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factor viii inhibitors

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https://www.readbyqxmd.com/read/29329462/silibinin-from-silybum-marianum-stimulates-embryonic-stem-cell-vascular-differentiation-via-the-stat3-pi3-k-akt-axis-and-nitric-oxide
#1
Enas Hussein Ali, Fatemeh Sharifpanah, Maria Wartenberg, Heinrich Sauer
Silibinin, the bioactive compound of milk thistle (Silybum marianum), exerts tissue protective and regenerative effects that may include stem cell differentiation toward vascular cells. The purpose of the present study was to investigate whether silibinin stimulates blood vessel formation from mouse embryonic stem (ES) cells and to unravel the underlying signaling cascade. Vascular branching points were assessed by confocal laser scanning microscopy and computer-assisted image analysis of CD31-positive cell structures...
January 12, 2018: Planta Medica
https://www.readbyqxmd.com/read/29324332/impaired-plasminogen-binding-in-patients-with-venous-thromboembolism-association-with-protein-carbonylation
#2
Jakub Siudut, Joanna Natorska, Michal Zabczyk, Dorota Zajac, Karolina Seweryn, Maria Rąpała-Kozik, Anetta Undas
INTRODUCTION: Venous thromboembolism (VTE) is associated with hypofibrinolysis. Its mechanisms are poorly understood. We investigated plasminogen-fibrin interaction and its association with fibrinolytic capacity and protein oxidation/carbonylation in VTE patients. MATERIALS AND METHODS: Plasma-purified plasminogen conversion to plasmin and surface plasmon resonance employed for plasminogen-fibrin interactions were individually evaluated in all healthy controls and non-anticoagulated patients following VTE, 10-23months since the event...
January 5, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29314552/australian-multicentre-study-of-current-real-world-prophylaxis-practice-in-severe-and-moderate-haemophilia-a-and-b
#3
J A Mason, S Parikh, H Tran, J Rowell, S McRae
INTRODUCTION: With the emergence of novel treatment products for haemophilia and an increasing focus on the benefits of pharmacokinetic driven individualized prophylaxis, robust national data with regard to current patterns of factor consumption and adherence are required. AIM: To characterize current Australian practice with regard to use of prophylactic clotting factor infusions in patients with moderate or severe haemophilia A (HA) and haemophilia B (HB). METHODS: This was a retrospective, non-interventional study utilizing Australian Bleeding Disorder Registry (ABDR) data collected over a 12 month period...
January 3, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/29314439/low-incidence-of-factor-viii-inhibitors-in-previously-untreated-patients-with-severe-haemophilia-a-treated-with-octanate%C3%A2-final-report-from-a-prospective-study
#4
A Klukowska, V Komrska, V Vdovin, A Pavlova, M Jansen, S Lowndes, L Belyanskaya, O Walter, P Laguna
INTRODUCTION: Octanate® is a human, plasma-derived, von Willebrand factor-stabilized coagulation factor VIII (FVIII) concentrate with demonstrated haemostatic efficacy in previously treated patients with haemophilia A. AIM: This prospective, open-label study aimed to assess the immunogenicity of octanate® in previously untreated patients (PUPs). METHODS: The study monitored development of FVIII inhibitors in 51 PUPs. Tolerability, viral safety, FVIII recovery and efficacy of octanate® for the prevention and treatment of bleeds and in surgical procedures were also assessed...
January 3, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/29296914/severe-platelet-dysfunction-in-nhl-patients-receiving-ibrutinib-is-absent-in-patients-receiving-acalabrutinib
#5
Alexander P Bye, Amanda J Unsworth, Michael J Desborough, Catherine A T Hildyard, Niamh Appleby, David Bruce, Neline Kriek, Sophie H Nock, Tanya Sage, Craig E Hughes, Jonathan M Gibbins
The Bruton tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding. Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side effects of ibrutinib. The second-generation Btk inhibitor acalabrutinib was developed with improved specificity for Btk over Tec. We investigated platelet function in patients with non-Hodgkin lymphoma (NHL) receiving ibrutinib or acalabrutinib by aggregometry and by measuring thrombus formation on collagen under arterial shear...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296836/long-term-safety-and-efficacy-of-emicizumab-in-a-phase-1-2-study-in-patients-with-hemophilia-a-with-or-without-inhibitors
#6
Midori Shima, Hideji Hanabusa, Masashi Taki, Tadashi Matsushita, Tetsuji Sato, Katsuyuki Fukutake, Ryu Kasai, Koichiro Yoneyama, Hiroki Yoshida, Keiji Nogami
Emicizumab (ACE910), a recombinant humanized bispecific monoclonal antibody, provides factor VIII (FVIII) cofactor bridging function to restore hemostasis in people with hemophilia A. In a phase 1 trial involving 18 Japanese patients with severe hemophilia A, once-weekly subcutaneous administration of emicizumab 0.3, 1, or 3 mg/kg (cohorts 1, 2, and 3, respectively) was well tolerated and substantially reduced annualized bleeding rates (ABRs) in the presence or absence of FVIII inhibitors. The current study represents an open-label, long-term extension of the previously reported 12-week phase 1 study, in which 16 of 18 patients continued to receive emicizumab for up to 33...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29285874/early-cellular-interactions-and-immune-transcriptome-profiles-in-human-factor-viii-exposed-hemophilia-a-mice
#7
J D Lai, D Cartier, R B Hartholt, L L Swystun, A S van Velzen, J M M den Haan, C Hough, J Voorberg, D Lillicrap
BACKGROUND: Developing factor VIII (FVIII) inhibitory antibodies is the most serious complication in hemophilia A treatment, representing a significant health and economic burden. A better understanding of the early events in an immune response leading to this outcome may provide insight into inhibitor development. OBJECTIVE: To identify early mediators of FVIII immunity and to detail immune expression profiles in the spleen and liver. METHODS: C57Bl/6 F8 E16 knockout mice were infused with 5-20 μg (2000-8000 IU/kg) of recombinant FVIII...
