11 results on '"Jovan Antovic"'
Search Results
2. Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
- Author
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Maria Jesus Iglesias, Laura Sanchez-Rivera, Manal Ibrahim-Kosta, Clément Naudin, Gaëlle Munsch, Louisa Goumidi, Maria Farm, Philip M. Smith, Florian Thibord, Julia Barbara Kral-Pointner, Mun-Gwan Hong, Pierre Suchon, Marine Germain, Waltraud Schrottmaier, Philip Dusart, Anne Boland, David Kotol, Fredrik Edfors, Mine Koprulu, Maik Pietzner, Claudia Langenberg, Scott M. Damrauer, Andrew D. Johnson, Derek M. Klarin, Nicholas L. Smith, David M. Smadja, Margareta Holmström, Maria Magnusson, Angela Silveira, Mathias Uhlén, Thomas Renné, Angel Martinez-Perez, Joseph Emmerich, Jean-Francois Deleuze, Jovan Antovic, Jose Manuel Soria Fernandez, Alice Assinger, Jochen M. Schwenk, Joan Carles Souto Andres, Pierre-Emmanuel Morange, Lynn Marie Butler, David-Alexandre Trégouët, and Jacob Odeberg
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Science - Abstract
Abstract Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
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- 2023
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3. Author Correction: Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
- Author
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Maria Jesus Iglesias, Laura Sanchez-Rivera, Manal Ibrahim-Kosta, Clément Naudin, Gaëlle Munsch, Louisa Goumidi, Maria Farm, Philip M. Smith, Florian Thibord, Julia Barbara Kral-Pointner, Mun-Gwan Hong, Pierre Suchon, Marine Germain, Waltraud Schrottmaier, Philip Dusart, Anne Boland, David Kotol, Fredrik Edfors, Mine Koprulu, Maik Pietzner, Claudia Langenberg, Scott M. Damrauer, Andrew D. Johnson, Derek M. Klarin, Nicholas L. Smith, David M. Smadja, Margareta Holmström, Maria Magnusson, Angela Silveira, Mathias Uhlén, Thomas Renné, Angel Martinez-Perez, Joseph Emmerich, Jean-Francois Deleuze, Jovan Antovic, Jose Manuel Soria Fernandez, Alice Assinger, Jochen M. Schwenk, Joan Carles Souto Andres, Pierre-Emmanuel Morange, Lynn Marie Butler, David-Alexandre Trégouët, and Jacob Odeberg
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Science - Published
- 2023
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4. Apixaban concentration variability and relation to clinical outcomes in real-life patients with atrial fibrillation
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Alenka Mavri, Nina Vene, Mojca Božič-Mijovski, Marko Miklič, Lisbeth Söderblom, Anton Pohanka, Rickard E. Malmström, and Jovan Antovic
- Subjects
Medicine ,Science - Abstract
Abstract In some clinical situations, measurements of anticoagulant effect of apixaban may be needed. We investigated the inter- and intra-individual apixaban variability in patients with atrial fibrillation and correlated these results with clinical outcome. We included 62 patients receiving either 5 mg (A5, n = 32) or 2.5 mg (A2.5, n = 30) apixaban twice-daily. We collected three trough and three peak blood samples 6–8 weeks apart. Apixaban concentration was measured by liquid chromatography-tandem mass-spectrometry (LC–MS/MS) and by anti-Xa. Patients on A2.5 were older, had lower creatinine clearance, higher CHA2DS2VASc (4.7 ± 1.0 vs. 3.4 ± 1.7) and lower trough (85 ± 39 vs. 117 ± 53 ng/mL) and peak (170 ± 56 vs. 256 ± 91 ng/mL) apixaban concentrations than patients on A5 (all p
- Published
- 2021
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5. Synergistic Effect of Bypassing Agents and Sequence Identical Analogue of Emicizumab and Fibrin Clot Structure in the In Vitro Model of Hemophilia A
- Author
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Yanan Zong, Aleksandra Antovic, Nida Mahmoud Hourani Soutari, Jovan Antovic, and Iva Pruner
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emicizumab ,bypassing agents ,fibrin clot ,hemophilia a ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Development of inhibitors to factor VIII (FVIII) occurs in approximately 30% of severe hemophilia A (HA) patients. These patients are treated with bypassing agents (activated prothrombin complex concentrate [aPCC] and recombinant activated FVII-rFVIIa). Recently, a bispecific FIX/FIXa- and FX/FXa-directed antibody (emicizumab) has been approved for the treatment of HA patients with inhibitors. However, the data from clinical studies imply that coadministration of emicizumab and bypassing agents, especially aPCC, could have a thrombotic effect. This study was aimed to address the question of potential hypercoagulability of emicizumab and bypassing agents' coadministration, we have investigated fibrin clot formation and structure in the in vitro model of severe HA after adding sequence-identical analogue (SIA) of emicizumab and bypassing agents. Combined overall hemostasis potential (OHP) and fibrin clot turbidity assay was performed in FVIII-deficient plasma after addition of different concentrations of SIA, rFVIIa, and aPCC. Pooled normal plasma was used as control. The fibrin clots were analyzed by scanning electron microscopy (SEM). OHP and turbidity parameters improved with the addition of aPCC, while therapeutic concentrations of rFVIIa did not show substantial improvement. SIA alone and in combination with rFVIIa or low aPCC concentration improved OHP and turbidity parameters and stabilized fibrin network, while in combination with higher concentrations of aPCC expressed hypercoagulable pattern and generated denser clots. Our in vitro model suggests that combination of SIA and aPCC could potentially be prothrombotic, due to hypercoagulable changes in fibrin clot turbidity and morphology. Additionally, combination of SIA and rFVIIa leads to the formation of stable clots similar to normal fibrin clots.
