Skip to main content
SpringerLink
Log in

Hemostatic Changes in Normal Pregnancy

  • Chapter
Book cover Disorders of Thrombosis and Hemostasis in Pregnancy

Abstract

Hemostasis represents a balance between pro- and anti-coagulant processes, with variations in this balance determining the net outcome. Significant physiological changes during pregnancy result in a hypercoagulable and hypofibrinolytic state that serves to protect the mother from bleeding complications at the time of placental separation. This chapter describes the effects of pregnancy on parameters of primary hemostasis, coagulation factors, anticoagulant pathways and the fibrinolytic system.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cadroy Y, Grandjean H, Pichon J, et al. Evaluation of six markers of haemostatic system in normal pregnancy and pregnancy complicated by hypertension or pre-eclampsia. Br J Obstet Gynaecol. 1993;100:416–20.

    CAS  PubMed  Google Scholar 

  2. Stirling Y, Woolf L, North WR, Seghatchian MJ, Meade TW. Haemostasis in normal pregnancy. Thromb Haemost. 1984;52:176–82.

    CAS  PubMed  Google Scholar 

  3. Bremme K, Ostlund E, Almqvist I, Heinonen K, Blomback M. Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. Obstet Gynecol. 1992;80:132–7.

    CAS  PubMed  Google Scholar 

  4. Boehlen F, Hohlfeld P, Extermann P, Perneger TV, de Moerloose P. Platelet count at term pregnancy: a reappraisal of the threshold. Obstet Gynecol. 2000;95:29–33.

    CAS  PubMed  Google Scholar 

  5. Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med. 1993;329:1463–6.

    CAS  PubMed  Google Scholar 

  6. Sainio S, Kekomaki R, Riikonen S, Teramo K. Maternal thrombocytopenia at term: a population-based study. Acta Obstet Gynecol Scand. 2000;79:744–9.

    CAS  PubMed  Google Scholar 

  7. Dahlstrom BL, Nesheim BI. Post partum platelet count in maternal blood. Acta Obstet Gynecol Scand. 1994;73:695–7.

    CAS  PubMed  Google Scholar 

  8. Wallenburg HC, van Kessel PH. Platelet lifespan in normal pregnancy as determined by a nonradioisotopic technique. Br J Obstet Gynaecol. 1978;85:33–6.

    CAS  PubMed  Google Scholar 

  9. Rakoczi I, Tallian F, Bagdany S, Gati I. Platelet lifespan in normal pregnancy and pre-eclampsia as determined by a non-radioisotope technique. Thromb Res. 1979;15:553–6.

    CAS  PubMed  Google Scholar 

  10. Fay RA, Hughes AO, Farron NT. Platelets in pregnancy: hyperdestruction in pregnancy. Obstet Gynecol. 1983;61:238–40.

    CAS  PubMed  Google Scholar 

  11. Sill PR, Lind T, Walker W. Platelet values during normal pregnancy. Br J Obstet Gynaecol. 1985;92:480–3.

    CAS  PubMed  Google Scholar 

  12. Burgess-Wilson ME, Morrison R, Heptinstall S. Spontaneous platelet aggregation in heparinised blood during pregnancy. Thromb Res. 1986;41:385–93.

    CAS  PubMed  Google Scholar 

  13. Morrison R, Crawford J, MacPherson M, Heptinstall S. Platelet behaviour in normal pregnancy, pregnancy complicated by essential hypertension and pregnancy-induced hypertension. Thromb Haemost. 1985;54:607–11.

    CAS  PubMed  Google Scholar 

  14. Karalis I, Nadar SK, Al Yemeni E, Blann AD, Lip GY. Platelet activation in pregnancy-induced hypertension. Thromb Res. 2005;116:377–83.

    CAS  PubMed  Google Scholar 

  15. O’Brien WF, Saba HI, Knuppel RA, Scerbo JC, Cohen GR. Alterations in platelet concentration and aggregation in normal pregnancy and preeclampsia. Am J Obstet Gynecol. 1986;155:486–90.

    PubMed  Google Scholar 

  16. Fitzgerald DJ, Mayo G, Catella F, Entman SS, FitzGerald GA. Increased thromboxane biosynthesis in normal pregnancy is mainly derived from platelets. Am J Obstet Gynecol. 1987;157:325–30.

    CAS  PubMed  Google Scholar 

  17. Douglas JT, Lowe GD, Forbes CD, Prentice CR. Beta-thromboglobulin and platelet counts – effect of malignancy, infection, age and obesity. Thromb Res. 1982;25:459–64.

