9,252 results on '"Factor V"'
Search Results
52. Association of prothrombin, FV Leiden and MTHFR gene polymorphisms in the Montenegrin patients with venous thromboembolism
- Author
-
Teofilov Slađana, Magić Zvonko, Miljanović Olivera, Ostojić Tatjana, and Bulatović Milena
- Subjects
factor v ,genes ,mutation ,polymorphism, genetic ,prothrombin ,thromboembolism ,Medicine (General) ,R5-920 - Abstract
Background/Aim. Polymorphisms of the factor V Leiden (FV G1691A), prothrombin (FII G20210A), and methylene-tetrahydrofolate reductase (MTHFR C677T) genes are the most commonly investigated inherited risk factors for developing venous thromboembolism (VTE). Despite this fact, there is insufficient data regarding their clinical burden and distribution in the Montenegrin population. The aim of the study was to determine the frequency of these polymorphisms in Montenegrin patients with VTE. Methods. This case-control study was conducted on 160 Caucasian subjects. The study group was composed of 80 patients (35 men and 45 women) with VTE. The control group consisted of 80 healthy individuals (32 men and 48 women) without previous thromboembolic episodes. Genotyping of the FV G1691A, FII G20210A, and MTHFR C677T polymorphisms was per-formed by allele-specific polymerase chain reaction (PCR). Results. The frequency of heterozygotes (HET) for FII G20210A and FV G1691A was significantly higher in the VTE group compared to the healthy control group (χ2 = 11.7; p = 0.001 and χ2 = 17.69; p < 0.001, respectively). The association of FII G20210A and FV G1691A polymorphisms with an increased risk of VTE [odds ratio (OR) 10.5; 95% confidence interval (CI) = 2.34 to 47.27, and OR 14.8; 95% CI = 3.34 to 65.43; p < 0.001, respectively] was confirmed. Recessive homozygotes (RH) for FII G20210A and FV G1691A were not found in any of the investigated groups. Regarding MTHFR C677T, the difference between the frequency of HET and RH in the control and VTE group was not significant. Conclusion. Our study showed that FII G20210A and FV G1691A polymorphisms are significantly associated with VTE. Detection of the above-mentioned polymorphisms prior to VTE development can contribute to the prevention of further VTE occurrence, especially among patients' relatives who are carriers of these polymorphisms.
- Published
- 2021
- Full Text
- View/download PDF
53. Reversing direct factor Xa or thrombin inhibitors: Factor V addition to prothrombin complex concentrate is beneficial in vitro
- Author
-
Herm Jan M. Brinkman, Frauke Swieringa, Marleen Zuurveld, Alicia Veninga, Sanne L. N. Brouns, Johan W. M. Heemskerk, and Joost C. M. Meijers
- Subjects
anticoagulants ,dabigatran ,factor V ,prothrombin complex concentrate ,rivaroxaban ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Background Prothrombin complex concentrate (PCC) is a human plasma‐derived mixture of partially purified vitamin K‐dependent coagulation factors (VKCF). Current therapeutic indication is treatment and perioperative prophylaxis of bleeding in acquired VKCF deficiency. Off‐label uses include treatment of direct factor Xa‐ or thrombin inhibitor‐associated bleeds, treatment of trauma‐induced coagulopathy, and hemorrhagic complications in patients with liver disease. Objective Considering PCC as a general prohemostatic drug, we argued that its clinical efficacy can benefit from supplementation with coagulation factors that are absent in the current PCC formulation. In this study, we focused on factor V. Methods We mimicked a coagulopathy in vitro by spiking whole blood or derived plasma with the direct oral anticoagulants (DOAC) rivaroxaban or dabigatran. We studied DOAC reversal by PCC and factor V concentrate (FVC) using a thrombin generation assay, thromboelastography, fibrin generation clot lysis test, and microfluidic thrombus formation under flow. Results In DOAC‐treated plasma, PCC increased the amount of thrombin generated. The addition of FVC alone or in combination with PCC caused a partial correction of the thrombin generation lag time and clotting time. In DOAC‐treated whole blood, the combination of PCC and FVC synergistically improved clotting time under static conditions, whereas complete correction of fibrin formation was observed under flow. Clot strength and clot resistance toward tissue plasminogen activator‐induced lysis were both increased with PCC and further enhanced by additional FVC. Conclusion Our in vitro study demonstrates a beneficial effect of the combined use of PCC and FVC in DOAC reversal.
