Elevated Levels of Prothrombin Activation Fragment 1+2 in Plasma from Patients with Heterozygous Arg506 to Gin Mutation in the Factor V Gene (APC-Resistance) and/or Inherited Protein S Deficiency

Benget Zöller; Johan Holm; Peter Svensson; Björn Dahlbäck

doi:10.1055/s-0038-1650259

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 75(02): 270-274
DOI: 10.1055/s-0038-1650259

Original Article

Schattauer GmbH Stuttgart

Elevated Levels of Prothrombin Activation Fragment 1+2 in Plasma from Patients with Heterozygous Arg⁵⁰⁶ to Gin Mutation in the Factor V Gene (APC-Resistance) and/or Inherited Protein S Deficiency

Authors

Benget Zöller

¹The Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Malmö, Sweden
Johan Holm

²Department of Cardiology, University of Lund, Malmö General Hospital, Malmö, Sweden
Peter Svensson

³Department for Coagulation Disorders, University of Lund, Malmö General Hospital, Malmö, Sweden
Björn Dahlbäck

¹The Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Malmö, Sweden

Abstract

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Summary

Inherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)⁵⁰⁶ with a Gin (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1+2 (F₁₊₂), which is a marker of hyper-coagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg⁵⁰⁶ to Gin mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F₁₊₂ was significantly higher both in 38 individuals carrying the FV:Q⁵⁰⁶ mutation in heterozygous state (1.7 ± 0.7 nM; mean ± SD) and in 48 protein S deficient cases (1.9 ± 0.9 nM), than in 100 unaffected relatives (1.3 ±0.5 nM). Warfarin therapy decreased the F₁₊₂ levels, even in those four patients who had combined defects (0.5 ± 0.3 nM). Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.

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References

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