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Heritable Thrombophilia-Hypofibrinolysis and Osteonecrosis of the Femoral Head
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Symposium: Molecular and Surgical Advances in Osteonecrosis
Heritable Thrombophilia-Hypofibrinolysis and Osteonecrosis of the Femoral Head
Charles J. Glueck1 , Richard A. Freiberg2 and Ping Wang1
| (1) |
Cholesterol Center, Jewish Hospital, ABC Building, 3200 Burnet Avenue, Cincinnati, OH 45229, USA |
| (2) |
Cincinnati Veteran’s Administration Hospital, Cincinnati, OH, USA |
Received: 3 April 2007 Accepted: 18 January 2008 Published online: 19 March 2008
Abstract We hypothesized that inherited thrombophilia and hypofibrinolysis were risk factors for osteonecrosis of the femoral head.
We compared measures of thrombophilia and hypofibrinolysis in referred new adult patients with idiopathic osteonecrosis (n = 71)
or secondary osteonecrosis (n = 62) with the same measures in sex- and race-matched healthy control subjects. Heritable thrombophilic
Factor VIII and hypofibrinolytic Lp(a) were more frequently high in the 71 patients with idiopathic osteonecrosis than in
control subjects. High Factor VIII, Factor V Leiden heterozygosity, and resistance to activated protein C, all heritable thrombophilias,
were more frequently present in the 62 patients with secondary osteonecrosis than in control subjects. Our data suggest inherited
thrombophilia and hypofibrinolysis are risk factors for both idiopathic and secondary osteonecrosis of the head of the femur.
Level of Evidence: Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
One or more of the authors (CJG) has received funding from the Jewish Hospital Medical Research Council.
Each author certifies that his or her institution has approved the human protocol for this investigation, that all investigations
were conducted in conformity with ethical principles of research, and that informed consent was obtained.
References
| 1. |
Aksoy MC, Aksoy DY, Haznedaroglu IC, Sayinalp N, Kirazli S, Alpaslan M. Enhanced tissue factor pathway inhibitor response
as a defense mechanism against ongoing local microvascular events of Legg-Calve-Perthes disease. Pediatr Hematol Oncol. 2005;22:391–399.
|
| |
| 2. |
Asano T, Takahashi KA, Fujioka M, Inoue S, Okamoto M, Sugioka N, Nishino H, Tanaka T, Hirota Y, Kubo T. ABCB1 C3435T and G2677T/A
polymorphism decreased the risk for steroid-induced osteonecrosis of the femoral head after kidney transplantation. Pharmacogenetics. 2003;13:675–682.
|
| |
| 3. |
Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME. Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum. 2002;32:94–124.
|
| |
| 4. |
Balasa VV, Gruppo RA, Glueck CJ, Stroop D, Becker A, Pillow A, Wang P. The relationship of mutations in the MTHFR, prothrombin,
and PAI-1 genes to plasma levels of homocysteine, prothrombin, and PAI-1 in children and adults. Thromb Haemost. 1999;81:739–744.
|
| |
| 5. |
Balasa VV, Gruppo RA, Glueck CJ, Wang P, Roy DR, Wall EJ, Mehlman CT, Crawford AH. Legg-Calve-Perthes disease and thrombophilia.
J Bone Joint Surg Am. 2004;86:2642–2647.
|
| |
| 6. |
Bank I, Libourel EJ, Middeldorp S, Hamulyak K, van Pampus EC, Koopman MM, Prins MH, van der Meer J, Buller HR. Elevated levels
of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis. J Thromb Haemost. 2005;3:79–84.
|
| |
| 7. |
Berger CE, Kluger R, Urban M, Kowalski J, Haas OA, Engel A. Elevated levels of lipoprotein(a) in familial bone marrow edema
syndrome of the hip. Clin Orthop Relat Res. 2000;377:126–131.
|
| |
| 8. |
Berger CE, Kroner A, Stiegler H, Erdel M, Haas OA, Engel A. Hypofibrinolysis, lipoprotein(a), and plasminogen activator inhibitor.