- Published
- 2022
- Full Text
- View/download PDF
54. Standardization of Coagulation Factor V Reference Intervals, Prothrombin Time, and Activated Partial Thromboplastin Time in Mice for Use in Factor V Deficiency Pathological Models
- Author
-
Juan A. De Pablo-Moreno, Antonio Liras, and Luis Revuelta
- Subjects
factor V ,prothrombin time ,activated partial thromboplastin time ,mouse ,measurement standardization ,transfusion ,Veterinary medicine ,SF600-1100 - Abstract
Factor V together with activated factor X forms the prothrombinase complex, which transforms prothrombin into thrombin. The Mus musculus species is characterized by very high levels of this factor and short clotting times, which hinders accurate measurements. For that reason, a detailed characterization of such parameters is indispensable. A method was designed as part of this study to provide an accurate determination and standardization of factor V levels, prothrombin time and activated partial thromboplastin time in Mus musculus. Those parameters were evaluated in a sample of 66 healthy animals using a semi-automated coagulometer and human diagnostic reagents in an attempt to determine the most appropriate time of day for the extractions. A mouse-based protocol was designed, capable of making corrections to the samples at dilutions of 1:100 for factor V and at of 1:3 for prothrombin time. The goal was to smoothen the calibration curves, which often present with steep slopes and narrow measurement ranges between one calibration point and another. It was found that the most stable period for blood sample extraction was that comprised between the first 6 h of light. No clinical differences were observed between the sexes and reference intervals were established for factor V (95.80% ± 18.14; 25.21 s ± 1.34), prothrombin time (104.31% ± 14.52; 16.85 s ± 1.32) and activated partial thromboplastin time (32.86 s ± 3.01). The results obtained are applicable to human or veterinary biomedical research, to transfusional medicine or to pathological models for diseases such as factor V deficiency.
- Published
- 2022
- Full Text
- View/download PDF
55. Kinetic analysis of prothrombinase assembly and substrate delivery mechanisms.
- Author
-
Gantseva AR, Gantseva ER, Sveshnikova AN, Panteleev MA, and Kovalenko TA
- Subjects
- Kinetics, Humans, Models, Biological, Phospholipids metabolism, Blood Coagulation physiology, Thrombin metabolism, Factor Va metabolism, Thromboplastin metabolism, Substrate Specificity, Factor V, Factor Xa metabolism, Prothrombin metabolism
- Abstract
Prothrombinase complex, composed of coagulation factors Xa (FXa) and Va (FVa) is a major enzyme of the blood coagulation network that produces thrombin via activation of its inactive precursor prothrombin (FII) on the surface of phospholipid membranes. However, pathways and mechanisms of prothrombinase formation and substrate delivery are still discussed. Here we designed a novel mathematical model that considered different potential pathways of FXa or FII binding (from the membrane or from solution) and analyzed the kinetics of thrombin formation in the presence of a wide range of reactants concentrations. We observed the inhibitory effect of large FVa concentrations and this effect was phospholipid concentration-dependent. We predicted that efficient FII activation occurred via formation of the ternary complex, in which FVa, FXa and FII were in the membrane-bound state. Prothrombin delivery was mostly membrane-dependent, but delivery from solution was predominant under conditions of phospholipid deficiency or FXa/FVa excess. Likewise, FXa delivery from solution was predominant in the case of FVa excess, but high FII did not switch the FXa delivery to the solution-dependent one. Additionally, the FXa delivery pathway did not depend on the phospholipid concentration, being the membrane-dependent one even in case of the phospholipid deficiency. These results suggest a flexible mechanism of prothrombinase functioning which utilizes different complex formation and even inhibitory mechanisms depending on conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
56. Joint effects of cancer and variants in the factor 5 gene on the risk of venous thromboembolism
- Author
-
Gran, Olga V, Smith, Erin N, Brækkan, Sigrid K, Jensvoll, Hilde, Solomon, Terry, Hindberg, Kristian, Wilsgaard, Tom, Rosendaal, Frits R, Frazer, Kelly A, and Hansen, John-Bjarne
