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Factor VIII inhibitor

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https://www.readbyqxmd.com/read/28920105/the-impact-of-von-willebrand-factor-on-factor-viii-memory-immune-responses
#1
Juan Chen, Jocelyn A Schroeder, Xiaofeng Luo, Qizhen Shi
Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis were used to study FVIII-primed CD4(+) T cells...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/28905885/long-term-correction-of-hemophilia-a-mice-following-lentiviral-mediated-delivery-of-an-optimized-canine-factor-viii-gene
#2
J M Staber, M J Pollpeter, C-G Anderson, M Burrascano, A L Cooney, P L Sinn, D T Rutkowski, W C Raschke, P B McCray
Current therapies for hemophilia A include frequent prophylactic or on-demand intravenous factor treatments which are costly, inconvenient and may lead to inhibitor formation. Viral vector delivery of factor VIII (FVIII) cDNA has the potential to alleviate the debilitating clotting defects. Lentiviral-based vectors delivered to murine models of hemophilia A mediate phenotypic correction. However, a limitation of lentiviral-mediated FVIII delivery is inefficient transduction of target cells. Here, we engineer a feline immunodeficiency virus (FIV) -based lentiviral vector pseudotyped with the baculovirus GP64 envelope glycoprotein to mediate efficient gene transfer to mouse hepatocytes...
September 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28903884/successful-outcome-of-severe-intra-cerebral-bleeding-associated-with-acquired-factor-v-inhibition-utilization-of-multiple-therapeutic-agents
#3
Panagiotis Andreadis, Katerina Kafantari, Aleka Agapidou, Sofia Vakalopoulou, Efthymia Vlachaki
BACKGROUND: Acquired coagulation Factor inhibitors are antibodies that either inhibit the activity or increase the clearance of a clotting factor leading to an increased risk of bleeding. Most of the times, the disorder is attributed to Factor VIII inhibition (Acquired Hemophilia A), however other coagulation factors could also be implicated. CASE REPORT: We herein would like to report an interesting case of a patient who underwent Coronary Artery Bypass Graft and received antibiotic treatment after surgery with a third-generation cephalosporin...
September 13, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28900904/lonoctocog-alfa-a-review-in-haemophilia-a
#4
Zaina T Al-Salama, Lesley J Scott
Lonoctocog alfa (rVIII-SingleChain; Afstyla(®)) is a novel single-chain recombinant factor VIII (FVIII) molecule, with a truncated B-domain and the heavy and light chains covalently linked to form a stable and homogenous drug that binds with high affinity to von Willebrand factor (VWF). Intravenous lonoctocog alfa is approved for the prophylaxis and treatment of bleeding in patients with haemophilia A in several countries worldwide. In two pivotal, multicentre trials, lonoctocog alfa was effective in the treatment of bleeding episodes and as prophylaxis, including for perioperative management in adults, adolescents and children...
September 12, 2017: Drugs
https://www.readbyqxmd.com/read/28884611/an-evaluation-of-the-activated-partial-thromboplastin-time-waveform
#5
Takeshi Matsumoto, Hideo Wada, Naoki Fujimoto, Junki Toyoda, Yasunori Abe, Kohshi Ohishi, Yoshiki Yamashita, Makoto Ikejiri, Kei Hasegawa, Kei Suzuki, Hiroshi Imai, Kaname Nakatani, Naoyuki Katayama
The activated partial thromboplastin time (APTT) waveform includes several parameters that are related to various underlying diseases. The APTT waveform was examined in various diseases. Regarding the pattern of APTT waveform, a biphasic pattern of the first or second derivative curve (DC) was observed in patients with hemophilia and patients positive for antiphospholipid (aPL) antibodies or coagulation factor VIII (FVIII) inhibitors. The time of the first and second DC and fibrin formation at 1/2 height were prolonged in patients with hemophilia, patients with inhibitors, patients positive for aPL, patients treated with anti-Xa agents, and patients with disseminated intravascular coagulation (DIC)...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28884475/chronic-exposure-of-interleukin-13-suppress-the-induction-of-matrix-metalloproteinase-1-by-tumor-necrosis-factor-%C3%AE-in-normal-and-scleroderma-dermal-fibroblasts-through-protein-kinase-b-akt
#6
Monica L Brown Lobbins, Bangalore R Shivakumar, Arnold E Postlethwaite, Karen A Hasty
OBJECTIVE: Peripheral blood mononuclear cells taken from patients with scleroderma express increased levels of IL-13. Moreover, the expression of MMP-1 from involved scleroderma skin fibroblasts is refractory to stimulation by tumor necrosis factor alpha. To elucidate the mechanism(s) involved, we examined the effect of IL-13 on TNF-α-induced matrix metalloproteinase-1 expression in normal and scleroderma human dermal fibroblast lines and studied the involvement of serine/threonine kinase B/Akt in this response...
