Validation of a rapid test (VWF-LIA) for the quantitative determination of von Willebrand factor antigen in type 1 von Willebrand disease diagnosis within the European multicenter study MCMDM-1VWD.
BACKGROUND
Accurate measurement of von Willebrand factor (VWF) is a critical requirement for the diagnosis of von Willebrand disease (VWD).


OBJECTIVE
To evaluate the diagnostic efficiency of a rapid quantitative test for the measurement of VWF antigen (VWF:Ag) in type 1 VWD.


METHODS
VWF:Ag was measured with an ELISA in a robotic instrument, as a reference method, and with a fully automated latex-immunoassay (LIA) on an ACL 9000 analyser in 1,716 subjects enrolled within the Molecular and Clinical Markers for Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD) Study. Among these subjects, 1,049 were healthy controls, 281 healthy family members and 386 affected members from 127 European families with type 1 VWD.


RESULTS
The assay linearity range was 10-125 IU/dL for LIA (R2=0.99) and 5-133 IU/dL for ELISA (R2=0.99). The inter-assay CV for low VWF levels (approximately 30 IU/dL) was 2% for the LIA test and 8.7 % for ELISA. The sensitivity for detection of type 1 VWD affected members was 86% and the specificity 91% for LIA, 87% and 90% for ELISA. A receiver-operator (ROC) analysis disclosed only a marginal difference between the two tests, LIA having a slightly greater area under the curve (0.94 vs. 0.93, p=0.03).


CONCLUSIONS
VWF:Ag LIA compared well to standard ELISA in this large population of patients and controls, showing better CV. However the lower detection limit for the VWF:Ag LIA compared to the VWF:Ag ELISA means that the LIA assay is less good at discriminating between type 3 VWD and moderate type 1 VWD.
Castaman
G
G
Department of Hematology, San Bortolo Hospital, Vicenza, Italy. castaman@hemato.ven.it
Tosetto
A
A
Cappelletti
A
A
Goodeve
A
A
Federici
A B
AB
Batlle
J
J
Meyer
D
D
Goudemand
J
J
Eikenboom
J C J
JC
Schneppenheim
R
R
Budde
U
U
Ingerslev
J
J
Lethagen
S
S
Hill
F
F
Peake
I R
IR
Rodeghiero
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057205:Automation, Laboratory; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D005060:Europe; D006801:Humans; D007841:Latex Fixation Tests / Q000592:standards; D008875:Middle Aged; D015588:Observer Variation; D011237:Predictive Value of Tests; D012372:ROC Curve; D012015:Reference Standards; D015203:Reproducibility of Results; D012371:Robotics; D012680:Sensitivity and Specificity; D055815:Young Adult; D056725:von Willebrand Disease, Type 1 / Q000097:blood / Q000175:diagnosis*; D014841:von Willebrand Factor / Q000032:analysis*
D015415:Biomarkers; D014841:von Willebrand Factor