The procoagulant effects of factor V Leiden may be balanced against decreased levels of factor V and do not reflect in vivo thrombin formation in newborns

Satu Hyytiäinen; Ulla Wartiovaara-Kautto; Veli-Matti Ulander; Risto Kaaja; Markku Heikinheimo; Jari Petäjä

doi:10.1160/TH05-05-0375

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(03): 434-440
DOI: 10.1160/TH05-05-0375

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

The procoagulant effects of factor V Leiden may be balanced against decreased levels of factor V and do not reflect in vivo thrombin formation in newborns

Satu Hyytiäinen

¹Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

,

Ulla Wartiovaara-Kautto

²Helsinki University Central Hospital Laboratory Services (HUSLAB), Department of Clinical Chemistry, Laboratory of Hematology, University of Helsinki, Helsinki, Finland

,

Veli-Matti Ulander

³Hospital for Women, University of Helsinki, Helsinki, Finland

,

Risto Kaaja

³Hospital for Women, University of Helsinki, Helsinki, Finland

,

Markku Heikinheimo

¹Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

⁴Department of Pediatrics, University and University Hospital of Tampere, Finland

⁵Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA

,

Jari Petäjä

¹Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

⁶Department of Pediatrics, Jorvi Hospital, University of Helsinki, Espoo, Finland

› Author Affiliations

Abstract

Summary

Thrombin regulation in newborns remains incompletely understood.We studied tissue factor-initiated thrombin formation in cord plasma in vitro, and the effects of Factor VLeiden (FVL) heterozygosity on thrombin regulation both in vitro and in vivo in newborns. Pregnant women with known thrombophilia (n=27) were enrolled in the study. Cord blood and venous blood at the age of 14 days were collected from 11 FVL heterozygous newborns (FVL-positive) and from 16 FVL-negative newborns. Prothrombin fragment F1+2 and coagulation factors were measured. Tissue factor-initiated thrombin formation was studied in cord platelet-poor plasma (PPP) of FVL-negative and -positive newborns, and in both PPP and platelet-rich plasma (PRP) of healthy controls. The endogenous thrombin potential (ETP) in cord PPP or PRP was ∼60% of that in adult plasma, while thrombin formation started ∼55% and ∼40% earlier in cord PPP and PRP, respectively. Further, in FVL-positive newborns thrombin formation started significantly earlier than in FVL-negative newborns. Exogenous activated protein C (APC) decreased ETP significantly more in cord than in adult PRP. In FVL-negative cord plasma 5nM APC decreased ETP by 17.4±3.5% (mean±SEM) compared with only 3.5±3.8% in FVL-positive cord plasma (p=0.01). FVL-positive newborns showed similar levels of F1+2 but significantly decreased levels of factor V compared with FVL negative newborns both in cord plasma (FV 0.82±0.07 U/ml vs. 0.98±0.05 U/ml, p=0.03) and at the age of two weeks (FV 1.15±0.04 U/ml vs. 1.32±0.05 U/ml, p=0.03). In conclusion, newborn plasma showed more rapid thrombin formation and enhanced sensitivity to APC compared with adult plasma. FVL conveyed APC resistance and a procoagulant effect in newborn plasma. Lack of elevated F1+2 levels in FVL-positive infants, however, suggested the existence of balancing mechanisms; one could be the observed lower level of factor V in FVL heterozygous newborns.

Keywords

Newborn - thrombin - activated protein C - factor V Leiden - platelet-rich plasma

Full Text

References

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