1,004
Views
0
CrossRef citations to date
0
Altmetric
Review

Addressing thrombosis concerns in immune thrombocytopenia: the role of fostamatinib in immune thrombocytopenia management

, &
Pages 55-66 | Received 06 Jun 2023, Accepted 09 Feb 2024, Published online: 19 Feb 2024

References

  • Provan D, Semple JW. Recent advances in the mechanisms and treatment of immune thrombocytopenia. EBioMedicine. 2022;76:103820. doi: 10.1016/j.ebiom.2022.103820
  • Cooper N, Kruse A, Kruse C, et al. Immune thrombocytopenia (ITP) world impact survey (iWish): patient and physician perceptions of diagnosis, signs and symptoms, and treatment. Am J Hematol. 2021;96(2):188–98. doi: 10.1002/ajh.26045
  • Nørgaard M, Cetin K, Mægbæk ML, et al. Risk of arterial thrombotic and venous thromboembolic events in patients with primary chronic immune thrombocytopenia: a Scandinavian population-based cohort study. Br J Haematol. 2016;174(4):639–42. doi: 10.1111/bjh.13787
  • Doobaree IU, Nandigam R, Bennett D, et al. Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis. Eur J Haematol. 2016;97(4):321–30. doi: 10.1111/ejh.12777
  • Sarpatwari A, Bennett D, Logie JW, et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom general practice research database. Haematologica. 2010;95(7):1167–1175. doi: 10.3324/haematol.2009.018390
  • Rodeghiero F. Is ITP a thrombophilic disorder? Am J Hematol. 2016;91(1):39–45. doi: 10.1002/ajh.24234
  • van Dijk WEM, Brandwijk ON, Heitink-Polle KMJ, et al. Hemostatic changes by thrombopoietin-receptor agonists in immune thrombocytopenia patients. Blood Rev. 2021;47:100774. doi: 10.1016/j.blre.2020.100774
  • Cooper N, Altomare I, Thomas MR, et al. Assessment of thrombotic risk during long-term treatment of immune thrombocytopenia with fostamatinib. Ther Adv Hematol. 2021;12:1–12. doi: 10.1177/20406207211010875
  • Ghanima W, Cooper N, Rodeghiero F, et al. Thrombopoietin receptor agonists: ten years later. Haematologica. 2019;104(6):1112–23. doi: 10.3324/haematol.2018.212845
  • Han X, Li C, Zhang S, et al. Why thromboembolism occurs in some patients with thrombocytopenia and treatment strategies. Thromb Res. 2020;196:500–9. doi: 10.1016/j.thromres.2020.10.005
  • Abou-Ismail MY, Kapoor S, Citla Sridhar D, et al. Thrombotic microangiopathies: an illustrated review. Res Pract Thromb Haemost. 2022;6(3):e12708. doi: 10.1002/rth2.12708
  • Saxon BR, Blanchette VS, Butchart S, et al. Reticulated platelet counts in the diagnosis of acute immune thrombocytopenic purpura. J Pediatr Hematol Oncol. 1998;20(1):44–8. doi: 10.1097/00043426-199801000-00007
  • Kaito K, Otsubo H, Usui N, et al. Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia. Br J Haematol. 2005;128(5):698–702. doi: 10.1111/j.1365-2141.2004.05357.x
  • Frojmovic M, Wong T. Dynamic measurements of the platelet membrane glycoprotein IIb-IIIa receptor for fibrinogen by flow cytometry. II. Platelet size-dependent subpopulations. Biophys J. 1991;59(4):828–837. doi: 10.1016/s0006-3495(91)82295-0
  • Karpatkin S. Heterogeneity of human platelets. II. Functional evidence suggestive of young and old platelets. J Clin Invest. 1969;48(6):1083–7. doi: 10.1172/jci106064
  • Thompson CB, Jakubowski JA, Quinn PG, et al. Platelet size as a determinant of platelet function. J Lab Clin Med. 1983;101(2):205–213.
