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INTRODUCTION

von Willebrand disease (VWD) is a result of quantitative and qualitative abnormalities in von Willebrand factor (VWF), a plasma protein serving as a carrier for factor VIII and as an adhesive link between platelets and damaged blood vessel walls. Table 80–1 presents the nomenclature used in discussing the functions of VWF.

TABLE 80–1von WILLEBRAND FACTOR AND FACTOR VIII TERMINOLOGY

ETIOLOGY AND PATHOGENESIS

  • VWF is synthesized in endothelial cells and megakaryocytes.

  • Posttranslational modification of the molecule involves glycosylation, sulfation, and multimer formation through extensive disulfide bond formation.

  • VWF is stored in platelets and in Weibel-Palade bodies in endothelial cells.

  • Secretion of VWF from Weibel-Palade bodies is both constitutive and regulated. High-molecular-weight multimers with the greatest activity are released in response to agents such as thrombin in vitro or desmopressin (DDAVP) in vivo.

  • A specific VWF processing protease can reduce the size of high-molecular-weight multimers in plasma.

  • VWF plays an important role in platelet aggregation at sites of vessel injury.

  • VWF stabilizes factor VIII through formation of a noncovalent complex between the two proteins.

  • A large number of mutations of the VWF gene have been discovered and more than 20 distinct subtypes of VWD have been described. Table 80–2 presents a simplified classification of VWD.

  • Types 1 and 3 are deficiencies of normal VWF, either partial (type 1) or complete (type 3).

  • Type 2 includes the qualitative abnormalities of VWF structure and/or function. The quantity of VWF (VWF antigen) in type 2 disease may be normal but is usually reduced.

  • Platelet-type VWD is an inherited platelet abnormality due to a mutation in glycoprotein Ib (CD42b, c). It is discussed in Chap. 76.

TABLE 80–2CLASSIFICATION OF VON WILLEBRAND DISEASE

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