Compositions and methods for treating nonsteroidal anti-inflammatory drug (NSAID) associated coagulopathy, thrombocytopenia, glanzmann's thrombasthenia, and/or thrombosis
The present invention relates to compositions and methods for modulating coagulation through modulating the level or activity of ENPP4.
1. A method of treating nonsteroidal anti-inflammatory drug (NSAID) associated coagulopathy in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of an isolated soluble ectonucleotide pyrophosphatase/phosphodiesterase 4 (ENPP4) polypeptide comprising amino acid residues 1-407 of SEQ ID NO:1.
2. The method of claim 1 , wherein the ENPP4 polypeptide is a recombinant ENPP4 polypeptide.
3. The method of claim 1 , wherein the ENPP4 polypeptide lacks the ENPP4 transmembrane domain.
4. The method of claim 1 , wherein the ENPP4 polypeptide consists of amino acid residues 1-407 of SEQ ID NO:1.
5. The method of claim 1 , wherein the ENPP4 polypeptide is administered to the mammal in combination with at least one other agent useful in treating bleeding.
6. The method of claim 1 , wherein the ENPP4 polypeptide is administered to the mammal acutely or chronically.
7. The method of claim 1 , wherein the ENPP4 polypeptide is administered to the mammal locally, regionally or systemically.
8. The method of claim 1 , wherein the mammal is a human subject.
9. A method of treating thrombocytopenia in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of an isolated soluble ectonucleotide pyrophosphatase/phosphodiesterase 4 (ENPP4) polypeptide comprising amino acid residues 1-407 of SEQ ID NO:1.
10. The method of claim 9 , wherein the ENPP4 polypeptide is a recombinant ENPP4 polypeptide.
11. The method of claim 9 , wherein the ENPP4 polypeptide lacks the ENPP4 transmembrane domain.
12. The method of claim 9 , wherein the ENPP4 polypeptide consists of amino acid residues 1-407 of SEQ ID NO: 1.
13. The method of claim 9 , wherein the ENPP4 polypeptide is administered to the mammal in combination with at least one other agent useful in treating bleeding.
14. The method of claim 9 , wherein the ENPP4 polypeptide is administered to the mammal acutely or chronically.
15. The method of claim 9 , wherein the ENPP4 polypeptide is administered to the mammal locally, regionally or systemically.
16. The method of claim 9 , wherein the mammal is a human subject.
17. A method of treating Glanzmann's thrombasthenia in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of an isolated soluble ectonucleotide pyrophosphatase/phosphodiesterase 4 (ENPP4) polypeptide comprising amino acid residues 1-407 of SEQ ID NO:1.
18. The method of claim 17 , wherein the ENPP4 polypeptide is a recombinant ENPP4 polypeptide.
19. The method of claim 17 , wherein the ENPP4 polypeptide lacks the ENPP4 transmembrane domain.
20. The method of claim 17 , wherein the ENPP4 polypeptide consists of amino acid residues 1-407 of SEQ ID NO: 1.
21. The method of claim 17 , wherein the ENPP4 polypeptide is administered to the mammal in combination with at least one other agent useful in treating bleeding.
22. The method of claim 17 , wherein the ENPP4 polypeptide is administered to the mammal acutely or chronically.
23. The method of claim 17 , wherein the ENPP4 polypeptide is administered to the mammal locally, regionally or systemically.
24. The method of claim 17 , wherein the mammal is a human subject.