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Thromb Haemost 2007; 98(01): 163-171
DOI: 10.1160/TH06-10-0574
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The effect of dalteparin on coagulation activation during pregnancy in women with thrombophilia

A randomized trial
Karim Abou-Nassar
1   Hematology, Ottawa Hospital, Ottawa, Ontario, Canada
,
Michael J. Kovacs
2   Hematology, Victoria Hospital, London, Ontario, Canada
,
Susan R. Kahn
3   Department of Medicine and Center for Clinical Epidemiology and Community Studies, Jewish General Hospital, Montreal, Quebec, Canada
,
Philip Wells
1   Hematology, Ottawa Hospital, Ottawa, Ontario, Canada
,
Steve Doucette
1   Hematology, Ottawa Hospital, Ottawa, Ontario, Canada
,
Tim Ramsay
1   Hematology, Ottawa Hospital, Ottawa, Ontario, Canada
,
Anne Marie Clement
1   Hematology, Ottawa Hospital, Ottawa, Ontario, Canada
,
Rshmi Khurana
4   Medicine, Royal Alexandra Hospital, Edmonton, Alberta, Canada
,
Karen MacKinnon
1   Hematology, Ottawa Hospital, Ottawa, Ontario, Canada
,
Mark Blostein
5   Hematology, S.M.B.D. Jewish General Hospital, Montreal, Quebec, Canada
,
Susan Solymoss
6   Hematology, St Mary‘s Hospital Center, Montreal, Quebec, Canada
,
John Kingdom
7   Department of Obstetrics, Mount Sinai Hospital, Toronto, Ontario, Canada
,
Matthew Sermer
7   Department of Obstetrics, Mount Sinai Hospital, Toronto, Ontario, Canada
,
Evelyne Rey
8   Medicine, Hopital Saint Justine, Montreal, Quebec, Canada
,
Marc Rodger
1   Hematology, Ottawa Hospital, Ottawa, Ontario, Canada
,
the TIPPS investigators › InstitutsangabenDisclosure: The TIPPS study was partially funded by Pharmacia (now Pfizer) in the form of an unrestricted grant. This support was withdrawn when Pfizer acquired Pharmacia in 2004. Pfizer was not involved in the design, analysis or interpretation of the study that is the subject of this manuscript. Doctors Rodger, Wells, Kahn, Kovacs and Solymoss have participated on Pfizer Advisory Boards and received compensation for this participation. Doctors Rodger, Wells, Solymoss, Kovacs and Kahn have received honoraria for lectures. Doctors Rodger, Wells, Kovacs and Rey have received grant funding from Pfizer. Pfizer is the current manufacturer of dalteparin.
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Publikationsverlauf

Received 10. Oktober 2006

Accepted after resubmission 03. April 2007

Publikationsdatum:
29. November 2017 (online)

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Summary

Low-molecular-weight heparin (LMWH) is increasingly being used for prophylaxis of venous thromboembolism (VTE) and prevention of pregnancy associated morbidity in pregnant women with thrombophilia. We sought to determine if the administration of prophylactic doses of LMWH downregulates coagulation activation in high risk pregnant women with thrombophilia. This sub-study was planned as part of a randomized open label controlled trial (Thrombophilia in Pregnancy Prophylaxis Study[TIPPS])in which patients at high risk of pregnancy complications with confirmed thrombophilia are randomized to receive either dalteparin (5,000 units/day until 20 weeks then 5,000 units q12h until 37 weeks or onset of labor) or no treatment. Blood samples were collected at baseline, day 7–9 (after starting study drug), week 20 (before increasing study drug), week 36 (prior to stopping study drug) and at the time of admission to the labor and delivery unit. Samples were not drawn at fixed times in relation to drug injection. These samples were analyzed for levels of thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1.2), D-dimer and anti-Xa activity. Generalized linear mixed models were used for statistical analysis and model results were controlled for age, smoking status, type of thrombophilia and predisposing risk factors. The effect of dalteparin onTAT levels was defined as the primary outcome. Of 198 patients eligible, 114 were enrolled in TIPPS. Ninety-one were eligible for the TIPPS coagulation activation sub-study and randomized. Thirty-nine patients were analyzed in the treatment group (dalteparin) and 46 patients in the control group (no intervention). Levels of coagulation activation factors F1.2, TAT and D-dimer increased significantly throughout pregnancy in both groups (p<0.0001). Dalteparin prophylaxis resulted in a significant increase in anti-Xa activity through pregnancy (p<0.0001) compared to controls. Dalteparin had no significant effects on the levels of TAT, F1.2 and D-dimer throughout pregnancy in thrombophilic women.A post-hoc Monte Carlo power analysis revealed that our study had 100% and 88% power to detect reductions in TAT values on treatment of 50% and 25%, respectively. Prophylaxis with dalteparin at doses used in this study did not reduce coagulation activation in high risk thrombophilic women during pregnancy.

Keywords

Low-molecular-weight heparin - pregnancy - thrombophilia - coagulation activation
 

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