September 7, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28865249/effects-of-ultra-low-dose-versus-standard-hormone-therapy-on-fibrinolysis-and-thrombin-generation-in-postmenopausal-women
#7
Magdalena Piróg, Robert Jach, Anetta Undas
OBJECTIVE: To assess the effects of different doses of oral hormone therapy (HT) on thrombin generation and fibrinolysis. STUDY DESIGN: One hundred fifty postmenopausal women were assigned in a randomized controlled study in which the effect of standard dose (1mg 17β-estradiol/5mg dydrogesterone), ultra-low-dose HT (0.5mg 17β-estradiol/2.5mg dydrogesterone) on fibrinolysis and coagulation was compared to controls. Factors measured included plasma clot lysis time (CLT), fibrinolysis activators and inhibitors, thrombin generation (prothrombin fragments 1+2 [F1+2], endogenous thrombin potential [ETP]), normalized activated protein C sensitivity ratio (nAPCsr), and factor (F)VIII activity and were determined before and after 24 weeks of HT...
August 22, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28857257/mir-200a-mediates-protection-of-thymosin-beta-4-in-cardiac-microvascular-endothelial-cells-as-a-novel-mechanism-under-hypoxia-reoxygenation-injury
#8
Yang Li, Xiaolong Zhu, Xiping Liu, Aolin Du, Bo Yu
Thymosin beta-4 (Tβ4) is a ubiquitous protein, which has been suggested to regulate multiple cell signal pathways and a variety of cellular functions. However, the role Tβ4 plays in the cardiac microvascular endothelial cells (CMECs) under myocardial ischemia/reperfusion injury (MIRI) is currently unknown. Here we investigated the effects of Tβ4 on hypoxia/reoxygenation (H/R) induced CMECs injury and its potential molecular mechanism. Cultured CMECs were positively identified by flow cytometry using antibody against CD31 and VWF/Factor VIII, which are constitutively expressed on the surface of CMECs...
August 31, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28836262/immune-status-of-patients-with-haemophilia-a-before-exposure-to-factor-viii-first-results-from-the-hemfil-study
#9
Letícia L Jardim, Daniel G Chaves, Amanda C O Silveira-Cassette, Ana Cristina Simões E Silva, Marcio P Santana, Monica H Cerqueira, Alessandra Prezotti, Claudia Lorenzato, Vivian Franco, Johanna G van der Bom, Suely M Rezende
Previous cross-sectional studies showed that some patients with haemophilia A (HA) without inhibitor presented a pro-inflammatory profile during factor VIII (FVIII) replacement therapy. Furthermore, an anti-inflammatory/regulatory state was described in HA patients after inhibitor development. However, no study investigated the levels of these biomarkers before exposure to exogenous FVIII. This study investigated the immunological profile of previously untreated patients (PUPs) with HA in comparison with non-haemophiliac boys...
