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Sir,

We read with interest the report of Michael Peek et al. concerning activated protein C (APC) resistance in normal pregnancy (Vol 104, September 1997)1. Unlike previous reports2–6 this study revealed only small changes in APC sensitivity ratios during pregnancy, and no cases of acquired APC resistance. The reason for this discrepancy is not clear. We are not aware of any changes to the standard Chromogenix Coatest APC Resistance kit which may account for this. Peek and colleagues suggest that the standard APC ratio could be used during pregnancy to screen for the factor V Leiden mutation, a suggestion with which our findings lead us to take issues.

Using the standard Chromogenix kit to determine APC sensitivity ratios, we observed the development of acquired APC resistance in 11 of 20 healthy women during the course of their pregnancies2. Only one of the 20 women was a carrier of the Factor V Leiden mutation. This led us to suggest that pre-existing APC resistance could not be reliably diagnosed during pregnancy using Am-based functional assays. Subsequently we showed that a modification of the standard assay, in which the test plasma is diluted with an excess of factor V deficient plasma, allowed reliable testing during pregnancy for factor-related APC resistance7. This modified assay is highly discriminant for factor V-related APC resistance and, other than factor V Leiden genotyping, is the method of choice to screen for the factor V Leiden mutation during pregnancy.

References

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  2. References
  • 1
    Peek MJ, Nelson-Piercy C, Manning RA, de Swiet M, Letsky EA. Activated protein C resistance in normal pregnancy. Br J Obstet Gynaecol 1997; 104: 10741076.
  • 2
    Cumming AM, Tait RC, Fildes S, Yoong A, Keeney S, Hay CRM. Development of resistance to activated protein C during pregnancy. BrJHaematol 1995; 90: 125727.
  • 3
    Vasse M, Leduc O, Borg J-Y, Chretien MH, Monconduit M. Resistance to activated protein C: evaluation of three functional assays. Thromb Res 1994; 764759.
  • 4
    Mathonnet F, de Mazancourt P, Bastenaire B, Morot M, Benattar N, Beufe S, Borg JY, Giudicelli Y. Activated protein C sensitivity ratio in pregnant women at delivery. Br J Haematol 1996; 92: 2446.
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  • 5
    Bokarewa MI, Bremme K, Blomback M. ArgSo6-Gln mutation in factor V and risk of thrombosis during pregnancy. Br J Haematol 1996; 92: 473478.
  • 6
    Walker MC, Gamer PR, Keely EJ, Rock GA, Reis MD. Changes in activated protein C resistance during normal pregnancy. Am J Obstet Gynecol 1997; 177: 162169.
  • 7
    Cumming AM, Tait RC, Fildes S, Hay CRM. Diagnosis of APC resistance during pregnancy Br J Haematol 1996; 92 102107.