  • Handtke S, Thiele T. Large and small platelets-(when) do they differ? J Thromb Haemost. 2020;18(6):1256–1267. doi: 10.1111/jth.14788
  • Alvarez-Roman MT, Fernandez-Bello I, Jimenez-Yuste V, et al. Procoagulant profile in patients with immune thrombocytopenia. Br J Haematol. 2016;175(5):925–34. doi: 10.1111/bjh.14412
  • Jy W, Johansen ME, Bidot C Jr., et al. Red cell-derived microparticles (RMP) as haemostatic agent. Thromb Haemost. 2013;110(4):751–760. doi:10.1160/TH12-12-0941
  • Zucker-Franklin D, Karpatkin S. Red-cell and platelet fragmentation in idiopathic autoimmune thrombocytopenic purpura. N Engl J Med. 1977;297(10):517–23. doi: 10.1056/nejm197709082971001
  • Greene LA, Chen S, Seery C, et al. Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia. Br J Haematol. 2014;166(4):592–600. doi: 10.1111/bjh.12929
  • Lukasik ZM, Makowski M, Makowska JS. From blood coagulation to innate and adaptive immunity: the role of platelets in the physiology and pathology of autoimmune disorders. Rheumatol Int. 2018;38(6):959–74. doi: 10.1007/s00296-018-4001-9
  • Ruiz-Irastorza G, Crowther M, Branch W, et al. Antiphospholipid syndrome. Lancet. 2010;376(9751):1498–509. doi: 10.1016/S0140-6736(10)60709-X
  • Enger C, Bennett D, Forssen U, et al. Comorbidities in patients with persistent or chronic immune thrombocytopenia. Int J Hematol. 2010;92(2):289–95. doi: 10.1007/s12185-010-0636-3
  • Severinsen MT, Engebjerg MC, Farkas DK, et al. Risk of venous thromboembolism in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol. 2011;152(3):360–2. doi: 10.1111/j.1365-2141.2010.08418.x
  • Nørgaard M, Severinsen MT, Lund Maegbaek M, et al. Risk of arterial thrombosis in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol. 2012;159(1):109–11. doi: 10.1111/j.1365-2141.2012.09231.x
  • Uthman I, Godeau B, Taher A, et al. The hematologic manifestations of the antiphospholipid syndrome. Blood Rev. 2008;22(4):187–194. doi:10.1016/j.blre.2008.03.005
  • Arfors L, Winiarski J, Lefvert AK. Prevalence of antibodies to cardiolipin in chronic ITP and reactivity with platelet membranes. Eur J Haematol. 1996;56(4):230–4. doi: 10.1111/j.1600-0609.1996.tb01934.x
  • Lipp E, von Felten A, Sax H, et al. Antibodies against platelet glycoproteins and antiphospholipid antibodies in autoimmune thrombocytopenia. Eur J Haematol. 1998;60(5):283–8. doi:10.1111/j.1600-0609.1998.tb01041.x
  • Stasi R, Stipa E, Masi M, et al. Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura. Blood. 1994;84(12):4203–8. doi: 10.1182/blood.V84.12.4203.bloodjournal84124203
  • Diz-Küçükkaya R, Hacihanefioğlu A, Yenerel M, et al. Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study. Blood. 2001;98(6):1760–1764. doi: 10.1182/blood.v98.6.1760
  • Pierrot-Deseilligny C, Khellaf M, Gouault M, et al. Prevalence and clinical significance of elevated antiphospholipid antibodies in adults with immune Thrombocytopenic Purpura. Blood. 2006;108(11):1083. doi: 10.1182/blood.V108.11.1083.1083
  • Bidot CJ, Jy W, Horstman LL, et al. Antiphospholipid antibodies in immune thrombocytopenic purpura tend to emerge in exacerbation and decline in remission. Br J Haematol. 2005;128(3):366–72. doi: 10.1111/j.1365-2141.2004.05314.x
  • Bidot CJ, Jy W, Horstman LL, et al. Antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) and antiphospholipid syndrome (APS). Am J Hematol. 2006;81(6):391–6. doi:10.1002/ajh.20571
  • Moulis G, Audemard-Verger A, Arnaud L, et al. Risk of thrombosis in patients with primary immune thrombocytopenia and antiphospholipid antibodies: a systematic review and meta-analysis. Autoimmun Rev. 2016;15(3):203–9. doi: 10.1016/j.autrev.2015.11.001
  • Sun S, Urbanus RT, Ten Cate H, et al. Platelet activation mechanisms and consequences of immune thrombocytopenia. Cells. 2021;10(12):3386. doi: 10.3390/cells10123386