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Prevention ,Clinical Research ,Cancer ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,Aged ,Aged ,80 and over ,Alleles ,Factor V ,Female ,Gene Frequency ,Genetic Variation ,Genotype ,Humans ,Incidence ,Kaplan-Meier Estimate ,Male ,Middle Aged ,Neoplasms ,Population Surveillance ,Proportional Hazards Models ,Risk ,Venous Thromboembolism ,Cardiorespiratory Medicine and Haematology ,Immunology ,Cardiovascular medicine and haematology - Abstract
Venous thromboembolism occurs frequently in cancer patients. Two variants in the factor 5 gene (F5), rs6025 encoding for the factor V Leiden mutation R506Q, and rs4524 encoding K858R, have been found to be associated with venous thromboembolism. We assessed the joint effect of active cancer and these two F5 variants on venous thromboembolism risk in a case-cohort study. Cases with a first venous thromboembolism (n=609) and a randomly selected age-weighted cohort (n=1,691) were sampled from the general population in Tromsø, Norway. Venous thromboembolism was classified as cancer-related if it occurred in the period 6 months before to 2 years after a diagnosis of cancer. Active cancer was associated with an 8.9-fold higher risk of venous thromboembolism (95% CI 7.2-10.9). The risk of cancer-related venous thromboembolism was 16.7-fold (95% CI 9.9-28.0) higher in subjects heterozygous for rs6025 compared with non-carriers of this variant without active cancer. In subjects with active cancer the risk of venous thromboembolism was 15.9-fold higher (95% CI 9.1-27.9) in those with one risk allele at rs4524, and 21.1-fold (95% CI 12.4-35.8) higher in those with two risk alleles compared with non-carriers without active cancer. A synergistic interaction was observed between active cancer and factor V Leiden (relative excess risk due to interaction 7.0; 95% CI 0.5-14.4) and rs4524 (relative excess risk due to interaction 15.0; 95% CI 7.5-29.2). The incidence of venous thromboembolism during the initial 6 months following a diagnosis of cancer was particularly high in subjects with risk alleles at these loci. This implies that the combination of cancer and F5 variants synergistically increases venous thromboembolism risk.
- Published
- 2016
57. Thrombin generation in a woman with heterozygous factor V Leiden and combined oral contraceptives: A case report
- Author
-
Maxime G. Zermatten, Debora Bertaggia Calderara, Alessandro Aliotta, and Lorenzo Alberio
- Subjects
contraception ,factor V ,thrombin ,thromboembolism ,thrombosis ,venous ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Combined oral contraceptives and factor V Leiden mutation are multiplicative risk factors for venous thromboembolism. However, it remains unknown whether this multiplicative effect is reflected in thrombin generation assays. We report here the evolution of the thrombin generation profile while taking combined oral contraceptives and after their discontinuation in a woman with heterozygous factor V Leiden mutation. The proband exhibited a distinctly prothrombotic thrombin generation profile including markedly decreased thrombomodulin (TM) sensitivity, compared to the control population. This profile possibly reflected a high thrombotic risk. After discontinuation of combined oral contraceptives, thrombin generation and TM sensitivity improved greatly, leaving only a slightly prothrombotic profile. Therefore, the multiplied thrombotic risk occurring with simultaneous combined oral contraceptives and factor V Leiden mutation is reflected by a thrombin generation assay performed without and with TM. This could be a promising tool to identify women taking combined oral contraceptives at high risk for venous thromboembolism. Further studies are needed to verify this hypothesis.
- Published
- 2020
- Full Text
- View/download PDF
58. Comparison between thrombophilic gene polymorphisms among high risk patients
- Author
-
Levkova Mariya, Hachmeriyan Mari, Stoyanova Milena, Miteva Valentina, and Angelova Lyudmila
- Subjects
thrombophilia ,factor v ,vascular diseases ,miscarriage ,genetic polymorphism ,Internal medicine ,RC31-1245 - Abstract
Introduction. The purpose of this study was to compare the role of the thrombophilic variants among two groups of high risk patients with vascular disorders and recurrent pregnancy loss.