December 28, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29285161/hemorrhagic-pleural-effusion-related-to-acquired-coagulation-factor-viii-deficiency-a-case-report
#8
Yu-Ping Liu, Xiang-Hua Lin, Xue-Ke Wang, Shang-Zhi Yang, Chang-Qing Fan
A patient with acquired hemophilia A (AHA) with hemorrhagic pericardial effusions was admitted to Xiamen Chang Gung Hospital (Xiamen, China) in August 2015. The patient had been experiencing progressive dyspnea for 1 week. Bloody effusion (~6.3 l) was drained from the membrane surrounding the heart over a period of 20 days. Biochemical, cytological and radiological examinations were unable to elucidate the reason for the effusion. Coincidentally, it was discovered that activated partial thromboplastin time prolongation could not be corrected by plasma mixing...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29276087/acquired-factor-viii-inhibitor-and-cardiopulmonary-bypass-a-case-report
#9
Matthias Längin, Mark Konrad, Bruno Reichart, Andreas Bauer, Susanne Lison
No abstract text is available yet for this article.
July 13, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/29258406/a-contemporary-look-at-fviii-inhibitor-development-still-a-great-influence-on-the-evolution-of-hemophilia-therapies
#10
Elena Santagostino, Guy Young, Manuel Carcao, Pier Mannuccio Mannucci, Susan Halimeh, Steve Austin
The development of inhibitors against factor VIII (FVIII) replacement therapy remains the most important challenge for clinicians in the treatment of hemophilia patients. This review focusses on risk factors and management of FVIII inhibitors, particularly in light of SIPPET study findings and subsequent analyses. Areas covered: A brief history and evolution of hemophilia therapies is provided, including an overview of conventional and new (including investigational) therapeutic approaches for the treatment of hemophilia...
December 19, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29243367/vaccinations-are-not-associated-with-inhibitor-development-in-boys-with-severe-haemophilia-a
#11
H Platokouki, K Fischer, S C Gouw, A Rafowicz, M Carcao, G Kenet, R Liesner, K Kurnik, G E Rivard, H M van den Berg
BACKGROUND: Inhibitor development in previously untreated patients (PUPs) with severe haemophilia A is a multifactorial event. It is unknown whether paediatric vaccinations given in close proximity to factor VIII (FVIII) are associated with inhibitor development. OBJECTIVE: To assess whether paediatric vaccinations in close proximity to FVIII within the first 75 exposure days (EDs) are associated with inhibitor development in PUPs with severe haemophilia A. METHODS: We included 375 PUPs with severe haemophilia A (<0...
December 15, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/29240027/congenital-hemophilia-a-presenting-with-hashimoto-s-encephalopathy-and-myocarditis-the-first-reported-case
#12
Ayse B Ergul, Yasemin Altuner Torun, Umut Altug, Fatma T Mutlu, Serkan F Celik, Ahmet S Guven
Here, we report a case of hemophilia A with myocarditis, encephalopathy, and spontaneous intramedullary hemorrhage. A 14-month-old male infant presented with loss of consciousness, generalized tonic-clonic convulsions, and cardiac failure. The neurological examination was normal. Myocarditis was diagnosed. After administration of fresh frozen plasma, the aPTT did not return to normal. The factor VIII (FVIII) level was 10.2% the normal level, and the patient was diagnosed with hemophilia A. The cerebrospinal fluid (CSF) evaluation was unremarkable, with the exception of elevated CSF protein levels...
