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Thromb Haemost 1999; 81(04): 527-531
DOI: 10.1055/s-0037-1614518
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Schattauer GmbH

APC Resistance and other Haemostatic Variables during Pregnancy and Puerperium

U. Kjellberg
1   From the Dept. Obstet. Gyn., Sahlgrenska University Hospital, Gothenburg, Sweden
,
N.-E. Andersson
2   Chromogenix AB, Mölndal, Sweden
,
S. Rosén
2   Chromogenix AB, Mölndal, Sweden
,
L. Tengborn
3   Coagulation Centre, Dept. Intern. Med., Sahlgrenska University Hospital, Gothenburg, Sweden
,
M. Hellgren
1   From the Dept. Obstet. Gyn., Sahlgrenska University Hospital, Gothenburg, Sweden
› Institutsangaben
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Publikationsverlauf

Received 15. Juli 1998

Accepted after resubmission 14. Dezember 1998

Publikationsdatum:
09. Dezember 2017 (online)

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Summary

Forty-eight healthy pregnant women were studied prospectively and longitudinally. Blood sampling was performed at 10-15, 23-25, 32-34 and 38-40 weeks of gestation, within one week and at eight weeks postpartum. Classic and modified activated protein C ratio decreased as pregnancy progressed. In the third trimester 92% of the ratios measured with the classic test were above the lower reference level whereas all modified test ratios were normal. Slight activation of blood coagulation was shown with increased levels of prothrombin fragment 1+2, soluble fibrin and D-dimer. Fibrinogen, factor VIII and plasminogen activator inhibitor type 1 and type 2 increased. Protein S and tissue plasminogen activator activity decreased. Protein C remained unchanged. No correlation was found between the decrease in classic APC ratio and changes in factor VIII, fibrinogen, protein S, prothrombin fragment 1+2 or soluble fibrin, nor between the increase in soluble fibrin and changes in prothrombin fragment 1+2, fibrinogen and D-dimer.

 