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- 2020
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6. Tissue Factor Positive Extracellular Vesicles and Risk of Thromboembolism in Diffuse Large B-Cell Lymphoma: A Prospective Exploratory Study
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Vladimir Otasevic, Charlotte Gran, Natasa Milic, Vojin Vukovic, Biljana Mihaljevic, Jawed Fareed, Nida Mahmoud Hourani Soutari, Jovan Antovic, and Darko Antic
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
7. [Routine screening with APTT is not indicated before surgery]
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Li, Bian, Fariba, Baghaei, Jovan, Antovic, Inger, Fagerberg Blixter, Andreas, Hillarp, Karin, Strandberg, David, Willman, and Tomas, L Lindahl
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Sweden ,Humans ,Mass Screening ,Hemorrhage ,Partial Thromboplastin Time ,Blood Coagulation Tests - Abstract
Activated partial thromboplastin time (APTT) is widely practiced in preoperative screening. The value of using this test to predict the risk of perioperative bleeding is not well documented in Sweden. In this article, a literature review is performed to determine whether unselected APTT testing can predict abnormal perioperative bleeding. The current literature does not support coagulation screening with APTT in routine perioperative bleeding assessment, as preoperative screening with APTT has a low sensitivity for detection of clinically significant bleeding disorder. While a comprehensive bleeding history is crucial, the APTT test should only be performed on patients with a history of increased bleeding tendency. The conclusion of this literature review is that patients with a negative bleeding history do not require routine screening with APTT prior to surgery, which, if implemented, would lead to a more cost-effective perioperative routine.
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- 2022
8. Elevated plasma Complement Factor H Regulating Protein 5 is associated with venous thromboembolism and COVID-19 severity
- Author
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Laura Sanchez-Rivera, Maria Jesus Iglesias, Manal Ibrahim-Kosta, Julia Barbara Kral-Pointner, Sebastian Havervall, Louisa Goumidi, Maria Farm, Gaëlle Munsch, Marine Germain, Philip Smith, Mun-Gwan Hong, Pierre Suchon, Clément Naudin, Anne Boland, David M Smadja, Margareta Holmström, Maria Magnusson, Angela Silveira, Mathias Uhlén, Thomas Renné, Angel Martinez-Perez, Joseph Emmerich, Jean-Francois Deleuze, Jovan Antovic, Alice Assinger, Jose Manuel Soria Fernandez, Charlotte Thålin, Jochen M Schwenk, Juan Carlos Souto Andres, Pierre-Emmanuel Morange, Lynn Marie Butler, David-Alexandre Trégouët, and Jacob Odeberg
- Abstract
Venous thromboembolism (VTE), comprising both deep vein thrombosis (DVT) and pulmonary embolism (PE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. We used multiplex proteomics profiling to screen plasma from patients with suspected acute VTE, and a case-control study of patients followed up after ending anticoagulant treatment for a first VTE. With replication in 5 independent studies, together totalling 1137 patients and 1272 controls, we identify Complement Factor H Related Protein (CFHR5), a regulator of the alternative pathway of complement activation, as a novel VTE associated plasma biomarker. Using GWAS analysis of 2967 individuals we identified a genome-wide significant pQTL signal on chr1q31.3 associated with CFHR5 levels. We showed that higher CFHR5 levels are associated with increased thrombin generation in patient plasma and that recombinant CFHR5 enhances platelet activationin vitro. Thrombotic complications are a frequent feature of COVID-19; in hospitalised patients we found CFHR5 levels at baseline were associated with short-time prognosis of disease severity, defined as maximum level of respiratory support needed during hospital stay. Our results indicate a clinically important role for regulation of the alternative pathway of complement activation in the pathogenesis of VTE and pulmonary complications in acute COVID-19. Thus, CFHR5 is a potential diagnostic and/or risk predictive plasma biomarker reflecting underlying pathology in VTE and acute COVID-19.
