Thromb Haemost 1984; 52(02): 176-182
DOI: 10.1055/s-0038-1661167
Original Article
Schattauer GmbH Stuttgart

Haemostasis in Normal Pregnancy

Yvonne Stirling
The MRC Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, Middlesex, U. K.
,
Linda Woolf
The MRC Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, Middlesex, U. K.
,
W R S North
The MRC Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, Middlesex, U. K.
,
M J Seghatchian
The MRC Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, Middlesex, U. K.
,
T W Meade
The MRC Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, Middlesex, U. K.
› Author Affiliations
Further Information

Publication History

Received 23 December 1983

Accepted 16 July 1984

Publication Date:
19 July 2018 (online)

Summary

A study has been undertaken in 72 women to provide systematic information on the changes that occur in a wide range of haemostatic variables during and after pregnancy. Factors VII, VIII :C, VIIIR:Ag, X, fibrinogen and α1 antitrypsin, rose markedly throughout pregnancy. Factors II and V and α2 macroglobulin all rose early on but then decreased steadily. Antithrombin III: C and Ag fell slightly. There was a marked decrease in fibrinolytic activity from 11-15 weeks onwards. Levels of fibrin degradation products rose from 21-25 weeks onwards. The rise in coagulation factors that occurs could be due to increased synthesis or increased activation by thrombin, or to both. The findings are consistent with a mild degree of local intravascular coagulation from early on in pregnancy in some women.

