Von Willebrand Disease profiling

Introduction

Von Willebrand disease (vWD) is the most commonly inherited (autosomally) bleeding disorder, present at about 1% in the general population. It may affect males and females.

Von Willebrand Factor (vWF) is a multimeric protein produced in endothelial cells and megakaryocytes1. It circulates in blood as multimers ranging from 500 to more than 20,000 kDa. vWF mediates platelet adhesion to subendothelium of the damaged blood vessel and serves as a carrier for Factor VIII, extending its half-life into the bloodstream. 2,3

Ultra-large multimers are proteolytically cleaved by ADAMTS13 into smaller and less active vWF forms. The biological function of vWF depends largely on the size of its multimers. Larger multimers are more likely to bind to platelets and collagen, and to promote platelet adhesion in
circulating blood. 2,3

Von Willebrand disease is classified on the basis of criteria developed by the vWF Subcommittee of the ISTH, intending to be clinically relevant to the treatment of vWD. Diagnostic categories were defined that encompassed distinct pathophysiologic mechanisms and correlated with the response to treatment with DDAVP or blood products. 4,5

Type Description
 Quantitative  Type1 vWD is characterized by a partial quantitive deficiency of vWF (most frequent, about 70 to 80% of cases)
Type3 vWD is characterized by a severe qualitative deficiency of vWF (about 1 to 5% of cases)
Qualitative Type2 Qualitative vWF defect (or abnormality)  (about 15 to 20% of cases)
  2A Decreased vWF-dependent platelet adhesion with selective deficiency of high-molecular-weight multimers
2B Increased affinity for platelet GPIb
2M Decreased vWF-dependent platelet adhesion without selective deficiency of high-molecular-weight multimers
2N Markedly decreased binding affinity for FVIII

Considering the heterogeneity of vWF concentration in the normal population, and in clinical manifestations, a complete biological study is necessary for vWD diagnosis, combining the assay of at least 3 parameters: FVIII:C activity, vWF activity (such as vWF:CBA or vWF RCo) and vWF antigen assay, and with regards to the ABO group and the familial context.

 

Overview Assays

Product Name Assay principle Reference Package
LIAPHENTM vWF:Ag (CE-IVD)  An Immunoturbidimetric assay for in vitro quantitative determination of von Willebrand Factor Antigen (vWF:Ag) on human citrated plasma, using a manuel of automated method. Reagents are in the liquid presentation, ready to use.  120206  R1: 4 x 5 ml

R2: 4 x 6 ml

ZYMUTESTTM vWF     (CE-IVD) An enzyme-immuno-assay for measuring human vWF in plasma, or in any fluid where vWF can be present. RK030A 96 tests
ZYMUTESTTM vWF:CBA (CE-IVD) A bio-immuno assay for measuring human vWF Collagen Binding Activity (CBA) in plasma, or in any fluid where vWF:CBA van be present RK038A 96 tests
 BIOPHENTM  FVIII:C  (CE-IVD)  A chromogenic assay for measuring the factor VIII:C activity in human plasma or in factor VIII:C concentrates, using a chromogenic method, manual or automated. 221402

221406 

2 x 2,5 ml

2 x 6 ml

 FVIII:C Deficient Plasma (CE-IVD)  A clotting assay for the measurement of Factor VIII:C activity in human citrated plasma, to be used in the presence of cephalin, activator and calcium (aPTT reagent).  DP040A

DP040K

1 x 1 ml

6 x 1 ml

 

References

  1. Ruggeri et al. Von Willebrand factor, platelets and endothelial cells interactions. J. Thromb. Haemost., Vol 1, No 7, 1335-1342, 2003.
  2.  Luo et al. von Willebrand Factor: more than a regulator of hemostasis and thrombosis. Acta Haematol, 2012, 128:158-169.
  3. Peyvandi et al. Role of von Willebrand Factor in the haemostasis. Blood Transfus, 2011, 9 suppl 2:s3-s8.
  4. Sadler JE(1), Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, Ingerslev J, Lee CA, Lillicrap D, Mannucci PM, et al. Update on the pathopphysiology and the classification of von Willebrand disease: a report of the Subcommitte on von Willebrand Factor. J Thromp Haemost 2006 Oct;4(10):2103-2114
  5. favaloro EJ. new developments in the diagnosis and treatment of von Willebrand disease. Clin. Invest. 2012 2(8), 781-795