December 12, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29225598/innovative-approaches-for-immune-tolerance-to-factor-viii-in-the-treatment-of-hemophilia-a
#13
REVIEW
Alexandra Sherman, Moanaro Biswas, Roland W Herzog
Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies ("inhibitors") remains. Overall, 20-30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29222310/novel-alternate-hemostatic-agents-for-patients-with-inhibitors-beyond-bypass-therapy
#14
REVIEW
Margaret V Ragni
Inhibitor formation is among the most severe complications of hemophilia treatment. With a cumulative incidence of ∼30% in those with severe hemophilia A and ∼3% in those with severe hemophilia B, inhibitors are caused by a T-cell response directed against infused coagulation factor; these inhibitors neutralize factor VIII or IX activity and disrupt normal hemostasis. Inhibitor patients become unresponsive to standard factor treatment and, as an alternative, use bypass treatment (eg, recombinant factor VIIa or factor VIII inhibitor bypass activity)...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29215814/safety-and-efficacy-of-b-domain-deleted-third-generation-recombinant-factor-viii-greengene-f%C3%A2-in-korean-patients-with-hemophilia-a-data-from-a-post-marketing-surveillance-study
#15
Soon Ki Kim, Ki Young Yoo, Kun Soo Lee, Taiju Hwang, Yong Mook Choi, Eun Jin Choi, Sang Kyu Park
BACKGROUND: New B-domain deleted third generation recombinant factor VIII (FVIII; GreenGene F™, beroctocog alfa) was launched in 2010. We determined safety and efficacy of GreenGene F™ during routine clinical practice in patients with hemophilia A over a period of 12 months. METHODS: From July 2010 to July 2014, a total of 136 hemophilia A patients were enrolled in a post-marketing surveillance (PMS) study. Among them, 134 patients were assessed for drug safety and 114 patients were analyzed for drug efficacy...
January 1, 2018: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/29214439/a-pharmacometric-approach-to-substitute-for-a-conventional-dose-finding-study-in-rare-diseases-example-of-phase-iii-dose-selection-for-emicizumab-in-hemophilia-a
#16
Koichiro Yoneyama, Christophe Schmitt, Naoki Kotani, Gallia G Levy, Ryu Kasai, Satofumi Iida, Midori Shima, Takehiko Kawanishi
BACKGROUND: Emicizumab (ACE910) is a bispecific antibody mimicking the cofactor function of activated coagulation factor VIII. In phase I-I/II studies, emicizumab reduced the bleeding frequency in patients with severe hemophilia A, regardless of the presence of factor VIII inhibitors, at once-weekly subcutaneous doses of 0.3, 1, and 3 mg/kg. METHODS: Using the phase I-I/II study data, population pharmacokinetic and repeated time-to-event (RTTE) modeling were performed to quantitatively characterize the relationship between the pharmacokinetics of emicizumab and reduction in bleeding frequency...
December 6, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29202211/acute-haemarthrosis-in-the-haemophilia-a-rat-generates-a-local-and-systemic-proinflammatory-response
#17
Karin M Lövgren, Kristine R Christensen, Wiktor Majewski, Olga Østrup, Søren Skov, Bo Wiinberg
Background Replacement therapy with coagulation factor VIII (FVIII) concurrent with bleeds (on-demand) in haemophilia A (HA) patients has been hypothesized to increase the risk for antidrug antibodies (inhibitors). A danger signal environment, characterized by tissue damage and inflammation at the site of a bleed, is thought to contribute to the anti-FVIII response. The nature of this inflammatory reaction is, however, not fully known, and new insights will be valuable for both managing inhibitors and understanding arthropathy development...
November 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29201221/leptin-upregulates-cox-2-and-its-downstream-products-in-aortic-endothelial-cells
#18
Yuelin Chen, Yuechun Shen, Ya Nie, Zhongxin Chen, Huang Wang, Huang Liao, Jun Li
The adipocyte-derived hormone leptin is associated with hypertension. The involvement of cyclooxygenase-2 (COX-2) and its downstream vasomotor products prostaglandin (PG) and thromboxane (TX)A2 in the mechanisms of action of leptin have remained elusive. The aim of the present study was to investigate the effects of leptin on the expression of COX-2 by rat aortic endothelial cells (RAECs) and the concentration of its products, represented by 6-keto PGF1α and TXB2, in the culture media. RAECs were isolated, cultured and identified by immunofluorescence staining...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29201071/hemostasis-in-overt-and-subclinical-hyperthyroidism
#19
REVIEW
Arash Ordookhani, Kenneth D Burman
Context: There are contradictory results on the effect of hyperthyroidism on hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). The present review focuses on hemostatic changes in overt and subclinical hyperthyroidism. Methods: A systematic literature search was conducted employing MEDLINE database. The following words were used for the search: Hyperthyroidism; thyrotoxicosis; Graves disease; goiter, nodular; hemostasis; blood coagulation factors; blood coagulation disorders; venous thromboembolism; bleeding; fibrinolysis...
July 2017: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29165739/inhibitors-in-patients-with-congenital-bleeding-disorders-other-than-hemophilia
#20
Massimo Franchini, Giuseppe Marano, Carlo Mengoli, Vanessa Piccinini, Simonetta Pupella, Stefania Vaglio, Giancarlo Maria Liumbruno
The most worrying complication of replacement therapy for severe hemophilia A and B is currently the occurrence of inhibitory alloantibodies against infused factor VIII and factor IX, respectively. Inhibitors compromise the management of hemorrhage in affected patients, with a considerable increase in complications, disability, and costs. While these alloantibodies have been extensively studied in the past years in hemophilia A and B, those occurring in patients with other inherited bleeding disorders are less well characterized and still poorly understood, mostly due to the rarity of these hemorrhagic conditions...
November 17, 2017: Seminars in Thrombosis and Hemostasis
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