 
  • References

  • 1 Gilabert J, Aznar J, Parrilla JJ, Reganon E, Villa V, Estelles A. Alterations in the coagulation and fibrinolysis system in pregnancy, labour and the puerperium, with special reference to a possible transitory state of intra-vascular coagulation during labour. Thromb Haemostas 1978; 40: 387-396
  • 2 Davidson ED, Phillips LL. Coagulation studies in the hypertensive toxaemias of pregnancy. Am J Obstet Gynecol 1972; 113: 905-910
  • 3 Fawer R, Dettling A, Weihs D, Welti H, Schelling JL. Effect of the menstrual cycle, oral contraception and pregnancy on forearm blood flow, venous distensibility and clotting factors. Eur J Clin Pharmacol 1978; 13: 251-257
  • 4 Hellgren M. Thromboembolism and pregnancy. Studies on blood coagulation and fibrinolysis and treatment with heparin and antithrombin. Thesis, Karolinska Institutet; Stockholm: 1981
  • 5 Bonnar J, McNicol GP, Douglas AS. Coagulation and fibrinolytic mechanisms during and after normal childbirth. Br Med J 1970; 2: 200-203
  • 6 Bonnar J, McNicol GP, Douglas AS. The blood coagulation and fibrinolytic systems in the newborn and the mother at birth. J Obstet Gynaecol Br Commonwealth 1971; 78: 355-360
  • 7 Linhard J, Diebolt G, Laurens A, Diakhate L, Blavy G. Etude de la coagulation chez la femme africaine durant 1a gestation, pendant le travail et après l’accouchement. Bull Soc Med Afr Noire Lang Fr 1978; 23: 109-114
  • 8 Condie RG. A serial study of coagulation factors XII, XI and X in plasma in normal pregnancy and in pregnancy compicated by preeclampsia. Br J Obstet Gynaecol 1976; 83: 636-639
  • 9 Condie RG, Ogston D. Sequential studies on components of the haemostatic mechanism in pregnancy with particular reference to the development of preeclampsia. Br J Obstet Gynaecol 1976; 83: 938-942
  • 10 van Royen EA. Haemostasis in human pregnancy and delivery. Thesis, University Hospital Wilhelminar Hasthius; Amsterdam: 1974
  • 11 Meade TW, Brozovic M, Chakrabarti R, Haines AP, North WR, Stirling Y. Ethnic group comparisons of variables associated with ischaemic heart disease. Br Heart J 1978; 40: 789-795
  • 12 Meade TW, North WR, Chakrabarti R, Haines AP, Stirling Y. Population based distributions of haemostatic variables. Br Med Bull 1977; 33: 283-288
  • 13 North WR, Stirling Y, Meade TW. Variation between batches in clotting factor assays. Thromb Haemostas 1982; 48: 274-276
  • 14 North WR, Stirling Y, Meade TW. Common units for clotting factors assayed against different standards. Thromb Haemostas 1982; 48: 270-273
  • 15 Denson KW, Borrett R, Biggs R. The specific assay of prothrombin using the Taipan snake venom. Br J Haematol 1971; 21: 219-226
  • 16 Denson KW. The specific assay of Prower-Stuart factor and factor VII. Acta Haematol 1961; 25: 105-120
  • 17 Laurell CB. Electroimmunoassay. Scand J Clin Lab Invest 1972; 29 (suppl) (Suppl. 124) 21-37
  • 18 Merskey C, Lalezari P, Johnson AJ. A rapid, simple sensitive method for measuring fibrinolytic split products in human serum. Proc Soc Exp Biol Med 1969; 11: 871-875
  • 19 Godai HC, Abildgaard U. Gelation of soluble fibrin in plasma by ethanol. Scand J Haematol 1966; 3: 342-350
  • 20 Poller L, Thomson JM. Clotting factors during oral contraception. Br Med J 1966; 2: 23-25
  • 21 Meade TW, Brozovic M, Chakrabarti R, Howarth DJ, North WR, Stirling Y. An epidemiological study of the haemostatic and other effects of oral contraceptives. Br J Haematol 1976; 34: 353-364
  • 22 Poller L, Thomson J, Coope J. Conjugated equine oestrogens and blood clotting: a follow-up report. Br Med J 1977; 1: 935-936
  • 23 Gentry PA, Liptrap RM. Plasma levels of specific coagulation factors and oestrogens in the bitch during pregnancy. J Small An Prac 1977; 18: 267-275
  • 24 Gentry PA, Liptrap RM, Black WD. Changes in blood coagulation profiles of dairy cows during pregnancy and in heifer calves after hormone treatment. Can J An Sci 1979; 59: 503-510
  • 25 Regoeczi E, Hobbs KR. Fibrinogen turnover in pregnancy. Scand J Haematol 1969; 6: 175-178
  • 26 Muller-Berghaus G, Moeller RM, Mahn I. Fibrinogen turnover in pregnant rabbits during the first and last thirds of gestation. Am J Obstet Gynaecol 1978; 131: 655-660
  • 27 Dalaker K, Prydz H. The coagulation factor VII in pregnancy. Br J Haematol 1984; 56: 233-241
  • 28 Colman RW. Kinetics of activation and inactivation by bovine thrombin. Biochemistry 1969; 8: 1438-1444
  • 29 Rappaport SI, Schiffman S, Patch MJ, Amess B. The importance of activation of antihaemophilic globulin and proaccelerin by traces of thrombin in the generation of intrinsic prothrombinase activity. Blood 1963; 21: 221-236
  • 30 Penick GD. Some factors that influence utilization of antihemophilic activity during clotting. Proc Soc Exp Biol Med 1957; 96: 277-281
  • 31 Lian EC, Nunez RL, Harkness DR. In vivo and in vitro effects of thrombin and plasmin on human FVIII (AHF). Am J Haematol 1976; 1: 481-485
  • 32 Pasquini R, Hershgold EJ. Effects of plasmin on human factor VIII (AHF). Blood 1973; 41: 105-111
  • 33 Atichartakam V, Marder VJ, Kirby EP, Budzynski AZ. Effects of enzymatic degradation on the subunit composition and biologic properties of human factor VIII. Blood 1978; 51: 281-297
  • 34 van RoyenE, TenCate JW. Antigen-biological activity ratio for factor VIII in late pregnancy. Lancet 1973; 2: 449-450
  • 35 Bonnar J. Coagulation Disorders. J Clin Pathol 1976; 29 (Suppl) (Suppl. 10) 35-41
  • 36 Bouma BN, Sixma JJ, van Mourik JA, Mochtar IA. Immunological determination of antihaemophilic factor A (factor VIII). Neth J Med 1973; 16: 54 (Abstr.)
  • 37 Radcliffe R, Nemerson Y. Activation and control of VII by Xa and thrombin. J Biol Chem 1975; 250: 388-395
  • 38 Gjønnoess H. Cold promoted activation of factor VII. I. Thrombos Diathes Haemorrh 1972; 28: 155-168
  • 39 Morrison-Silverberg SA, Jesty J. The role of activated factor X in the control of bovine coagulation factor VII. J Biol Chem 1981; 256: 1625-1630
  • 40 Walker FJ, Sexton PW, Esmon CT. The inhibition of blood coagulation by activated Protein C through the selective inactivation of activated factor V. Biochim Biophys Acta 1979; 571: 333-342
  • 41 Marlar RA, Kleiss AJ, Griffin JH. Human Protein C inactivation of factors V and VIII in plasma by the activated molecule. Ann N Y Acad Sci 1981; 370: 303-310
  • 42 Laurell CB. Aspects on biochemistry and pathophysiology of α1antitrypsin. The chemistry and physiology of the human plasma proteins. Bing DH. (Ed.) Pergamon press; 1978. pp 329-341
  • 43 Rosenberg RD. Mechanisms of anti-thrombin action and the structural basis of heparin anticoagulant function. Chemistry and pathophysiology of the human plasma proteins. Bing DH. (Ed.) Pergamon press; 1978. pp 353-368
  • 44 Harpel PC. α2macroglobulin. The Chemistry and pathophysiology of the human plasma proteins. Bing DH. (Ed.) Pergamon press; 1978. pp 385-399
  • 45 Uszynski M, Abildgaard U. Separation and characterisation of two fibrinolytic inhibitors from human placenta. Thrombos Diathes Haemorrh 1971; 25: 580-589
  • 46 Astedt B, Isacson S, Nilsson IM, Pandolf M. Fibrinolytic activity of veins during pregnancy. Acta Obstet Gynaecol Scand 1970; 49: 171-173
  • 47 Brozovic M, Mackie I. Hypercoagulability. In: Topical Reviews in Haematology. Roath S. (Ed) John Wright & Sons; Bristol: 1980. 1 33-49
  • 48 Koj A. In: Structure and function of plasma proteins. Allison AC. (Ed.) Plenum press; London, New York: 1974. 1 73-131
  • 49 Hawkey CJ, Stirling Y, Chakrabarti R, Brozovic M, Cox AG, Meade TW. Haemostatic changes following surgery. Thromb Res 1983; 32: 223-227
  • 50 Fletcher AP, Alkjaersig NK, Burstein R. The influence of pregnancy upon blood coagulation and plasma fibrinolytic enzyme function. Am J Obstet Gynecol 1979; 134: 743-751
  • 51 Bonnar J, Prentice CR M, McNicol GP, Douglas AS. Haemostatic mechanism in the uterine circulation during placental separation. Br Med J 1970; 2: 564-567
  • 52 Sheppard BL, Bonnar J. The ultrastructure of the human placenta in early and late pregnancy. J Obstet Gynecol Br Commonwealth 1974; 81: 497-511
  • 53 Meade TW, Chakrabarti R, Haines AP, North WR, Stirling Y. Haemostatic function and cardiovascular death. Early results of a prospective study Lancet 1980; 1: 1050-1054
  • 54 Clayton JK, Anderson JA, McNicol GP. Preoperative prediction of postoperative deep vein thrombosis. Br Med J 1976; 2: 910-912