  • Machin N, Ragni MV, Comer DM, et al. Prevalence and correlates of thrombosis in adults with immune thrombocytopenia: an NIS study. Thromb Res. 2018;172:80–5. doi:10.1016/j.thromres.2018.10.017
  • Kristinsson SY, Gridley G, Hoover RN, et al. Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up. Haematologica. 2014;99(2):392–8. doi: 10.3324/haematol.2013.092460
  • Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829–3866. doi: 10.1182/bloodadvances.2019000966
  • Bussel J, Arnold DM, Grossbard E, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018;93(7):921–30. doi: 10.1002/ajh.25125
  • Bussel JB, Provan D, Shamsi T, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373(9664):641–8. doi: 10.1016/s0140-6736(09)60402-5
  • Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011;377(9763):393–402. doi: 10.1016/s0140-6736(10)60959-2
  • Wong RSM, Saleh MN, Khelif A, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017;130(23):2527–36. doi: 10.1182/blood-2017-04-748707
  • Bussel JB, Kuter DJ, Aledort LM, et al. A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood. 2014;123(25):3887–94. doi: 10.1182/blood-2013-07-514398
  • Jurczak W, Chojnowski K, Mayer J, et al. Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia. Br J Haematol. 2018;183(3):479–90. doi: 10.1111/bjh.15573
  • Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371(9610):395–403. doi: 10.1016/s0140-6736(08)60203-2
  • Bussel JB, Kuter DJ, Pullarkat V, et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood. 2009;113(10):2161–71. doi: 10.1182/blood-2008-04-150078
  • Gernsheimer TB, George JN, Aledort LM, et al. Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP). J Thromb Haemost. 2010;8(6):1372–82. doi: 10.1111/j.1538-7836.2010.03830.x
  • Kuter DJ, Bussel JB, Newland A, et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol. 2013;161(3):411–23. doi: 10.1111/bjh.12260
  • Janssens A, Rodeghiero F, Anderson D, et al. Changes in bone marrow morphology in adults receiving romiplostim for the treatment of thrombocytopenia associated with primary immune thrombocytopenia. Ann Hematol. 2016;95(7):1077–87. doi: 10.1007/s00277-016-2682-2
  • Guitton Z, Terriou L, Lega J-C, et al. Risk of thrombosis with anti-phospholipid syndrome in systemic lupus erythematosus treated with thrombopoietin-receptor agonists. Rheumatology. 2018;57(8):1432–8. doi: 10.1093/rheumatology/key119
  • Girolami A, de Marinis GB, Bonamigo E, et al. Arterial and venous thromboses in patients with idiopathic (immunological) thrombocytopenia: a possible contributing role of cortisone-induced hypercoagulable state. Clin Appl Thromb Hemost. 2013;19(6):613–618. doi: 10.1177/1076029612452114
  • Arnold DM. Bleeding complications in immune thrombocytopenia. Hematology. 2015;2015(1):237–42. doi: 10.1182/asheducation-2015.1.237
  • Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780–3817. doi: 10.1182/bloodadvances.2019000812
  • Cohen YC, Djulbegovic B, Shamai-Lubovitz O, et al. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med. 2000;160(11):1630–8. doi: 10.1001/archinte.160.11.1630
  • Moulis G, Palmaro A, Montastruc JL, et al. Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France. Blood. 2014;124(22):3308–3315. doi:10.1182/blood-2014-05-578336
  • Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood. 1999;94(3):909–13. doi:10.1182/blood.V94.3.909.415k02_909_913
  • Schoonen WM, Kucera G, Coalson J, et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database. Br J Haematol. 2009;145(2):235–44. doi: 10.1111/j.1365-2141.2009.07615.x
  • Swan D, Newland A, Rodeghiero F, et al. Thrombosis in immune thrombocytopenia - current status and future perspectives. Br J Haematol. 2021;194(5):822–834. doi: 10.1111/bjh.17390
