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Factor VIII antibody

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https://www.readbyqxmd.com/read/28507083/frequency-and-epitope-specificity-of-anti-factor-viii-c1-domain-antibodies-in-acquired-and-congenital-hemophilia-a
#1
Joerg Kahle, Aleksander Orlowski, Diana Stichel, John F Healey, Ernest T Parker, Marc Jaquemin, Manuela Krause, Andreas Tiede, Dirk Schwabe, Pete Lollar, Christoph Königs
Several studies showed that neutralizing anti-factor VIII (fVIII) antibodies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study the frequency and epitope specificity of anti-C1 antibodies were analyzed in acquired and congenital hemophilia inhibitor patients (n=178). The domain specificity of antibodies was studied by homologue-scanning mutagenesis (HSM) with single human domain human/porcine fVIII proteins and antibody binding to human A2, C1 and C2 domains presented as human serum albumin (HSA) fusion proteins...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28492697/cd32-inhibition-and-high-dose-of-rhfviii-suppress-murine-fviii-specific-recall-response-by-distinct-mechanisms-in-vitro
#2
Nadine Vollack, Julia Friese, Sabine Bergmann, Andreas Tiede, Sonja Werwitzke
Development of neutralising antibodies (inhibitors) against factor VIII (FVIII) is a frequent and severe complication of replacement therapy in haemophilia A. Previous data from haemophilia A mouse model demonstrates that both CD32 inhibition and high doses of rhFVIII prevent the differentiation of FVIII-specific memory B cells (MBCs) into antibody secreting cells (ASCs). Here, cellular targets responsible for the suppression of ASC formation by means of CD32 inhibition and high dose of rhFVIII were analysed...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28478688/gene-delivery-of-activated-factor-vii-using-alternative-aav-serotype-improves-hemostasis-in-hemophiliac-mice-with-fviii-inhibitors-and-aav-neutralizing-antibodies
#3
Junjiang Sun, Baolai Hua, R Jude Samulski, Chengwen Li
While therapeutic expression of coagulation factors from adeno-associated virus (AAV) vectors has been successfully achieved in patients with hemophilia, neutralizing antibodies to the vector and inhibitory antibodies to the transgene severely limit efficacy. Indeed, approximately 40% of mice transduced with human Factor VIII using the AAV8 serotype developed inhibitory antibodies to Factor VIII (FVIII inhibitor), as well as extremely high titers (≥ 1:500) of neutralizing antibodies to AAV8. To correct hemophilia in these mice we used AAV9, a serotype with low in vitro cross-reactivity (≤ 1:5) to anti-AAV8, to deliver mouse activated Factor VII (mFVIIa)...
May 6, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28470674/acquired-hemophilia-a-updated-review-of-evidence-and-treatment-guidance
#4
REVIEW
Rebecca Kruse-Jarres, Christine L Kempton, Francesco Baudo, Peter W Collins, Paul Knoebl, Cindy A Leissinger, Andreas Tiede, Craig M Kessler
Acquired hemophilia A (AHA) is a rare disease resulting from autoantibodies (inhibitors) against endogenous factor VIII (FVIII) that leads to bleeding, which is often spontaneous and severe. AHA tends to occur in elderly patients with comorbidities and is associated with high mortality risk from underlying comorbidities, bleeding, or treatment complications. Treatment, which consists of hemostatic management and eradication of the inhibitors, can be challenging to manage. Few data are available to guide the management of AHA-related bleeding and eradication of the disease-causing antibodies...
