Treatment of von Willebrand disease
Provided herein are methods and compositions for treating von Willebrand disease with platelets, platelet derivatives, and/or thrombosomes.
1. A method of treating von Willebrand disease in a subject, the method comprising:
administering a therapeutically effective amount of freeze-dried platelet derivatives intravenously to the subject in need thereof, wherein the plasma of the subject is deficient in von Willebrand factor, and the therapeutically effective amount of freeze-dried platelet derivatives is an amount sufficient to form clots in plasma of the subject, wherein the therapeutically effective amount of freeze-dried platelet derivatives is at least 8.5×10 8 particles/kg of the subject, and wherein the surface expression of CD42b on the freeze-dried platelet derivatives is between 25% and 50% of the surface expression of CD42b on normal platelets, and wherein the freeze-dried platelet derivatives are loaded with an anti-fibrinolytic agent selected from ε-aminocaproic acid, aprotinin, aminomethylbenzoic acid, tranexamic acid, and fibrinogen.
2. The method of claim 1 , wherein the von Willebrand disease is von Willebrand disease type 1, von Willebrand disease type 2, or von Willebrand disease type 3.
3. The method of claim 1 , wherein the von Willebrand disease is acquired von Willebrand disease.
4. The method of claim 1 , wherein the surface expression of CD42b on the therapeutically effective amount of freeze-dried platelet derivatives is between 30% and 50% of the surface expression of CD42b on normal platelets.
5. The method of claim 1 , wherein the anti-fibrinolytic agent is ε-aminocaproic acid.
6. The method of claim 5 , wherein the freeze-dried platelet derivatives provide a time to clot that is shorter than the time to clot for treatment of the subject with the same amount of a free anti-fibrinolytic compound that is not loaded into the freeze-dried platelet derivatives.
7. The method of claim 1 , wherein the anti-fibrinolytic agent is one of ε-aminocaproic acid, aprotinin, aminomethylbenzoic acid, and tranexamic acid.
8. The method of claim 7 , wherein the therapeutically effective amount of freeze-dried platelet derivatives is at least 8.49×10 9 particles/kg.
9. The method of claim 7 , wherein the surface expression of CD42b on the therapeutically effective amount of freeze-dried platelet derivatives is between 40% and 50% of the surface expression of CD42b on normal platelets.
10. The method of claim 7 , wherein the surface expression of CD42b on the therapeutically effective amount of freeze-dried platelet derivatives is between 40% and 50% of the surface expression of CD42b on normal platelets, and wherein the therapeutically effective amount of freeze-dried platelet derivatives is at least 8.49×10 9 particles/kg.
11. The method of claim 7 , wherein the therapeutically effective amount of freeze-dried platelet derivatives forms clots in von Willebrand factor deficient plasma in from about 70% to about the same time as in normal plasma.
12. The method of claim 11 , wherein the therapeutically effective amount of freeze-dried platelet derivatives forms clots in von Willebrand factor deficient plasma in about 70% to about 80% of the time as in normal plasma.
13. The method of claim 7 , wherein the freeze-dried platelet derivatives provide a time to clot that is shorter than the time to clot for treatment of the subject with the same amount of a free anti-fibrinolytic compound that is not loaded into the freeze-dried platelet derivatives.
14. The method of claim 7 , wherein the surface expression of CD42b on the therapeutically effective amount of freeze-dried platelet derivatives is between 30% and 50% of the surface expression of CD42b on normal platelets.
15. The method of claim 7 , wherein the freeze-dried platelet derivatives have less than 10% crosslinking of platelet membranes via proteins and/or lipids present on the membranes.
16. The method of claim 7 , wherein at least 60% of the freeze-dried platelet derivatives have a particle size in the range of 0.3 μm to 5.0 μm.
17. A method of treating a coagulopathy in a subject, wherein the coagulopathy is caused by von Willebrand disease, the method comprising administering intravenously to the subject in need thereof a therapeutically effective amount of a composition comprising freeze-dried platelet derivatives and an incubating agent comprising one or more salts, a buffer, and a cryoprotectant, wherein the composition is administered to the subject having von Willebrand disease, wherein the plasma of the subject is deficient in von Willebrand factor, and the freeze-dried platelet derivatives in the composition is an amount sufficient to form clots in plasma of the subject, wherein the therapeutically effective amount of the composition is at least 8.5×10 8 particles/kg of the subject, wherein the surface expression of CD42b on the freeze-dried platelet derivatives is between 25% and 50% of the surface expression of CD42b on normal platelets, and wherein the freeze-dried platelet derivatives are loaded with an anti-fibrinolytic agent selected from ε-aminocaproic acid, aprotinin, aminomethylbenzoic acid, tranexamic acid, and fibrinogen.
18. The method of claim 17 , wherein the von Willebrand disease is von Willebrand disease type 1, von Willebrand disease type 2, von Willebrand disease type 3, or acquired von Willebrand disease.
19. The method of claim 17 , wherein the incubating agent comprises an organic solvent and a saccharide comprising trehalose, and wherein the cryoprotectant comprises polysucrose in a concentration of 3 to 10% (w/v).
20. The method of claim 17 , wherein the surface expression of CD42b on the freeze-dried platelet derivatives in the therapeutically effective amount of the composition is between 30% and 50% of the surface expression of CD42b on normal platelets, and wherein the anti-fibrinolytic agent is selected from ε-aminocaproic acid, aprotinin, aminomethylbenzoic acid, and tranexamic acid.