Clin Orthop Relat Res. 2002;397:342–349.
|
| |
| 9. |
Bjorkman A, Burtscher IM, Svensson PJ, Hillarp A, Besjakov J, Benoni G. Factor V Leiden and the prothrombin 20210A gene mutation
and osteonecrosis of the knee. Arch Orthop Trauma Surg. 2005;125:51–55.
|
| |
| 10. |
Bjorkman A, Svensson PJ, Hillarp A, Burtscher IM, Runow A, Benoni G. Factor V Leiden and prothrombin gene mutation: risk factors
for osteonecrosis of the femoral head in adults. Clin Orthop Relat Res. 2004;425:168–172.
|
| |
| 11. |
Blanche P, Si-Larbi AG, Jouve P. Femoral head necrosis and hyperhomocysteinemia. J Rheumatol. 2001;28:1469.
|
| |
| 12. |
Boss JH, Misselevich I. Osteonecrosis of the femoral head of laboratory animals: the lessons learned from a comparative study
of osteonecrosis in man and experimental animals. Vet Pathol. 2003;40:345–354.
|
| |
| 13. |
Boss JH, Misselevich I, Bejar J, Norman D, Zinman C, Reis DN. Experimentally gained insight-based proposal apropos the treatment
of osteonecrosis of the femoral head. Med Hypotheses. 2004;62:958–965.
|
| |
| 14. |
Celik A, Tekis D, Saglam F, Tunali S, Kabakci N, Ozaksoy D, Manisali M, Ozcan MA, Meral M, Gulay H, Camsari T. Association
of corticosteroids and Factor V, prothrombin, and MTHFR gene mutations with avascular osteonecrosis in renal allograft recipients.
Transplant Proc. 2006;38:512–516.
|
| |
| 15. |
Chao YC, Wang SJ, Chu HC, Chang WK, Hsieh TY. Investigation of alcohol metabolizing enzyme genes in Chinese alcoholics with
avascular necrosis of hip joint, pancreatitis and cirrhosis of the liver. Alcohol Alcohol. 2003;38:431–436.
|
| |
| 16. |
Chen WM, Liu YF, Lin MW, Chen IC, Lin PY, Lin GL, Jou YS, Lin YT, Fann CS, Wu JY, Hsiao KJ, Tsai SF. Autosomal dominant avascular
necrosis of femoral head in two Taiwanese pedigrees and linkage to chromosome 12q13. Am J Hum Genet. 2004;75:310–317.
|
| |
| 17. |
Coca M, Cucuianu M, Hancu N. Effect of abdominal obesity on prothrombotic tendency in type 2 diabetes. Behavior of clotting
Factors VII and VIII, fibrinogen and von Willebrand factor. Rom J Intern Med. 2005;43:115–126.
|
| |
| 18. |
Coogan PG, Urbaniak JR. Multicenter experience with free vascularized fibular grafts for osteonecrosis of the femoral head.
In: Urbaniak JR, Jones JP Jr, eds. Osteonecrosis: Etiology, Diagnosis, and Treatment. Rosemont, IL: American Academy of Orthopedic Surgeons; 1997:327–352.
|
| |
| 19. |
Eldridge J, Dilley A, Austin H, El-Jamil M, Wolstein L, Doris J, Hooper WC, Meehan PL, Evatt B. The role of protein C, protein
S, and resistance to activated protein C in Legg-Perthes disease. Pediatrics. 2001;107:1329–1334.
|
| |
| 20. |
Ficat P. Cortisone associated necrosis of bone. In: Hungerford D, ed. Ischemia and Necrosis of Bone. Baltimore, MD: Williams & Wilkins; 1980:171–176.
|
| |
| 21. |
Garino JP, Steinberg ME. Total hip arthroplasty in patients with avascular necrosis of the femoral head: a 2- to 10-year follow-up.
