Тромбоз, гемостаз и реология

Tromboz, Gemostaz I Reologiya
scientific and practical journal

ISSN 2078–1008 (Print); ISSN 2687-1483 (online)
2026, Review
2026

Hemostasis disorders in the pathogenesis of femoral head avascular necrosis (review)

Review
Nadezda A. Vorobyeva
Northern State Medical University, Ministry of Health of the Russian Federation; 51 Troitsky Avenue, Arkhangelsk 163000, Russia
Svetlana V. Bragina
Northern State Medical University, Ministry of Health of the Russian Federation; 51 Troitsky Avenue, Arkhangelsk 163000, Russia
Uliana A. Menshikova
Northern State Medical University, Ministry of Health of the Russian Federation; 51 Troitsky Avenue, Arkhangelsk 163000, Russia
Anna R. Vasenkova
Northern State Medical University, Ministry of Health of the Russian Federation; 51 Troitsky Avenue, Arkhangelsk 163000, Russia
Ksenia G. Trufanova
Northern State Medical University, Ministry of Health of the Russian Federation; 51 Troitsky Avenue, Arkhangelsk 163000, Russia

Keywords

femoral head avascular/aseptic necrosis
FHAN
osteonecrosis
coagulopathy
hypercoagulation
hypofibrinolysis
  Full Text

Abstract

Summary. Femoral head avascular necrosis (FHAN) is a serious disease that leads to irreversible loss of joint function, mainly affecting young and middle-aged individuals. Despite the recognized multifactorial etiology, the contribution of hemostasis disorders to its non-traumatic forms has long remained understudied. The authors used data from open electronic databases of PubMed/MEDLINE, ScienceDirect, CyberLeninka, and eLibrary to analyze information and identify relevant publications on the role of hereditary and acquired coagulopathies in FHAN development. Following a comprehensive review and analysis of the literature published between 2002 and 2025, the evidence indicates that a key pathogenic mechanism involves dysregulation among the coagulation, anticoagulation, and fibrinolytic systems. Hypercoagulation driven by hereditary factors such as factor V Leiden mutation and hypofibrinolysis associated with a decrease in tissue plasminogen activator (tPA) and an increase in its inhibitor — plasminogen activator inhibitor-1 (PAI-1) promotes microvascular thrombosis and ischemic bone damage. Special attention is paid to the iatrogenic glucocorticosteroids effects, which induce persistent hypercoagulation through endothelial dysfunction and inhibition of fibrinolysis. A high incidence of hemostasis disorders has been confirmed in patients with FHAN, including cases associated with COVID-19. Thus, shifting the focus of understanding the FHAN etiology toward systemic hemostasis disorders justifies the need for targeted screening of at-risk patients for hypercoagulability and hypofibrinolysis. Identified hemostasis disorders, as part of the FHAN etiopathogenesis, may provide the opportunity for targeted therapy to slow or halt the progression of this debilitating disease.

For citation: Vorobyeva N.A., Bragina S.V., Menshikova U.A., Vasenkova A.R., Trufanova K.G. Hemostasis disorders in the pathogenesis of femoral head avascular necrosis (review). Tromboz, gemostaz i reologiya. 2026;(2):14–20. (In Russ.).

References 

1.      Mustafin R.N., Khusnutdinova E.K. Avascular necrosis of the femoral head. Tikhookeanskiy meditsinskiy zhurnal. 2017;(1):27–35. (In Russ.). DOI: 10.17238/PmJ1609-1175.2017.1.27-35.

2.      Khan B., Gowda S.N., Kaur H. et al. Role of anticoagulation with apixaban in left ventricular thrombus: A systematic review and meta-analysis. Cardiovasc Revasc Med. 2023;46:70–8. DOI: 10.1016/j. carrev.2022.09.013.

3.      Parakhin I.V., Parshikov M.V., Guryev V.V., Jarigin N.V. Method for minimally invasive multiple tunnelization of the femoral head in case of its aseptic necrosis. Vestnik travmatologii i ortopedii imeni N.N. Priorova. 2025;32(1):211–20. (In Russ.). DOI: 10.17816/vto632509.

4.      Slepchenko K. V., Aksyonov A. V., Cherniakova Yu.M., ZenchenkoA.V.Avascular necrosis of the both femoral heads complicated by septic arthritis of hip joints. Problemy zdorov’ya i ekologii. 2025;22(3):144–52. (In Russ.). DOI: 10.51523/2708-6011.202522-3-15.

