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Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis
C J Glueck1, R Freiberg, T Tracy
1Cholesterol Center, Jewish Hospital, Cincinnati, OH 45229, USA.
Insights
Coagulation disorders like thrombophilia and hypofibrinolysis are common in osteonecrosis patients. These blood clotting issues may cause hip osteonecrosis by blocking blood flow in the femur.
Area of Science:
- Hematology
- Orthopedics
- Vascular Biology
Background:
- Osteonecrosis, particularly of the hip, affects numerous patients.
- A significant portion of osteonecrosis cases are initially classified as idiopathic.
- Known risk factors include glucocorticoid use, alcoholism, and sickle cell disease.
Purpose of the Study:
- To investigate the prevalence of primary coagulation disorders in patients with osteonecrosis.
- To determine the association between specific coagulation defects and the etiology of osteonecrosis (idiopathic vs. secondary).
- To explore the potential role of thrombophilia and hypofibrinolysis in the pathogenesis of osteonecrosis.
Main Methods:
- Patient cohort: 31 individuals with osteonecrosis (primarily hip).
- Coagulation assessment: Evaluation for thrombophilia (e.g., resistance to activated protein C, low protein C) and hypofibrinolysis (e.g., high lipoprotein(a), low tissue plasminogen activator activity).
- Comparative analysis: Comparison of coagulation factor prevalence between patients and healthy controls.
Main Results:
- 74% of osteonecrosis patients exhibited one or more primary coagulation disorders.
- In idiopathic osteonecrosis (18 patients), 83% had coagulation disorders, with hypofibrinolysis being most common (50%).
- In secondary osteonecrosis (13 patients), 62% had coagulation disorders, with hypofibrinolysis also prevalent (30%).
- Specific defects like resistance to activated protein C and high lipoprotein(a) were more frequent in patients than controls.
Conclusions:
- Primary thrombophilia or hypofibrinolysis may cause osteonecrosis through venous occlusion and subsequent bone death.
- Coagulation disorders are significantly associated with both idiopathic and secondary osteonecrosis.
- Further research is warranted to elucidate the causal link between these clotting abnormalities and osteonecrosis development.
Abstract:
In 31 patients with osteonecrosis (primarily of the hip), 74% had 1 or more primary coagulation disorders. In 18 patients, 15 (83%) who had coagulation disorders, the osteonecrosis was initially identified as idiopathic and was not associated with known underlying drugs (glucocorticoids) or diseases (alcoholism, sickle cell disease, Gaucher's disease). In 13 patients, 8 (62 %) who had coagulation disorders, the osteonecrosis was initially identified as secondary, and was associated with glucocorticoids in 12 patients, and with alcoholism in 1. The coagulation disorders included thrombhophilia (increased tendency to intravascular thrombosis) and hypofibrinolysis (reduced ability to lyse thrombi). Of the 18 patients initially thought to have idiopathic osteonecrosis, thrombophilia alone was found in 12% (resistance to activated protein C in 6%, low protein C in 6%), hypofibrinolysis alone was found in 50% (high lipoprotein(a) in 44%, low stimulated tissue plasminogen activator activity was found in 6%), and mixed thrombophilia hypofibrinolysis was found in 22%. Resistance to activated protein C was more common in these 18 patients than in healthy controls (11% versus 0%), as was high lipoprotein(a) (67% versus 20%). Of the 13 patients with secondary osteonecrosis, thrombophilia alone was found in 8% (low protein C), hypofibrinolysis alone was found in 30% (high Lp(a) in 15%, low tissue plasminogen activator activity in 15%), and mixed thrombophilia hypofibrinolysis was found in 23%. Low tissue plasminogen activator activity was more common in the 13 patients with secondary osteonecrosis than in controls (27% versus 7%), as was low protein C (23% versus 0%). In aggregate, these findings lead us to the speculation that primary, heritable thrombophilia or hypofibrinolysis causes thrombotic venous occlusion in the head of the femur, leading to venous hypertension and hypoxic death of bone (osteonecrosis).