Abstract Number: PB1533
Meeting: ISTH 2020 Congress
Background: Von Willebrand Disease (VWD) is the most prevalent bleeding disorder, causing excessive bleeding and bruising in 1% of the population. vWF mediates platelet collagen interactions under high shear by binding to CD42b. Murine vWF does not interact with human CD42b. Thrombosomes®, or lyophilized human platelets (LHP), are a stabilized platelet derived hemostatic agent currently under clinical development.
Aims: To determine the role, if any, that vWF plays in the promotion of hemostasis by LHP.
Methods: Surface expression of vWF binding sites on LHP and fresh platelets was measured by flow cytometry using the CD42b function blocking antibody clone AN51. The ristocetin cofactor assay was performed to measure ristocetin induced binding of vWF and subsequent agglutination of LHP relative to fresh and fixed platelets. Ristocetin induced platelet aggregation (RIPA) was performed in PRP and in plasma supplemented with LHP. The Total Thrombus-formation Analysis System (T-TAS) was used to assess thrombus formation by LHP and fresh platelets under shear in thromboplastin-collagen coated microcapillaries using normal and VWD Type 3 plasma. The in vivo hemostatic capability of LHP was assessed via tail bleeding times in NOD/SCID mice.
Results: Binding of αCD42b was reduced by 55.6% in LHP relative to fresh platelets as shown by mean fluorescent intensity. The average agglutination for LHP in the ristocetin cofactor assay was reduced by 83.5% compared to fixed platelet controls. Fresh platelets but not LHP supported RIPA. Occlusion to collagen under flow by LHP occurred similarly in normal and Type 3 VWD plasma. Average bleeding time in mice receiving LHP was reduced to 4.2 minutes relative to > 9 minutes in untreated mice and mice administered fresh platelets.
Conclusions: LHP may work independently of vWF in vitro yet support thrombus formation and hemostasis in vivo, suggesting that LHP may therapeutically promote hemostasis in patients with VWD.
To cite this abstract in AMA style:Ishler B, Dickerson M, Lee A, Hale A, Moskowitz K. Lyophilized Human Platelets Show Hemostatic Function Independent of von Willebrand Factor [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/lyophilized-human-platelets-show-hemostatic-function-independent-of-von-willebrand-factor/. Accessed December 6, 2023.
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