Treatment of myelosuppression
Methods are presented for attenuating myelosuppressive side effects of treatment regimens, promoting thrombopoiesis and neutrophil production, and increasing efficacy of treatment regimens, by administering PF4-interacting heparinoids.
1. A method of treating thrombocytopenia other than heparin-induced thrombocytopenia, comprising:
administering a substantially non-anticoagulating PF4-interacting heparinoid to a subject with thrombocytopenia other than heparin-induced thrombocytopenia in an amount effective to promote thrombopoiesis.
2. The method of claim 1 , wherein the amount of PF4-interacting heparinoid is sufficient to maintain platelet levels above levels that indicate grade 3 thrombocytopenia.
3. The method of claim 2 , further comprising:
determining an initial platelet count in a blood sample from the patient.
4. A method of treating neutropenia, comprising:
administering a substantially non-anticoagulating PF4-interacting heparinoid to the subject with neutropenia in an amount effective to promote neutrophil production.
5. The method of claim 4 , wherein the amount of PF4-interacting heparinoid is sufficient to maintain neutrophil levels above levels that indicate grade 3 neutropenia.
6. The method of claim 5 , further comprising:
determining an initial neutrophil count in a blood sample from the patient.
7. The method of claim 1 or 4 , wherein the PF4-interacting heparinoid is capable of binding to PF-4.
8. The method of claim 1 or 4 , wherein the heparinoid is at least 90% desulfated at each of the 2-O and 3-O positions.
9. The method of claim 8 , wherein the heparinoid is at least 95% desulfated at each of the 2-O and 3-O positions.
10. The method of claim 8 , wherein the heparinoid is produced by cold alkaline hydrolysis of unfractionated heparin.
11. The method of claim 8 , wherein the heparinoid has an average molecular weight of about 8 kDa to about 15 kDa.
12. The method according to claim 11 , wherein the PF4-interacting heparinoid has an average molecular weight of about 11 kDa to about 13 kDa.
13. The method of claim 1 or 4 , wherein the heparinoid has less anticoagulant activity than unfractionated heparin.
14. The method of claim 1 or 4 , wherein the heparinoid has reduced affinity for anti-thrombin III as compared to unfractionated heparin.
15. The method of claim 1 or 4 , wherein the heparinoid has reduced anti-Xa activity as compared to unfractionated heparin.
16. The method of claim 1 or 4 , wherein the PF4-interacting heparinoid is administered parenterally.
17. The method of claim 16 , wherein the PF4-interacting heparinoid is administered intravenously.
18. The method of claim 17 , wherein the PF4-interacting heparinoid is administered as one or more bolus injections.
19. The method according to claim 18 , wherein the one or more bolus injections are administered at a dose of about 1 mg/kg to about 10 mg/kg.
20. The method of claim 17 , wherein the PF4-interacting heparinoid is administered as a continuous infusion.
21. The method of claim 20 , wherein the continuous infusion is administered at a dose of about 0.2 mg/kg/hr to about 2 mg/kg/hr.
22. The method of claim 17 , wherein the PF4-interacting heparinoid is administered as a bolus followed or preceded by a continuous infusion.