- Published
- 2020
- Full Text
- View/download PDF
59. Novel single nucleotide mutations in exon-10 of human coagulation Factor V gene in patients with pulmonary thromboembolism
- Author
-
Latheef Kasala, Rajasekhar Durgaprasad, and Vanajakshamma Velam
- Subjects
pulmonary thromboembolism ,factor v ,mutations ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Introduction: Acute pulmonary thromboembolism (PTE) presents with wide spectrum and has variable prognosis. Factor V Leiden (FVL) is the most common inherited thrombophilia, with a prevalence of 3%-7% in the general US population, approximately 5% in Whites, 2.2% in Hispanics and 1.2% in Blacks. PTE most commonly originates from venous thrombosis. The occurrence of venous thromboembolism is a culmination of environmental and genetic risk factors. The current study was sought to identify the mutations in exon-10 of FV gene in patients with PTE. Methods: Sixty cases diagnosed with PTE and 50 healthy controls were enrolled in the present study. Mutation studies in exon-10 of Factor V gene included PCR-DNA sequencing method. Results: Of 60 patients, we found two novel transition type point mutations: c.1538 G>A and c.1601 G>A in exon-10 of Factor V which is responsible for the cleavage site for aPC. These point mutations resulted in single amino acid change in protein sequence at p.Arg513Lys and p.Arg534Gln respectively. These mutations prevent efficient inactivation of Factor V and Factor V remains active which facilitates over production of thrombin leading to generation of excess fibrin and excess coagulation which results in deep vein thrombosis and PTE. Conclusion: We report two novel point mutations (c.1538 G>A and c.1601 G>A) in exon-10 of Factor V gene in Indian patients with PTE.
- Published
- 2020
- Full Text
- View/download PDF
60. Association of Factor II G20210A, Factor V G1691A and methylenetetrahydrofolate reductase C677T gene polymorphism with different forms of myocardial infarction: ST segment elevation and non-ST segment elevation
- Author
-
Ćućuz-Jokić Milica, Ilić Vesna, Cikota-Aleksić Bojana, Obradović Slobodan, and Magić Zvonko
- Subjects
genes ,factor v ,prothrombin ,st elevation myocardial infarction ,non-st elevated myocardial infarction ,polymorphism, genetic ,risk factor ,Medicine (General) ,R5-920 - Abstract
Background/Aim. Coagulation Factor II G20210A and Factor V G1691A variants are moderately associated with coronary artery disease. Polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene C677T is associated with myocardial infarction (MI) in some ethnical groups. At the present time there are rare studies which try to differentiate two forms of MI, ST-elevation MI (STEMI) and non ST-elevation MI (NSTEMI) according to the genetic background. The aim of the study was investigate the association of polymorphisms of Factor II G20210A, Factor V G1691A and MTHFR C677T with different forms of MI: STEMI and NSTEMI. Methods. The study included 82 patients, divided into two cohorts: patients with STEMI (49 patients) and NSTEMI (33 patients). Genetic factors that would be different in those two entities, included in response to plaque rupture and occlusion of coronary artery, were examined. The peripheral blood lymphocytes were used as DNA source. Genotypes were determined on the polymerase chain reaction (PCR) based methodology. Results. The frequency of MTHFR C677T CT genotype was higher in the patients with NSTEMI in comparison with the patients with STEMI [odds ratio (OR) 3.33; 95% confidence interval (CI) 1.22–9.15; p = 0.02]. Logistic regression analysis shows MTHFR CT genotype as an independent prognostic factor for development of NSTEMI (OR 3.15; 95% CI 1.20–8.29; p = 0.02). There were no differences between two patients groups in frequency of Factor II G20210A and Factor V G1691A gene polymorphism. Conclusion. MTHFR C677T CT genotype was significantly associated with the NSTEMI development examined patients.
