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Osteoarthritis, a degenerative disease of the joints, is the most common form of arthritis in the knee. Total joint arthoplasty is a commonly used treatment for joint degeneration and osteoarthritis, and due to these factors, TJA for hip and knee joints is projected to grow by 137% and 601% between 2005 and 2030. Matrix metalloproteases are enzymes found in the extracellular matrix that cleave matrix components. Normally MMPs are downregulated in tissues by Tissue Inhibitors of Metalloproteases, or TIMPs. The relative concentration of TIMPs also may denote some of the activity of the MMPs found in serum. Lubricin (proteoglycan 4) is a molecule found in the synovial fluid that protects joints by dissipating strain energy during locomotion. Lubricin synovial fluid concentration is also diminished in many patients with osteoarthritis, but not all. Given the importance of these three sets of molecules, our lab investigated the correlation between circulating lubricin, MMP levels and TIMPs levels. Blood plasma samples were obtained from de-identified subjects undergoing total joint arthroplasty at Loyola University Medical Center and the University of Utah. Normal blood plasma from pooled healthy individuals served as a control. We analyzed biomarker levels in plasma using ELISA. Our data show that MMP-1 and 9 were increased in TJA patients compared to normal controls, while MMP-2 and 13 were decreased. We also found decreased lubricin and tissue factor in surgical patients relative to controls. These data support the idea that lubricin is vital in protecting the synovial joint and that MMPs play a complex role in the destruction of the joint.

Background: Total joint arthroplasty (TJA) patients are mostly of advanced age and with comorbidities such as increased body mass index (BMI) and impaired glucose tolerance. These factors and type of surgery may affect the fibrinolytic system. Aim: To investigate the effect of age, sex, BMI, type of surgery, and tranexamic acid (TXA) treatment on the fibrinolytic system in TJA patients. Methods: Ninety-nine patients undergoing TJA (32 total hip arthroplasty [THA] and 67 total knee arthroplasty [TKA]) were included in this study. Blood samples were drawn at preoperative clinic appointments and on postoperative day 1. Antigenic levels of d-dimer, plasminogen activator inhibitor 1 (PAI-1), and tissue plasminogen activator (tPA) were measured using a commercially available enzyme-linked immunosorbent assay kit. Antiplasmin activity was measured using functional method. Age, gender, hemoglobin (Hb) levels, and BMI were collected from the records. Results: Preoperative d-dimer and tPA levels were positively correlated with age, whereas preoperative antiplasmin was negatively correlated with age. Body mass index was only associated with preoperative tPA levels. There was no significant difference in postoperative levels of d-dimer, PAI-1, tPA, or antiplasmin between patients treated with TXA or without TXA. Percentage change in d-dimer and tPA showed significantly lower values in patients treated with TXA compared to the nontreated group. Type of surgery did not affect the fibrinolytic markers. Conclusion: These results confirm that advanced age and elevated BMI positively contribute to fibrinolytic dysregulation in TJA patients, whereas TXA seems to decrease the fibrinolytic activity.

Background: The alterations of the fibrinolytic components in osteoarthritic joint disease and their postsurgical modulation are not clearly understood. Preexisting hemostatic dysfunction may lead to both thrombotic and bleeding events in these patients. Aim: To profile fibrinolytic parameters in patients undergoing total joint arthroplasty prior to and on postoperative day 1. Methods: A total of 98 total joint arthroplasty patients were included in this study. Blood samples were drawn preoperatively and on postoperative day 1 status posttotal knee or total hip arthroplasty surgery. d-Dimer, plasminogen activator inhibitor 1 (PAI-1), and tissue plasminogen activator (tPA) were measured using commercially available enzyme-linked immunosorbent assay kits. Antiplasmin activity was measured by using a functional method. Results: Preoperative PAI-1, d-dimer, and tPA levels were significantly higher in arthroplasty patients compared to healthy controls. Preoperative antiplasmin level was lower than controls. Postoperative levels of PAI-1 and d-dimer were increased compared to preoperative values. Postoperative antiplasmin values were lower than preoperative levels. Changes in tPA was not significant. There was no correlation between preoperative PAI-1 and d-dimer levels. Pre- and postoperative percentage changes in each individual were calculated for PAI-1, d-dimer, tPA, and antiplasmin. There was a positive correlation between d-dimer and PAI-1. Negative correlations between antiplasmin and d-dimer and between antiplasmin and PAI-1 were noted. Conclusion: These results confirm the perturbation in the fibrinolytic system of patients undergoing total joint arthroplasty surgery. Surgical intervention may also enhance the observed changes. The alterations in the fibrinolytic system may lead to the observed hemostatic complications such as bleeding, hematoma formation, or potential need for blood transfusion.