von Willebrand disease testing

Specimen:

Refer to individual tests (von Willebrand factor Ag VWF:RCo, VWF: CB and von Willebrand factor multimer studies)

Method:

Initial screening testing includes the following: von Willebrand factor Ag (VWF:Ag) VWF activity (Ristocetin cofactor activity [VWF:RCo] and VWF collagen binding [VWF:CB]) FVIII.

If these studies are normal, then testing for other bleeding disorders may be indicated depending on the clinical, bleeding and family history.

Repeat testing may be appropriate in some circumstances especially if borderline results and high clinical suspicion.

If these initial studies are abnormal, further testing to confirm and classify the type of VWD is indicated – please consult pathologist or haematologist. These tests may include:

  • Repeat initial VWD assays
  • Ratio of VWF:RCo to VWF:Ag
  • von Willebrand factor multimer studies
  • Ristocetin-induced platelet aggregation (RIPA) or platelet binding
  • FVIII binding
  • DNA sequencing
  • Platelet VWF studies
Reference Interval:

See individual test.

Application:

Investigation in patients with suspected von Willebrand's disease based on personal or family bleeding risk history.

Interpretation:

Please consult pathologist or haematologist if testing abnormal.

The findings of the above tests are interpreted together, in conjunction with the family and bleeding history. VWD is classified into three major types:

Type 1 VWD – a partial quantitative deficiency of VWF.

Type 2 VWD – a qualitative abnormality as demonstrated by VWF multimer studies, RIPA, ratio of VWF activity to antigen ratio, or other special assays.

Type 2 VWD is classified into four subtypes:

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 of FVIII

Type 3 VWD – virtually complete deficiency of VWF

Acquired von Willebrand syndrome may occur when there are defects in VWF concentration or function due to other medical disorders (such as autoimmune disorders, lymphoproliferative disease, monoclonal gammopathies, hypothyroidism, cardiovascular lesions and myleoproliferative and some other neoplasms).

Systemic inflammation, pregnancy, oral contraceptives and stress may increase plasma levels of VWF and mask lower baseline levels. Therefore repeated testing is sometimes required to identify low levels. ABO blood group also has an effect of VWF levels, with lower levels in individuals with blood group O compared with other blood group types.

Reference:

The Diagnosis, Evaluation, and Management of von Willebrand Disease. National Heart, Lung, and Blood Institute and National Institutes of Health. 2007