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https://www.readbyqxmd.com/read/28432221/biological-considerations-of-plasma-derived-and-recombinant-factor-viii-immunogenicity
#1
Jesse Lai, Christine Hough, Julie Tarrant, David Lillicrap
In hemophilia A, the most severe complication of factor VIII (FVIII) replacement therapy involves the formation of FVIII neutralizing antibodies, also known as inhibitors, in 25-30% of patients. This adverse event is associated with a significant increase in morbidity and economic burden, thus highlighting the need to identify methods to limit FVIII immunogenicity. Inhibitor development is regulated by a complex balance of genetic factors, such as FVIII genotype, and environmental variables, such as coexistent inflammation...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28431990/a-common-polymorphism-decreases-lrp1-mrna-stability-and-is-associated-with-increased-plasma-factor-viii-levels
#2
Jiann-Der Lee, Kuang-Ming Hsiao, Pey-Jium Chang, Chih-Cheng Chen, Ya-Wen Kuo, Yen-Chu Huang, Huan-Lin Hsu, Ya-Hui Lin, Chih-Ying Wu, Ying-Chih Huang, Meng Lee, Chia-Yu Hsu, Yi-Ting Pan, Chih-Yu Kuo, Chun-Hsien Lin
The low-density lipoprotein receptor-related protein 1 (LRP1) gene is associated with increased levels of plasma factor VIII (FVIII). We aimed to explore eight functional genetic LRP1 variants for their potential roles in regulating FVIII levels and acute ischemic stroke (AIS). This genetic association study enrolled 192 patients with AIS and 134 controls. There were no significant differences in the genetic frequency of the eight functional single-nucleotide polymorphisms (SNPs) between the control and AIS groups...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28430963/integrated-care-for-older-populations-and-its-implementation-facilitators-and-barriers-a-rapid-scoping-review
#3
Diane E Threapleton, Roger Y Chung, Samuel Y S Wong, Eliza Wong, Patsy Chau, Jean Woo, Vincent C H Chung, Eng-Kiong Yeoh
Purpose: Inform health system improvements by summarizing components of integrated care in older populations. Identify key implementation barriers and facilitators. Data sources: A scoping review was undertaken for evidence from MEDLINE, the Cochrane Library, organizational websites and internet searches. Eligible publications included reviews, reports, individual studies and policy documents published from 2005 to February 2017. Study selection: Initial eligible documents were reviews or reports concerning integrated care approaches in older/frail populations...
April 20, 2017: International Journal for Quality in Health Care
https://www.readbyqxmd.com/read/28430338/yap-taz-and-areg-expression-in-eighth-cranial-nerve-schwannoma
#4
Alessandro Martini, Gino Marioni, Elisabetta Zanoletti, Rocco Cappellesso, Roberto Stramare, Elena Fasanaro, Chiara Faccioli, Luciano Giacomelli, Luca Denaro, Domenico D'Avella, Antonio Mazzoni, Ambrogio Fassina
BACKGROUND: Although the diagnosis and treatment of eighth cranial nerve (VIII CN) schwannoma (acoustic neuroma) has improved over the years, no factors capable of predicting tumor growth have been identified as yet. This study is a preliminary investigation of the expression in sporadic VIII CN schwannomas of Yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), and amphiregulin (AREG), a direct target gene of YAP and TAZ. The expression of YAP, TAZ and AREG was correlated with the volumetric dimensions of tumors on contrast-enhanced magnetic resonance imaging (ceMRI)...
April 7, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28428025/adipokines-as-atherothrombotic-risk-factors-in-obese-subjects-associations-with-haemostatic-markers-and-common-carotid-wall%C3%A2-thickness
#5
É Csongrádi, M Káplár, B Nagy, C A Koch, A Juhász, L Bajnok, Z Varga, I Seres, Z Karányi, M T Magyar, L Oláh, A Facskó, J Kappelmayer, G Paragh
BACKGROUND AND AIMS: Some crucial associations between obesity-related altered adipokine levels and the main factors of atherosclerotic, atherothrombotic processes are not fully known. We analysed the relationships of classic adipokines, namely leptin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) with the markers of platelet activation, including mean platelet volume (MPV), platelet surface/soluble P-selectin, platelet-derived microparticles (PMPs), the parameters of coagulation abnormalities and common carotid intima-media thickness (IMT) in obese patients with or without atherosclerotic comorbidities in comparison to age- and sex-matched controls...