    CAS  PubMed  Google Scholar 

  18. Mahieu B, Jacobs N, Mahieu S, et al. Haemostatic changes and acquired activated protein C resistance in normal pregnancy. Blood Coagul Fibrinolysis. 2007;18:685–8.

    CAS  PubMed  Google Scholar 

  19. Clark P, Brennand J, Conkie JA, McCall F, Greer IA, Walker ID. Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thromb Haemost. 1998;79:1166–70.

    CAS  PubMed  Google Scholar 

  20. Hellgren M, Blomback M. Studies on blood coagulation and fibrinolysis in pregnancy, during delivery and in the puerperium. I. Normal condition. Gynecol Obstet Invest. 1981;12:141–54.

    CAS  PubMed  Google Scholar 

  21. Sanchez-Luceros A, Meschengieser SS, Marchese C, et al. Factor VIII and von Willebrand factor changes during normal pregnancy and puerperium. Blood Coagul Fibrinolysis. 2003;14:647–51.

    CAS  PubMed  Google Scholar 

  22. Kjellberg U, Andersson NE, Rosen S, Tengborn L, Hellgren M. APC resistance and other haemostatic variables during pregnancy and puerperium. Thromb Haemost. 1999;81:527–31.

    CAS  PubMed  Google Scholar 

  23. Sie P, Caron C, Azam J, et al. Reassessment of von Willebrand factor (VWF), VWF propeptide, factor VIII:C and plasminogen activator inhibitors 1 and 2 during normal pregnancy. Br J Haematol. 2003;121:897–903.

    CAS  PubMed  Google Scholar 

  24. Brenner B, Zwang E, Bronshtein M, Seligsohn U. von Willebrand factor multimer patterns in pregnancy-induced hypertension. Thromb Haemost. 1989;62:715–7.

    CAS  PubMed  Google Scholar 

  25. Bergmann F, Rotmensch S, Rosenzweig B, How H, Chediak J. The role of von Willebrand factor in pre-eclampsia. Thromb Haemost. 1991;66:525–8.

    CAS  PubMed  Google Scholar 

  26. Sanchez-Luceros A, Farias CE, Amaral MM, et al. von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non-pregnant women, pregnant and post-delivery women. Thromb Haemost. 2004;92:1320–6.

    CAS  PubMed  Google Scholar 

  27. Mannucci PM, Canciani MT, Forza I, Lussana F, Lattuada A, Rossi E. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood. 2001;98:2730–5.

    CAS  PubMed  Google Scholar 

  28. Feys HB, Deckmyn H, Vanhoorelbeke K. ADAMTS13 in health and disease. Acta Haematol. 2009;121:183–5.

    CAS  PubMed  Google Scholar 

  29. Mann KG. Thrombin formation. Chest. 2003;124:4S–10.

    CAS  PubMed  Google Scholar 

  30. Savage B, Cattaneo M, Ruggeri ZM. Mechanisms of platelet aggregation. Curr Opin Hematol. 2001;8:270–6.

    CAS  PubMed  Google Scholar 

  31. Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci U S A. 1989;86:2839–43.

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Bogdanov VY, Balasubramanian V, Hathcock J, Vele O, Lieb M, Nemerson Y. Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med. 2003;9:458–62.

    CAS  PubMed  Google Scholar 

  33. Falati S, Liu Q, Gross P, et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med. 2003;197:1585–98.

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Mackman N. Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler Thromb Vasc Biol. 2004;24:1015–22.

    CAS  PubMed  Google Scholar 

  35. Aharon A, Brenner B, Katz T, Miyagi Y, Lanir N. Tissue factor and tissue factor pathway inhibitor levels in trophoblast cells: implications for placental hemostasis. Thromb Haemost. 2004;92:776–86.

    CAS  PubMed  Google Scholar 

  36. Krikun G, Schatz F, Mackman N, Guller S, Demopoulos R, Lockwood CJ. Regulation of tissue factor gene expression in human endometrium by transcription factors Sp1 and Sp3. Mol Endocrinol. 2000;14:393–400.

    CAS  PubMed  Google Scholar 

  37. Dusse LM, Carvalho MG, Cooper AJ, Lwaleed BA. Tissue factor and tissue factor pathway inhibitor: a potential role in pregnancy and obstetric vascular complications? Clin Chim Acta. 2006;372:43–6.

