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Weinstein P.K.,University of Central Florida | Amirkhosravi A.,Florida Hospital Center for Thrombosis Research | Angelopoulos T.J.,University of Central Florida | Bushy A.,University of Central Florida | And 2 more authors.
Journal of Cardiovascular Nursing

BACKGROUND:: Women with systemic lupus erythematosus (SLE) display a 7- to 10-fold increased risk for cardiovascular disease (CVD) compared with non-SLE controls, yet many are unaware of this risk despite years spent in the healthcare system. It is not clear why they lack awareness of increased CVD risk or which factors influence awareness. OBJECTIVE:: The purpose of this study was to assess in women with SLE their perceived CVD risk, the association between clinically identified and perceived CVD risk factors, and factors that influenced CVD risk awareness and adoption of risk-reducing behaviors. METHODS:: Questionnaires, face-to-face meetings, and clinical assessments were used to collect data on demographics, perceived CVD risk, perceived CVD risk factors, actual CVD risk factors, risk-reducing behaviors, and healthcare provider counseling from 60 women with SLE. Regression analyses identified factors that influenced risk awareness and adoption of risk-reducing behaviors. RESULTS:: Two-thirds of the participants perceived themselves at increased CVD risk when compared with women without SLE, but the same number did not perceive an increase in their absolute CVD risk. Age was a significant predictor (P = .05) for awareness of increased absolute risk; younger age correlated with increased awareness. Most women received information about heart disease from public media. On average, participants had 4 CVD risk factors but perceived that they had only 2. Age (P = .001) and the number of perceived risk factors (P = .004) predicted adoption of risk-reducing behaviors (P = .03). CONCLUSION:: Participants underestimated their CVD risk factors and did not personalize their increased CVD risk. Healthcare providers' identification and discussion of CVD risk factors in women with SLE may enhance their CVD risk awareness and the adoption of risk-reducing behaviors. © 2014 Wolters Kluwer Health Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Source

Davila M.,Florida Hospital Center for Thrombosis Research | Robles-Carrillo L.,Florida Hospital Center for Thrombosis Research | Unruh D.,University of Cincinnati | Huo Q.,University of Central Florida | And 7 more authors.
Journal of Thrombosis and Haemostasis

Background: Tumor-derived tissue factor (TF) activates coagulation in vitro and in vivo in an orthotopic model of human pancreatic cancer. Here, we further characterized tumor-derived TF in this model. Methods: Conditioned medium (CM) of L3.6pl human pancreatic tumor cells and plasma from nude mice bearing L3.6pl tumors were ultracentrifuged, and the pellets were filtered through membranes with different pore sizes. The size distribution of particles was analyzed in CM or plasma fractions with nanoparticle tracking and dynamic light scattering. Human TF antigen and activity were measured in pellets and supernatants with ELISA and clotting or thrombin generation assays, respectively. Human alternatively spliced TF (asTF) was measured with ELISA. Human TF and thrombin-antithrombin complex (TAT) concentrations were assessed in plasma of mice injected with filtered fractions of CM. Results: Particles in both CM and plasma were < 0.4 μm. TF antigen and activity in the CM were mainly associated with microparticles (MP). Approximately 50% of antigen and 20% of activity were associated with particles of < 0.1 μm. Injection of < 0.1-μm particles into mice caused a 30% drop in platelet counts and an increase in TAT levels. In contrast, ~ 90% of TF antigen in tumor-bearing mice plasmas was non-sedimentable, whereas TF activity was exclusively associated with MP. Particles of < 0.1 μm and the supernatants of both CM and plasma gained TF activity after addition of exogenous phospholipids. Although asTF was found in MP-free CM supernatants, it was also present in CM and plasma pellets. Conclusions: Tumor-derived particles of < 0.1 μm and non-sedimentable TF are or can become procoagulant in the presence of phospholipids, and may contribute to the procoagulant potential of circulating TF. © 2013 International Society on Thrombosis and Haemostasis. Source

Claussen C.,Onkologisches Zentrum Universitares Cancer Center Hamburg | Rausch A.-V.,Universitatsklinikum Eppendorf | Lezius S.,Universitatsklinikum Eppendorf | Amirkhosravi A.,Florida Hospital Center for Thrombosis Research | And 8 more authors.
Thrombosis Research