  • References

  • 1 Department of Health and Social Security Report 1991 on Confidential Enquiries into Maternal Deaths in England and Wales 1985-87. HMSO; London.:
  • 2 Franks AL, Atrash HK, Lawson HW, Colberg KS. Obstetrical pulmonary embolism mortality.United States;1970-85. Am J Public Health 1990; 80: 720-2.
    CrossrefPubMedGoogle Scholar
  • 3 Högberg U. Maternal mortality in Sweden. Thesis, Umeå; Sweden.: 1985: 118.
    Google Scholar
  • 4 Greer IA. Hemostasis and thrombosis in pregnancy. In Hemostasis and Thrombosis. Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. eds. Edingburgh: Churchill Livingstone; 1978: 987-8.
    Google Scholar
  • 5 Lindoff C, Lecander I, Åstedt B. Fibrinolytic components in individual consecutive plasma samples during normal pregnancy. Fibrinolysis 1993; 7: 190-4.
    PubMedGoogle Scholar
  • 6 Lecander I, Åstedt B. Isolation of a new specific plasminogen activator inhibitor from pregnancy plasma. Br J Haematol 1986; 62: 221-8.
    CrossrefPubMedGoogle Scholar
  • 7 Hellgren M, Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am J Obstet Gynecol 1995; 173: 210-3.
    CrossrefPubMedGoogle Scholar
  • 8 Zöller B, Svensson PJ, He X, Dahlbäck B. Identification of the same factor V gene mutation in 47 out of 50 thrombosisprone families with inherited resistance to activated protein C J Clin Invest. 1994; 94: 2521-4.
    PubMedGoogle Scholar
  • 9 Zöller B, Hillarp A, Berntorp E, Dahlbäck B. Activated protein C resistance due to a common factor V gene mutation is a major risk factor for venous thrombosis. Annu Rev Med 1997; 48: 45-58.
    CrossrefPubMedGoogle Scholar
  • 10 Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for factor V Leiden (Activated protein C resistance). Blood 1995; 85: 1504-8.
    PubMedGoogle Scholar
  • 11 Vasse M, Leduc O, Borg J-Y, Chrétien MH, Monconduit M. Resistance to activated protein C: Evaluation of three functional assays. Thromb Res 1994; 76: 47-59.
    CrossrefPubMedGoogle Scholar
  • 12 Cumming AM, Tait RC, Fildes S, Yoong A, Keeney S, Hay CRM. Development of resistance to activated protein C during pregnancy. Br J Haematol. 1995; 90: 725-7.
    PubMedGoogle Scholar
  • 13 Mathonnet F, Mazancourt Pde, Bastenaire B, Morot M, Benattar N, Beufé S, Borg J-Y, Giudicelli Y. Activated protein C sensitivity ratio in pregnant women at delivery. Br J Haematol 1996; 92: 244-6.
    CrossrefPubMedGoogle Scholar
  • 14 Schlit A-F, Col-de Beys C, Moriau M, Lavenne-Pardonge E. Acquired activated protein C resistance in pregnancy. Thromb Res 1996; 84: 203-6.
    CrossrefPubMedGoogle Scholar
  • 15 Peek MJ, Nelson-Piercy C, Manning RA, Swiet M de, Letsky EA. Activated protein C resistance in normal pregnancy. Br J Obstet Gynaecol 1997; 104: 1084-6.
    CrossrefPubMedGoogle Scholar
  • 16 Cumming AM, Tait RC, Fildes S, Hay CRM. Diagnosis of APC resistence during pregnancy. Br J Haematol 1996; 92: 1026-7.
    CrossrefPubMedGoogle Scholar
  • 17 Hathaway WE, Bonnar J. Hemostatic disorders of pregnant woman and newborn infant. New York: Elsevier; 1987: 42-5.
    Google Scholar
  • 18 Stirling Y, Woolf L, North WRS, Seghatchian MJ, Meade TW. Haemostasis in normal pregnancy. Thromb Haemost 1984; 52 (02) 176-82.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 19 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.
    CrossrefPubMedGoogle Scholar
  • 20 Bremme K, Östlund E, Almqvist I, Heinonen K, Blombäck M. Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. Obstet Gynecol 1992; 80: 132-7.
    Google Scholar
  • 21 Ginsberg JS, Siragusa S, Douketis J, Johnston M, Moffat K, Stevens P, Brill-Edvards P, Panju A, Patel A. Evaluation of a soluble fibrin assay in patients with suspected deep vein thrombosis. Thromb Haemost 1995; 74: 833-6.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 22 Bremme K, Lind H, Blombäck M. The effect of prophylactic heparin treatment on enhanced thrombin generation in pregnancy. Obstet Gynecol 1993; 81: 78-83.
    PubMedGoogle Scholar
  • 23 Comeglio P, Fedi S, Liotta AA, Cellai AP, Chiarantini E, Prisco D, Mecatti F, Parretti E, Mello G, Abbate R. Blood clotting activation during normal pregnancy. Thromb Res 1996; 84: 199-202.
    CrossrefPubMedGoogle Scholar
  • 24 Ishii A, Yamada S, Yamada R, Hamada H. t-PA activity in peripheral blood obtained from pregnant women. J Perinat Med 1994; 22: 113-7.
    CrossrefPubMedGoogle Scholar
  • 25 Estellés A, Gilabert J, Andrés C, España F, Aznar J. Plasminogen activator inhibitors type 1 and type 2 and plasminogen activators in amniotic fluid during pregnancy. Thromb Haemost 1990; 64: 281-5.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 26 Sörensen JD, Secher NJ, Jespersen J. Perturbed (progoagulant) endothelium and deviations within the fibrinolytic system during the third trimester of normal pregnancy. Acta Obstet Gynecol Scand 1995; 74: 257-61.
    CrossrefPubMedGoogle Scholar
  • 27 Halligan A, Bonnar J, Sheppard B, Darling M, Walshe J. Haemostatic, fibrinolytic and endothelial variables in normal pregnancies and preeclampsia. Br J Obstet Gynaecol 1994; 101: 488-92.
    CrossrefPubMedGoogle Scholar
  • 28 Nolan TE, Smith RP, Devoe LD. Maternal plasma D-dimer levels in normal and complicated pregnancies. Obstet Gynecol 1993; 81: 235-8.
    PubMedGoogle Scholar
  • 29 Francalanci I, Comeglio P, Liotta AA, Cellai AP, Fedi S, Parretti E, Mello G, Prisco D, Abbate R. D-dimer concentrations during normal pregnancy, as measured by Elisa. Thromb Res 1995; 78: 399-405.
    CrossrefPubMedGoogle Scholar
  • 30 Koh SCL, Chew CYC, Viegas OAC, Choo M, Ratnam SS. Influence of circulating D-dimer levels on assays of fibrinogen. Ann Acad Med Singapore 1994; 23: 856-60.
    PubMedGoogle Scholar
  • 31 Ronde H de, Bertina RM. Laboratory diagnosis of APC-resistance: A critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 1994; 72: 880-6.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 32 Baker R, Thom J, Barden A, Beilin L, Ritchie J, Graham D, Bocksmeer F, van Walters B, Michael C. Platelet derived microvesicles cause acquired activated protein C resistance in preeclampsia and normal pregnancy. Abstract at XVth Congress of the International Society on Trombosis and Haemostasis. Florence, Italy 1997. 317 Published in suppliment page June 1997
    PubMedGoogle Scholar
  • 33 Walker MC, Garner PR, Keely EJ, Rock GA, Reis MD. Changes in activated protein C resistance during normal pregnancy. Am J Obstet Gynecol 1997; 177: 162-9.
    CrossrefPubMedGoogle Scholar