PATHOGENESIS/PATHOPHYSIOLOGY

THE STUDY ON PRETHROMBOTIC STATE OF NONTRAUMATIC OSTEONECROSIS OF THE FEMORAL HEAD

Zheng Zhaomin, MD, PhD, Lu Xuhua.MD, Zhang Shuhui, MD
Department of Orthopedic Surgery. the Second Affiliated Hospital, Henan Medical University
Zheng Zhou,450003,PR China
Dong Tianghua.MD, Huang Lixin, MD.PhD,
Department of Orthopedic Surgery. the First Affiliated Hospital,
Suzhou Medical College, Suzhou, PR China

Introduction: Nontraumatic osteonecrosis of the femoral head is a common disease of young people or middle-aged which is difficult to be treated. With its high disabling rate, nontraumatic osteonecrosis of the femoral head severely affects the patient's health. Epidemiologic studies have revealed associations between osteonecrosis and a multitude of factors, but the exact mechanism is uncertain now. The theory of intravascular coagulation considers that intravascular coagulation as an intermediary event is the most likely final common pathway producing intraosseous thrombosis, intramedullary hemorrhage and bone necrosis. The aim of study based on an animal experiments is to reveal the existing of prethrombotic state at all stages of NONFH. The study will be helpful to find the hematology proof of IC theory. Meanwhile, the sensitive molecular symbols are selected for the diagnosis of early stage and the distinction of people with high risks. The similar study has not been reported in China. The objects of this study are: 1.to observe the changes of platelet GMP-140 concentration in patients with NONFH and to explore the role of the activity of platelet or hypercoagulable tendency in the pathogenesis of NONFH; 2. to observe the changes of plasma PC concentration in patients with NONFH and to evaluate the role of anti-coagulation proteins in the pathogenesis of NONFH; 3. to observe the changes of plasma PAI and D-Dimer level and to analyze the change of the activity of fibrinolysis and vascular endothelial cell injury; 4. to explore the probable mechanism of NONFH by analyzing the relation between GMP-140, PC, PAI and D-Dimer so as to found the proof for IC; 5. to form discriminant functions by selecting sensitive molecular symbols and to evaluate the reliance of these functions.

Mateial and Method: The study subjects were divided into three groups: 1. NONFH early stage group (n=30); 2. NONFH late stage group (n=30); 3. the normal control group(n=30). The diagnosis of NONFH was based on clinical symptoms combined with MRI, ECT and X-ray film. Blood samples from elbow veius were collected. GMP-140, PC, D-Dimer were examined with use of ELISA. PAI was examined with chromogenic assay.

Results: 1. The ptatelet GMP-140 levels of early or late stage groups NONFH (11739;A2485 moleculars/platelet, 14179;A2887 moleculars/platelet, respectively) was significantly higher than that of the control group (8481;Al109 moleculars/platelet, both P<0.05)The severer the NONFH, the higher the platelet GMP-140 level ,there were significant differences in the platelet GMP-140 level among two groups(P<0.05); 2. The plasma PC levels of both NONFH early stage and late stage group (4.79; A0.88µg/ml, 3.81; A0.98µg/ml, respectively) were significantly lower than that of the control group(6.61; Al.17µg/ml,both P<0.05).The worse the osteonecrosis, the lower the plasma PC concentration ,there was significant difference between the NONFH early stage and late stage (P<0.05); 3. The plasma PAI activity of NONFH early stage, late stage group (0.50; A0.10AU/ml, 0.87;A0.15AU/ml, respectively)increased significantly as compared with the control group (0.31; A0.05AU/ml, both P<0.05).The worse the osteonecrosis, the higher the PAI activity, there was significant difference in the plasma PAI activity between NONFH early and late stage group(P<0.05); 4. The plasma D-Dimer concentrations of NONFH early stage, late stage group (197.50; A63.99µg/L,460.47; A113.64µg/L, respectively) were significantly higher than that of the control group (118.43; A22.28µg/L, both P<0.05),The worse the osteonecrosis, the higher the D-Dimer concentration, there was significant difference between NONFH early stage and late stage group, (P<0.05); 5. At NONFH early stage, there was a significant positive correlation between the level of platelet GMP-140 and plasma PAI activity or plasma D-Dimer level (r=0.35 or 0.60, P<0.05 or <0.001). 6. Three types discriminant functions of NONFH early stage, late stage and normal control were set up by PAI, D-Dimer, PC which were discriminanted. The functions' efficiency is 97.78%.

Conclusion: 1. The platelet GMP-140 concentration was increased in patients with NONFH. The worse the osteonecrosis, the higher the platelet GMP-140 concentration. NONFH patients have the tendency of hypercoagulability: 2. The plasma PC level was decreased in patients with NONFH. The hereditary deficiencies of the natural anticoagulant mechanism implies venous thrombosis: 3. The plasma PAI activity was increased in patients with NONFH which implies hypofibrinolysis; 4. The plasma D-Dimer level was increased in patient with NONFH. This means that the tendency of coagulability is at all stage of NONFH and secondary fibrinolysis with reperfusion injury may exist; 5. Three types discriminant functions of NONFH early stage, NONFH late stage and normal control were set up based on PAI. D-Dimer and PC which were sensitive molecular symbols of prethrombotic state in patients with NONFH. The method is easy, economic, non-invasive and efficient for the diagnosis of early stage of NONFH.

Key words: femoral head osteonecrosis, nontraumatic prethrombotic state discriminant analysis.