Von-Willebrand-Factor

The vWf mediates not (mly platelet adhesion but also thrombus fomation at intermediate and high shear rates.  

In contrast to platelets adhering to a collagen surface platelets adhering to the vWf surface are mainly single platelets. Small numbers of vWf molecules are sufficient to attract and slow down platelets flowing near the surface. The subsequent processes of adhesion and activation are mediated by the interaction between direct platelet receptors with collagen (see chapter 4.4). 

a multifunctional membrane glycoprotein also known as GPIIIb and GPIV, is a member of a recently discovered family of scavenger receptors, members of which so far recorded are LIMPIP, CLA-D , FAT , and SR-BP . 

The FAT protein of adipocyte membranes is 58% homologous with that of CD36 identified in human platelets and is involved in binding and transportation of long-chain fatty acids . 

The fimction of CD36 as a collagen receptor is discussed in detail at a later stage. 

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Coagulation factors are glycoproteins named by roman numbers (the numbers being ascribed at the time of the components definition, not sequence of activation) (Table 1). Besides von Willebrand factor (vWF), the coagulation factors are synthesized in the liver. They have very different half-lifes and different concentrations in the plasma. Several coagulation factors are stored in platelets and endothelial cells and can be released during activation of these cells, which can result in a much higher local concentration of the respective factor (e.g., vWF). 

The human histamine Hi-receptor is a 487 amino acid protein that is widely distributed within the body. Histamine potently stimulates smooth muscle contraction via Hi-receptors in blood vessels, airways and in the gastrointestinal tract. In vascular endothelial cells, Hi-receptor activation increases vascular permeability and the synthesis and release of prostacyclin, plateletactivating factor, Von Willebrand factor and nitric oxide thus causing inflammation and the characteristic wheal response observed in the skin. Circulating histamine in the bloodstream (from, e.g. exposure to antigens or allergens) can, via the Hi-receptor, release sufficient nitric oxide from endothelial cells to cause a profound vasodilatation and drop in blood pressure (septic and anaphylactic shock). Activation of... 

The von Willebrand factor (vWf) is a heterogeneous multimeric plasma glycoprotein produced by megakaryocytes and endothelial cells which is found in platelets, plasma and the subendothelium. Subendothelial vWf facilitates platelet adhesion, especially under high shear stress, by binding to glycoprotein GPIb-V-IX, a complex of four leucine-rich repeat proteins on platelets. 

Glycoprotein llb/llla Platelets allbps ICAM-2 Fibrinogen, fibronectin, von Willebrand factor Platelet adhesion and aggregation... 

Sobel M, McNeill PM, Carlson P, Kermode JC, Adehnan B, Conroy R, Marques D. Heparin inhibition of von Willebrand factor in vitro and in vivo. J Clin Invest 1991 87 1787-1793. 

Sobel M, Soler DF, Kermode JC, Harris RB. Localization and characterization of a heparin binding domain peptide of human von Willebrand factor. J Biol Chem 1992 267 8857-8862. 

Pharmacologic Therapy Treatments used to decrease bleeding time in patients with uremic bleeding include cryoprecipitate, which contains various components important in platelet aggregation and clotting, such as von Willebrand factor and fibrinogen. Cryoprecipitate decreases bleeding time within 1 hour in 50% of patients. However, cost and the risk of infection have limited the use of cryoprecipitate. 

Desmopressin (DDAVP) increases the release of factor VIII (von Willebrand factor) from endothelial tissue in the vessel wall. Bleeding time is promptly reduced, within 1 hour of administration, and is sustained for 4 to 8 hours.42 Doses used for uremic bleeding are 0.3 to 0.4 mcg/kg intravenously over 20 to 30 minutes, 0.3 mcg/kg subcutaneously, or 2 to 3 mcg/kg intranasally. Repeated doses can cause tachyphylaxis by... 

Type 1 patients unresponsive to desmopressin, patients with types 2 and 3 von Willebrand s disease, and major surgery patients require replacement therapy with plasma-derived intermediate- and high-purity factor VIII virus-inactivated factor VIII concentrates containing von Willebrand factor. 

