Prospective Evaluation of Hemostatic System Activation and Thrombin Potential in Healthy Pregnant Women with and without Factor V Leiden

Sabine Eichinger; Ansgar Weltermann; Karl Philipp; Erich Hafner; Alexandra Kaider; Eva-Maria Kittl; Brigitte Brenner; Christine Mannhalter; Klaus Lechner; Paul A. Kyrle

doi:10.1055/s-0037-1614366

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1999; 82(04): 1232-1236
DOI: 10.1055/s-0037-1614366

Review Article

Schattauer GmbH

Prospective Evaluation of Hemostatic System Activation and Thrombin Potential in Healthy Pregnant Women with and without Factor V Leiden

Authors

Sabine Eichinger

¹From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, University Vienna, Department of Gynecology and Obstetrics and Department of Laboratory Medicine, Donauspital, Vienna, Institute of Biometrics, University Vienna, Department of Laboratory Medicine, University Vienna, Austria
Ansgar Weltermann

¹From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, University Vienna, Department of Gynecology and Obstetrics and Department of Laboratory Medicine, Donauspital, Vienna, Institute of Biometrics, University Vienna, Department of Laboratory Medicine, University Vienna, Austria
Karl Philipp

¹From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, University Vienna, Department of Gynecology and Obstetrics and Department of Laboratory Medicine, Donauspital, Vienna, Institute of Biometrics, University Vienna, Department of Laboratory Medicine, University Vienna, Austria
Erich Hafner

¹From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, University Vienna, Department of Gynecology and Obstetrics and Department of Laboratory Medicine, Donauspital, Vienna, Institute of Biometrics, University Vienna, Department of Laboratory Medicine, University Vienna, Austria
Alexandra Kaider

¹From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, University Vienna, Department of Gynecology and Obstetrics and Department of Laboratory Medicine, Donauspital, Vienna, Institute of Biometrics, University Vienna, Department of Laboratory Medicine, University Vienna, Austria
Eva-Maria Kittl

¹From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, University Vienna, Department of Gynecology and Obstetrics and Department of Laboratory Medicine, Donauspital, Vienna, Institute of Biometrics, University Vienna, Department of Laboratory Medicine, University Vienna, Austria
Brigitte Brenner

¹From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, University Vienna, Department of Gynecology and Obstetrics and Department of Laboratory Medicine, Donauspital, Vienna, Institute of Biometrics, University Vienna, Department of Laboratory Medicine, University Vienna, Austria
Christine Mannhalter

¹From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, University Vienna, Department of Gynecology and Obstetrics and Department of Laboratory Medicine, Donauspital, Vienna, Institute of Biometrics, University Vienna, Department of Laboratory Medicine, University Vienna, Austria
Klaus Lechner

¹From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, University Vienna, Department of Gynecology and Obstetrics and Department of Laboratory Medicine, Donauspital, Vienna, Institute of Biometrics, University Vienna, Department of Laboratory Medicine, University Vienna, Austria
Paul A. Kyrle

¹From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, University Vienna, Department of Gynecology and Obstetrics and Department of Laboratory Medicine, Donauspital, Vienna, Institute of Biometrics, University Vienna, Department of Laboratory Medicine, University Vienna, Austria

Abstract

Summary

Normal pregnancy is associated with alterations of the hemostatic system towards a hypercoagulable state and an increased risk of venous thromboembolism. The risk of venous thrombosis is higher in pregnant women with factor V Leiden (FVL) than in those with wildtype factor V. Routine laboratory assays are not useful to detect hypercoagulable conditions. A prospective and systematic evaluation of hemostatic system activation in women with and without FVL during an uncomplicated pregnancy employing more sensitive markers of hypercoagulability, such as prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), D-Dimer, or the endogenous thrombin potential (ETP), an indicator of the plasma’s potential to generate thrombin, has not been performed. We prospectively followed 113 pregnant women with (n = 11) and without (n = 102) FVL and measured F1+2, TAT, D-Dimer and the ETP at the 12^th, 22^nd and 34^th gestational week as well as 3 months after delivery (baseline) in each subject. None of the women developed clinical signs of venous thromboembolism during pregnancy or postpartum. Pregnant women with and without FVL exhibited substantial activation of the coagulation and fibrinolytic system as indicated by a gradual increase of F1+2, TAT and D-Dimer throughout uncomplicated pregnancy up to levels similar to those found in acute thromboembolic events (p < 0.0001 by analysis of variance for each parameters). Levels of F1+2 and TAT were comparable between women with and without FVL, but levels of D-Dimer were significantly higher in women with FVL than in those without the mutation (p = 0.0005). The ETP remained unchanged in both women with and without FVL at all timepoints. Our data demonstrate a substantial coagulation and fibrinolytic system activation in healthy women with and without FVL during uncomplicated pregnancy. An elevated F1+2, TAT or D-Dimer level during pregnancy is not necessarily indicative for an acute thromboembolic event. The normal ETP in both women with and without FVL suggests that the capacity of the plasma to generate thrombin after in vitro activation of the clotting system is not affected by pregnancy. Higher levels of D-Dimer in women with FVL than in women with wildtype factor V at baseline as well as during pregnancy indicate increased fibrinolytic system activation in carriers of the mutation.

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Referenzen

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