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Eric Paulus, Kathy Komperda, Gabriel Park, Julie Fusco
Factor VII (FVII) deficiency is the most prevalent rare bleeding disorder in the USA and affects approximately 1 out of every 500,000 people. Warfarin inhibits the synthesis of FVII, in addition to other clotting factors. Warfarin is contraindicated in patients with bleeding tendencies or blood dyscrasias; therefore, the literature regarding the use of warfarin in FVII deficiency is very limited. We report a successful re-challenge of warfarin therapy in a patient with FVII deficiency. A 70-year-old woman with FVII deficiency experienced a significant decrease in FVII activity and subsequent vaginal bleeding roughly 5 weeks after starting warfarin for atrial fibrillation...
December 2016: Drug Saf Case Rep
Pierre-Olivier Sevenet, Daniel A Kaczor, Francois Depasse
Factor VII (FVII) deficiency is a rare inheritable bleeding disorder affecting 1/500 000 individuals. Clinical manifestations are heterogeneous, from asymptomatic to severe and potentially fatal bleeding. These clinical manifestations do not correlate well with FVII plasma levels. For this reason, FVII-deficient patient management during surgery or for long-term prophylaxis remains challenging. Laboratory testing for FVII activity is, however, the first-line method for FVII deficiency diagnosis and is helpful for managing patients in combination with clinical history...
October 3, 2016: Clinical and Applied Thrombosis/hemostasis
Lin Peng, Wendian Xiong, Yanfei Cai, Yun Chen, Yang He, Jianfeng Yang, Jian Jin, Huazhong Li
Enhanced transfection efficiency of transient gene expression (TGE) and electroporation is a useful approach for improvement of recombinant therapeutic proteins in mammalian cells. A novel method is described here in which CHO cells expressing recombinant FVII (rFVII) were labeled with fluorescent dye and analyzed by confocal microscopy. Cells with or without rFVII encoding gene were detectable by flow cytometry. Thus, we were able to distinguish positive cells (with rFVII encoding gene) and quantify their percentages...
September 27, 2016: Bioengineered
D Woehrle, M Martinez, D Bolliger
BACKGROUND: A hereditary deficiency in coagulation factor VII (FVII) may affect the international normalized ratio (INR) value. However, FVII deficiency is occasionally associated with a tendency to bleed spontaneously. We hypothesized that perioperative substitution with coagulation factor concentrates might not be indicated in most patients. METHODS: In this retrospective data analysis, we included all patients with hereditary heterozygous FVII deficiency who underwent surgical procedures at the University Hospital Basel between December 2010 and November 2015...
October 2016: Der Anaesthesist
Siniša Sić, Norbert M Maier, Andreas M Rizzi
The potential and benefits of isotope-coded labeling in the context of MS-based glycan profiling are evaluated focusing on the analysis of O-glycans. For this purpose, a derivatization strategy using d0/d5-1-phenyl-3-methyl-5-pyrazolone (PMP) is employed, allowing O-glycan release and derivatization to be achieved in one single step. The paper demonstrates that this release and derivatization reaction can be carried out also in-gel with only marginal loss in sensitivity compared to in-solution derivatization...
September 7, 2016: Analytica Chimica Acta
Alexander Y Mitrophanov, Fania Szlam, Roman M Sniecinski, Jerrold H Levy, Jaques Reifman
BACKGROUND: The use of prothrombin complex concentrates in trauma- and surgery-induced coagulopathy is complicated by the possibility of thromboembolic events. To explore the effects of these agents on thrombin generation (TG), we investigated combinations of coagulation factors equivalent to 3- and 4-factor prothrombin complex concentrates with and without added antithrombin (AT), as well as recombinant factor VIIa (rFVIIa), in a dilutional model. These data were then used to develop a computational model to test whether such a model could predict the TG profiles of these agents used to treat dilutional coagulopathy...
September 2016: Anesthesia and Analgesia
Luca Spiezia, Elena Campello, Fabio Dalla Valle, Barry Woodhams, Paolo Simioni
The activation of the extrinsic coagulation pathway occurs after endothelial injury when the tissue factor (TF), a transmembrane protein located outside the vasculature, binds factor VII (FVII) or activated FVII (FVIIa). Once formed, the TF-VIIa complex activates both factor IX and X and initiates the coagulation process. The TF-VIIa complex is inhibited by both TF pathway inhibitor (TFPI) and antithrombin (AT). The interaction between TF-VIIa and AT induces FVIIa-AT complex formation, which is released into the plasma...
August 15, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
Alessio Branchini, Mattia Ferrarese, Silvia Lombardi, Rosella Mari, Francesco Bernardi, Mirko Pinotti
BACKGROUND: Whereas the rare homozygous nonsense mutations causing factor VII (FVII) deficiency may predict null conditions that are virtually incompatible with life, they can be associated with both life as well as appreciable differences in hemorrhagic symptoms. The misrecognition of premature stop codons (readthrough) may account for variable levels of functional full-length proteins. OBJECTIVES: To experimentally evaluate the basal and drug-induced levels of FVII produced by the homozygous p...
August 11, 2016: Journal of Thrombosis and Haemostasis: JTH
W-S Q See, K-O Chang, D K-L Cheuk, Y-Y R Leung, G C-F Chan, S-C Chan, S-Y Ha
Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis...
September 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
Piotr Kuta, Barbara Hauck-Dlimi, Julian Strobel, Robert Zimmermann, Reinhold Eckstein
BACKGROUND: Uncontrolled hemorrhage in polytrauma patients usually results in rapid need of blood products. Despite the shorter thawing times of microwave devices for heating fresh frozen plasma (FFP), their use has remained controversial, and just a few laboratory analyses have been published on this topic. The aim of this study was to analyse the quality of clotting factors immediately after thawing FFP with a microwave device and after 48-hour post thaw storage at 4 degrees C. METHODS: 24 FFP units of all four ABO blood groups (six of each blood group) were thawed with a Transfusio-therm 2000 and later stored at 4 degrees C for 48 hours...
