Thromb Haemost 2002; 88(02): 236-241
DOI: 10.1055/s-0037-1613193
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Schattauer GmbH

Reduced Activation of the Gla19Ala FX Variant via the Extrinsic Coagulation Pathway Results in Symptomatic CRMred FX Deficiency

M. Pinotti
1   Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Ferrara
,
G. Marchetti
1   Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Ferrara
,
M. Baroni
1   Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Ferrara
,
F. Cinotti
2   Dipartimento di Ematologia e Centro Emofilia Ospedale Careggi, Firenze, Italy
,
M. Morfini
2   Dipartimento di Ematologia e Centro Emofilia Ospedale Careggi, Firenze, Italy
,
F. Bernardi
1   Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Ferrara
› Institutsangaben
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Publikationsverlauf

Received 24. Oktober 2001

Accepted after resubmission 26. April 2002

Publikationsdatum:
07. Dezember 2017 (online)

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Summary

We characterized a symptomatic CRMred factor X (FX) deficiency produced by the Glu19Ala mutation in the γ-carboxyglutamic-rich domain. FX activity levels in plasma were markedly reduced in prothrombin time assays (< 1-5%), whereas in activated partial thromboplastin assays (16%) and in RVV assays (17%) the reduction in activity mirrored that in antigen levels (17%). Activation of recombinant 19Ala-FX by factor IXa/factor VIIIa or RVV, and the activity in thrombin generation assays, were comparable to those of wild-type FX. Differently, complete activation of recombinant 19AlaFX required a factor VIIa/TF concentration 30-fold higher than that of wild-type FX. The recombinant FVIIa significantly reduced PT values in 19Ala-FX reconstituted plasma, thus suggesting an alternative approach for treatment of FX deficiencies characterized by defective FX activation.

The study of this FX deficiency provides an “in vivo” and “in vitro” model for the investigation of Gla domain interactions.