Thromb Haemost 2004; 91(05): 935-940
DOI: 10.1160/TH03-11-0719
Blood Coagulation, Fibrinolysis and Celluar Haemostasis
Schattauer GmbH

Prospective evaluation of coagulation activation in pregnant women receiving low-molecular weight heparin

Matthias Hoke
1   Department of Internal Medicine I, Division of Haematology and Haemostasis, University Vienna, Austria
,
Paul A. Kyrle
1   Department of Internal Medicine I, Division of Haematology and Haemostasis, University Vienna, Austria
2   Ludwig Boltzmann Institute for Thrombosis Research, Austria
,
Karl Philipp
3   Department of Gynecology and Obstetrics, Donauspital, Vienna, Austria
,
Ingrid Pabinger
1   Department of Internal Medicine I, Division of Haematology and Haemostasis, University Vienna, Austria
,
Alexandra Kaider
4   Institute of Medical Computersciences, University Vienna, Austria
,
Verena Schönauer
1   Department of Internal Medicine I, Division of Haematology and Haemostasis, University Vienna, Austria
,
Peter Quehenberger
4   Institute of Medical Computersciences, University Vienna, Austria
5   Department of Laboratory Medicine, University Vienna, Austria
,
Sabine Eichinger
1   Department of Internal Medicine I, Division of Haematology and Haemostasis, University Vienna, Austria
2   Ludwig Boltzmann Institute for Thrombosis Research, Austria
› Author Affiliations
Financial support: The study was supported by a grant (10386) of the Jubilaeumsfonds of the Oesterreichische Nationalbank.
Further Information

Publication History

Received 26 November 2003

Accepted after resubmission 21 January 2004

Publication Date:
01 December 2017 (online)

Summary

Pregnancy is a major risk factor for venous thromboembolism (VTE), and low-molecular weight heparin (LMWH) seems to be safe and effective in pregnant women. Normal pregnancy is accompanied by a state of hypercoagulability, indicated by an increase in markers of coagulation activation. In a prospective cohort study, we followed 61 women who received LMWH thromboprophylaxis throughout pregnancy because of a history of VTE, hereditary thrombophilia and/or previous pregnancyrelated complications. The control group consisted of 113 healthy pregnant women without antithrombotics. D-Dimer, prothrombin fragment F1+2 (F1+2) and the resistance to activated protein C (APC-ratio) were measured in all women during the first, second and third trimester. Patients and controls did not significantly differ with regard to baseline characteristics and pregnancy outcome. A (recurrent)VTE was seen in one patient despite LMWH. D-Dimer levels significantly increased among patients and controls during pregnancy (p <0.0001), and were significantly higher among patients compared with the controls (p <0.0001) [395 ng/ml (95% CI 340-458) and 249 ng/ml (95%CI 234-266); 710 ng/ml (95% CI 602-838) and 475 ng/ml (95% CI 431-523); 1089 ng/ml (95% CI 931-1273) and 822 ng/ml (95% CI 741-911); respectively]. Levels of F1+2 significantly increased while the APC-ratio significantly decreased during pregnancy among patients and controls. Despite LMWH, pregnancy is accompanied by a substantial activation of the coagulation system.

 
  • References

  • 1 Koonin LM, MacKay AP, Berg CJ. et al. Pregnancy-related mortality surveillance – United States, 1987-1990. MMWR CDC Surveill Summ 1997; 46: 17-36.
  • 2 Greer IA. Thrombosis in pregnancy: maternal and fetal issues. Lancet 1999; 353: 1258-65.
  • 3 Brenner B, Hoffman R, Blumenfeld Z. et al. Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin. Thromb Haemost 2000; 83: 693-7.
  • 4 Nelson-Piercy C, Letsky EA, de Swiet M. Low-molecular-weight heparin for obstetric thromboprophylaxis: experience of sixty-nine pregnancies in sixty-one women at high risk. Am J Obstet Gynecol 1997; 176: 1062-8.
  • 5 Hunt BJ, Doughty HA, Majumdar G. et al. Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies. Thromb Haemost 1997; 77: 39-43.
  • 6 Carp H, Dolitzky M, Inbal A. Thromboprophylaxis improves the live birth rate in women with consecutive recurrent miscarriages and hereditary thrombophilia. J Thromb Haemost 2003; 01: 433-8.
  • 7 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.
  • 8 de Moerloose P, Amiral J, Vissac AM. et al. Longitudinal study on activated factors XII and VII levels during normal pregnancy. Br J Haematol 1998; 100: 40-4.
  • 9 Eichinger S, Weltermann A, Philipp K. et al. Prospective evaluation of hemostatic system activation and thrombin potential in healthy pregnant women with and without factor V Leiden. Thromb Haemost 1999; 82: 1232-6.
  • 10 Clark P, Walker ID. The phenomenon known as acquired activated protein C resistance. Br J Haematol 2001; 115: 767-73.
  • 11 Dahlbäck 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.
  • 12 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.
  • 13 Clark P, Brennand J, Conkie JA. et al. Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thromb Haemost 1998; 79: 1166-70.
  • 14 Crowder MJ, Hand DJ. Analysis of Repeated Measures. Chapman and Hall; London: 1990
  • 15 Stirling Y, Woolf L, North WR. et al. Haemostasis in normal pregnancy. Thromb Haemost 1984; 52: 176-82.
  • 16 Ginsberg JS, Brill-Edwards P, Burrows RF. et al. Venous thrombosis during pregnancy: leg and trimester of presentation. Thromb Haemost 1992; 67: 519-20.
  • 17 Pabinger I, Grafenhofer H, Kyrle PA. et al. Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism. Blood 2002; 100: 1060-2.
  • 18 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.
  • 19 Walker MC, Garner PR, Keely EJ. et al. Changes in activated protein C resistance during normal pregnancy. Am J Obstet Gynecol 1997; 177: 162-9.
  • 20 Cumming AM, Tait RC, Fildes S. et al. Diagnosis of APC Resistance during pregnancy. Br J Haematol 1996; 92: 1026-9.
  • 21 Benedetto C, Marozio L, Tavella AM. et al. Response to activated protein C decreases throughout pregnancy. Acta Obstet Gynecol Scand 2002; 81: 1028-32.
  • 22 Brill-Edwards P, Ginsberg JS, Gent M. et al. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of clot in this pregnancy study group. N Engl J Med 2000; 343: 1439-44.