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Journal of Hematology and Blood Disorder | Volume 2
allied
academies
August 23-24, 2018 | London, UK
Hematology and Oncology
2 nd International Conference on
Acomplete set of von Willebrand factor (VWF) assays is used
for the diagnosis and classification of vonWillebrand disease
(VWD) according to European Clinical Laboratory and Molecular
(ECLM) criteria (Clinical Applied Thrombosis/Hemostasis
2017;23(6):518). The aim is to evaluated the von Willebrand
factor (VWF) assays VWF:GPIbM and VWF:GPIbR in von
Willebrand disease (VWD) against the use of ECLM criteria as the
gold standard for VWD classification anno 2018. Methods. The
complete set of VWF assays include Platelet Function Analyser
closure time (PFA-CT) von Willebrand factor (VWF) antigen
(Ag), ristocetine cofactor activity (RCo), collagen binding (CB),
propeptide (pp), ristocetine induced platelet aggregation (RIPA),
the rapid VWF activity assay VWF:GPIbM based on glycoprotein
Ib (GPIb) binding to particles coated with G233V and M239V
mutants in the absence of ristocetin, the rapid VWF:GPIbR assay
in the presence of ristocetine, and the responses to DDAVP of
FVIII:CandVWFparameters topick up secretionand/or clearance
defects of resulted in VWF:RCo/Ag, VWF:GPIbM/Ag and
VWF:GPIbRratiosarecompletelynormal(above0.7)inallvariants
of VWD type 1 and Low VWF. The VWF:RCo/Ag, GPIbR/Ag and
GPIbM/Ag ratios vary around the cut off level of 0.70 in VWD
due to multimerization defect in the D3 domain and therefore
diagnosed as either type 1 E or type 2E. The VWF:GPIbM/Ag and
VWF:GPIbR/Ag ratios are pronounced decreased as compared
to VWF:RCo/Ag and VWF:CB/Ag ratios in dominant VWD 2A and
VWD 2B due to proteolytic loss of large and intermediate VWF
multimers caused by VWF mutations in the A2 and A1 domain.
VWD 2M due to loss of function mutation in the A3 domain is
featured by decreased VWF:Rco/Ag ratio and normal VWF:CB/
Ag ratio, whereas the VWF:GPIbR/Ag ratio (range 0.14-28) and
the VWF:GPIbM/Ag ratio (range 0.32 to 0.36) were decreased
indicating the need to retain the VWF:CB assay tomake a correct
diagnosis of VWD 2M. The introduction of the rapid VWF:GPIbM
or VWF:GPIbR assays as compared to the classical VWF:RCo assay
did change VWD type 2 into type 1 in about 10 to 12%. VWD type
1 due to a heterozygous mutation in the D1 domain is featured
by persistence of proVWF as the cause of VWF secretion/
multimerization and FVIII binding defect mimicking VWD type 3
togetherwithdecreasedvalues forVWFpp, VWFpp/Ag ratios. The
majority of 22 different missensemutations in the D3 domain are
of type 1 or 2 Emultimerization defect usually associated with an
additional secretion defect (increased FVIII:C/VWF:Ag ratio) and
or clearance defect (increased VWFpp/Ag ratio). The majority
of VWF mutations in the D4 and C1 to C6 are VWD type 1 SD
with smeary (1sm) or normal (1m) multimers with no or a minor
clearance defect. The heterozygous S2179F mutation in the D4
domain is featured by VWD type 1 secretion and clearance (SCD).
Thus it is concluded that a complete set of sensitive FVIII:C and
VWF assays related to domain location of the molecular defect
is mandatory for correct diagnosis and classification of VWD.
Speaker Biography
Jan Michiels Professor of Nature Medicine & Health Blood Coagulation & Vascular
Medicine Center in Netherlands. He also serves as an Editorial board member for many
scientific journals.
e:
Jan Michiels
Good Heart Centre, The Netherlands
Evaluation of classical and novel von Willebrand Factor assays in ECLM defined von
Willebrand disease patients