2016: Clinical Laboratory
K Amano, I Seita, S Higasa, A Sawada, M Kuwahara, M Shima
INTRODUCTION: Patients with acquired haemophilia A (AHA) have autoantibodies against factor VIII (FVIII), and may develop spontaneous bleeding that requires treatment with FVIII inhibitor bypassing agents such as recombinant activated FVII (rFVIIa, NovoSeven(®) ). However, data regarding the use of rFVIIa are limited. AIM: To investigate the use, efficacy and safety of rFVIIa for the treatment of AHA by analysis of 10-year multicentre Japanese postmarketing surveillance data...
July 25, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
Shirin Shahbazi, Maryam Khorasani, Reza Mahdian
OBJECTIVES: The ectopic expression of coagulation Factor VII has been shown in various cancers. Recently, F7 gene has been identified as a direct target of the androgen receptor in breast cancer. In this study, we examined the mRNA expression of F7 and AR in clinical sample series of prostate cancer and BPH. MATERIAL AND METHODS: All the prostate cancer patients were new cases with no medical history of surgery or chemotherapy. The tissue samples were assigned as either prostate cancer tumor (n= 45) harboring at least 80% tumor cell content, or BPH (n= 36)...
July 8, 2016: Cancer Biomarkers: Section A of Disease Markers
Fahri Bayram, Halit Diri, Elif Funda Sener, Munis Dundar, Yasin Simsek
PURPOSE: The aim of this study was to evaluate the roles of factors associated with coagulation in the etiology and pathogenesis of Sheehan's syndrome (SS) which is a frequent cause of hypopituitarism in underdeveloped and developing regions of the world. METHODS: Mean prothrombin time (PT), activated partial thromboplastin time (APTT) and expression levels of genes, which included methylenetetrahydrofolate reductase (MTHFR), angiotensin I converting enzyme (ACE), coagulation factor V (FV), FVII, FVIII and FIX in 44 patients with SS were compared with 43 healthy subjects...
July 16, 2016: Gynecological Endocrinology
P de Moerloose, J-F Schved, D Nugent
Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII...
July 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
Yi Zeng, Le Zhang, Zhiping Hu, Qidong Yang, Mingming Ma, Baoqiong Liu, Jian Xia, Hongwei Xu, Yunhai Liu, Xiaoping Du
Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway which have similar structure, linked function and nearby gene sites. The aims of this study were to investigate whether the common variants of PZ and FVII genes are associated with the risk of cerebral hemorrhage (CH) and to explore the combined effects of PZ and FVII polymorphisms for CH risk. We performed genotyping analysis for two single-nucleotide polymorphisms (SNPs) of FVII (rs510317 and rs6046) and three SNPs of PZ (rs2273971, rs3024718 and rs3024731) both in a population-based case-control study and in a family-based association study...
June 2016: Journal of Genetics
Elena Barbon, Silvia Pignani, Alessio Branchini, Francesco Bernardi, Mirko Pinotti, Matteo Bovolenta
Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters...
2016: Scientific Reports
M Napolitano, M N D Di Minno, A Batorova, A Dolce, M Giansily-Blaizot, J Ingerslev, J-F Schved, G Auerswald, G Kenet, M Karimi, T Shamsi, A Ruiz de Sáez, R Dolatkhah, A Chuansumrit, M A Bertrand, G Mariani
INTRODUCTION: A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency. AIM: Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences. METHODS: A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed...
September 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
Wei Peng, Shuxin Zhang, Xin Liu, Yanan Gu, Yan Wang
OBJECTIVE: To provide mutation analysis and prenatal diagnosis for a family affected with congenital factor VII(FVII) deficiency. METHODS: DNA was extracted from peripheral blood samples from the proband and his parents. All exons and flanking sequence of the FVII gene were amplified with PCR and subjected to direct sequencing. Prenatal diagnosis was performed by amniocentesis. RESULTS: A homozygous mutation (NM_000131.3) c.572-1G>A was identified in the proband...
June 2016: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Patrícia Nessralla Alpoim, Lara Carvalho Godoi, Melina de Barros Pinheiro, Letícia Gonçalves Freitas, Maria das Graças Carvalho, Luci Maria Dusse
We have recently investigated the association between the risk of developing PE and clinical, hemostatic, inflammatory and genetic parameters of 108 severe preeclamptic women. A multivariate logistic regression analysis was performed to assess what variables are independent risk factors for PE. Univariate analysis was performed including the variables in age, smoking condition, multiple pregnancy, blood group, phenotypes and alleles of IL-4, IL-5, IL-10, IL-6, IL-8, IL-12, IL-1β, IFN-γ, TNF-α, and the plasma levels of FVII, FVIIa, FVIIa-AT, FVIII, FVW, ADAMTS13, D-Di, PAI-1, ADMA...
August 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Yanni Mi, Xue Xiao, Dongzheng Liu, Nana Ping, Yanbing Zhu, Bo Li, Lihui Long, Yongxiao Cao
The main vitamin K-deficient model, minidose warfarin, is different from the pathological mechanism of vitamin K deficiency, which is a shortage of vitamin K. The objective of this study was to establish a new method of vitamin K-deficient model combining a vitamin K-deficient diet with the intragastrical administration of gentamicin in rats. The clotting was assayed by an automated coagulation analyser. The plasma PIVKA-II was assayed by ELISA. The vitamin K status was detected by an HPLC-fluorescence system...
April 2016: International Journal of Experimental Pathology
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