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- 2022
9. Clinical significance of diagnostic algorithm in detection of mild hemostasis disorders in women with menorrhagia
- Author
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M Ivana Simic-Vukomanovic, M Svetlana Djukic, Aleksandar Djukic Lj., V Nebojsa Andjelkovic, R Vladimir Vukomanovic, and P Jovan Antovic
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von willebrand disease ,lcsh:R5-920 ,medicine.medical_specialty ,business.industry ,Hemostasis ,medicine ,Pharmacology (medical) ,Clinical significance ,Radiology ,hemostasis, disorders ,lcsh:Medicine (General) ,business ,anemia - Abstract
Background/Aim. Coagulation disorders could be a cause of menorrhagia in women of reproductive age. The aim of the study was to estimate frequency of coagulation disorders and design an appropriate algorithm for detection of coagulation disorders. Methods. We investigated coagulation in 115 women (36.1 ? 9.6 years) with anamnestic data of menorrhagia, verified using semiquantitative method ? Pictorial Bleeding Assessment Chart (PBAC) with score ? 100. Results. Menorrhagia was objectively verified in sixty-four women (55.7%) and in comparison with those with normal menstruation they had higher PBAC score of menstrual cycle [median (Md) = 150.0 vs. Md = 50.0; p < 0.001] but not its duration (7.2 ? 2.1 days vs. 7.3 ? 1.9 days; p > 0.05). Coagulation defects was found in 12 (10.4%) women ? decreased F IX: Ac in 4 (3.5%), decreased F VII: Ac in 1 (0.9%), decreased F X: Ac in 1 (0.9%), decreased F XI: Ac in 1 woman (0.9%), while 5 (4.3%) women matched criteria for mild von Willebrand disease (VWD) type 1. Women with coagulation disorders had prolonged prothrombin time (PT) [Md = 13.1 s, range: 12.2?14.8 s vs. Md = 12.5 s, range 10.6?18.3 s; p = 0.032]. Anemia was diagnosed in 61 (53.0%) women. The strongest predictor of the hemostasis disorder was menorrhagia (Quotient of probability 0.018), then anemia presence (12.43), P? (2.35), menstrual cycle duration (1.16) and the PBAC score (0.98). Conclusion. The results of the study indicate the need to form a diagnostic algorithm for hemostasis disorders, primarily VWD. Sophisticated analysis of hemostasis is required, especially if predictive factors of statistical models are detected: objectively verified menorrhagia, anemia, prolonged menstrual cycle, PBAC score > 100 and extended PT.
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- 2020
10. Thrombin activatable fibrinolysis inhibitor antigen could not be detected in cerebrospinal fluid
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Margareta Blombäck, Michael Nekludov, Jan Hannerz, and Jovan Antovic
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Pathology ,medicine.medical_specialty ,business.industry ,Vascular biology ,Thrombin-Activatable Fibrinolysis Inhibitor ,Hematology ,medicine.disease ,Thrombosis ,Cerebrospinal fluid ,Antigen ,Hemostasis ,Immunoenzyme techniques ,Medicine ,business ,Fibrinolysis inhibitor - Abstract
Thrombinactivatable fibrinolysis inhibitor antigencouldnot be detected in cerebrospinalf luid
- Published
- 2005
11. Coagulation Abnormalities Associated with Severe Isolated Traumatic Brain Injury Cerebral Arterio-Venous Differences in Coagulation and Inflammatory Markers.
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Michael Nekludov, Jovan Antovic, Sixteen Bredbacka, and Margareta Blombäck
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BLOOD coagulation , *BRAIN injuries , *FLOCCULATION , *AGGLOMERATION (Materials) - Abstract
Although coagulopathy is known to be the major contributor to a poor outcome of traumatic brain injury (TBI), the mechanisms that trigger coagulation abnormalities have not been studied in detail. We undertook a prospective observational study at a neurosurgical ICU (NICU) in a university hospital. We examined 11 patients with severe isolated TBI, at admittance to the hospital and during the next 3 days. We collected cerebrovenous blood samples from a jugular bulb catheter, arterial blood, and cerebrospinal fluid (CSF) samples. We measured concentrations of thombin-antithrombin complex (TAT), fibrin D-dimer (DD), prothrombin fragment 1 2 (F1 2), interleukin-6 (IL-6), and complement complex (C5b-9). All patients had some degree of consumption coagulopathy at the study start and a tendency to thrombocytopenia during the next few days. Levels of DD (3.6 ± 2.7 mgL), TAT (86 ± 72 μgL) and F1 2 (5.9 ± 6.8 nmolL) were significantly increased shortly after the trauma compared to reference values, with considerable transcranial gradients for TAT (49 μgL) and F1 2 (3.2 nmolL). Compared to controls, IL-6 levels were increased more than a hundredfold in both blood (283 ± 192 ngL) and CSF (424 ± 355 ngL) samples, with a transcranial gradient at the study start (107 ngL). C5b-9 levels were moderately increased in blood samples, 270 ± 114 μgL, versus controls, 184 ± 39 (p< 0.05). We conclude that activation of the coagulation system takes place during the passage of blood through the damaged brain, and is already evident hours after the trauma. IL-6 and activation of the complement system (C5b-9) co-vary with hemostatic parameters in TBI patients. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
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