  • Rodeghiero F. ITP and thrombosis: an intriguing association. Blood Adv. 2017;1(24):2280. Epub 20171114. doi: 10.1182/bloodadvances.2017007989
  • Justo Sanz R, Monzon Manzano E, Fernandez Bello I, et al. Platelet apoptosis and PAI-1 are involved in the pro-coagulant state of immune thrombocytopaenia patients treated with thrombopoietin receptor agonists. Thromb Haemost. 2019;119(4):645–59. doi: 10.1055/s-0039-1678706
  • Alvarez Roman MT, Fernandez Bello I, Arias-Salgado EG, et al. Effects of thrombopoietin receptor agonists on procoagulant state in patients with immune thrombocytopenia. Thromb Haemost. 2014;112(1):65–72. doi: 10.1160/TH13-10-0873
  • US Food & Drug Administration. FDA approves fostamatinib tablets for ITP. [ Updated 2018 Apr 18; cited 2023 Dec 20] Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fostamatinib-tablets-itp
  • European Medicines Agency. Tavlesse. fostamatinib. [ Updated 2022 Sep 12; cited 2023 Dec 20]. Availablefrom: https://www.ema.europa.eu/en/medicines/human/EPAR/tavlesse
  • Newland A, Lee EJ, McDonald V, et al. Fostamatinib for persistent/chronic adult immune thrombocytopenia. Immunotherapy. 2018;10(1):9–25. doi: 10.2217/imt-2017-0097
  • Bussel JB, Arnold DM, Boxer MA, et al. Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program. Am J Hematol. 2019;94(5):546–53. doi: 10.1002/ajh.25444
  • Boccia R, Cooper N, Ghanima W, et al. Fostamatinib is an effective second-line therapy in patients with immune thrombocytopenia. Br J Haematol. 2020;190(6):933–8. doi: 10.1111/bjh.16959
  • Kuwana M, Ito T, Kowata S, et al. Fostamatinib for the treatment of Japanese patients with primary immune thrombocytopenia: a phase 3, placebo-controlled, double-blind, parallel-group study. Br J Haematol. 2023;200(6):802–11. doi: 10.1111/bjh.18582
  • Lhermusier T, van Rottem J, Garcia C, et al. The Syk-kinase inhibitor R406 impairs platelet activation and monocyte tissue factor expression triggered by heparin-PF4 complex directed antibodies. J Thromb Haemost. 2011;9(10):2067–76. doi: 10.1111/j.1538-7836.2011.04470.x
  • Spalton JC, Mori J, Pollitt AY, et al. The novel syk inhibitor R406 reveals mechanistic differences in the initiation of GPVI and CLEC-2 signaling in platelets. J Thromb Haemost. 2009;7(7):1192–9. doi:10.1111/j.1538-7836.2009.03451.x
  • Strich JR, Ramos-Benitez MJ, Randazzo D, et al. Fostamatinib inhibits neutrophils extracellular traps induced by COVID-19 patient plasma: a potential therapeutic. J Infect Dis. 2021;223(6):981–4. doi: 10.1093/infdis/jiaa789
  • Strich JR, Tian X, Samour M, et al. Fostamatinib for the treatment of hospitalized adults with COVD-19 a randomized trial. Clin Infect Dis. 2022;75(1):e491–8. doi: 10.1093/cid/ciab732
  • Wigerblad G, Warner SA, Ramos-Benitez MJ, et al. Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19. Sci Adv. 2023;9(1):eade8272. doi: 10.1126/sciadv.ade8272
  • Clinicaltrials.gov. Double-blind, randomized, placebo-controlled, multi-center phase 3 study to evaluate the efficacy and safety of fostamatinib in COVID-19 subjects. [ Updated 2023 Aug 18; cited 2023 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT04629703?term=fostamatinib&cond=COVID-19&draw=2&rank=2
  • Clinicaltrials.gov. Inflammatory signal inhbitors for COVID-19 (MATIS). [ Updated Jul 2022; cited 20 Dec 2023]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04581954
  • Clinicaltrials.gov. Novel experimental COVID-19 therapies affecting host response (NECTAR). [ Updated 2023 Dec 5; cited 2023 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT04924660?term=fostamatinib&cond=COVID-19&draw=2&rank=4
  • Ruggeri M, Tosetto A, Palandri F, et al. Thrombotic risk in patients with primary immune thrombocytopenia is only mildly increased and explained by personal and treatment-related risk factors. J Thromb Haemost. 2014;12(8):1266–73. doi: 10.1111/jth.12636