March 8, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28420167/treatment-and-prevention-of-bleeds-in-haemophilia-patients-with-inhibitors-to-factor-viii-ix
#6
REVIEW
Angiola Rocino, Massimo Franchini, Antonio Coppola
The development of alloantibodies neutralising therapeutically administered factor (F) VIII/IX (inhibitors) is currently the most severe complication of the treatment of haemophilia. When persistent and at a high titre, inhibitors preclude the standard replacement treatment with FVIII/FIX concentrates, making patients' management challenging. Indeed, the efficacy of bypassing agents, i.e., activated prothrombin complex concentrates (aPCC) and recombinant activated factor VII (rFVIIa), needed to overcome the haemostatic interference of the inhibitor, is not comparable to that of factor concentrates...
April 17, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28416360/primary-hepatic-angiosarcoma-and-liver-transplantation-radiological-surgical-histological-findings-and-clinical-outcome
#7
M Tran Minh, A Mazzola, F Perdigao, F Charlotte, G Rousseau, F Conti
Angiosarcoma is a rare type of soft tissue sarcoma that accounts for less than 1% of all sarcomas and only 2% of all primary hepatic tumours. Thorotrast, arsenic, and vinyl chloride monomer are frequently listed as occupational exposure risks. The estimated latency is long (10-40 years) in occupational cases and very long (60 years or more) in non-occupational cases. The symptoms and CT-scan appearance of hepatic angiosarcoma (HAS) are non-specific. We present a case of a 65-year-old Caucasian male with history of cryptogenic cirrhosis, low alpha-foetoprotein levels and a single, 4-cm nodule of potential atypical hepatocellular carcinoma (no washout at MRI and CT-scan) in segment VIII...
April 14, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28413832/statistical-analysis-plan-for-the-woman-etaplat-study-effect-of-tranexamic-acid-on-platelet-function-and-thrombin-generation
#8
Kastriot Dallaku, Haleema Shakur, Phil Edwards, Danielle Beaumont, Ian Roberts, Sumaya Huque, Maria Delius, Ulrich Mansmann
Background. Postpartum haemorrhage (PPH) is a potentially life-threatening complication for women, and the leading cause of maternal mortality. Tranexamic acid (TXA) is an antifibrinolytic used worldwide to treat uterine haemorrhage and to reduce blood loss in general surgery. TXA may have effects on thrombin generation, platelet function and coagulation factors as a result of its inhibition on the plasmin. Methods. WOMAN ETAPlaT is a sub-study of the World Maternal Antifibrinolitic trial (WOMAN trial). All adult women clinically diagnosed with PPH after a vaginal delivery or caesarean section, are eligible for inclusion in the study...
December 15, 2016: Wellcome Open Research
https://www.readbyqxmd.com/read/28411016/gene-therapy-for-hemophilia
#9
REVIEW
Arthur W Nienhuis, Amit C Nathwani, Andrew M Davidoff
The X-linked bleeding disorder hemophilia causes frequent and exaggerated bleeding that can be life-threatening if untreated. Conventional therapy requires frequent intravenous infusions of the missing coagulation protein (factor VIII [FVIII] for hemophilia A and factor IX [FIX] for hemophilia B). However, a lasting cure through gene therapy has long been sought. After a series of successes in small and large animal models, this goal has finally been achieved in humans by in vivo gene transfer to the liver using adeno-associated viral (AAV) vectors...
April 11, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28403881/glucocorticoid-receptor-represses-brain-derived-neurotrophic-factor-expression-in-neuron-like-cells
#10
Hui Chen, Marc Lombès, Damien Le Menuet
Brain-derived neurotrophic factor (BDNF) is involved in many functions such as neuronal growth, survival, synaptic plasticity and memorization. Altered expression levels are associated with many pathological situations such as depression, epilepsy, Alzheimer's, Huntington's and Parkinson's diseases. Glucocorticoid receptor (GR) is also crucial for neuron functions, via binding of glucocorticoid hormones (GCs). GR actions largely overlap those of BDNF. It has been proposed that GR could be a regulator of BDNF expression, however the molecular mechanisms involved have not been clearly defined yet...