5.      Odarchenko D.I., Dzyuba G.G., Erofeev S.A., Kuznetsov N.K. Problems of diagnosis and treatment of aseptic necrosis of the femoral head in contemporary traumatology and orthopedics (literature review). Genij ortopedii. 2021;27(2):270–6. (In Russ.). DOI 10.18019/1028–4427–2021–27–2–270–276.

  1. Torgashin A.N., Rodionova S.S., Shumskiy A.A. et al. Treatment of aseptic necrosis of the femoral head. Clinical guidelines. Nauchnoprakticheskaya revmatologiya. 2020;58(6):637–45. (In Russ.). DOI: 10. 47360/1995-4484-2020-637-645.
  2. Panin M.A., Zagorodniy N.V., Boiko A.V., Petrosyan A.S. Efficacy of necrosis decompression techniques in the treatment of early stages of avascular necrosis of the femoral head. Vestnik travmatologii i ortopedii imeni N.N. Priorova. 2022;29(1):57–64. (In Russ.). DOI: 10.17816/vto100047.
  3. Bialik V.E., Makarov M.A., Byalik E.I. et al. Avascular necrosis of bone tissue: Definition, epidemiology, types, risk factors, pathogenesis of the disease. Analytical review of the literature. Nauchnoprakticheskaya revmatologiya. 2023;61(2):220–35. (In Russ.). DOI: 10.47360/1995-4484-2023-220-235.
  4. Adachi J.D., Olszynski W.P., Hanley D.A. et al. Management of corticosteroid-induced osteoporosis. Semin Arthritis Rheum. 2000;29(4):228–51. DOI: 10.1016/s0049-0172(00)80011-6.
  5. Pouya F., Kerachian M.A. Avascular necrosis of the femoral head: Are any genes involved? Arch Bone Jt Surg. 2015;3(3):149–55.
  6. Guan X.-Y., Han D. Role of hypercoagulability in steroid-induced femoral head necrosis in rabbits. J Orthop Sci. 2010;15(3):365–70. DOI: 10.1007/s00776-010-1452-6.
  7. Aldridge J.M., Urbaniak J.R. Avascular necrosis of the femoral head: etiology, pathophysiology, classification, and current treatment guidelines. Am J Orthop (Belle Mead NJ). 2004;33(7):327–32.
  8. Bejar J., Peled E., Boss J.H. Vasculature deprivation — induced osteonecrosis of the rat femoral head as a model for therapeutic trials. Theor Biol Med Model. 2005;2:24. DOI: 10.1186/1742-4682-2-24.
  9. Bushueva N.A., Vorobyeva N.A. Physiology and pathophysiology of the hemostatic system in athletes (review). Vestnik Severnogo (Arkticheskogo) federal’nogo universiteta. Seriya: medikobiologicheskie nauki. 2015;(2):62–70. (In Russ.). DOI: 10.17238/ issn2308-3174.2015.2.62.
  10. Mirzamuradova M.A., Boboeva Z.N. Violations of the rheological properties of blood during the development of chronic diseases. Eurasian Journal of Academic Research. 2024;4(5 Part 3):20–4. (In Russ.). DOI: 10.5281/zenodo.11394215.
  11. Rezus E., Tamba B.I., Badescu M.C. et al. Osteonecrosis of the femoral head in patients with hypercoagulability — from pathophysiology to therapeutic implications. Int J Mol Sci. 2021;22(13):6801. DOI: 10.3390/ijms22136801.
  12. Drescher W., Weigert K.P., Bünger M.H. et al. Femoral head blood flow reduction and hypercoagulability under 24 h megadose steroid treatment in pigs. J Orthop Res. 2004;22(3):501–8. DOI: 10.1016/j. orthres.2003.10.002.
  13. Vaganov A.A., Taranushenko T.E., Luzan N.A. et al. Aptamers regulating the hemostasis system. Molecules. 2022;27(23):8593. DOI: 10.3390/molecules27238593.
  14. Singh M., Singh B., Sharma K. et al. Molecular troika of angiogenesis, coagulopathy and endothelial dysfunction in the pathology of avascular necrosis of femoral head: a comprehensive review. Cells. 2023;12(18):2278. DOI: 10.3390/cells12182278.
  15. Garcia F.L., Junior E.L., Picado C.H. Coagulation disorders in patients with femoral head osteonecrosis. Acta Ortop Bras. 2013;21(1):43–5. DOI: 10.1590/S1413-78522013000100009.
