Skip to main content
SpringerLink
Log in
Book cover

Disorders of Thrombosis and Hemostasis in Pregnancy pp 1–13Cite as

Hemostatic Changes in Normal Pregnancy

  • Chapter
  • First Online:

  • 1118 Accesses

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.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about 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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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 USA. 1989;86:2839–43.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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 USA. 1977;74:5260–4.

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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 USA. 2006;103:3106–11.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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 USA. 1993;90:1004–8.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

  109. Liston W. Haemorrhage. In: Lewis G, editor. The confidential enquiry into maternal and child health (CEMACH). Saving mothers’ lives: reviewing maternal deaths to make motherhood safer – 2003–2005. The seventh report on confidential enquiries into maternal deaths in the United Kingdom. London: CEMACH; 2007.

    Google Scholar 

  110. Drife J. Centre for Maternal and Child Enquiries (CMACE). Saving Mothers’ Lives: reviewing maternal deaths to make motherhood safer: 2006–08. The Eighth Report on Confidential Enquiries into Maternal Deaths in the United Kingdom. G. Lewis (ed.). BJOG 2011;118(Suppl. 1):57–65 and 71–6.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Haematology, Hammersmith Campus, Imperial College London, Du Cane Road, London, W12 0NN, UK

    Carolyn Millar MD, MRCP, FRCPath & Mike Laffan DM, FRCP, FRCPath

Authors
  1. Carolyn Millar MD, MRCP, FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mike Laffan DM, FRCP, FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carolyn Millar MD, MRCP, FRCPath .

Editor information

Editors and Affiliations

  1. Aberdare Gardens 36, London, NW6 3QA, United Kingdom

    Hannah Cohen

  2. Dept. Obstetrics & Gynaecology, University College Hospital, Chenies Mews 86-96, London, WC1E 6HX, United Kingdom

    Patrick O'Brien

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag London

About this chapter

Cite this chapter

Millar, C., Laffan, M. (2012). Hemostatic Changes in Normal Pregnancy. In: Cohen, H., O'Brien, P. (eds) Disorders of Thrombosis and Hemostasis in Pregnancy. Springer, London. https://doi.org/10.1007/978-1-4471-4411-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4411-3_1

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4410-6

  • Online ISBN: 978-1-4471-4411-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation