Von Willebrand Disease Screen (Plasma)

Diagnostic Use

von Willebrand Disease (vWD) is the most common inherited bleeding disorder affecting up to 1% of the population. Patients have defects in, or reduced levels of von Willebrand Factor (vWF) – a plasma protein made in platelets and endothelial cells. It has one main function: to facilitate binding of platelets to sites of vascular damage. This initiates platelet plug formation as one of the first steps in the coagulation cascade. Von Willebrand Factor also acts as a carrier protein for factor VIII and thus prevent factor VIII degradation in the circulation.
vWF exists in the plasma in different multimer sizes – the larger or high molecular weight subtypes are more important in platelet adhesion and aggregation.
vWF is a heterogeneous disorder which is divided into various subtypes. Accurate classification is important as different approaches to therapy are necessary for some subtypes.
Clinical expression is variable in individuals and within families, but most patients have mild to moderate bleeding of mucocutaneous type e.g. easy bruising, epistaxis, menorrhagia. Some patients present with excess bleeding after surgery, dental extractions or aspirin ingestion.
The importance of a full personal and family bleeding history and drug history cannot be over-emphasised. This is of more clinical relevance than laboratory test results.
vWD is a heterogeneous disorder:

Type I vWD partial quantitative deficiency of vWF – accounts for 70% vWD
Type 2 vWD qualitative abnormality of vWF. Four main subtypes the commonest being 2a (vWF lower than vWF:Ag) and 2b (increased binding to platelets often leads to thrombocytopenia)
Type 3 vWD severe quantitative defect.

Interpretation

The platelet function screen (PFA) is a useful screening test for von Willebrand disease. Prolongation of both closure times supports the diagnosis of vWD, whereas a normal result virtually excludes the diagnosis. A normal PFA result makes the diagnosis of von Willebrand disease very unlikely. The interpretation of the vWF assays can be very difficult. The vWF:Ag is an acute phase protein that fluctuates that fluctuates through menstrual cycle, and rises with oestrogen therapy, pregnancy, in response to stress and chronic disease. The presence of these conditions may mask mild vWD. Levels are about 25% lower in those with blood group O.

All abnormal results should be confirmed and diagnosis only made after consistent and significant abnormalities (usually less than 35%) are shown in one or more parameters.  Repeat testing is advisable in:

• patients with equivocal results
• patients with minor abnormalities in only one test
• where there is a strong personal or family history to suggest an inherited bleeding disorder and initial laboratory results are normal.

Reference Intervals

Test	Reference interval	Uncertainty of measurement
FVIII	55 – 150%	18%
vWF:Ag	55 – 150%	9%
vWF:AC (Siemens Innovance)	55 – 150%	14%
vWF:CB	55 – 150%	16%