    CAS  PubMed  Google Scholar 

  38. Morrison SA, Jesty J. Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma. Blood. 1984;63:1338–47.

    CAS  PubMed  Google Scholar 

  39. Osterud B, Rapaport SI. Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. Proc Natl Acad Sci U S A. 1977;74:5260–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Esmon CT, Owen WG, Jackson CM. The conversion of prothrombin to thrombin. V. The activation of prothrombin by factor Xa in the presence of phospholipid. J Biol Chem. 1974;249:7798–807.

    CAS  PubMed  Google Scholar 

  41. Dahlback B, Stenflo J. The activation of prothrombin by platelet-bound factor Xa. Eur J Biochem. 1980;104:549–57.

    CAS  PubMed  Google Scholar 

  42. Szecsi PB, Jorgensen M, Klajnbard A, Andersen MR, Colov NP, Stender S. Haemostatic reference intervals in pregnancy. Thromb Haemost. 2010;103:718–27.

    CAS  PubMed  Google Scholar 

  43. Dalaker K, Prydz H. The coagulation factor VII in pregnancy. Br J Haematol. 1984;56:233–41.

    CAS  PubMed  Google Scholar 

  44. Nilsson IM, Kullander S. Coagulation and fibrinolytic studies during pregnancy. Acta Obstet Gynecol Scand. 1967;46:273–85.

    CAS  PubMed  Google Scholar 

  45. Todd ME, Thompson Jr JH, Bowie EJ, Owen Jr CA. Changes in blood coagulation during pregnancy. Mayo Clin Proc. 1965;40:370–83.

    CAS  PubMed  Google Scholar 

  46. Beller FK, Ebert C. The coagulation and fibrinolytic enzyme system in pregnancy and in the puerperium. Eur J Obstet Gynecol Reprod Biol. 1982;13:177–97.

    CAS  PubMed  Google Scholar 

  47. Fresh JW, Ferguson JH, Lewis JH. Blood-clotting studies in parturient women and the newborn. Obstet Gynecol. 1956;7:117–27.

    CAS  PubMed  Google Scholar 

  48. Phillips LL, Rosano L, Skrodelis V. Changes in factor XI (plasma thromboplastin antecedent) levels during pregnancy. Am J Obstet Gynecol. 1973;116:1114–6.

    CAS  PubMed  Google Scholar 

  49. Nossel HL, Lanzkowsky P, Levy S, Mibashan RS, Hansen JD. A study of coagulation factor levels in women during labour and in their newborn infants. Thromb Diath Haemorrh. 1966;16:185–97.

    CAS  PubMed  Google Scholar 

  50. Persson BL, Stenberg P, Holmberg L, Astedt B. Transamidating enzymes in maternal plasma and placenta in human pregnancies complicated by intrauterine growth retardation. J Dev Physiol. 1980;2:37–46.

    CAS  PubMed  Google Scholar 

  51. Di Bitondo R, Hall AJ, Peake IR, Iacoviello L, Winship PR. Oestrogenic repression of human coagulation factor VII expression mediated through an oestrogen response element sequence motif in the promoter region. Hum Mol Genet. 2002;11:723–31.

    PubMed  Google Scholar 

  52. Smith R, Smith JI, Shen X, et al. Patterns of plasma corticotropin-releasing hormone, progesterone, estradiol, and estriol change and the onset of human labor. J Clin Endocrinol Metab. 2009;94:2066–74.

    CAS  PubMed  Google Scholar 

  53. Bajaj MS, Birktoft JJ, Steer SA, Bajaj SP. Structure and biology of tissue factor pathway inhibitor. Thromb Haemost. 2001;86:959–72.

    CAS  PubMed  Google Scholar 

  54. Huang ZF, Wun TC, Broze Jr GJ. Kinetics of factor Xa inhibition by tissue factor pathway inhibitor. J Biol Chem. 1993;268:26950–5.

    CAS  PubMed  Google Scholar 

  55. Broze Jr GJ, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletich JP. The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action. Blood. 1988;71:335–43.

    CAS  PubMed  Google Scholar 

  56. Weiner CP, Brandt J. Plasma antithrombin III activity in normal pregnancy. Obstet Gynecol. 1980;56:601–3.

    CAS  PubMed  Google Scholar 

  57. Massouh M, Jatoi A, Gordon EM, Ratnoff OD. Heparin cofactor II activity in plasma during pregnancy and oral contraceptive use. J Lab Clin Med. 1989;114:697–9.