Primary therapy is based on disease severity and type of hemorrhage.7 Most patients with mild to moderate disease and a minor bleeding episode can be treated with l-desamino-8-D-arginine vasopressin [desmopressin acetate (DDAVP)], a synthetic analog of the antidiuretic hormone vasopressin. DDAVP causes release of von Willebrand factor (vWF) and factor VIII from endogenous storage sites. This formulation increases plasma factor VIII levels by three- to fivefold within 30 minutes. The recommended dose is 0.3 mcg/kg intravenously (in 50 mL normal saline infused over 15 to 30 minutes) or subcutaneously or 300 meg intranasally via concentrated nasal spray every 12 hours. Peak effect with intranasal administration occurs 60 to 90 minutes after administration, which is somewhat later than with intravenous administration. Desmopressin infusion may be administered daily for up to 2 to 3 days. Tachyphylaxis, an attenuated response with repeated administration, may occur after several doses.8... 

APCC, activated prothrombin complex concentrate PCC, prothrombin complex concentrate vWF, von Willebrand factor. 

Von Willebrand disease (vWD) is the most common inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand factor. The disease prevalence is estimated at 30 to 100 cases per million. In contrast to hemophilia, vWD is inherited as an autosomal dominant disorder (although autosomal recessive cases exist), ensuing equal frequency in male and females.16... 

Von Willebrand factor (VWF) is a large multimeric glycoprotein with two main functions in hemostasis to aid the platelet adhesion to injured blood vessel walls and to carry and stabilize factor VIII in plasma. Table 64—4 represents three main vWD phenotypes, their frequency, and genetic transmission.17... 

Cryoprecipitate Component of blood obtained by freezing and thawing plasma that is rich in clotting factors. One unit of cryoprecipitate derived from a unit of whole blood contains a volume of 10 to 20 mL, 80 to 100 units of factor VIII which consists of both the procoagulant activity and the von Willebrand factor, 150 to 250 mg of fibrinogen, 50 to 100 units of factor XIII, and 50 to 60 mg of fibronectin. 

Middleton J, Americh L, Gayon R, et al. A comparative study of endothelial cell markers expressed in chronically inflamed human tissues MECA-79, Duffy antigen receptor for chemokines, von Willebrand factor, CD31, CD34, CD 105 and CD146. J Pathol 2005 206(3) 260-268. 

Elumate-P Antihemophilic factor/von Willebrand factor complex Centeon Pharma Treatment and prevention of bleeding in hemophilia A... 

The procoagulant factors produced by endothelial cells are the coagulation factors von Willebrand factor (WF), F-V, F-VIII, tissue factor (TF), and plasminogen activator inhibitor (PAI), which blocks the activators u-PA and t-PA and counteracts fibrinolysis (G21, FI6). It has been shown that under the influence of complement activation (C9), in response to endotoxin in vitro (C24), in experimental E. coli sepsis in baboons (D30), and after stimulation with TNF (Al, N6), endothelial cells up-regulate the expression of TF, down-regulate TM and inhibit the production of t-PA and PAF. Thus, the balance may shift in the procoagulant direction with a large excess of PAI-1. 

G21. DeGroot, P. G Gonsalves, M. D., Loesberg, C., Van Buul-Wortelboer, M. F., Van Aken, W. G and Van Mourik, J. A., Thrombin-induced release of von Willebrand factor from endothelial cells is mediated by phospholipid methylation. J. Biol. Chem. 259, 13329-13333 (1984). 

V3. Vermes, I., Spooren, P. F. M. J., Kalsbeek-Batenburg, E. M., and Haanen, C., In addition to von Willebrand factor and urinary albumin excretion, plasma endothelin is an indicator of endothelial dysfunction in diabetes mellitus. Diabetes 36,472-473 (1993). 

In the intact blood vessel, ligands involved in adhesion to platelets, such as collagen, fibronectin, and von Willebrand factor, are sequestered in the subendothelium, thus preventing access to platelet adhesive receptors. Table 1 summarizes the functions of platelet membrane integrin receptors. 

A Vitronectin Von Willebrand factor Fibrinogen Fibronectin Adhesion... 

CD41/61 representing the GPIIb-IIIa complex, which is a receptor for fibrinogen, von Willebrand factor, fibronectin, and vitronectin. This complex is essential for platelet aggregation. 

Kroll M. H., Harris T. S., Moake J. L Handin R. I Shafer A. I. Von Willebrand factor binding to platelet GP lb initiates signals for platelet activation. J Clin Invest 1991 88, 1568-73. 

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