August 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28804837/detection-and-measurement-of-factor-inhibitors
#10
Geoffrey Kershaw
Specific coagulation factor inhibitors, most notably to coagulation factor VIII, can develop in patients with hemophilia after exposure to replacement factor or as an acquired (autoimmune) event. Such inhibitors can be detected by a combination of prolonged coagulation screening tests, such as the activated partial thromboplastin time, plus a non-correcting mixing test. Non-correction may only be evident, or else may be extenuated, with incubation at 37 °C. The Bethesda assay for quantitation of inhibitor strength is based on a combination of mixing tests followed by specific factor assays...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28804828/lupus-anticoagulant-testing-diluted-russell-viper-venom-time-drvvt
#11
Vittorio Pengo, Elisa Bison, Alessandra Banzato, Giacomo Zoppellaro, Seena Padayattil Jose, Gentian Denas
Diluted Russell Viper Venom Time (dRVVT) has become the most popular test to detect Lupus Anticoagulant (LA). dRVVT is more sensitive than other global tests employed to detect LA and is not affected by inhibitors of factor VIII or IX. The test is most successfully implemented if you observe three steps in its execution: screening, mixing, and confirmatory studies. Interference due to the presence of heparin in tested plasma must be excluded by means of thrombin time (TT). The prior use of Vitamin K Antagonists (VKAs) or Non-vitamin K Oral Anticoagulants (NOACs) must also be evaluated by means of International Normalized Ratio, or specific tests, respectively...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28804823/an-overview-of-thrombophilia-and-associated-laboratory-testing
#12
Martina Montagnana, Giuseppe Lippi, Elisa Danese
Venous thromboembolism, usually entailing deep vein thrombosis, pulmonary embolism, or both, is a complex and multifactorial disorder, in which a number of putative conditions interplay and finally contribute to propel the individual risk over a certain degree, so ultimately culminating in the development of venous occlusive disorders. Thrombophilia is commonly defined as a propensity to develop venous thromboembolism on the basis of an underlying hypercoagulable state attributable to inherited or acquired disorders of blood coagulation or fibrinolysis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28795528/limit-of-detection-and-threshold-for-positivity-of-the-centers-for-disease-control-and-prevention-assay-for-factor-viii-inhibitors
#13
Connie H Miller, Brian Boylan, Amy D Shapiro, Steven R Lentz, Brian M Wicklund
BACKGROUND: The Bethesda assay (BA) for measurement of factor VIII (FVIII) inhibitors called for quantitation of positive inhibitors using dilutions producing 25-75% residual activity (RA), corresponding to 0.4-2.0 Bethesda units, recommending use of "more sensitive methods" for samples with RA closer to 100%. The Nijmegen modification (NBA) changed the reagents used but not these calculations. Some specimens negative by NBA have been shown to have FVIII antibodies detectable by sensitive immunologic methods...
August 10, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28767473/acquired-hemophilia-a-after-hepatic-yttrium-90-radioembolization-a-case-report
#14
Susanna Tribuzi, Alessia Naccarato, Lorella Pelagalli, Marco Covotta, Giulia Torregiani, Claudia Claroni, Ester Forastiere
Acquired hemophilia is a rare but potentially life-threatening bleeding disorder caused by the development of autoantibodies (inhibitors) directed against plasma coagulation factors, most frequently factor VIII. We report a case of a 65-year-old man with hepatocellular carcinoma who bled massively after a hepatic Yttrium-90 radioembolization procedure (Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres [SIRTex]). An acquired deficiency of factor VIII was diagnosed and successfully treated with recombinant activated factor VII and immunosuppression...
August 1, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28764183/acquired-inhibitor-of-factor-viii-presenting-as-delayed-wound-healing
#15
Sushma Nayar, Kishore Babu Esakkimuthu Parvathi, Mayilananthi Kaliannan, Premlatha Sivasailam
Acquired coagulation factor VIII inhibitor leads to a rare disease i.e., acquired haemophilia which is idiopathic in majority of cases and is seen with autoimmune diseases, haematologic and solid tumours, infections, in the post-partum period and also with certain long-term use of drugs like penicillin and its derivatives, phenytoin, sulfa antibiotics, chloramphenicol, methyldopa, chlorpromazine, levodopa, interferon-α, fludarabine, clopidogrel. We report a case here, with acquired Factor VIII (FVIII) inhibitor acquisition which presented with delayed wound healing as a result of protracted bleeding into the wound...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28756381/acquired-haemophilia-a-with-a-recalcitrant-high-titre-factor-viii-inhibitor-in-the-setting-of-interstitial-lung-disease
#16
Lova Sun, David B Sykes
Acquired haemophilia A (AHA) is a bleeding disorder that results from autoantibodies against factor VIII (FVIII). A 70-year-old man with a history of interstitial lung disease presented with spontaneous bleeding into his thigh. He had undetectable FVIII levels and a high-titre FVIII inhibitor (>2000ââ'¬â€°Bethesda units/mL) and was diagnosed with AHA. He had several relapses, required multiple haemostatic and immunosuppressive treatments but eventually achieved a stable remission after 2ââ'¬â€°years of therapy...
