Analysis of biological phenotypes from 42 patients with inherited factor VII deficiency: can biological tests predict the bleeding risk?
OBJECTIVE
Inherited factor VII (FVII) deficiency is a rare bleeding disorder characterized by a poor relationship between reported FVII clotting activity (FVII:C) and bleeding tendency. Our study was aimed at defining biological parameters that are possibly predictive for bleeding risk in this condition.


METHODS
Forty-two FVII-deficient patients (FVII:C <30%) were classified into two opposite clinical groups defined as severe and non-or-mild bleeders. For each patient, plasma samples were collected and then investigated for FVII:C (using a sensitive method and human recombinant thromboplastin as the reagent), FVII antigen, activated FVII coagulant activity (FVIIa:C) and the free-form of tissue factor pathway inhibitor.


RESULTS
None of these tests could be used as highly accurate predictors of bleeding. Nevertheless, both FVII:C and FVIIa:C differed significantly between the two clinical groups. Using ROC-curve analysis, two critical values of 8% and 3mIU/mL for FVII:C and FVIIa:C, respectively, could be proposed to discriminate between severe bleeders and non-or-mild bleeders.


CONCLUSIONS
A highly accurate diagnostic test for predicting bleeding tendency in inherited FVII deficiency still eludes definition, highlighting the fact that factors other than FVII itself interfere with the expression of bleeding phenotypes in this condition. Nevertheless, potential critical values using sensitive FVII:C and FVIIa:C methods may be useful in clinical laboratories for FVII-deficient patients. Those patients with FVII:C levels higher than 8% FVII:C or FVIIa:C higher than 3 mIU/mL, with no other hemostatic defect, seem to have a minimal risk of severe bleeding. Extended clinical studies are needed to support these findings.
Giansily-Blaizot
Muriel
M
Laboratory of Haematology, CHU Montpellier, France. m-giansily@chu-montpellier.fr
Verdier
Régis
R
Biron-Adréani
Christine
C
Schved
Jean-François
JF
Bertrand
M A
MA
Borg
J Y
JY
Le Cam-Duchez
V
V
LeCam-Duchez
V
V
Briquel
M E
ME
Chambost
H
H
Pouymayou
K
K
Dutrillaux
F
F
Favier
R
R
Martin-Toutain
I
I
Verdy
E
E
Gay
V
V
Goudemand
J
J
Navarro
R
R
Durin
A
A
d'Oiron
R
R
Lambert
T
T
Pernod
G
G
Barrot
C
C
Peynet
J
J
Bastenaire
B
B
Sie
P
P
Stieltjes
N
N
Torchet
M F
MF
de Moerloose
P
P
D000293:Adolescent; D000328:Adult; D025861:Blood Coagulation Disorders, Inherited; D002648:Child; D002675:Child, Preschool; D005167:Factor VII / Q000032:analysis*; D005168:Factor VII Deficiency / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006470:Hemorrhage / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012306:Risk; D012720:Severity of Illness Index
D005167:Factor VII