Page 197 - 2022_02-Haematologica-web

Sulfated non-anticoagulant heparin in SCD treatment
Disclosures
SAM holds a US patent on S-NACH28 and other related US patents. None of the authors has any conflicts of interest.
Contributions
SAM designed the study and is the Principal Investigator; OA, NHED, VM-C and MAT conducted the experiment; OA did the data analysis; OA and NHED contributed equally to the manu- script write up and data interpretation.All authors have approved the final version of the manuscript.
Acknowledgments
We appreciate Dr. Kelly A. Keating, Pharmaceutical Research Institute (PRI), for her excellent editing of this manuscript.
Funding
This project was funded by Vascular Vison Pharmaceuticals Co. to PRI and an NIH STTR Phase 1 grant (1R41HL147737- 01-A1, NIH/NHLB “Multi-modal Mechanisms of Novel Sulfated Non-Anticoagulant Heparin (S-NACH) in Sickle Cell Disease Management”) subaward to Children’s Hospital of Philadelphia (CHOP), university of Pennsylvania.
References
1. Ilesanmi OO. Pathological basis of symp- toms and crises in sickle cell disorder: implications for counseling and psy- chotherapy. Hematol Rep. 2010;2(1):e2.
2.Lu L, Li X, Vekilov PG, Karniadakis GE. Probing the twisted structure of sickle hemoglobin fibers via particle simulations. Biophys J. 2016;110(9):2085-2093.
3. Telen MJ. Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell dis- ease. Blood. 2016;127(7):810-819.
4. Connes P, Alexy T, Detterich J, Romana M, Hardy-Dessources MD, Ballas SK. The role of blood rheology in sickle cell disease. Blood Rev. 2016;30(2):111-118.
5. Hebbel RP, Eaton JW, Steinberg MH, White JG. Erythrocyte/endothelial interactions and the vasocclusive severity of sickle cell disease. Progr Clin Biol Res. 1981;55:145- 162.
6. Kaul DK, Fabry ME, Costantini F, Rubin EM, Nagel RL. In vivo demonstration of red cell-endothelial interaction, sickling and altered microvascular response to oxygen in the sickle transgenic mouse. J Clin Invest. 1995;96(6):2845-2853.
7. Noguchi CT, Schechter AN, Rodgers GP. Sickle cell disease pathophysiology. Baillieres Clin Haematol. 1993;6(1):57-91.
8. de Jong K, Larkin SK, Styles LA, Bookchin RM, Kuypers FA. Characterization of the phosphatidylserine-exposing subpopula- tion of sickle cells. Blood. 2001;98(3):860- 867.
9.Wautier MP, Heron E, Picot J, Colin Y, Hermine O, Wautier JL. Red blood cell phos- phatidylserine exposure is responsible for increased erythrocyte adhesion to endothe- lium in central retinal vein occlusion. J Thromb Haemost. 2011;9(5):1049-1055.
10. Setty BNY, Kulkarni S, Stuart MJ. Role of erythrocyte phosphatidylserine in sickle red cell–endothelial adhesion. Blood. 2002;99(5):1564-1571.
11. Proenca-Ferreira R, Brugnerotto AF, Garrido VT, et al. Endothelial activation by platelets from sickle cell anemia patients. PLoS One. 2014;9(2):e89012.
12. Belcher JD, Marker PH, Weber JP, Hebbel RP, Vercellotti GM. Activated monocytes in sickle cell disease: potential role in the acti- vation of vascular endothelium and vaso- occlusion. Blood. 2000;96(7):2451-2459.
13. Ataga KI, Key NS. Hypercoagulability in sickle cell disease: new approaches to an old problem. Hematology Am Soc Hematol Educ Program. 2007;91-96.
14. FDA approves new treatment for sickle cell disease. 2017 [accessed September 11, 2020]; Available from: https:// www.fda.gov/news-events/press- announcements/fda-approves-new-treat-
ment-sickle-cell-disease
15. Lee JO, Lee JY, Chun EJ, et al. Incidence and
predictors of venous thromboembolism in medically ill hospitalized elderly cancer patients: a prospective observational study. Support Care Cancer. 2019;27(7):2507- 2515.
16. FDA approves voxelotor for sickle cell dis- ease. 2019 [accessed November 25, 2019]; Available from: https://www.fda.gov/ drugs/resources-information-approved- drugs/fda-approves-voxelotor-sickle-cell- disease
17. Matte A, Zorzi F, Mazzi F, Federti E, Olivieri O, De Franceschi L. New therapeu- tic options for the treatment of sickle cell disease. Mediterr J Hematol Infect Dis. 2019;11(1):e2019002.