Background Tissue factor (TF) is involved in tumor growth and metastasis and contributes to venous thromboembolism (VTE) in cancer, including gynecological malignancies. The diagnostic value of microvesicle-associated TF procoagulant activity (MV TF PCA) in women with suspected ovarian cancer, however, has not been studied. Objective To evaluate MV TF PCA as a diagnostic tool in women with an ovarian mass of unknown etiology and as a predictive biomarker for perioperative VTE. Methods Plasma MVs were isolated by high-speed centrifugation and analyzed for TF-specific PCA by single-stage clotting assay. In addition, plasma TF antigen and soluble P-selectin (sCD62P) were measured by ELISA. Results D-Dimer, MV TF PCA, and sCD62P, but not the tumor marker, CA-125, significantly differentiated patients with malignant (n = 40) from those with benign tumors (n = 15) and healthy controls (n = 34). In cancer patients, only D-Dimer and CA-125 correlated with the FIGO stage. An abnormal D-dimer had the highest sensitivity for the diagnosis of cancer, while MV TF PCA above the ROC curve-derived cut-off value of 182 U/mL had the highest specificity. By multivariate logistic regression analysis, addition of MV TF PCA conferred diagnostic benefit to the single variables, CA-125 (p = 0.052) and D-dimer (p = 0.019). Perioperative VTE occurred in 16% of cancer patients and was associated with an advanced FIGO stage, but not MV TF PCA. There was no difference in plasma TF antigen levels between study groups. Conclusions MV TF PCA, but not plasma TF antigen, may provide valuable additional information for the diagnostic work-up of women with suspected ovarian cancer. © 2016 Elsevier Ltd. All rights reserved. Source

Amirkhosravi A.,Florida Hospital Center for Thrombosis Research | Mousa S.A.,Albany College of Pharmacy and Health Sciences | Amaya M.,Florida Hospital Center for Thrombosis Research | Meyer T.,Florida Hospital Center for Thrombosis Research | And 3 more authors.
Methods in Molecular Biology

It is well established that the blood coagulation system is activated in cancer. In addition, there is considerable evidence to suggest that clotting activation plays an important role in the biology of malignant tumors, including the process of blood-borne metastasis. For many years our laboratory has used experimental models of lung metastasis to study the events that follow the introduction of procoagulant-bearing tumor cells into circulating blood. This chapter focuses on the basic methods involved in assessing the anti-metastatic effects of anticoagulants and anti-platelet agents using rodent models of experimental metastasis. In addition, it summarizes our experience with these models, which collectively suggests that intravascular coagulation and platelet activation are a necessary prelude to lung tumor formation and that interruption of coagulation pathways or platelet aggregation may be an effective anti-metastatic strategy. © 2010 Springer Science+Business Media, LLC. Source

Dicke C.,Universitatsklinikum Eppendorf | Amirkhosravi A.,Florida Hospital Center for Thrombosis Research | Spath B.,Universitatsklinikum Eppendorf | Jimenez-Alcazar M.,Universitatsklinikum Eppendorf | And 5 more authors.
Experimental Hematology and Oncology

Background: In acute myeloid leukemia (AML), disseminated intravascular coagulation (DIC) contributes to morbidity and mortality, but the underlying pathomechanisms remain incompletely understood. Methods: We conducted a prospective study on 69 patients with newly diagnosed AML to further define the correlates of systemic coagulation activation in this hematological malignancy. Tissue factor procoagulant activity (TF PCA) of isolated peripheral blood mononuclear cells (PBMCs) and TF expression by circulating microparticles (MPs) were assessed by single-stage clotting and thrombin generation assay, respectively. Soluble plasma TF antigen and secretion of vascular endothelial growth factor (VEGF) by cultured PBMCs were measured by ELISA. Cell-free plasma DNA was quantified by staining with a fluorescent dye. Result: TF PCA of PBMCs was significantly increased in AML patients as compared to healthy controls. Furthermore, TF PCA was significantly associated with decompensated DIC at presentation, as defined by a plasma fibrinogen level of ≤1 g/L (n = 11). In addition to TF PCA and circulating blasts, serum lactate dehydrogenase, a surrogate marker for leukemic cell turnover, correlated with plasma D-Dimer in the total patient cohort and was significantly increased in DIC patients, suggesting a role for myeloblast apoptosis/necrosis in activation of the TF-dependent coagulation pathway. Consistently, TF-bearing plasma MPs were more frequently detected and levels of soluble TF antigen were significantly higher in DIC vs. non-DIC patients. No association was found between TF PCA expression and VEGF secretion by isolated PBMCs, but significantly increased levels of cell-free plasma DNA pointed to a contribution of the intrinsic contact pathway to systemic coagulation activation in the total patient cohort and in patients with lower TF PCA expression. While PBMC-associated TF PCA had no effect on long-term survival, DIC occurrence at presentation increased the risk of early mortality. Conclusion: In newly diagnosed AML, TF expression by PBMCs and shedding of TF-bearing plasma MPs are central to the pathogenesis of DIC, but additional pathways, such as DNA liberation, may contribute to systemic coagulation activation. © 2015 Dicke et al. Source

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