RESUMO
PURPOSE: Posterior spinal fusion (PSF) activates the fibrinolytic protease plasmin, which is implicated in blood loss and transfusion. While antifibrinolytic drugs have improved blood loss and reduced transfusion, variable blood loss has been observed in similar PSF procedures treated with the same dose of antifibrinolytics. However, both the cause of this and the appropriate measures to determine antifibrinolytic efficacy during high-blood-loss spine surgery are unknown, making clinical trials to optimize antifibrinolytic dosing in PSF difficult. We hypothesized that patients undergoing PSF respond differently to antifibrinolytic dosing, resulting in variable blood loss, and that specific diagnostic markers of plasmin activity will accurately measure the efficacy of antifibrinolytics in PSF. METHODS: A prospective study of 17 patients undergoing elective PSF with the same dosing regimen of TXA was conducted. Surgery-induced plasmin activity was exhaustively analyzed in perioperative blood samples and correlated to measures of inflammation, bleeding, and transfusion. RESULTS: While markers of in vivo plasmin activation (PAP and D-dimer) suggested significant breakthrough plasmin activation and fibrinolysis (P < 0.01), in vitro plasmin assays, including TEG, did not detect plasmin activation. In vivo measures of breakthrough plasmin activation correlated with blood loss (R2 = 0.400, 0.264; P < 0.01), transfusions (R2 = 0.388; P < 0.01), and complement activation (R2 = 0.346, P < 0.05). CONCLUSIONS: Despite all patients receiving a high dose of TXA, its efficacy among patients was variable, indicated by notable intra-operative plasmin activity. Markers of in vivo plasmin activation best correlated with clinical outcomes. These findings suggest that the efficacy of antifibrinolytic therapy to inhibit plasmin in PSF surgery should be determined by markers of in vivo plasmin activation in future studies. LEVEL OF EVIDENCE: Level II-diagnostic.
Assuntos
Antifibrinolíticos , Fusão Vertebral , Ácido Tranexâmico , Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Fibrinolisina , Humanos , Estudos Prospectivos , Fusão Vertebral/métodos , Ácido Tranexâmico/uso terapêuticoRESUMO
BACKGROUND: Slipped capital femoral epiphysis (SCFE) is strongly associated with childhood obesity, yet the prevalence of obesity is orders of magnitude greater than the prevalence of SCFE. Therefore, it is hypothesized that obesity is not, by itself, a sufficient condition for SCFE, but rather one component of a multifactorial process requiring preexisting physeal pathology. Leptin elevation is seen to varying degrees in patients with obesity, and as leptin has been shown to cause physeal pathology similar to the changes seen in SCFE, we propose that leptin may be a factor distinguishing between patients with SCFE and equally obese children without hip abnormalities. METHODS: Serum leptin levels were obtained from 40 patients with SCFE and 30 control patients with approximate body mass index (BMI) matching. BMI percentiles were calculated according to Centers for Disease Control and Prevention population data by patient age and sex. Patients were compared by demographic characteristics, leptin levels, odds of leptin elevation, and odds of SCFE. RESULTS: The odds of developing SCFE was increased by an odds ratio of 4.9 (95% confidence interval [CI], 1.31 to 18.48; p < 0.02) in patients with elevated leptin levels, regardless of obesity status, sex, and race. When grouping patients by their obesity status, non-obese patients with SCFE showed elevated median leptin levels at 5.8 ng/mL compared with non-obese controls at 1.7 ng/mL (p = 0.006). Similarly, obese patients with SCFE showed elevated median leptin levels at 17.9 ng/mL compared with equally obese controls at 10.5 ng/mL (p = 0.039). Serum leptin levels increased in association with obesity (p < 0.001), with an increase in leptin of 0.17 ng/mL (95% CI, 0.07 to 0.27 ng/mL) per BMI percentile point. CONCLUSIONS: To our knowledge, this study is the first to clinically demonstrate an association between elevated serum leptin levels and SCFE, regardless of BMI. This adds to existing literature suggesting that SCFE is a multifactorial process and that leptin levels may have profound physiological effects on the development of various disease states. Despite a strong association with adiposity, leptin levels vary between patients of equal BMI and may be a vital resource in prognostication of future obesity-related comorbidities. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Assuntos
Leptina/sangue , Obesidade/sangue , Escorregamento das Epífises Proximais do Fêmur/sangue , Criança , Articulação do Quadril/patologia , Humanos , Obesidade/complicações , Prognóstico , Fatores de Risco , Escorregamento das Epífises Proximais do Fêmur/etiologiaRESUMO
BACKGROUND: Slipped capital femoral epiphysis (SCFE) and tibia vara (Blount disease) are associated with childhood obesity. However, the majority of obese children do not develop SCFE or tibia vara. Therefore, it is hypothesized that other obesity-related biological changes to the physis, in addition to increased biomechanical stress, potentiate the occurrence of SCFE and tibia vara. Considering that hypertension can impose pathologic changes in the physis similar to those observed in these obesity-related diseases we set out to determine the prevalence of hypertension in patients with SCFE and tibia vara. METHODS: Blood pressure measurements were obtained in 44 patients with tibia vara and 127 patients with SCFE. Body mass index and blood pressure were adjusted for age, sex, and height percentiles utilizing normative distribution data from the CDC. These cohorts were compared with age-matched and sex-matched cohorts derived from an obesity clinic who did not have either bone disease. A multivariable proportional odds model was used to determine association. RESULTS: The prevalence of prehypertension/hypertension was significantly higher in the tibia vara (64%) and SCFE cohort (64%) compared with respective controls (43%). Patients diagnosed with either SCFE or tibia vara had 2.5-fold higher odds of having high blood pressure compared with age-matched and sex-matched obese patients without bone disease. Sex, age, and race did not have a significant effect on a patient's blood pressure. CONCLUSIONS: This is the first study to establish that the obesity-related bone diseases, SCFE and tibia vara, are significantly associated with high blood pressure. These data have immediate clinical impact as they demonstrate that children with obesity-related developmental bone disease have increased prevalence of undiagnosed and untreated hypertension. Furthermore, this prevalence study supports the hypothesis that hypertension in conjunction with increased biomechanical forces together potentiate the occurrence of SCFE and tibia vara. If proven true, it is plausible that hypertension may represent a modifiable risk factor for obesity-related bone disease. LEVEL OF EVIDENCE: Level III-case-control study.