Clin Orthop Relat Res. 1997;334:108–115.
|
| |
| 22. |
Glueck CJ, Brandt G, Gruppo R, Crawford A, Roy D, Tracy T, Stroop D, Wang P, Becker A. Resistance to activated protein C and
Legg-Perthes disease. Clin Orthop Relat Res. 1997;338:139–152.
|
| |
| 23. |
Glueck CJ, Crawford A, Roy D, Freiberg R, Glueck H, Stroop D. Association of antithrombotic factor deficiencies and hypofibrinolysis
with Legg-Perthes disease. J Bone Joint Surg Am. 1996;78:3–13.
|
| |
| 24. |
Glueck CJ, Fontaine RN, Gruppo R, Stroop D, Sieve-Smith L, Tracy T, Wang P. The plasminogen activator inhibitor-1 gene, hypofibrinolysis,
and osteonecrosis. Clin Orthop Relat Res. 1999;366:133–146.
|
| |
| 25. |
Glueck CJ, Freiberg R, Glueck HI, Tracy T, Stroop D, Wang Y. Idiopathic osteonecrosis, hypofibrinolysis, high plasminogen
activator inhibitor, high lipoprotein(a), and therapy with Stanozolol. Am J Hematol. 1995;48:213–220.
|
| |
| 26. |
Glueck CJ, Freiberg R, Oghene J, Fontaine RN, Wang P. Association between the T-786C eNOS polymorphism and idiopathic osteonecrosis
of the head of the femur. J Bone Joint Surg Am. 2007;89:1–26.
|
| |
| 27. |
Glueck CJ, Freiberg R, Tracy T, Stroop D, Wang P. Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis.
Clin Orthop Relat Res. 1997;334:43–56.
|
| |
| 28. |
Glueck CJ, Freiberg RA, Crawford A, Gruppo R, Roy D, Tracy T, Sieve-Smith L, Wang P. Secondhand smoke, hypofibrinolysis, and
Legg-Perthes disease. Clin Orthop Relat Res. 1998;352:159–167.
|
| |
| 29. |
Glueck CJ, Freiberg RA, Fontaine RN, Sieve-Smith L, Wang P. Anticoagulant therapy for osteonecrosis associated with heritable
hypofibrinolysis and thrombophilia. Exp Opin Investig Drugs. 2001;10:1309–1316.
|
| |
| 30. |
Glueck CJ, Freiberg RA, Fontaine RN, Tracy T, Wang P. Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop Relat Res. 2001;386:19–33.
|
| |
| 31. |
Glueck CJ, Freiberg RA, Sieve L, Wang P. Enoxaparin prevents progression of stages I and II osteonecrosis of the hip. Clin Orthop Relat Res. 2005;435:164–170.
|
| |
| 32. |
Glueck CJ, Freiberg RA, Wang P. Role of thrombosis in osteonecrosis. Curr Hematol Rep. 2003;2:417–422.
|
| |
| 33. |
Glueck CJ, Glueck HI, Greenfield D, Freiberg R, Kahn A, Hamer T, Stroop D, Tracy T. Protein C and S deficiency, thrombophilia,
and hypofibrinolysis: pathophysiologic causes of Legg-Perthes disease. Pediatr Res. 1994;35:383–388.
|
| |
| 34. |
Glueck CJ, Glueck HI, Mieczkowski L, Tracy T, Speirs J, Stroop D. Familial high plasminogen activator inhibitor with hypofibrinolysis,
a new pathophysiologic cause of osteonecrosis? Thromb Haemost. 1993;69:460–465.
|
| |
| 35. |
Glueck CJ, Iyengar S, Goldenberg N, Smith LS, Wang P. Idiopathic intracranial hypertension: associations with coagulation
disorders and polycystic-ovary syndrome. J Lab Clin Med. 2003;142:35–45.
