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207. Effect of Unfractionated Heparin on TFPI Elimination

Author

Appa, Rupa Shree, Øie, Cristina Ionica, Hilden, Ida, Brodin, Ellen, Smedsrød, Bård, and Hansen, John-Bjarne

Subjects
VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710
Abstract

This paper is part of Cristina Ionica Øie's doctoral thesis, which is available in Munin at http://hdl.handle.net/10037/2910 Background: Tissue factor pathway inhibitor (TFPI) plays an important role for the anticoagulant effect of heparin. Depletion of intravascular TFPI by treatment with unfractionated heparin (UFH), and not by low molecular weight heparin (LMWH), has been suggested to explain the superiority of LMWH in treatment of both arterial and venous thrombosis. The present study was undertaken to investigate the impact of UFH on clearance kinetics, and organs and cells responsible for the clearance of recombinant human full length TFPI purified from baby hamster kidney cells (TFPIBHK) and from E.Coli (TFPIE.Coli). Methods: Male Sprague-Dawley rats were used as research animals. TFPIBHK and TFPIE.Coli were labelled with 125I, and used to study clearance in vivo. Results: Surface Plasmon Resonance (SPR) analysis revealed that both types of TFPI bound to UFH in vitro, but TFPIE.Coli exhibited a faster association rate and a much slow dissociation rate. Intravenous administration of 100 IU/kg UFH immediately prior to TFPI decreased the circulatory survival (t1/2α) of TFPIBHK from 1.99 ± 0.10 min to 1.17 ± 0.13 min (pE.Coli. Presence of UFH significantly increased the circulatory survival during the slow t1/2β phase of TFPIE.Coli from 27.44 ± 1.91 min to 36.88 ± 1.87 min (p1/2β of TFPIBHK. Hepatocellular distribution of radiolabeled ligands showed that both forms of TFPI were mainly taken up by PCs in the absence of UFH (≥ 90%). UFH administration switched the hepatocellular distribution of TFPIE.Coli from PCs towards LSECs, without affecting the distribution of TFPIBHK. Conclusions: Our findings revealed a specific increase in the elimination of TFPIBHK during UFH treatment. This observation may represent the underlying mechanism for depletion of endogenous TFPI in humans during UFH treatment.

Published
2010

208. Asialoglycoprotein Receptor (ASGP-R) is Liver Parenchymal Cells is Involved in Elimination of Recombinant Human TFPI

Author

Appa, Rupa Shree, Øie, Cristina Ionica, Brodin, Ellen, Hansen, John-Bjarne, and Smedsrød, Bård

Subjects
TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710
Abstract

This article is part of Cristina Ionica Øie's doctoral thesis, which is available in Munin at http://hdl.handle.net/10037/2910 We here report on a study carried out to determine the early clearance kinetics, and organ, cell(s) and receptor(s) responsible for the clearance of full length TFPI purified from BHK cells (TFPIBHK). Following intravenous administration, 125I-TFPIBHK was cleared with a biphasic elimination curve, and with a significantly slower t1/2α compared to recombinant human TFPI from E.Coli (TFPIE.Coli) (1.95±0.10 versus 1.42±0.07 min, respectively, pBHK and 81% of TFPIE.Coli, whereas the nonparenchymal cells (NPCs) were responsible for 4% and 19%, respectively. Pre-administration of excessive amounts of unlabeled TFPIBHK prolonged blood clearance of 125I-TFPIBHK. Unlabelled TFPIBHK inhibited endocytosis of 125I-TFPIBHK in PCs in vitro, whereas blocking of LDL-receptor related protein-1 (LRP-1) by receptor-associated protein (RAP) affected neither blood clearance nor endocytosis of 125I-TFPIBHK in PCs. In addition, TFPIBHK was also found in the kidneys and this could be reduced in the presence of RAP. Asialoorosomucoid (ASOR), a potent inhibitor of the asialoglycoprotein receptor (ASGP-R), prolonged the circulatory survival of 125I-m-TFPI by 1.5-fold (pIn vitro, ASOR and other ASGP-R antagonists significantly inhibited endocytosis of 125I-TFPIBHK in PCs. Moreover, unlabelled TFPIBHK markedly decreased endocytosis of 125I-asialofetuin. In conclusion, our findings suggest that ASGP-R mediated endocytosis in the liver is involved in the clearance of TFPIBHK.

