Inflammatory Biomarker Profiling in Elderly Patients With Acute Hip Fracture Treated With Heparins

Abstract

Hip fracture is common in the elderly patients with associated high risk of venous thromboembolic complications. Pathogenic activation results in the generation of various surrogate markers in plasma. This study is designed to identify unique biomarkers in elderly patients with hip fracture using protein chip array enzyme-linked immunosorbent assay (ELISA) methods. Plasma from a randomized hip fracture study (PK-532; n = 341) treated with either enoxaparin (40 mg once daily) or unfractionated heparin (UFH; 5000 IU twice daily) were collected prior to and at 1, 3, 5, and 7 days. A total of 52 samples were analyzed using proteomic surface-enhanced laser desorption/ ionization-time of flight (SELDI-TOF) mass spectrometry to identify unique biomarkers in the molecular weight range of 0 to 150 kd. Twenty-nine healthy volunteer's and pooled plasma from total hip replacement/total knee replacement patients with a unique biomarker at 11.9 kd were used as quality controls. In the 29 healthy individuals, the biomarker profile did not reveal the presence of any unique peak in comparison to the reference normal human plasma (NHP). Plasma obtained prior to surgery exhibits unique biomarkers in 4 of 52 (7.6%) of the samples. On day 1 postoperatively, 41 of 51 (80.3%) showed a distinct peak at 11.9 kd. On day 3, 43 of 49 (87.8%) patients showed the presence of this biomarker most often at its strongest intensity. In all, 22 of 44 (50%) showed this biomarker on day 5 and 4 of 23 (17.9%) on day 7. C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), and serum amyloid A were also increased after surgery. Tissue factor pathway inhibitor (TFPI) antigen levels were increased due to the treatment modalities.