May 3, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28458935/successful-management-of-acquired-hemophilia-a-associated-with-bullous-pemphigoid-a-case-report-and-review-of-the-literature
#5
Quentin Binet, Catherine Lambert, Laurine Sacré, Stéphane Eeckhoudt, Cedric Hermans
Background. Acquired hemophilia A (AHA) is a rare condition, due to the spontaneous formation of neutralizing antibodies against endogenous factor VIII. About half the cases are associated with pregnancy, postpartum, autoimmune diseases, malignancies, or adverse drug reactions. Symptoms include severe and unexpected bleeding that may prove life-threatening. Case Study. We report a case of AHA associated with bullous pemphigoid (BP), a chronic, autoimmune, subepidermal, blistering skin disease. To our knowledge, this is the 25th documented case of such an association...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28458688/long-term-safety-of-pegylated-coagulation-factor-viii-in-the-immune-deficient-rowett-nude-rat
#6
Caroline E Rasmussen, Jette Nowak, Julie M Larsen, Emma Moore, David Bell, Kai Chiu Liu, Nanna Skall Sorensen, Wendela A Kappers, Thomas Krogh-Meibom, Hanne Offenberg
Turoctocog alfa pegol (N8-GP) is a glycoPEGylated human recombinant factor VIII for the treatment of hemophilia A. The safety profile of rFVIII, and polyethylene glycols (PEG) technology, is well-established. Conducting long-term toxicity studies in animals using human proteins can be complicated by anti-drug antibody (ADA) development. To evaluate long-term safety of N8-GP, 26- and 52-week toxicity studies were conducted in immune-deficient rats dosed intravenously every fourth day with 0, 50, 150, 500, or 1200 IU/kg N8-GP...
2017: Journal of Toxicology
https://www.readbyqxmd.com/read/28447409/factor-viii-inhibitors-advances-in-basic-and-translational-science
#7
REVIEW
J D Lai, D Lillicrap
In the treatment of hemophilia A, the 20%-30% risk of developing of anti-factor VIII (FVIII) antibodies, or inhibitors, is the dominant concern among healthcare providers. Immune tolerance induction remains the only effective method of eradicating inhibitors in approximately 75% of patients, but is accompanied by significant emotional and economical burden. While certain risk factors, such as the type of FVIII mutation, offer some insight, there remains no strategy to confidently predict the development of an inhibitor...
May 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28438758/diabetes-mellitus-and-acquired-haemophilia-new-association
#8
Carlos Tavares Bello, Yuliya Vasylenko, José Esteves, Carlos Augusto Vasconcelos
Diabetes mellitus encompasses a group of highly prevalent carbohydrate metabolic disorders with an increasing incidence. Some subtypes are thought to be associated with other immune-mediated diseases. Acquired haemophilia on the other hand is a quite rare autoimmune disease that is thought to be secondary to the emergence of inhibiting anticoagulation factor VIII antibodies (inhibitors) in patients with previously normal haemostatic function. More recently, numerous different diseases have been associated with acquired haemophilia namely immune-mediated diseases, drugs and solid and haematologic neoplasms...
April 24, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28432221/biological-considerations-of-plasma-derived-and-recombinant-factor-viii-immunogenicity
#9
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/28401801/thrombophilia-in-153-patients-with-premature-cardiovascular-disease-%C3%A2-age-45
#10
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/28397397/the-structural-basis-for-the-functional-comparability-of-factor-viii-and-the-long-acting-variant-recombinant-factor-viii-fc-fusion-protein
#11
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
Essentials Recombinant factor VIII (rFVIII) Fc fusion protein has a 1.5-fold longer half-life than rFVIII. Five orthogonal methods were used to characterize the structure of rFVIIIFc compared to rFVIII. The C-terminal Fc fusion does not perturb the structure of FVIII in rFVIIIFc. The FVIII and Fc components of rFVIIIFc are flexibly tethered and functionally independent. SUMMARY: 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 recombinant FVIII Fc (rFVIIIFc) fusion protein, which has a 1...
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
#12
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/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
#13
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/28384443/effect-of-platelet-derived-%C3%AE-thromboglobulins-on-coagulation
#14
Karl Egan, Johanna P van Geffen, Hui Ma, Barry Kevane, Aine Lennon, Seamus Allen, Elaine Neary, Martin Parsons, Patricia Maguire, Kieran Wynne, Richard O' Kennedy, Johan W M Heemskerk, Fionnuala Ní Áinle
BACKGROUND: β-thromboglobulins are derived from the cleavage of the CXC chemokine platelet basic protein and are released in high concentrations by activated platelets. Platelet-derived β-thromboglobulins (βTG) share 70% homology with platelet factor 4 (PF4), another CXC chemokine released by activated platelets. PF4 modulates coagulation by inhibiting heparin-antithrombin interactions, promoting protein C activation, and attenuating the activity of activated protein C. In contrast, the effect of βTG on coagulation is unknown...