Published
2010

210. Response to Letter Regarding Article, “Impact of Incident Venous Thromboembolism on Risk of Arterial Thrombotic Diseases”

Author

Lind, Caroline, primary, Flinterman, Linda E., additional, Enga, Kristin F., additional, Severinsen, Marianne T., additional, Kristensen, Søren R., additional, Brækkan, Sigrid K., additional, Mathiesen, Ellisiv B., additional, Njølstad, Inger, additional, Cannegieter, Suzanne C., additional, Overvad, Kim, additional, and Hansen, John-Bjarne, additional

Published
2014
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211. Association Between the Metabolic Syndrome, Its Individual Components, and Unprovoked Venous Thromboembolism

Author

Ageno, Walter, primary, Di Minno, Matteo N.D., additional, Ay, Cihan, additional, Jang, Moon Ju, additional, Hansen, John-Bjarne, additional, Steffen, Lyn M., additional, Vayà, Amparo, additional, Rattazzi, Marcello, additional, Pabinger, Ingrid, additional, Oh, Doyeun, additional, Di Minno, Giovanni, additional, Braekkan, Sigrid K., additional, Cushman, Mary, additional, Bonet, Elena, additional, Pauletto, Paolo, additional, Squizzato, Alessandro, additional, and Dentali, Francesco, additional

Published
2014
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214. Time trends in incidence rates of venous thromboembolism in a large cohort recruited from the general population.

Author

Arshad, Nadia, Isaksen, Trond, Hansen, John-Bjarne, and Brækkan, Sigrid

Subjects
THROMBOEMBOLISM, THROMBOSIS, VENOUS thrombosis, PULMONARY embolism, PREVENTIVE medicine
Abstract

Changes in the incidence of venous thromboembolism (VTE) during the last two decades have not been extensively studied. Therefore, we studied time trends in the incidence rates (IRs) of deep vein thrombosis (DVT) and pulmonary embolism (PE) in a cohort of 26,855 subjects, aged 25-97 years, enrolled in the Tromsø study in 1994/1995. The subject were followed-up throughout 2012, and all symptomatic, objectively confirmed, incident VTEs were identified using multiple sources (hospital discharge-, radiology procedure- and autopsy registry) and validated by review of medical records. Age-adjusted biennial IR per 100,000 person years (PY) with 95% confidence intervals (CI) were calculated using Poisson regression. Between January 1996 and December 2012, 693 VTEs occurred during 368,150 PY of follow up. The IR of VTE increased from 158 (95% CI 116-199) in 1996/1997 to 201 (95% CI 160-243) in 2010/2011. There was a marked increase in the rates of PE (with/without concurrent DVT) ranging from 45 (95% CI 23-67) in 1996/1997 to 113 (95% CI 82-144) in 2010/2011, whereas the rates of isolated DVT decreased (112, 95% CI 77-146 in 1996/1997 and 88, 95% CI 61-115 in 2010/2011). Despite advances in prophylaxis, the IR of VTE has increased slightly during the last 15 years, mainly due to an increase in PE. Although the introduction of better diagnostic tools to some extent may explain the increase in PE rates, our findings suggest that there is still a need for improvement in risk factor management and prevention strategies of first time VTE. [ABSTRACT FROM AUTHOR]

Published
2017
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215. Myocardial infarction and future risk of cancer in the general population-the Tromsø Study.