|
| |
| 36. |
Glueck CJ, McMahon RE, Bouquot JE, Triplett D. Exogenous estrogen may exacerbate thrombophilia, impair bone healing and contribute
to development of chronic facial pain. Cranio. 1998;16:143–153.
|
| |
| 37. |
Glueck CJ, McMahon RE, Bouquot JE, Triplett D, Gruppo R, Wang P. Heterozygosity for the Leiden mutation of the Factor V gene,
a common pathoetiology for osteonecrosis of the jaw, with thrombophilia augmented by exogenous estrogens. J Lab Clin Med. 1997;130:540–543.
|
| |
| 38. |
Glueck CJ, Munjal J, Aregawi D, Agloria M, Winiarska M, Khalil Q, Wang P. Thrombophilia-hypofibrinolysis and atherothrombotic
cardiovascular disease <age 45. Transl Res. 2007;150:93–100.
|
| |
| 39. |
Glueck CJ, Phillips HG, Cameron D, Wang P. Estrogen replacement in a protein S deficient patient leads to diarrhea, hyperglucagonemia,
and osteonecrosis. JOP. 2001;2:323–329.
|
| |
| 40. |
Gomes MP, Deitcher SR. Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement
therapy: a clinical review. Arch Intern Med. 2004;164:1965–1976.
|
| |
| 41. |
Gruppo R, Glueck CJ, Wall E, Roy D, Wang P. Legg-Perthes disease in three siblings, two heterozygous and one homozygous for
the Factor V Leiden mutation. J Pediatr. 1998;132:885–888.
|
| |
| 42. |
Hofmann S, Mazieres B. Osteonecrosis: natural course and conservative therapy [in German]. Orthopade. 2000;29:403–410.
|
| |
| 43. |
Jones JP. Risk factors potentially activating intravascular coagulation and causing nontraumatic osteonecrosis. In: Urbaniak
JR, Jones JP Jr, eds. Osteonecrosis: Etiology, Diagnosis, and Treatment. Rosemont, IL: American Academy of Orthopedic Surgeons; 1997:89–97.
|
| |
| 44. |
Jones LC, Mont MA, Le TB, Petri M, Hungerford DS, Wang P, Glueck CJ. Procoagulants and osteonecrosis. J Rheumatol. 2003;30:783.
|
| |
| 45. |
Kamphuisen PW, Eikenboom JC, Vos HL, Pablo R, Sturk A, Bertina RM, Rosendaal FR. Increased levels of Factor VIII and fibrinogen
in patients with venous thrombosis are not caused by acute phase reactions. Thromb Haemost. 1999;81:680–683.
|
| |
| 46. |
Koo KH, Kim R, Cho SH, Song HR, Lee G, Ko GH. Angiography, scintigraphy, intraosseous pressure, and histologic findings in
high-risk osteonecrotic femoral heads with negative magnetic resonance images. Clin Orthop Relat Res. 1994;308:127–138.
|
| |
| 47. |
Koo KH, Kim R, Ko GH, Song HR, Jeong ST, Cho SH. Preventing collapse in early osteonecrosis of the femoral head. A randomised
clinical trial of core decompression. J Bone Joint Surg Br. 1995;77:870–874.
|
| |
| 48. |
Koo KH, Lee JS, Lee YJ, Kim KJ, Yoo JJ, Kim HJ. Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic
femoral head osteonecrosis. J Orthop Res. 2006;24:1722–1728.
|
| |
| 49. |
Korompilias AV, Gilkeson GS, Ortel TL, Seaber AV, Urbaniak JR. Anticardiolipin antibodies and osteonecrosis of the femoral
head. Clin Orthop Relat Res. 1997;345:174–180.
|
| |
| 50. |
Korompilias AV, Ortel TL, Urbaniak JR. Coagulation abnormalities in patients with hip osteonecrosis. Orthop Clin North Am. 2004;35:265–271, vii.
