia
N
Mahieu
Sarah
S
Naelaerts
Kristine
K
Vertessen
Francine
F
Weyler
Joost
J
Jacquemyn
Yves
Y
Van der Planken
Marc
M
D020016:Activated Protein C Resistance / Q000097:blood*; D000328:Adult; D003430:Cross-Sectional Studies; D005165:Factor V / Q000032:analysis; D005169:Factor VIII / Q000032:analysis; D005260:Female; D006801:Humans; D010314:Partial Thromboplastin Time / Q000379:methods; D011247:Pregnancy; D011264:Pregnancy Trimesters / Q000097:blood*; D011486:Protein C / Q000032:analysis*; D020151:Protein C Deficiency / Q000097:blood*; D017293:Protein S / Q000032:analysis; D018455:Protein S Deficiency / Q000097:blood; D012307:Risk Factors; D014841:von Willebrand Factor / Q000032:analysis
D011486:Protein C; D017293:Protein S; D014841:von Willebrand Factor; D005165:Factor V; D005169:Factor VIII