Author

Rinde, Ludvig, Småbrekke, Birgit, Hald, Erin, Brodin, Ellen, Njølstad, Inger, Mathiesen, Ellisiv, Løchen, Maja-Lisa, Wilsgaard, Tom, Brækkan, Sigrid, Vik, Anders, and Hansen, John-Bjarne

Subjects
MYOCARDIAL infarction risk factors, CANCER risk factors, CANCER-related mortality, PHYSICAL activity, DEATH rate
Abstract

The association between myocardial infarction (MI) and future risk of incident cancer is scarcely investigated. Therefore, we aimed to study the risk of cancer after a first time MI in a large cohort recruited from a general population. Participants in a large population-based study without a previous history of MI or cancer (n = 28,763) were included and followed from baseline to date of cancer, death, migration or study end. Crude incidence rates (IRs) and hazard ratios (HRs) for cancer after MI were calculated. During a median follow-up of 15.7 years, 1747 subjects developed incident MI, and of these, 146 suffered from a subsequent cancer. In the multivariable-adjusted model (adjusted for age, sex, BMI, systolic blood pressure, diabetes mellitus, HDL cholesterol, smoking, physical activity and education level), MI patients had 46% (HR 1.46; 95% CI: 1.21-1.77) higher hazard ratio of cancer compared to those without MI. The increased cancer incidence was highest during the first 6 months after the MI, with a 2.2-fold higher HR (2.15; 95% CI: 1.29-3.58) compared with subjects without MI. After a 2-year period without higher incidence rate, MI patients displayed 60% (HR 1.60; 95% CI: 1.27-2.03) higher HR of future cancer more than 3 years after the event. The increased IRs were higher in women than men. Patients with MI had a higher short- and long-term incidence rate of cancer compared to subjects without MI. Our findings suggest that occult cancer and shared risk factors of MI and cancer may partly explain the association. [ABSTRACT FROM AUTHOR]

Published
2017
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216. Serum osteoprotegerin and renal function in the general population: the Tromsø Study.

Author

Vik, Anders, Brodin, Ellen E., Mathiesen, Ellisiv B., Brox, Jan, Jørgensen, Lone, Njølstad, Inger, Brækkan, Sigrid K., and Hansen, John-Bjarne

Subjects
KIDNEY disease treatments, OSTEOPROTEGERIN, KIDNEY function tests
Abstract

Background: Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. Methods: We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounderswere used to study the association between OPG and eGFR. Analyseswere stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. Results: In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73m2) eGFR increased by 0.35 mL/min/1.73m2 (95% CI 0.13-0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73m2), eGFR decreased by 1.54 (95% CI - 2.06 to - 1.01) per 1 SD increase in serum OPG. Conclusions: OPGwas associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function. [ABSTRACT FROM AUTHOR]

Published
2017
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217. Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism: An Individual Participant Data Meta-Analysis of Prospective Studies.

Author

Mahmoodi, Bakhtawar K., Cushman, Mary, Næss, Inger Anne, Allison, Matthew A., Jan Bos, Willem, Brækkan, Sigrid K., Cannegieter, Suzanne C., Gansevoort, Ron T., Gona, Philimon N., Hammerstrøm, Jens, Hansen, John-Bjarne, Heckbert, Susan, Holst, Anders G., Lakoski, Susan G., Lutsey, Pamela L., Manson, JoAnn E., Martin, Lisa W., Kunihiro Matsushita, Meijer, Karina, and Overvad, Kim

Published
2017
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224. Impact of Incident Venous Thromboembolism on Risk of Arterial Thrombotic Diseases

Author

Lind, Caroline, primary, Flinterman, Linda E., additional, Enga, Kristin F., additional, Severinsen, Marianne T., additional, Kristensen, Søren R., additional, Brækkan, Sigrid K., additional, Mathiesen, Ellisiv B., additional, Njølstad, Inger, additional, Cannegieter, Suzanne C., additional, Overvad, Kim, additional, and Hansen, John-Bjarne, additional

Published
2014
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232. A Retrospective Comparison of Ultrasound-Assisted Catheter-Directed Thrombolysis and Catheter-Directed Thrombolysis Alone for Treatment of Proximal Deep Vein Thrombosis.