July 28, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28750470/clot-waveform-analysis-using-cs-2000i%C3%A2-distinguishes-between-very-low-and-absent-levels-of-factor-viii-activity-in-patients-with-severe-haemophilia-a
#17
T Matsumoto, K Nogami, Y Tabuchi, K Yada, K Ogiwara, H Kurono, N Arai, M Shima
INTRODUCTION: A recently developed method to assess comprehensive coagulation function, clot waveform analysis (CWA), accurately detect low levels (<1 IU/dL) of factor VIII activity (FVIII:C) in haemophilia A patients (HA-pts). Improvements are needed, however, to differentiate patients with very low from absent levels of FVIII:C. AIM: We attempted to optimize CWA using the coagulation analyser CS-2000i™ to distinguish between very low levels and absent FVIII:C in severe HA-pts...
July 27, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28729433/selective-factor-viii-activation-by-the-tissue-factor-factor-viia-factor-xa-complex
#18
Yuichi Kamikubo, G Loredana Mendolicchio, Antonella Zampolli, Patrizia Marchese, Andrea S Rothmeier, Jennifer Nagrampa Orje, Andrew J Gale, Sriram Krishnaswamy, András Gruber, Henrik Østergaard, Lars C Petersen, Wolfram Ruf, Zaverio M Ruggeri
Safe and effective antithrombotic therapy requires understanding of mechanisms that contribute to pathological thrombosis but have lesser impact on hemostasis. We found that the extrinsic tissue factor (TF) coagulation initiation complex can selectively activate the anti-hemophilic cofactor, FVIII, triggering the hemostatic intrinsic coagulation pathway independently of thrombin feedback loops. In a mouse model with a relatively mild thrombogenic lesion, TF-dependent FVIII activation sets the threshold for thrombus formation through contact phase-generated FIXa...
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28727494/efficacy-of-standard-prophylaxis-versus-on-demand-treatment-with-bayer-s-sucrose-formulated-recombinant-fviii-rfviii-fs-in-chinese-children-with-severe-hemophilia-a
#19
Yongqiang Zhao, Juan Xiao, Renchi Yang, Runhui Wu, Yu Hu, Horst Beckmann, Junde Wu, Qingsong Hou, Jing Sun
In China, care of patients with severe hemophilia primarily involves insufficient dosing of on-demand treatment and secondary low-dose prophylaxis (10 IU/kg 2× /wk). We sought to evaluate 3× /wk, standard-dose prophylaxis with sucrose-formulated recombinant factor VIII (rFVIII-FS; Bayer) compared with on-demand treatment in Chinese children with severe hemophilia A. Children and adolescents aged 2-16 years with severe hemophilia A, no inhibitors, and no prophylaxis for >6 consecutive months before study entry were eligible for this 24-week, interventional, sequential-treatment study...
July 20, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/28716745/gut-derived-endotoxin-stimulates-factor-viii-secretion-from-endothelial-cells-implications-for-hypercoagulability-in-cirrhosis
#20
Carnevale Roberto, Raparelli Valeria, Nocella Cristina, Bartimoccia Simona, Novo Marta, Severino Anna, De Falco Elena, Cammisotto Vittoria, Pasquale Chiara, Crescioli Clara, Sili Scavalli Antonio, Riggio Oliviero, Basili Stefania, Violi Francesco
BACKGROUND & AIMS: Patients with cirrhosis display enhanced blood levels of factor VIII, which may result in harmful activation of the clotting system; however, the underlying mechanism is unknown. METHODS: We performed a cross-sectional study in cirrhotic patients (n=61) and matched controls (n=61) comparing blood levels of factor VIII, von Willebrand factor (vWf), lipopolysaccharide (LPS) and positivity for Escherichia Coli DNA. Furthermore, we performed an in-vitro study to investigate if LPS, in a range of concentration similar to that found in the peripheral circulation of cirrhotic patients, was able to elicit factor VIII secretion from human umbilical vein endothelial cells (HUVEC)...
July 14, 2017: Journal of Hepatology
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