New Treatments of von Willebrand Disease: Plasma Derived von Willebrand Factor Concentrates

Ménaché, D; Aronson, David L.

doi:10.1055/s-0038-1657590

Cited by 32 publications

(30 citation statements)

References 21 publications

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“…Improvement of the VWF multimer pattern in plasma, and the shortening of bleeding time, are important determinants of hemostatic capacity in the concentrates and cannot be described with ordinary pharmacokinetic variables. Furthermore, pharmacokinetic parameters such as half life, in-vivo recovery (IVR), and others, depend on the type of VWF concentrate; the recovery of FVIII:C, VWF:Ag, and VWF: RCo have been shown to differ markedly [9,11,13,15,16,[19][20][21][22][23][36][37][38]. Table 3 shows the pharmacokinetic parameters of selected concentrates.…”

Section: Pharmacokinetic Of Von Willebrand Factor/factor VIII Concentmentioning

confidence: 99%

“…The intermediate-purity and high-purity VWF/FVIII concentrates contain large amounts of FVIII and VWF; high postinfusion levels of these moieties are consistently obtained. There is also a sustained rise in plasma FVIII:C, higher than predicted from the doses infused, lasting up to 24 h. This pattern is due to the stabilizing effect of exogenously infused VWF [12,18,36]. The efficacy and safety of VHP VWF concentrates has been evaluated in a large series of patients [40].…”

Section: Very High Purity Factor VIII Concentratesmentioning

confidence: 99%

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Von Willebrand factor/factor VIII concentrates in the treatment of von Willebrand disease

Batlle

López-Fernández

Fraga

et al. 2009

Blood Coagulation &Amp; Fibrinolysis

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Therapy for von Willebrand disease (VWD) aims to restore the hemostatic function conferred by von Willebrand factor (VWF), which facilitates platelet adhesion and aggregation, and serves to increase potentially low coagulation factor VIII (FVIII) in plasma. In patients unresponsive to desmopressin (DDAVP), the preferred treatment is with plasma-derived VWF-containing FVIII concentrates. Only a few of the available VWF/FVIII concentrates have been licensed for use in VWD based on prospective studies. The efficacy of VWF/FVIII concentrates depends on the content and quality of VWF and FVIII. Several studies have demonstrated the variability of the VWF contents, as well as the differences in the VWF multimer patterns (including the high molecular weight VWF multimers that are most effective in restoring hemostasis), among these concentrates. Treating physicians should be aware of these disparities and the potential clinical implications for patients with different VWD subtypes. Dosing has traditionally been calculated based on the FVIII content of the products, although dosing based on VWF functional activity [e.g., VWF ristocetin cofactor activity (VWF:RCo)] addresses the primary protein deficiency in VWD patients. Several clinical studies have demonstrated the efficacy of concentrates dosed according to VWF:RCo. Dosing is generally consistent across VWD subtypes, although patients with severe phenotypes or undergoing major procedures may require more infusions or longer treatment duration. Other considerations for the use of VWF-containing concentrates include laboratory monitoring of efficacy and safety issues such as thrombosis risk and thromboprophylaxis.

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Section: Pharmacokinetic Of Von Willebrand Factor/factor VIII Concentmentioning

confidence: 99%

Section: Very High Purity Factor VIII Concentratesmentioning

confidence: 99%

Von Willebrand factor/factor VIII concentrates in the treatment of von Willebrand disease

Batlle

López-Fernández

Fraga

et al. 2009

Blood Coagulation &Amp; Fibrinolysis

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“…13,14 Patients with more severe forms of vWd and those nonresponsive to DDAVP therapy are treated with plasma concentrates containing FVIII and vWf. 13,15 Recombinant human interleukin 11 (rhIL-11, Neumega; Wyeth/ Genetics Institute, Cambridge, MA) is a pleiotropic cytokine with both thrombopoietic and anti-inflammatory activity that is approved for platelet restoration following high-dose chemotherapy. [16][17][18] During preliminary clinical trials, in addition to increases in platelet count, elevations in vWf and fibrinogen were also observed.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 11 significantly increases plasma von Willebrand factor and factor VIII in wild type and von Willebrand disease mouse models

Denis

Kwack

Saffaripour

et al. 2001

Blood

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Interleukin (IL)-11 is a cytokine with thrombopoietic activity that has been shown to increase plasma von Willebrand factor (vWf) in preliminary clinical studies. This led to further evaluation of the effect of recombinant human (rh)IL-11 on vWf and factor VIII (FVIII) secretion. In vitro, rhIL-11 did not increase vWf production by cultured endothelial cells, which suggests an indirect mechanism. Also, in vivo, plasma vWf was not elevated in mice shortly after a single intravenous (IV) bolus injection of 250 or 1000 g/kg rhIL-11. The effect of continuous exposure to rhIL-11 was accessed by treating wild type mice for 7 consecutive days with subcutaneous 250 g/kg/d rhIL-11. Platelet counts increased by 25% and 40% after 4 and 7 days, respectively. Plasma vWf and FVIII levels increased 2-fold after 4 and 7 days. Surprisingly, no effect of rhIL-11 on vWf or FVIII messenger RNA was observed, which suggests that the regulation by rhIL-11 occurs after transcription. No increase in soluble P-selectin was observed after rhIL-11 treatment, indicating that platelet activation is not the source of elevated vWf. Similarly to wild type mice, vWf heterozygous mice responded to rhIL-11 treatment by a significant increase in platelet counts and vWf and FVIII levels. Importantly, in vWf-deficient mice, rhIL-11 also induced a significant increase in FVIII independent of vWf and was able to reduce skin bleeding time. These results suggest that a clinical evaluation of the effects of rhIL-11-induced vWf/FVIII elevation in maintaining hemostasis in mild hemophilia A or von Willebrand disease would be worthwhile. (Blood. 2001;97: 465-472)

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“…90,98 Cryoprecipitate from a single donor who has been pretreated with DDAVP contains supraphysiologic amounts of vWF and is another treatment option. 90,100,101 The latter product is not yet licensed by the FDA for use in vWD. 44 In addition, highpurity plasma-derived (monoclonal antibody-derived) FVIII as well as rFVIII cannot be used to treat vWD because they do not contain appreciable amounts of vWF.…”

Section: Exogenous Von Willebrand Factor Replacementmentioning

confidence: 99%

Transfusion of the Patient with Congenital Coagulation Defects

Shusterman¹,

Manno²

2007

Blood Banking and Transfusion Medicine

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New Treatments of von Willebrand Disease: Plasma Derived von Willebrand Factor Concentrates

Cited by 32 publications

References 21 publications

Von Willebrand factor/factor VIII concentrates in the treatment of von Willebrand disease

Von Willebrand factor/factor VIII concentrates in the treatment of von Willebrand disease

Interleukin 11 significantly increases plasma von Willebrand factor and factor VIII in wild type and von Willebrand disease mouse models

Transfusion of the Patient with Congenital Coagulation Defects

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