    CAS  PubMed  Google Scholar 

  58. Uchikova EH, Ledjev II. Changes in haemostasis during normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 2005;119:185–8.

    CAS  PubMed  Google Scholar 

  59. Bellart J, Gilabert R, Cabero L, Fontcuberta J, Monasterio J, Miralles RM. Heparin cofactor II: a new marker for pre-eclampsia. Blood Coagul Fibrinolysis. 1998;9:205–8.

    CAS  PubMed  Google Scholar 

  60. Esmon CT. The protein C pathway. Chest. 2003;124:26S–32.

    CAS  PubMed  Google Scholar 

  61. Maruyama I, Bell CE, Majerus PW. Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblast of human placenta. J Cell Biol. 1985;101:363–71.

    CAS  PubMed  Google Scholar 

  62. Esmon CT, Esmon NL, Harris KW. Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and factor V activation. J Biol Chem. 1982;257:7944–7.

    CAS  PubMed  Google Scholar 

  63. Hackeng TM, Sere KM, Tans G, Rosing J. Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor. Proc Natl Acad Sci U S A. 2006;103:3106–11.

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Hackeng TM, van’t Veer C, Meijers JC, Bouma BN. Human protein S inhibits prothrombinase complex activity on endothelial cells and platelets via direct interactions with factors Va and Xa. J Biol Chem. 1994;269:21051–8.

    CAS  PubMed  Google Scholar 

  65. van de Poel RH, Meijers JC, Bouma BN. The interaction between anticoagulant protein S and complement regulatory C4b-binding protein (C4BP). Trends Cardiovasc Med. 2000;10:71–6.

    PubMed  Google Scholar 

  66. Dahlback B. Inhibition of protein Ca cofactor function of human and bovine protein S by C4b-binding protein. J Biol Chem. 1986;261:12022–7.

    CAS  PubMed  Google Scholar 

  67. Maurissen LF, Thomassen MC, Nicolaes GA, et al. Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation. Blood. 2008;111:3034–41.

    CAS  PubMed  Google Scholar 

  68. van de Poel RH, Meijers JC, Bouma BN. C4b-binding protein inhibits the factor V-dependent but not the factor V-independent cofactor activity of protein S in the activated protein C-mediated inactivation of factor VIIIa. Thromb Haemost. 2001;85:761–5.

    PubMed  Google Scholar 

  69. Maurissen LFA, Castoldi E, Simioni P, Rosing J, Hackeng TM. Thrombin generation-based assays to measure the activity of the TFPI-protein S pathway in plasma from normal and protein S-deficient individuals. J Thromb Haemost. 2010;8:750–8.

    CAS  PubMed  Google Scholar 

  70. Comp PC, Thurnau GR, Welsh J, Esmon CT. Functional and immunologic protein S levels are decreased during pregnancy. Blood. 1986;68:881–5.

    CAS  PubMed  Google Scholar 

  71. Malm J, Laurell M, Dahlback B. Changes in the plasma levels of vitamin K-dependent proteins C and S and of C4b-binding protein during pregnancy and oral contraception. Br J Haematol. 1988;68:437–43.

    CAS  PubMed  Google Scholar 

  72. Matsumoto M, Tachibana D, Nobeyama H, et al. Protein S deposition at placenta: a possible role of protein S other than anticoagulation. Blood Coagul Fibrinolysis. 2008;19:653–6.

    CAS  PubMed  Google Scholar 

  73. Faught W, Garner P, Jones G, Ivey B. Changes in protein C and protein S levels in normal pregnancy. Am J Obstet Gynecol. 1995;172:147–50.

    CAS  PubMed  Google Scholar 

  74. Mannucci PM, Vigano S, Bottasso B, et al. Protein C antigen during pregnancy, delivery and puerperium. Thromb Haemost. 1984;52:217.

    CAS  PubMed  Google Scholar 

  75. Torricelli M, Sabatini L, Florio P, et al. Levels of antibodies against protein C and protein S in pregnancy and in preeclampsia. J Matern Fetal Neonatal Med. 2009;22:993–9.

    CAS  PubMed  Google Scholar 

  76. de Moerloose P, Mermillod N, Amiral J, Reber G. Thrombomodulin levels during normal pregnancy, at delivery and in the postpartum: comparison with tissue-type plasminogen activator and plasminogen activator inhibitor-1. Thromb Haemost. 1998;79:554–6.

    PubMed  Google Scholar 

  77. Boffa MC, Valsecchi L, Fausto A, et al. Predictive value of plasma thrombomodulin in preeclampsia and gestational hypertension. Thromb Haemost. 1998;79:1092–5.