|
| |
| 51. |
Kubo T, Tsuji H, Yamamoto T, Nakahara H, Nakagawa M, Hirasawa Y. Antithrombin III deficiency in a patient with multifocal
osteonecrosis. Clin Orthop Relat Res. 2000;378:306–311.
|
| |
| 52. |
Laroche M. Intraosseous circulation from physiology to disease. Joint Bone Spine. 2002;69:262–269.
|
| |
| 53. |
Lavigne G, Mercier E, Quere I, Dauzat M, Gris JC. Thrombophilic families with inheritably associated high levels of coagulation
Factors VIII, IX and XI. J Thromb Haemost. 2003;1:2134–2139.
|
| |
| 54. |
Legnani C, Cini M, Cosmi B, Poggi M, Boggian O, Palareti G. Risk of deep vein thrombosis: interaction between oral contraceptives
and high Factor VIII levels. Haematologica. 2004;89:1347–1351.
|
| |
| 55. |
Li YZ, Yue T. Intraosseous pressure measurement and bone marrow venography in idiopathic necrosis of femoral head [in Chinese].
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1989;11:338–343.
|
| |
| 56. |
Lieberman JR. Core decompression for osteonecrosis of the hip. Clin Orthop Relat Res. 2004;418:29–33.
|
| |
| 57. |
Liu SL, Ho TC. The role of venous hypertension in the pathogenesis of Legg-Perthes disease. A clinical and experimental study.
J Bone Joint Surg Am. 1991;73:194–200.
|
| |
| 58. |
McKee MD, Waddell JP, Kudo PA, Schemitsch EH, Richards RR. Osteonecrosis of the femoral head in men following short-course
corticosteroid therapy: a report of 15 cases. CMAJ. 2001;164:205–206.
|
| |
| 59. |
Mont MA, Glueck CJ, Pacheco IH, Wang P, Hungerford DS, Petri M. Risk factors for osteonecrosis in systemic lupus erythematosus.
J Rheumatol. 1997;24:654–662.
|
| |
| 60. |
Mont MA, Jones LC, Rajadhyaksha AD, Shuler MS, Hungerford DS, Sieve-Smith L, Wang P, Cordista AG, Glueck CJ. Risk factors
for pulmonary emboli after total hip or knee arthroplasty. Clin Orthop Relat Res. 2004;422:154–163.
|
| |
| 61. |
Montella BJ, Nunley JA, Urbaniak JR. Osteonecrosis of the femoral head associated with pregnancy. A preliminary report. J Bone Joint Surg Am. 1999;81:790–798.
|
| |
| 62. |
Nilsson IM, Krook H, Sternby NH, Soderberg E, Soderstrom N. Severe thrombotic disease in a young man with bone marrow and
skeletal changes and with a high content of an inhibitor in the fibrinolytic system. Acta Med Scand. 1961;169:323–337.
|
| |
| 63. |
Norman D, Miller Y, Sabo E, Misselevich I, Peskin B, Zinman C, Levin D, Reis DN, Boss JH. The effects of enoxaparin on the
reparative processes in experimental osteonecrosis of the femoral head of the rat. APMIS. 2002;110:221–228.
|
| |
| 64. |
Petersen NH, Schmied AB, Zeller JA, Plendl H, Deuschl G, Zunker P. Lp(a) lipoprotein and plasminogen activity in patients
with different etiology of ischemic stroke. Cerebrovasc Dis. 2007;23:188–193.
|
| |
| 65. |
Pierre-Jacques H, Glueck CJ, Mont MA, Hungerford DS. Familial heterozygous protein-S deficiency in a patient who had multifocal
osteonecrosis. A case report. J Bone Joint Surg Am. 1997;79:1079–1084.
|
| |
| 66. |
Posan E, Szepesi K, Gaspar L, Csernatony Z, Harsfalvi J, Ajzner E, Toth A, Udvardy M. Thrombotic and fibrinolytic alterations
in the aseptic necrosis of femoral head. Blood Coagul Fibrinolysis. 2003;14:243–248.