March 30, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28352491/acquired-factor-viii-deficiency-two-case-reports-and-a-review-of-literature
#15
Lan Mo, George C Bao
BACKGROUND: Acquired factor VIII (FVIII) deficiency, or acquired hemophilia A (AHA), is a rare autoimmune disorder involving antibody-mediated depletion of coagulation FVIII, leading to severe, life-threatening bleeding. The condition is often associated with other autoimmune disorders, and its treatment involves replacement of FVIII and various modes of immunosuppression. Recently, a few noteworthy therapeutic advances have been made. We present two cases of severe AHA in Chinese women...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28285015/tnf%C3%AE-contributes-to-diabetes-impaired-angiogenesis-in-fracture-healing
#16
Jason C Lim, Kang I Ko, Marcelo Mattos, Miao Fang, Citong Zhang, Daniel Feinberg, Hisham Sindi, Shuai Li, Jazia Alblowi, Rayyan A Kayal, Thomas A Einhorn, Louis C Gerstenfeld, Dana T Graves
Diabetes increases the likelihood of fracture, interferes with fracture healing and impairs angiogenesis. The latter may be significant due to the critical nature of angiogenesis in fracture healing. Although it is known that diabetes interferes with angiogenesis the mechanisms remain poorly defined. We examined fracture healing in normoglycemic and streptozotocin-induced diabetic mice and quantified the degree of angiogenesis with antibodies to three different vascular markers, CD34, CD31 and Factor VIII. The role of diabetes-enhanced inflammation was investigated by treatment of the TNFα-specific inhibitor, pegsunercept starting 10days after induction of fractures...
March 8, 2017: Bone
https://www.readbyqxmd.com/read/28262242/an-extra-x-does-not-prevent-acquired-hemophilia-pregnancy-associated-acquired-hemophilia-a
#17
REVIEW
Assaf A Barg, Tami Livnat, Gili Kenet
Acquired hemophilia A (AHA) is a severe bleeding disorder caused by autoantibodies against clotting factor VIII (FVIII). With an estimated annual incidence of 1.3 to 1.5 per million, AHA is a rare disease. An extremely rare form of AHA has been described among women in the peripartum period, and may present with peripartum hemorrhage. Notably, although hemorrhagic symptoms commonly present 1-4 months around delivery, they may occur up to 1 year after parturition. When caring for a mother with AHA it is important to note that Factor VIII inhibitor may be transferred via the placenta from the mother to the fetus...
March 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28258054/thrombophilia-risk-is-not-increased-in-children-after-perinatal-stroke
#18
Colleen Curtis, Aleksandra Mineyko, Patricia Massicotte, Michael Leaker, Xiu Yan Jiang, Amalia Floer, Adam Kirton
Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable but mechanisms are poorly understood. Evidence suggests possible associations between arterial perinatal stroke and prothrombotic disorders but population-based, controlled, disease-specific studies are limited. Understanding thrombophilia in perinatal stroke informs pathogenesis models and clinical management. We conducted a population-based, prospective, case-control study to determine the association of specific perinatal stroke diseases with known thrombophilias...
March 3, 2017: Blood
https://www.readbyqxmd.com/read/28164173/tgf-%C3%AE-1-along-with-other-platelet-contents-augments-treg-cells-to-suppress-anti-fviii-immune-responses-in-hemophilia-a-mice
#19
Dipica Haribhai, Xiaofeng Luo, Juan Chen, Shuang Jia, Linzheng Shi, Jocelyn A Schroeder, Hartmut Weiler, Richard H Aster, Martin J Hessner, Jianda Hu, Calvin B Williams, Qizhen Shi
Platelets are a rich source of many cytokines and chemokines including transforming growth factor β 1 (TGF-β1). TGF-β1 is required to convert conventional CD4(+) T (Tconv) cells into induced regulatory T (iTreg) cells that express the transcription factor Foxp3. Whether platelet contents will affect Treg cell properties has not been explored. In this study, we show that unfractionated platelet lysates (pltLys) containing TGF-β1 efficiently induced Foxp3 expression in Tconv cells. The common Treg cell surface phenotype and in vitro suppressive activity of unfractionated pltLys-iTreg cells were similar to those of iTreg cells generated using purified TGF-β1 (purTGFβ-iTreg) cells...
December 13, 2016: Blood Advances
https://www.readbyqxmd.com/read/28157676/inhibitory-antibodies-against-factor-viii-c1-domain
#20
Gary E Gilbert
No abstract text is available yet for this article.
October 20, 2016: Blood
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