    CAS  PubMed  Google Scholar 

  78. Astedt B, Hagerstrand I, Lecander I. Cellular localisation in placenta of placental type plasminogen activator inhibitor. Thromb Haemost. 1986;56:63–5.

    CAS  PubMed  Google Scholar 

  79. Wright JG, Cooper P, Astedt B, et al. Fibrinolysis during normal human pregnancy: complex inter-relationships between plasma levels of tissue plasminogen activator and inhibitors and the euglobulin clot lysis time. Br J Haematol. 1988;69:253–8.

    CAS  PubMed  Google Scholar 

  80. Lockwood CJ. Regulation of plasminogen activator inhibitor 1 expression by interaction of epidermal growth factor with progestin during decidualization of human endometrial stromal cells. Am J Obstet Gynecol. 2001;184:798–804; discussion −5.

    CAS  PubMed  Google Scholar 

  81. Halligan A, Bonnar J, Sheppard B, Darling M, Walshe J. Haemostatic, fibrinolytic and endothelial variables in normal pregnancies and pre-eclampsia. Br J Obstet Gynaecol. 1994;101:488–92.

    CAS  PubMed  Google Scholar 

  82. Cerneca F, Ricci G, Simeone R, Malisano M, Alberico S, Guaschino S. 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. Eur J Obstet Gynecol Reprod Biol. 1997;73:31–6.

    CAS  PubMed  Google Scholar 

  83. Kruithof EK, Tran-Thang C, Gudinchet A, et al. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood. 1987;69:460–6.

    CAS  PubMed  Google Scholar 

  84. Robb AO, Mills NL, Din JN, et al. Acute endothelial tissue plasminogen activator release in pregnancy. J Thromb Haemost. 2009;7:138–42.

    CAS  PubMed  Google Scholar 

  85. Shimada H, Takashima E, Soma M, et al. Source of increased plasminogen activators during pregnancy and puerperium. Thromb Res. 1989;54:91–8.

    CAS  PubMed  Google Scholar 

  86. Mousa HA, Downey C, Alfirevic Z, Toh CH. Thrombin activatable fibrinolysis inhibitor and its fibrinolytic effect in normal pregnancy. Thromb Haemost. 2004;92:1025–31.

    CAS  PubMed  Google Scholar 

  87. Ku DH, Arkel YS, Paidas MP, Lockwood CJ. Circulating levels of inflammatory cytokines (IL-1 beta and TNF-alpha), resistance to activated protein C, thrombin and fibrin generation in uncomplicated pregnancies. Thromb Haemost. 2003;90:1074–9.

    CAS  PubMed  Google Scholar 

  88. Chabloz P, Reber G, Boehlen F, Hohlfeld P, de Moerloose P. TAFI antigen and D-dimer levels during normal pregnancy and at delivery. Br J Haematol. 2001;115:150–2.

    CAS  PubMed  Google Scholar 

  89. Watanabe T, Minakami H, Sakata Y, Matsubara S, Sato I, Suzuki M. Changes in activity of plasma thrombin activatable fibrinolysis inhibitor in pregnancy. Gynecol Obstet Invest. 2004;58:19–21.

    CAS  PubMed  Google Scholar 

  90. Chen J, Fu X, Wang Y, et al. Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood. 2010;115:706–12.

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Rosen T, Kuczynski E, O’Neill LM, Funai EF, Lockwood CJ. Plasma levels of thrombin-antithrombin complexes predict preterm premature rupture of the fetal membranes. J Matern Fetal Med. 2001;10:297–300.

    CAS  PubMed  Google Scholar 

  92. Comeglio P, Fedi S, Liotta AA, et al. Blood clotting activation during normal pregnancy. Thromb Res. 1996;84:199–202.

    CAS  PubMed  Google Scholar 

  93. Huissoud C, Carrabin N, Benchaib M, et al. Coagulation assessment by rotation thromboelastometry in normal pregnancy. Thromb Haemost. 2009;101:755–61.

    CAS  PubMed  Google Scholar 

  94. Steer PL, Krantz HB. Thromboelastography and Sonoclot analysis in the healthy parturient. J Clin Anesth. 1993;5:419–24.

    CAS  PubMed  Google Scholar 

  95. Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci U S A. 1993;90:1004–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Bertina RM, Koeleman BP, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994;369:64–7.