April 12, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28401801/thrombophilia-in-153-patients-with-premature-cardiovascular-disease-%C3%A2-age-45
#11
Alexander Milgrom, Kevin Lee, Matan Rothschild, Frini Makadia, Greg Duhon, Sarah Min, Ping Wang, Charles J Glueck
We assessed contributions of thrombophilia to premature cardiovascular disease (CVD) events (≤ age 45) in 153 patients. Test results of thrombophilia-hypofibrinolysis were obtained in 153 patients with CVD ≤ age 45, 110 healthy normal controls, and 110 patients who had venous thromboembolism (VTE) without CVD. Of the 153 patients with CVD, 121 (79%) had sustained myocardial infarction, 70 (46%) had coronary artery stenting, and 53 (35%) had coronary artery bypass grafts. The first CVD events occurred at ages >20 to 35 in 47 patients and at ages >35 to 45 in 106 patients...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28401658/kreuth-iv-european-consensus-proposals-for-treatment-of-haemophilia-with-coagulation-factor-concentrates
#12
P L F Giangrande, F Peyvandi, B O'Mahony, M-E Behr-Gross, A Hilger, W Schramm, P M Mannucci
INTRODUCTION: This report summarizes recommendations relating to haemophilia therapy arising from discussions among experts from 36 European countries during the 'Kreuth IV' meeting in May 2016. AIM: The objective of the meeting was for experts in the field of haemophilia from across Europe to draft resolutions regarding current issues relating to the treatment of haemophilia. RESULTS: Hospitals providing clinical care for people with haemophilia and related disorders are strongly recommended to seek formal designation as either European Haemophilia Treatment Centres (EHTC) or European Haemophilia Comprehensive Care Centres (EHCCC)...
April 12, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28397442/predictive-factors-of-thrombosis-for-patients-with-essential-thrombocythaemia-a-single-center-study
#13
Iwona Prajs, Kazimierz Kuliczkowski
BACKGROUND: Thrombotembolic complications are the leading cause of mortality in essential thrombocythemia (ET), but the definition of thrombotic risk remains far from clear. OBJECTIVES: The aim of this study was to evaluate the prognostic markers for thrombosis to identify ET patients at risk. MATERIAL AND METHODS: Forty-five consecutive patients with ET were studied. This group was divided into two subgroups ET patients with (A) and without (B) history of thrombosis...
January 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28397397/the-structural-basis-for-the-functional-comparability-of-factor-viii-and-the-long-acting-variant-recombinant-factor-viii-fc-fusion-protein
#14
N C Leksa, P-L Chiu, G M Bou-Assaf, C Quan, Z Liu, A B Goodman, M G Chambers, S E Tsutakawa, M Hammel, R T Peters, T Walz, J D Kulman
BACKGROUND: Fusion of the human IgG1 Fc domain to the C-terminal C2 domain of B domain-deleted (BDD) factor VIII (FVIII) results in the rFVIIIFc fusion protein that has a 1.5-fold longer half-life in humans. OBJECTIVE: To assess the structural properties of rFVIIIFc by comparing its constituent FVIII and Fc elements with their respective isolated components and evaluating their structural independence within rFVIIIFc. METHODS: rFVIIIFc and its isolated FVIII and Fc components were compared by hydrogen-deuterium exchange mass spectrometry (HDX-MS)...
