Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders.
BACKGROUND
The European Network of Rare Bleeding Disorders (EN-RBD) was established to bridge the gap between knowledge and practise in the care of patients with RBDs.


OBJECTIVE
To explore the relationship between coagulation factor activity level and bleeding severity in patients with RBDs.


METHODS
Cross-sectional study using data from 489 patients registered in the EN-RBD. Coagulation factor activity levels were retrieved. Clinical bleeding episodes were classified into four categories according to severity.


RESULTS
The mean age of patients at data collection was 31 years (range, 7 months to 95 years), with an equal sex distribution. On linear regression analysis, there was a strong association between coagulation factor activity level and clinical bleeding severity for fibrinogen, factor (F) X, FXIII, and combined FV and FVIII deficiencies. A weaker association was present for FV and FVII deficiencies. There was no association between coagulation factor activity level and clinical bleeding severity for FXI. The coagulation factor activity levels that were necessary for patients to remain asymptomatic were: fibrinogen, > 100 mg dL(-1); FV, 12 U dL(-1); combined FV + VIII, 43 U dL(-1); FVII, 25 U dL(-1); FX, 56 U dL(-1) ; FXI, 26 U dL(-1); FXIII, 31 U dL(-1). Moreover, coagulation factor activity levels that corresponded with Grade III bleeding were: undetectable levels for fibrinogen, FV and FXIII, < 15 U dL(-1) for combined FV + VIII; < 8 U dL(-1) for FVI; < 10 U dL(-1) for FX; and < 25 U dL(-1) for FXI.


CONCLUSIONS
There is a heterogeneous association between coagulation factor activity level and clinical bleeding severity in different RBDs. A strong association is only observed in fibrinogen, FX and FXIII deficiencies.
UOS Dipartimentale per la Diagnosi e la Terapia delle Coagulopatie, A Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano and Luigi Villa Foundation, Milan, Italy. flora.peyvandi@unimi.it
F
F
Peyvandi
R
R
Palla
M
M
Menegatti
S M
SM
Siboni
S
S
Halimeh
B
B
Faeser
H
H
Pergantou
H
H
Platokouki
P
P
Giangrande
K
K
Peerlinck
T
T
Celkan
N
N
Ozdemir
C
C
Bidlingmaier
J
J
Ingerslev
M
M
Giansily-Blaizot
J F
JF
Schved
R
R
Gilmore
A
A
Gadisseur
M
M
Benedik-Dolničar
L
L
Kitanovski
D
D
Mikovic
K M
KM
Musallam
F R
FR
Rosendaal
D000293:Adolescent; D000328:Adult; D000347:Afibrinogenemia / Q000097:blood / Q000175:diagnosis; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000097:blood / Q000175:diagnosis*; D001779:Blood Coagulation Factors / Q000032:analysis*; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005060:Europe; D005171:Factor X Deficiency / Q000097:blood / Q000175:diagnosis; D005177:Factor XIII Deficiency / Q000097:blood / Q000175:diagnosis; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007223:Infant; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D035583:Rare Diseases / Q000097:blood / Q000175:diagnosis*; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D014421:Turkey; D055815:Young Adult
D015415:Biomarkers; D001779:Blood Coagulation Factors