Subscribe to RSS
DOI: 10.1055/s-0037-1615718
The Impact of Dalteparin (Fragmin®) on Thrombin Generation in Pregnant Women with Venous Thromboembolism: Significance of the Factor V Leiden Mutation
Publication History
Received
14 June 2000
Accepted after resubmission
22 December 2000
Publication Date:
11 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200105/lookinside/thumbnails/10-1055-s-0037-1615718-1.jpg)
Summary
Hypercoagulability is observed in patients with inherited thrombophilia, e.g. factor V Leiden (FVL) mutation. Pregnancy represents a hypercoagulable state as well. This study addresses the effects of the FVL mutation on haemostatic activation during pregnancy as indicated by prothrombin fragments (F1+2). 233 pregnant women with no history of venous thromboembolism were studied. Additionally, two patient groups (25 pregnant FVL carriers and 36 pregnant women without thrombophilic diathesis) in whom low molecular weight heparin (dalteparin) was used prophylactically against rethrombosis were investigated.
None of the women developed clinical signs of venous thromboembolism during pregnancy or after delivery. Untreated women exhibited substantial hypercoagulability. F1+2 levels were similar in FVL carriers and non-carriers (difference n. s.). After sufficient adjustment for anti-factor Xa activity (≥0.15; ≤0.4 U/mL), heparinized women without any thrombophilic diathesis had significantly lower levels of F1+2 than untreated pregnant women. This was evident only in the first and second trimenon (p <0.01). F1+2 levels in heparinized FVL carriers were quite similar to the levels observed in untreated pregnant women, however. In conclusion, our data support the thesis that in comparison to asymptomatic patients, thrombin generation is exaggerated in symptomatic FVL carriers. Coagulation activation during pregnancy can be reduced by dalteparin.
-
References
- 1 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
- 2 Simioni P, Scarano L, Gavasso S, Sardella C, Girolami B, Scudeller A, Girolami A. Prothrombin fragment 1+2 and thrombin-antithrombin complex levels in patients with inherited APC resistance due to factor V Leiden mutation. Br J Haematol 1996; 92: 435-41.
- 3 Zöller B, Holm J, Svensson P, Dahlbäck B. Elevated levels of prothrombin activation fragment 1+2 in plasma form patients with heterozyous Arg506 to Gln mutation in the factor V gene (APC-resistance) and/or inherited protein S deficiency. Thromb Haemost 1996; 75: 270-4.
- 4 Comeglio P, Fedi S, Liotta AA, Cellai AP, Chiarantini E, Prisco D, Mecacci F, Parretti E, Mello G, Abbate R. Blood clotting activation during normal pregnancy. Thromb Res 1996; 84: 199-202.
- 5 Kjellberg U, Andersson N-E, Rosen S, Tengborn L, Hellgren M. APC resistance and other haemostatic variables during pregnancy and puerperium. Thromb Haemost 1999; 81: 527-31.
- 6 Hunt BJ, Doughty H-A, Majumdar G, Copplestone A, Kerslake S, Buchanan N, Hughes G, Khamashta M. Thromboprophylaxis with low molecular weight heparin (Fragmin®) in high risk pregnancies. Thromb Haemost 1997; 77: 39-43.
- 7 Geisen U, Abou-Mandour N, Grossmann R, Schambeck CM, Zilly M, Keller F. Long-term thromboprophylaxis with low-molecular-weight heparin (dalteparin) in high-risk pregnancies. Haemostasis 1998; 28 (Suppl. 03) 137.
- 8 Pettilä V, Kaaja R, Leinonen P, Ekblad U, Kataja M, Ikkala E. Thromboprophylaxis with low molecular weight heparin (Dalteparin) in pregnancy. Thromb Res 1999; 96: 275-82.
- 9 Bremme K, Lind H, Blombäck M. The effect of prophylactic heparin treatment on enhanced thrombin generation in pregnancy. Obstet Gynecol 1993; 81: 78-83.
- 10 Schwender S, Groβmann R, Keller F. High prevalence of factor V Leiden mutation is detected in a north to south axis through Germany. J Lab Med 1997; 21: 347-52.
- 11 Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337: 688-98.
- 12 Blombäck M, Bremme K, Hellgren M, Lindberg H. A pharmacokinetic study of dalteparin (Fragmin®) during late pregnancy. Blood Coag Fibrinol 1998; 9: 343-50.
- 13 Eichinger S, Weltermann A, Philipp K, Hafner E, Kaider A, Kittl E-M, Brenner B, Mannhalter C, Lechner K, Kyrle PA. 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.
- 14 Lindqvist PG, Svensson PJ, Marsal K, Grennert L, Luterkort M, Dahlbäck B. Activated protein C resistance (FV:Q506) and pregnancy. Thromb Haemost 1999; 81: 532-7.
- 15 Gerbasi FS, Bottoms S, Farag A, Mammen E. Increased intravascular coagulation associated with pregnancy. Obstet Gynecol 1990; 75: 385-9.
- 16 Lindqvist PG, Svensson PJ, Dahlbäck B, Marsal K. Factor V Q 506 mutation (activated protein C resistance) associated with reduced intrapartum blood loss – a possible evolutionary selection mechanism. Thromb Haemost 1998; 79: 69-73.
- 17 Ginsberg JS, Hirsh J. Use of antithrombotic agents during pregnancy. Chest 1995; 108 suppl 305S-11S.
- 18 McColl MD, Greer IA. The role of inherited thrombophilia in venous thromboembolism associated with pregnancy. Br J Obstet Gynaecol 1999; 106: 756-66.
- 19 Tengborn L, Bergqvist D, Mätzsch T, Bergqvist A, Hedner U. Recurrent thromboembolism in pregnancy and puerperium: is there a need for thromboprophylaxis?. Am J Obstet Gynecol 1989; 160: 90-4.
- 20 Barbour LA, Pickard J. Controversies in thromboembolic disease during pregnancy: a critical review. Obstet Gynecol 1995; 86: 621-33.