Changes in activated protein C resistance during normal pregnancy


      OBJECTIVE: The objective of this study was to determine the changes in activated protein C resistance that occur during normal pregnancy. STUDY DESIGN: In this cross-sectional study activated protein C was measured in 128 women with normal pregnancies in the first, second, and third trimesters and in nonpregnant control subjects with 24 to 39 women in each group. In addition, factor V, factor VIII, free protein S, and functional protein C were measured and correlated with activated protein C levels. Polymerase chain reaction for factor V Leiden mutation was performed. RESULTS: There was a significant fall in the activity of activated protein C in the second and third trimesters of pregnancy (p < 0.05). This was related to increased factor VIII and decreased free protein S levels (p = 0.002, R2 = 0.20). The prevalence of the factor V Leiden mutation was 7.3%. CONCLUSION: Resistance to activated protein C is increased in the second and third trimesters of pregnancy. This is related to the alterations in other coagulation proteins, a phenomenon normally occurring during pregnancy. (Am J Obstet Gynecol 1997;177:162-9.)


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        • Esmon C.
        The roles of protein C and thrombomodulin in the regulation of blood coagulation.
        J Biol Chem. 1989; 264: 4743-4746
        • Dahlback B.
        Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulation system.
        Thromb Haemost. 1991; 66: 49-61
        • Shen L
        • Dahlback B.
        Factor V and protein S as synergistic cofactors to activated protein C in degradation of factor VIIIa.
        J  Biol Chem. 1994; 269: 18735-18738
        • Svensson PJ
        • Dahlback B.
        Resistance to activated protein C as a basis for venous thrombosis.
        N Engl J Med. 1994; 330: 517-522
        • Tabernero MD
        • Tomas JF
        • Alberca I
        • Orafo A
        • Borrasca AL
        • Vicente V.
        Incidence and clinical characteristics of hereditary disorders associated with venous thrombosis.
        Am J Hematol. 1991; 36: 249-254
        • Malm J
        • Laurell I
        • Nilsson M
        • Dahlback B.
        Thromboembolic disease: critical evaluation of laboratory investigation.
        Thromb Haemost. 1992; 68: 7-13
        • Heijboer H
        • Brandjes D
        • Buller H
        • Sturk A
        ten Cate J. Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep venous thrombosis.
        N Engl J Med. 1990; 323: 1512-1518
        • Dahlback B
        • Hildebrand B.
        Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V.
        Proc Natl Acad Sci U S A. 1994; 91: 1396-1400
        • Bertina R
        • Koeleman B
        • Koster T
        • Rosendaal FR
        • Dirven RJ
        • de Ronde H
        • et al.
        Mutation in blood coagulation factor V associated with resistance to activated protein C.
        Nature. 1994; 369: 64-67
        • Sun X
        • Evatt B
        • Griffin J.
        Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia.
        Blood. 1994; 83: 3120-3125
        • Mercer BM
        • Garner P.
        Thrombophlebitis in pregnancy.
        in: Principles of medical therapy in pregnancy. Appleton & Lange, New York1991: 1284-1296
        • Sachs B
        • Brown D
        • Briscoll S
        • Schulman E
        • Acker D
        • Ransil BJ
        • et al.
        Maternal mortality in Massachusetts: trends and prevention.
        N Engl J Med. 1987; 316: 667-672
        • Bonnar J.
        Acute and chronic coagulation problems in pregnancy.
        in: Recent advances in blood coagulation. Churchill Livingstone, Edinburgh1977: 363-378
        • Sipes S
        • Weiner C.
        Venous thromboembolic disease in pregnancy.
        Semin Perinatol. 1990; 14: 103-118
        • Hellgren M
        • Svensson PJ
        • Dahlback B.
        Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives.
        Am J Obstet Gynecol. 1995; 273: 210-213
        • Cumming AM
        • Tait RC
        • Fildes S
        • Yoong A
        • Keeney S
        • Hay CR.
        Development of resistance to activated protein C during pregnancy.
        Br J Haematol. 1995; 90: 725-727
        • Mathonnet F
        • Demazancourt P
        • Bastenaire B
        • Morot M
        • Benattar N
        • Beufe S
        • et al.
        Activated protein C sensitivity ratio in pregnant women at delivery.
        Br J Haematol. 1996; 92: 244-246
        • Zoller B
        • Svensson PJ
        • He X
        • Dahlback B.
        Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C.
        J Clin Invest. 1994; 94: 2521-2524
        • Guillerm C
        • Lellouche F
        • Darnige L
        • Schandlelong A
        • Geffroy F
        • Dorval I.
        Rapid detection of the G1691A mutation of coagulation factor V by PCR-mediated site-directed mutagenesis.
        Clin Chem. 1996; 42: 329
        • Stirling Y
        • Woolf L
        • North WRS
        • Seghatchian MJ
        • Mead TW.
        Hemostasis in normal pregnancy.
        Thromb Haemost. 1984; 52: 176-182
        • Faught W
        • Garner P
        • Jones G
        • Ivey B.
        Changes in protein C and protein S levels in normal pregnancy.
        Am J Obstet Gynecol. 1995; 172: 147-150
        • Comp PC
        • Thurnau GR
        • Welsh J
        • Esmon C.
        Functional and immunologic protein S are decreased during pregnancy.
        Blood. 1986; 68: 881-885
        • de Ronde K
        • Bertina RM.
        Laboratory diagnosis of APC-resistance: a critical evaluation of the test and the development of diagnostic criteria.
        Thromb Haemost. 1994; 72: 880-886
        • Lee DH
        • Henderson PA
        • Blajchman MA.
        Prevalence of factor V Leiden in a Canadian blood donor population.
        Can Med Assoc J. 1996; 155: 285-289