Von Willebrand’s factor

Intact factor VIII, as usually purified from the blood, consists of two distinct gene products factor VIII and (multiple copies of) von Willebrand s factor (vWF Figure 12.6). This complex displays a molecular mass ranging from 1 to 2 MDa, of which up to 15 per cent is carbohydrate. The fully intact factor VIII complex is required to enhance the rate of activation of factor IX of the intrinsic system. 

Because it is stable, desmopressin is preferred for treatments especially if pressor effects are not desired. The primary indication for therapy is central diabetes insipidus, a disorder that results when ADH secretion is reduced and that is characterized by polydipsia, polyuria, and dehydration. Desmopressin is also used to reduce primary nocturnal enuresis, or bedwetting, in children. It is useful in people with mild hemophilia A or with some types of von Willebrand s disease, in which von Willebrand s factor is present at low levels. In these cases, desmopressin is given when excessive bleeding occurs or before surgery to help reduce bleeding indirectly by increasing the amounts of coagulation factors. 

Factor VIII von Willebrand s factor complex [SY for an intermediate]... 

In one second-generation recombinant factor VIII product, ReFacto , hemophilic dogs were used to demonstrate utility for bleeding time correction, association with von Willebrand s factor, and evaluating pharmacokinetics... 

The next paper, presented by Ruben Carbonell (North Carolina State University), focused on affinity ligands produced from combinatorial peptide libraries. The use of this technology for designing peptide affinity ligands for the purification of s-protein, von Willebrand s factor, and fibrinogen was presented. The effects of peptide density and orientation on the interaction of proteins with the chromatographic surface was also described. 

Fresh frozen plasma contains the components of the coagulation system and is indicated for the replacement of deficient coagulation factors II, V, VII, X, XI, and XIII. Factor VIII and IX deficiencies are treated with specific factor concentrates. Fresh frozen plasma is also used for the rapid reversal of warfarin anticoagulation and in the treatment of disseminated intravascular coagulation. Thrombotic thrombocytopenic purpura is treated by means of therapeutic plasma exchange with fresh frozen plasma as the replacement fluid. Cryo-precipitate, which contains factor VIII, von Willebrand s factor, and fibrinogen, is indicated for the treatment of von Willebrand s disease that does not respond to desmopressin acetate, and for fibrinogen replacement (see Chap. 100). 

Abciximab inhibits platelet glycoprotein (GP) Ilb/IIIa binding to fibrinogen, as well as von Willebrand s factor and other adhesive molecules. This decreases platelet aggregation ( stickiness ). 

Lastly, several groups (46-53) have isolated cDNA clones for human von Willebrand s factor (vWf). Again, the predicted amino acid sequence of vWf revealed that 90% of the polypeptide consisted of four types of repeat elements designated A to D. These repeat sequences are unique to vWf except for the A repeat which has limited sequence identity with a region of complement factor B. 

Figure 10. Schematic representation of the structure of the von Willebrand s factor precursor (taken from ref. 51). The A, B, C and D repeats are indicated. The open region represents the prosequence the solid region represents the plasma von Willebrand s sequence. See text for details. The positions of the RGD tripeptides are shown by the triangles. The scale at the top represents 500 amino acid residues.

Bovine aortic endothelial, smooth muscle and adventitial cells Rat tail tendon collagen Formed multilayered structure resembling artery with a lining of endothelial cells that produced Von Willebrand s factor and prostacyclin Weinberg et al. (1986)... 

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