Author

Tichelaar, Vladimir, Brodin, Ellen, Vik, Anders, Isaksen, Trond, Skjeldestad, Finn, Kumar, Satish, Trasti, Nora, Singh, Kulbir, Hansen, John-Bjarne, Tichelaar, Vladimir Y I G, Brodin, Ellen E, Skjeldestad, Finn Egil, and Trasti, Nora C

Subjects
THERAPEUTIC use of fibrinolytic agents, POSTTHROMBOTIC syndrome, CATHETERS, COMPARATIVE studies, FEMORAL vein, HEALTH surveys, ILIAC vein, INTRAVENOUS catheterization, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, QUALITY of life, QUESTIONNAIRES, RESEARCH, THROMBOLYTIC therapy, VENOUS thrombosis, ULTRASONIC imaging, VENOGRAPHY, EVALUATION research, TREATMENT effectiveness, RETROSPECTIVE studies, PREVENTION, EQUIPMENT & supplies
Abstract

Background: Recent studies have suggested that catheter-directed thrombolysis (CDT) reduces development of post-thrombotic syndrome (PTS). Ultrasound-assisted CDT (USCDT) might enhance the efficiency of thrombolysis. We aimed to compare USCDT with CDT on efficacy, safety, development of PTS, and quality of life after long-term follow-up.Methods: We describe a retrospective case series of 94 consecutive patients admitted with iliofemoral or more proximal deep vein thrombosis (DVT) to the University Hospital from 2002 to 2011, treated either with CDT or USCDT. Scheduled follow-up visits took place between April 2013 and January 2014. Venography measured the degree of residual luminal obstruction of the affected veins. Each patient completed the Short Form 36-item health survey assessment and the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms questionnaires. PTS was assessed using the Villalta scale.Results: Risk factors of DVT were equally distributed between groups. In the USCDT group, we observed a significant decline in the duration of thrombolytic treatment (<48 h: 27 vs. 10 %), shortened hospital stay (median 6.0 days (IQR 5.0-9.0) vs. 8.0 (IQR 5.8-12.0)), and less implantation of (intravenous) stents (30 vs. 55 %). There was no difference in patency (76 vs. 79 % fully patent), prevalence of PTS (52 vs. 55 %), or quality of life between groups after long-term follow-up (median 65 months, range: 15-141).Conclusions: In this observational study, USCDT was associated with shortened treatment duration, shorter hospital stay, and less intravenous stenting, compared to CDT alone without affecting the long-term prevalence of PTS or quality of life. [ABSTRACT FROM AUTHOR]

Published
2016
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237. Association of Mild to Moderate Chronic Kidney Disease With Venous Thromboembolism

Author

Mahmoodi, Bakhtawar K., primary, Gansevoort, Ron T., additional, Næss, Inger Anne, additional, Lutsey, Pamela L., additional, Brækkan, Sigrid K., additional, Veeger, Nic J.G.M., additional, Brodin, Ellen E., additional, Meijer, Karina, additional, Sang, Yingying, additional, Matsushita, Kunihiro, additional, Hallan, Stein I., additional, Hammerstrøm, Jens, additional, Cannegieter, Suzanne C., additional, Astor, Brad C., additional, Coresh, Josef, additional, Folsom, Aaron R., additional, Hansen, John-Bjarne, additional, and Cushman, Mary, additional

Published
2012
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247. Circulating monocytes mirror the imbalance in TF and TFPI expression in carotid atherosclerotic plaques with lipid-rich and calcified morphology

Author

Basavaraj, Manjunath Goolyam, primary, Sovershaev, Mikhail A., additional, Egorina, Elena M., additional, Gruber, Franz X., additional, Bogdanov, Vladimir Y., additional, Fallon, John T., additional, Østerud, Bjarne, additional, Mathiesen, Ellisiv B., additional, and Hansen, John-Bjarne, additional

Published
2012
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248. Abstract P255: Association of Mild Chronic Kidney Disease with Venous Thromboembolism: Pooled Analysis of Prospective General Population Cohorts

Author

Mahmoodi, Bakhtawar K, primary, Gansevoort, Ron T, additional, Naess, Inger Anne, additional, Lutsey, Pamela L, additional, Braekkan, Sigrid K, additional, Veeger, Nic J, additional, Brodin, Ellen E, additional, Meijer, Karina, additional, Sang, Yingying, additional, Matsushita, Kunihiro, additional, Hallan, Stein, additional, Hammerstrøm, Jens, additional, Astor, Brad C, additional, Coresh, Josef, additional, Folsom, Aaron R, additional, Hansen, John-Bjarne, additional, and Cushman, Mary, additional

Published
2012
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