April 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28393618/regulatory-b-cells-are-functionally-impaired-in-patients-having-hemophilia-a-with-inhibitors
#15
Mohamed-Rachid Boulassel, Maryam Al-Ghonimi, Badriya Al-Balushi, Amal Al-Naamani, Zahra Al-Qarni, Yasser Wali, Mohamed Elshinawy, Maryam Al-Shezawi, Hamad Khan, Hanan Nazir, Doaa Khater, Anil Pathare, Salam Al-Kindi
Development of inhibitors remains a major clinical complication in patients with hemophilia A receiving replacement therapy with factor VIII (FVIII). Understanding the immune mechanisms involved in the development of inhibitors can provide valuable information about pathways to human tolerance. Recent evidence indicates that B regulatory (Breg) cells play a pivotal role in controlling the production of antibodies (Abs) while promoting follicular T helper (Tfh) cells and monocytes, expressing the low-density lipoprotein receptor-related protein (LRP/CD91), which is involved in FVIII intake from the circulation...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28393468/the-association-between-health-utility-and-joint-status-among-people-with-severe-haemophilia-a-findings-from-the-kappa-register
#16
M Osooli, K Steen Carlsson, F Baghaei, M Holmström, S Rauchensteiner, P A Holme, L Hvitfeldt, J Astermark, E Berntorp
INTRODUCTION: People with severe haemophilia A have reportedly impaired health related quality of life (utility) mainly due to recurrent bleeding, arthropathy and treatment burden. AIM: To estimate utilities and evaluate their potential correlates - most importantly the joint status - among people with severe haemophilia A. METHODS: In this cross-sectional study, eligible participants had severe haemophilia A, were aged ≥15, negative for factor VIII inhibitor and included in the KAPPA register of Denmark, Norway and Sweden...
April 10, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28388959/autosomal-recessive-inherited-bleeding-disorders-in-pakistan-a-cross-sectional-study-from-selected-regions
#17
Arshi Naz, Muhammad Younus Jamal, Samina Amanat, Ikram Din Ujjan, Akber Najmuddin, Humayun Patel, Fazle Raziq, Nisar Ahmed, Ayisha Imran, Tahir Sultan Shamsi
BACKGROUND: Autosomal recessive bleeding disorders (ARBDs) include deficiencies of clotting factors I, II, V, VII, X, XI, XIII, vitamin K dependent clotting factors, combined factor V & VIII, Von Willebrand Disease (vWD) type 3, Glanzmann's thrombasthenia (GT) and Bernard-Soulier syndrome. Patients with primary bleeding disorders from all the major provincial capitals of Pakistan were screened for ARBDs. Prothrombin (PT), activated partial thromboplastin time (APTT), bleeding time (BT) and fibrinogen levels were measured...
April 7, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28388863/perioperative-coagulation-management-of-a-hemophilia-a-patient-during-cardiac-surgery
#18
Patrick Odonkor, Archana Srinivas, Erik Strauss, Brittney Williams, Michael Mazzeffi, Kenichi A Tanaka
Perioperative management of cardiovascular surgical procedures requiring cardiopulmonary bypass (CPB) in patients with hemophilia A poses a clinical challenge in coagulation management. Use of CPB requires the administration of an anticoagulant, usually unfractionated heparin, and also causes dilutional coagulopathy, platelet dysfunction or platelet consumption coagulopathy. Hypothermia and activation of the inflammatory cascade also affect coagulation. The effects of CPB on circulating levels of factor VIII have not been clearly defined...
April 1, 2017: Seminars in Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28387451/large-scale-studies-assessing-anti-factor-viii-antibody-development-in-previously-untreated-haemophilia-a-what-has-been-learned-what-to-believe-and-how-to-learn-more
#19
REVIEW
Alfonso Iorio, Kathelijn Fischer, Michael Makris
Minimizing the risk of inhibitor development by acting on modifiable risk factors remains a sensible goal for treatment optimization in haemophilia A. By critically appraising published studies assessing inhibitor development, this review addresses the role of studies in previously untreated patients (PUPs) for establishing the immunogenicity of new concentrates, suggest novel research design to be adopted in future studies and discuss clinical practice implications of the reported differential immunogenicity of Kogenate Bayer and Advate factor VIII concentrates...
April 7, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28384907/a-study-of-haematological-and-haemostasis-parameters-and-hypercoagulable-state-in-tuberculosis-patients-in-northern-india-and-the-outcome-with-anti-tubercular-therapy
#20
Aditya Singh Kutiyal, Naresh Gupta, Sandeep Garg, Harmanjit Singh Hira
INTRODUCTION: Tuberculosis is one of the leading infectious diseases with high morbidity and mortality in the developing countries. Tuberculosis is also rarely associated with hypercoagulable state and very limited literature is available on this association. AIM: To study the haematological and haemostasis laboratory parameters, to correlate the abnormalities for a hypercoagulable state and to study the outcome with anti-tubercular therapy. MATERIALS AND METHODS: The study population included 128 patients with newly diagnosed tuberculosis...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
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