  16. Panin M.A., Zagorodniy N.V., Samokhodskaya L.M., Lipov A.V. The role of the genetic polymorphismof thrombocyte integrins (ITGα2, ITGβ3) in the pathogenesis of non-traumatic aseptic necrosis of the femoral head. Medicinskij vestnik Severnogo Kavkaza. 2020;15(1):84– 7. (In Russ.). DOI: 10.14300/mnnc.2020.15019.
  17. Leo M., Milena F., Ruggero C. Biophysical stimulation in osteonecrosis of the femoral head. Indian J Orthop. 2009;43(1):17–21. DOI: 10.4103/0019-5413.45319.
  18. GlueckC.J., FreibergR.A., BorielG. et al. The role of the factor V Leiden mutation in osteonecrosis of the hip. Clin Appl Thromb Hemost. 2013;19(5):499–503. DOI: 10.1177/1076029612449901.
  19. Goncharova Z.A., Megeryan V.A. Aseptic necrosis of femoral head in patients with multiple sclerosis — a rare complication of glucocorticosteroid treatment. Prakticheskaya medicina. 2014;(2):129– 32. (In Russ.).
  20. Petrov V.M. The effect of alcohol on the nervous, cardiovascular system, metabolism, hemocoagulation, electrolyte metabolism (literature review). Medicina Kyrgyzstana. 2012;(1):20–5. (In Russ.).
  21. Agarwala S.R., Vijayvargiya M., Pandey P. Avascular necrosis as a part of ‘long COVID-19’. BMJ Case Rep. 2021;14(7):e242101. DOI: 10.1136/bcr-2021-242101.
  22. Lee M.S., Chang Y.-H., Chao E.-K., Shih C.-H. et al. Conditions before collapse of the contralateral hip in osteonecrosis of the femoral head. Chang Gung Med J. 2002;25(4):228–37.
  23. Zalavras C., Dailiana Z., Elisaf M. et al. Potential aetiological factors concerning the development of osteonecrosis of the femoral head. Eur J Clin Invest. 2000;30(3):215–21. DOI: 10.1046/j.1365-23 62.2000.00621.x.
  24. Nasonov E.L., Beketova T.V., Reshetnyak T.M. et al. Coronavirus disease 2019 (COVID-19) and immune-mediated inflammatory rheumatic diseases: at the crossroads of thromboinflammation and autoimmunity. Nauchno-prakticheskaya revmatologiya. 2020;58(4):353– 67. (In Russ.). DOI: 10.47360/1995-4484-2020-353-367.
  25. Glukhov A.V., Lapukhin A.O., Gusev S.S. Early diagnosis and treatment of aseptic bone necrosis amid COVID-19 consequences. Mediko-biologicheskie i social’no-psihologicheskie problemy bezopasnosti v chrezvychajnyh situaciyah. 2023;(3):29–37. (In Russ.). DOI: 10.25016/2541-7487-2023-0-3-29-37.
  26. Zuo Y., Zuo M., Yalavarthi S. et al. Neutrophil extracellular traps and thrombosis in COVID-19. J Thromb Thrombolysis. 2021;51(2):446– 53. DOI: 10.1007/s11239-020-02324-z.
  27. Fan B.E., Umapathi T., Chua K. et al. Delayed catastrophic thrombotic events in young and asymptomatic post COVID-19 patients. J Thromb Thrombolysis. 2021;51(4):971–7. DOI: 10.1007/ s11239-020-02332-z.
  28. Bashkova I.B., Madyanov I.V. Multiple non-traumatic osteonecrosis of large joints in a young man, triggered by short-term treatment with glucocorticoids. RMZh. 2016;24(2):125–8. (In Russ.).
  29. Dorris S.L., Peebles R.S. PGI2 as a regulator of inflammatory diseases. Mediators Inflamm. 2012;2012:926968. DOI: 10.1155/2012/ 926968.
  30. Kerachian M.A., Séguin C., Harvey E.J. Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J Steroid Biochem Mol Biol. 2009;114(3–5):121–8. DOI: 10.1016/j.jsbmb.2009.02.007.
  31. Koo K.-H., Kim R., Kim Y.-S. et al. Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment. Clin Rheumatol. 2002;21(4):299–303. DOI: 10.1007/s100670200078.
  32. Mont M., Jones L., Hungerford D. Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am. 2006;88(5):1117– 32. DOI: 10.2106/JBJS.E.01041.
  33. Kubo T., Ueshima K., Saito M. et al. Clinical and basic research on steroid-induced osteonecrosis of the femoral head in Japan. J Orthop Sci. 2016;21(4):407–13. DOI: 10.1016/j.jos.2016.03.008.