18.Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376(5):429-439.
19. Oksenberg D, Dufu K, Patel MP, et al. GBT 440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease. Br J Haematol. 2016;175(1):141-153.
20. Hutchaleelaha A, Patel M, Washington C, et al. Pharmacokinetics and pharmacody- namics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease. Br J Clin Pharmacol. 2019;85(6):1290-1302.
21.Metcalf B, Chuang C, Dufu K, et al. Discovery of GBT440, an orally bioavail- able R-state stabilizer of sickle cell hemo- globin. ACS Med Chem Lett. 2017; 8(3):321-326.
22.Khandros E, Huang P, Peslak SA, et al. Understanding heterogeneity of fetal hemoglobin induction through compara- tive analysis of F and A erythroblasts. Blood. 2020;135(22):1957-1968.
Haemost. 2006;96(6):816-821.
27.Alyahya R, Sudha T, Racz M, Stain SC,
Mousa SA. Anti-metastasis efficacy and safety of non-anticoagulant heparin deriva- tive versus low molecular weight heparin in surgical pancreatic cancer models. Int J Oncol. 2015;46(3):1225-1231.
28. Mousa SA, inventor Oxidized heparin frac- tions and their use in inhibiting angiogene- sis. US patent no. 8,071,569. 2011 Dec 6.
29. Sudha T, Phillips P, Kanaan C, Linhardt RJ, Borsig L, Mousa SA. Inhibitory effect of non-anticoagulant heparin (S-NACH) on pancreatic cancer cell adhesion and metas- tasis in human umbilical cord vessel seg- ment and in mouse model. Clin Exp Metastastis. 2012;29(5):431-439.
30. Alshaiban A, Muralidharan-Chari V, Nepo A, Mousa SA. Modulation of sickle red blood cell adhesion and its associated changes in biomarkers by sulfated nonanti- coagulant heparin derivative. Clin Applied Thromb Hemost. 2016;22(3):230-238.
31. Petaja J. Inflammation and coagulation. An overview. Thromb Res. 2011;127(Suppl 2):S34-37.
32. Hijiya N, Horiuchi K, Asakura T. Morphology of sickle cells produced in solutions of varying osmolarities. J Lab Clin Med. 1991;117(1):60-66.
33. Abdulmalik O, Safo MK, Chen Q, et al. 5- hydroxymethyl-2-furfural modifies intra- cellular sickle haemoglobin and inhibits sickling of red blood cells. Br J Haematol. 2005;128(4):552-561.
34. Asakura T, Mayberry J. Relationship between morphologic characteristics of sickle cells and method of deoxygenation. J Lab Clin Med. 1984;104(6):987-994.
35. Horiuchi K, Ohata J, Hirano Y, Asakura T. Morphologic studies of sickle erythrocytes by image analysis. J Lab Clin Med. 1990;115(5):613-620.
36. Abdulmalik O, Ghatge MS, Musayev FN, et al. Crystallographic analysis of human hemoglobin elucidates the structural basis of the potent and dual antisickling activity of pyridyl derivatives of vanillin. Acta Crystallogr D Biol Crystallogr. 2011;67(Pt 11):920-928.
23.
24.
25.
26.
Green NS, Barral S. Emerging science of hydroxyurea therapy for pediatric sickle cell disease. Pediatr Res. 2014;75(1-2):196- 204.
Charneski L, Congdon HB. Effects of antiplatelet and anticoagulant medications on the vasoocclusive and thrombotic com- plications of sickle cell disease: a review of the literature. Am J Health Syst Pharm. 2010;67(11):895-900.
Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: antithrom- botic therapy and prevention of thrombo- sis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e24S- 43S.
Mousa SA, Linhardt R, Francis JL, Amirkhosravi A. Anti-metastatic effect of a non-anticoagulant low-molecular-weight heparin versus the standard low-molecular- weight heparin, enoxaparin. Thromb
37.
Abdulmalik O, Safo MK, Lerner NB, et al. Characterization of hemoglobin bassett (a94Asp→ Ala), a variant with very low oxygen affinity. Am J Hematol. 2004; 77(3):268-276.
38. Abdulmalik O, Safo MK, Seeholzer SH, Asakura T, Hasbrouck NC, Russell JE. Hb Baden: structural and functional characteri- zation. Am J Hematol. 2010;85(11):848- 852.
39. Leishman WB. Note on a simple and rapid method of producing Romanowsky stain- ing in malarial and other blood films. Br Med J. 1901;2(2125):757-758.
haematologica | 2022; 107(2)
539