    CAS  PubMed  Google Scholar 

  97. Bokarewa MI, Bremme K, Falk G, Sten-Linder M, Egberg N, Blomback M. Studies on phospholipid antibodies, APC-resistance and associated mutation in the coagulation factor V gene. Thromb Res. 1995;78:193–200.

    CAS  PubMed  Google Scholar 

  98. Laffan MA, Manning R. The influence of factor VIII on measurement of activated protein C resistance. Blood Coagul Fibrinolysis. 1996;7:761–5.

    CAS  PubMed  Google Scholar 

  99. Lowe GD, Rumley A, Woodward M, Reid E, Rumley J. Activated protein C resistance and the FV:R506Q mutation in a random population sample–associations with cardiovascular risk factors and coagulation variables. Thromb Haemost. 1999;81:918–24.

    CAS  PubMed  Google Scholar 

  100. Kemmeren JM, Algra A, Meijers JC, et al. Effect of second- and third-generation oral contraceptives on the protein C system in the absence or presence of the factor VLeiden mutation: a randomized trial. Blood. 2004;103:927–33.

    CAS  PubMed  Google Scholar 

  101. Mathonnet F, de Mazancourt P, Bastenaire B, et al. Activated protein C sensitivity ratio in pregnant women at delivery. Br J Haematol. 1996;92:244–6.

    CAS  PubMed  Google Scholar 

  102. 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;90:725–7.

    CAS  PubMed  Google Scholar 

  103. Bokarewa MI, Wramsby M, Bremme K, Blomback M. Variability of the response to activated protein C during normal pregnancy. Blood Coagul Fibrinolysis. 1997;8:239–44.

    CAS  PubMed  Google Scholar 

  104. Clark P, Sattar N, Walker ID, Greer IA. The Glasgow outcome, APCR and lipid (GOAL) pregnancy study: significance of pregnancy associated activated protein C resistance. Thromb Haemost. 2001;85:30–5.

    CAS  PubMed  Google Scholar 

  105. Bonnar J, Prentice CR, McNicol GP, Douglas AS. Haemostatic mechanism in the uterine circulation during placental separation. Br Med J. 1970;2:564–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Higgins JR, Walshe JJ, Darling MR, Norris L, Bonnar J. Hemostasis in the uteroplacental and peripheral circulations in normotensive and pre-eclamptic pregnancies. Am J Obstet Gynecol. 1998;179:520–6.

    CAS  PubMed  Google Scholar 

  107. Bretelle F, Sabatier F, Desprez D, et al. Circulating microparticles: a marker of procoagulant state in normal pregnancy and pregnancy complicated by preeclampsia or intrauterine growth restriction. Thromb Haemost. 2003;89:486–92.

    CAS  PubMed  Google Scholar 

  108. Germain SJ, Sacks GP, Sooranna SR, Sargent IL, Redman CW. Systemic inflammatory priming in normal pregnancy and preeclampsia: the role of circulating syncytiotrophoblast microparticles. J Immunol. 2007;178:5949–56.

    CAS  PubMed  Google Scholar 

  109. Knight M, Kenyon S, Brocklehurst P, Neilson J, Shakespeare J, Kurinczuk JJ (Eds.) on behalf of MBRRACE-UK. Saving Lives, Improving Mothers’ Care - Lessons learned to inform future maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2009–12. Oxford: National Perinatal Epidemiology Unit, University of Oxford 2014.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Haematology, Faculty of Medicine, Hammersmith Campus, Imperial College, London, W12 0NN, UK

    Carolyn M. Millar MB ChB, MD, FRCP, FRCPath & Michael Laffan MB ChB, DM, FRCP, FRCPath

Authors
  1. Carolyn M. Millar MB ChB, MD, FRCP, FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Laffan MB ChB, DM, FRCP, FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carolyn M. Millar MB ChB, MD, FRCP, FRCPath .

Editor information

Editors and Affiliations

  1. Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom

    Hannah Cohen

  2. Institute for Women's Health, University College London Hospitals NHS Foundation Trust, London, United Kingdom

    Patrick O'Brien

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag London

About this chapter

Cite this chapter

Millar, C.M., Laffan, M. (2015). Hemostatic Changes in Normal Pregnancy. In: Cohen, H., O'Brien, P. (eds) Disorders of Thrombosis and Hemostasis in Pregnancy. Springer, Cham. https://doi.org/10.1007/978-3-319-15120-5_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-15120-5_1

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-15119-9

  • Online ISBN: 978-3-319-15120-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation