Thoracic tumor effects on plasmatic coagulation: role of hemeoxygenase-1.

OBJECTIVES: Lung cancer is an important health threat worldwide, and is associated with a 3.8-13.9% incidence of thrombophilia. Of interest, patients with lung tumors have been noted to have an increase in endogenous carbon monoxide production via upregulation of hemeoxygenase-1 activity. Given that it has been demonstrated that carbon monoxide enhances plasmatic coagulation in vitro and in vivo via formation of carboxyhemefibrinogen, we sought to determine if patients with thoracic tumors undergoing lung resection/pneumonectomy had an increase in endogenous carbon monoxide and concurrent plasmatic hypercoagulability. MATERIALS AND METHODS: Nonsmoking patients with thoracic tumors (n=19) had preoperative carboxyhemoglobin (a measure of carbon monoxide production) determined, and a thromboelastometric method to assess citrated plasma coagulation kinetics and the formation of carboxyhemefibrinogen was utilized. Thoracic tumor patient coagulation kinetics was compared with normal subject (n=30) plasma samples. RESULTS AND CONCLUSION: Patients with thoracic tumors were determined to have an abnormally increased carboxyhemoglobin concentration of 2.1±0.6%, indicative of hemeoxygenase-1 upregulation. It was found that 84% of thoracic tumor patients had plasma clot strength that exceeded the 95% confidence interval value observed in normal subjects, and 44% of this hypercoagulable subgroup had carboxyhemefibrinogen formation. Future investigation of the role played by plasmatic hypercoagulability and hemeoxygenase-1 derived carboxyhemefibrinogen in the pathogenesis of thoracic tumor related thrombophilia is warranted.

Hemeoxygenase-1 mediated hypercoagulability in a patient with thyroid cancer.

Thyroid cancers can cause significant regional thrombotic morbidity and mortality. Of interest, thyroid cancer cell lines can have upregulation of the carbon monoxide-producing enzyme, hemeoxygenase-1. Carbon monoxide has been demonstrated to markedly enhance plasmatic coagulation in vitro and in vivo via enhancement of fibrinogen's substrate properties by binding to a fibrinogen-associated heme group(s). We present a patient undergoing removal of a malignant thyroid tumour who was serendipitously found to have abnormally increased carboxyhaemoglobin concentration (2.4%) and plasmatic hypercoagulability with a carbon monoxide-mediated clot strength as determined by a thrombelastographic method. This initial observation serves as a rationale to further investigate the role played by hemeoxygenase-1 upregulation in the setting of cancers associated with increased endogenous carbon monoxide production.

Anterior cruciate ligament-injured subjects have smaller anterior cruciate ligaments than matched controls: a magnetic resonance imaging study.

BACKGROUND: Very few studies examining the predisposing anatomical factors leading to anterior cruciate ligament (ACL) injuries have examined the ACL itself, and none of these directly examined the difference in ACL properties between injured and matched control subjects. HYPOTHESIS: The ACL total volume in people who have experienced a noncontact ACL injury is smaller than that of matched controls. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Contours of the ACL were manually identified in sagittal magnetic resonance images, and volumes were calculated for 27 contralateral, healthy knees of individuals after noncontact ACL injury and for 27 control subjects matched for gender, height, age, and weight. Validation of this method was performed on 5 porcine knees. Stepwise multiple regression was used to determine the difference in ACL volume between injured and control subjects while considering gender, height, weight, and age as potential covariates. RESULTS: Contralateral ACL volume for injured subjects was significantly smaller than for noninjured subjects (P = .0208) by 231 mm(3) after adjusting for weight, which was also a significant contributor to ACL volume (P < .0001). At the average body mass of 72.7 kg, subjects with a noncontact ACL injury had an average contralateral ACL volume of 1921 mm(3), while the corresponding control group had an average volume of 2151 mm(3). Gender, height, and age were not significant when weight was included in the regression model. CONCLUSION: This study shows that there are anthropometric differences between the knees of subjects with a noncontact ACL injury and those without an ACL injury, suggesting that ACL volume may play a direct role in noncontact ACL injury.

Trabecular shear stress amplification and variability in human vertebral cancellous bone: relationship with age, gender, spine level and trabecular architecture.

Trabecular shear stress magnitude and variability have been implicated in damage formation and reduced bone strength associated with bone loss for human vertebral bone. This study addresses the issue of whether these parameters change with age, gender or anatomical location, and if so whether this is independent of bone mass. Additionally, 3D-stereology-based architectural parameters were examined in order to establish the relationship between stress distribution parameters and trabecular architecture. Eighty cancellous bone specimens were cored from the anterior region of thoracic 12 and donor-matched lumbar 1 vertebrae from a randomly selected population of 40 cadavers. The specimens were scanned at 21-microm voxel size using microcomputed tomography (microCT) and reconstructed at 50microm. Bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), bone surface-to-volume ratio (BS/BV), degree of anisotropy (MIL1/MIL3), and connectivity density (-#Euler/Vol) were calculated directly from micro-CT images. Large-scale finite element models were constructed and superoinferior compressive loading was simulated. Apparent cancellous modulus (EFEM) was calculated. The average trabecular von Mises stress generated per uniaxial apparent stress (sigma (-)VM / sigmaapp) and coefficient of variation of trabecular von Mises stresses (COV) were calculated as measures of the magnitude and variability of shear stresses in the trabeculae. Mixed-models and regression were used for analysis. sigma(-)VM / sigmaapp and COV were not different between genders and vertebrae. Both sigma(-)VM / sigmaapp and COV increased with age accompanied by a decrease in BV/TV. Strong relationship of sigma(-)VM / sigmaapp with BV/TV was found whereas COV was strongly related to EFEM/(BV/TV). The results from T12 and L1 were not different and highly correlated with each other. The relationship of sigma(-)VM / sigmaapp with COV was observed to be different between males and females. This difference could not be explained by architectural parameters considered in this study. Our results support the relevance of trabecular shear stress amplification and variability in age-related vertebral bone fragility. The relationships found are expected to help understand the micro-mechanisms by which cancellous bone mass and mechanical properties are modulated through a collection of local stress parameters.