|
| |
| 67. |
Research Committee of the British Thoracic Society. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary
embolism. Lancet. 1992;340:873–876.
|
| |
| 68. |
Salvati EA, Della Valle AG, Westrich GH, Rana AJ, Specht L, Weksler BB, Wang P, Glueck CJ. The John Charnley Award: heritable
thrombophilia and development of thromboembolic disease after total hip arthroplasty. Clin Orthop Relat Res. 2005;441:40–55.
|
| |
| 69. |
Schambeck CM, Hinney K, Haubitz I, Mansouri Taleghani B, Wahler D, Keller F. Familial clustering of high Factor VIII levels
in patients with venous thromboembolism. Arterioscler Thromb Vasc Biol. 2001;21:289–292.
|
| |
| 70. |
Stulberg BN, Davis AW, Bauer TW, Levine M, Easley K. Osteonecrosis of the femoral head. A prospective randomized treatment
protocol. Clin Orthop Relat Res. 1991;268:140–151.
|
| |
| 71. |
Sun W, Li ZR, Shi ZC, Zhang NF, Zhang YC. Changes in coagulation and fibrinolysis of post-SARS osteonecrosis in a Chinese
population. Int Orthop. 2006;30:143–146.
|
| |
| 72. |
Szepesi K, Posan E, Harsfalvi J, Ajzner E, Szucs G, Gaspar L, Csernatony Z, Udvardy M. The most severe forms of Perthes’ disease
associated with the homozygous Factor V Leiden mutation. J Bone Joint Surg Br. 2004;86:426–429.
|
| |
| 73. |
Tao SN. Hemodynamics changes in proximal femur of patients with femoral head necrosis [in Chinese]. Zhonghua Wai Ke Za Zhi. 1991;29:452–454, 464.
|
| |
| 74. |
Tosetto A, Castaman G, Cappellari A, Rodeghiero F. The VITA Project: heritability of resistance to activated protein C. Vincenza
Thrombophilia and Arteriosclerosis. Thromb Haemost. 2000;84:811–814.
|
| |
| 75. |
Tripodi A. Issues concerning the laboratory investigation of inherited thrombophilia. Mol Diagn. 2005;9:181–186.
|
| |
| 76. |
Van Veldhuizen PJ, Neff J, Murphey MD, Bodensteiner D, Skikne BS. Decreased fibrinolytic potential in patients with idiopathic
avascular necrosis and transient osteoporosis of the hip. Am J Hematol. 1993;44:243–248.
|
| |
| 77. |
Wahlander K, Larson G, Lindahl TL, Andersson C, Frison L, Gustafsson D, Bylock A, Eriksson BI. Factor V Leiden (G1691A) and
prothrombin gene G20210A mutations as potential risk factors for venous thromboembolism after total hip or total knee replacement
surgery. Thromb Haemost. 2002;87:580–585.
|
| |
| 78. |
Westrich GH, Weksler BB, Glueck CJ, Blumenthal BF, Salvati EA. Correlation of thrombophilia and hypofibrinolysis with pulmonary
embolism following total hip arthroplasty: an analysis of genetic factors. J Bone Joint Surg Am. 2002;84:2161–2167.
|
| |
| 79. |
Zalavras C, Dailiana Z, Elisaf M, Bairaktari E, Vlachogiannopoulos P, Katsaraki A, Malizos KN. Potential aetiological factors
concerning the development of osteonecrosis of the femoral head. Eur J Clin Invest. 2000;30:215–221.
|
| |
| 80. |
Zalavras CG, Vartholomatos G, Dokou E, Malizos KN. Genetic background of osteonecrosis: associated with thrombophilic mutations?
Clin Orthop Relat Res. 2004;422:251–255.
|
| |
|
|
|
|
|
|