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The von Willebrand factor (VWF) is a multimeric adhesive glycoprotein that is important for platelet-platelet and platelet-vessel hemostatic interactions. In addition, plasma VWF serves as a carrier protein for coagulation factor VIII, stabilizing its procoagulant activity. VWF circulates in the blood in 2 distinct compartments; plasma VWF mainly reflects VWF synthesis and release from vascular endothelial cells, and platelet VWF (about 10% of the blood VWF) reflects VWF synthesis by bone marrow megakaryocytes with storage primarily in the alpha granules of circulating platelets. VWF antigen measurement assesses the mass of plasma VWF protein, but does not reflect VWF functions or platelet VWF. The major function of VWF (mediating platelet-platelet or platelet-vessel interaction) is most commonly assessed by measurement of plasma ristocetin cofactor activity.
Decreased VWF antigen may be seen in:
-Congenital von Willebrand disease
-Acquired VWD that may be associated with monoclonal gammopathies, lymphoproliferative disorders, autoimmune disorders, and hypothyroidism
Increased VWF antigen may be seen in association with:
-Pregnancy and/or estrogen use
-Inflammation (acute-phase reactant)
-Exercise or stress
-Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
von Willebrand factor (VWF) antigen measurement is most effective when it is combined with measurement of VWF ristocetin cofactor activity and factor VIII coagulant activity, preferably as a panel of tests with reflexive testing and interpretive reporting. Within this context, VWF antigen measurement can be useful for:
-Diagnosis of von Willebrand disease (VWD) and differentiation of VWD subtype
-Differentiation of VWD from hemophilia A (in conjunction with factor VIII coagulant assay)
Monitoring therapeutic efficacy of treatment with DDAVP (desmopressin) or VWF concentrates in patients with VWD
von Willebrand factor (VWF) antigen assay results generally must be used together with assays of VWF ristocetin cofactor activity and factor VIII coagulant activity, for optimum clinical utility and diagnostic efficiency. The diagnosis of von Willebrand disease (VWD) requires a combination of clinical and laboratory information. We suggest ordering VWPR / von Willebrand Profile.
Patients with congenital severe type III VWD have a markedly decreased or undetectable level of VWF antigen in the plasma (and in the platelets), in addition to a plasma ristocetin cofactor activity that is very low, or not detectable.
Patients with types IIA and IIB variants of VWF (with abnormal plasma VWF function and multimeric structure) may have normal or decreased plasma VWF antigen. However, they typically have decreased plasma ristocetin cofactor activity, along with decreased higher molecular-weight VWF multimers in the plasma.
Patients with types IIM or IIN VWD have normal levels of VWF antigen. In spite of this, they either have decreased vWF ristocetin cofactor activity, not caused by absence of higher molecular weight vWF multimers (type IIM VWD), or decreased factor VIII coagulant activity (type IIN VWD)
Patients with type I VWD (with decreased but normally functioning plasma VWF) have concordantly decreased plasma VWF antigen and ristocetin cofactor activity.
Patients with acquired VWD may have either normal or decreased plasma VWF antigen.
Lipemic specimens may lead to an underestimation of the von Willebrand factor (VWF) level.
The presence of rheumatoid factor may lead to an overestimation of the VWF level.
VWF is an acute-phase reactant and may be elevated above baseline in association with a variety of conditions including inflammation, stress, exercise, liver disease, pregnancy or estrogen therapy. Baseline VWF levels also increase with aging. These conditions may obscure diagnosis of the milder forms of von Willebrand disease (VWD). Repeat testing may be indicated.
Low normal levels of VWF antigen do not exclude possible diagnosis of VWD.
Borderline low or slightly decreased levels of VWF antigen may be observed in clinically normal individuals of blood group "O."
Note: Individuals of blood group "O" may have lower plasma von Willebrand factor (VWF) antigen than those of other ABO blood groups, such that apparently normal individuals of blood group "O" may have plasma VWF antigen as low as 40% to 50%, whereas the lower limit of the reference range for individuals of other blood groups may be 60% to 70%.
Children: Neonates, infants, and children have normal or mildly increased plasma VWF antigen, with respect to the adult reference range.
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