- Published
- 2020
- Full Text
- View/download PDF
61. Effects of factor v Leiden polymorphism on the pathogenesis and outcomes of preeclampsia
- Author
-
G. K. Ababio, K. Adu-Bonsaffoh, E. Abindau, G. Narh, D. Tetteh, F. Botchway, D. Morvey, J. Neequaye, and I. K. Quaye
- Subjects
Factor V ,Leiden ,Preeclampsia ,Polymerase chain reaction ,Restriction ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Factor V Leiden polymorphism is a well-recognized genetic factor in the etiology of preeclampsia. Considering that Ghana is recording high incidence of preeclampsia, we examined if factor V Leiden is a contributory factor to its development and pregnancy outcomes. Methods STROBE consensus checklist was adopted to recruit eighty-one (81) consenting subjects after ethical clearance. Subjects were followed up till delivery to obtain outcomes of PE. Routine blood chemistry and proteinuria were done on all samples. Factor V Leiden was characterized by polymerase chain reaction and restriction fragment length polymorphism (RFLP). The data was captured as protected health information (PHI) and analyzed with SPSS version 22. Results Overall allelic frequencies found in FVL exon 10 were 0.67 and 0.33 for G and A alleles respectively. The FVL mutation was more in PE and hypertensive patients. Increased white blood cells, increased uric acid and a three – fold increment of AST / ALT ratio was observed in PE cases when stratified by FVL exons (exon 8 and 10). Significant differences were also observed between FVL and age, systolic blood pressure (SBP), diastolic blood pressure (DBP), liver enzymes, white blood cells (wbc), hemoglobin levels. Conclusion FVL mutation allele frequency was 0.33, a first report. The mutation was associated with increased uric acid, liver enzymes and blood cell indices suggestive of acute inflammation.
- Published
- 2019
- Full Text
- View/download PDF
62. Coagulation factor V in breast cancer: a p53-regulated tumor suppressor and predictive marker for treatment response to chemotherapy.
- Author
-
Lind SM, Sletten M, Hellenes M, Mathelier A, Tekpli X, Tinholt M, and Iversen N
- Subjects
- Female, Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Apoptosis drug effects, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Blood Coagulation drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cyclophosphamide therapeutic use, Epirubicin pharmacology, Epirubicin therapeutic use, Fluorouracil therapeutic use, Fluorouracil pharmacology, MCF-7 Cells, Mutation, RNA, Messenger metabolism, RNA, Messenger genetics, Treatment Outcome, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Factor V genetics, Factor V metabolism, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Protein p53 genetics
- Abstract
Background: Patients with cancer are at an increased risk of developing coagulation complications, and chemotherapy treatment increases the risk. Tumor progression is closely linked to the hemostatic system. Breast cancer tumors express coagulation factor V (FV), an essential factor in blood coagulation. The functional role of FV during treatment with chemotherapy is poorly understood and was explored in this study., Objectives: We aimed to investigate the role of FV in breast cancer progression by exploring associations with treatment response, gene regulation, and the functional effects of FV., Methods: The receiver operating characteristic plotter was used to explore the predictive value of FV mRNA (F5) expression for treatment with FEC (5-fluorouracil, anthracycline, and cyclophosphamide). Breast cancer cohorts were analyzed to study treatment response to FEC. The effect of chemotherapy on F5 expression, the regulation of F5, and the functional effects of FV dependent and independent of chemotherapy were studied in breast cancer cell lines., Results: F5 tumor expression was significantly higher in responders to FEC than in nonresponders. In vitro experiments revealed that anthracycline treatment increased the expression of F5. Inhibition and knockdown of p53 reduced the anthracycline-induced F5 expression. Mutation of a p53 half-site (c.158+1541/158+1564) in a luciferase plasmid reduced luciferase activity, suggesting that p53 plays a role in regulating F5. FV overexpression increased apoptosis and reduced proliferation slightly during anthracycline treatment., Conclusion: Our study identified F5 as a p53-regulated tumor suppressor candidate and a promising marker for response to chemotherapy. FV may have functional effects that are therapeutically relevant in breast cancer., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
63. Membrane binding and lipid-protein interaction of the C2 domain from coagulation factor V.
- Author
-
Ohkubo YZ, Radulovic PW, Kahira AN, and Madsen JJ
- Abstract
Anchoring of coagulation factors to anionic regions of the membrane involves the C2 domain as a key player. The rate of enzymatic reactions of the coagulation factors is increased by several orders of magnitude upon membrane binding. However, the precise mechanisms behind the rate acceleration remain unclear, primarily because of a lack of understanding of the conformational dynamics of the C2-containing factors and corresponding complexes. We elucidate the membrane-bound form of the C2 domain from human coagulation factor V (FV-C2) by characterizing its membrane binding the specific lipid-protein interactions. Employing all-atom molecular dynamics simulations and leveraging the highly mobile membrane-mimetic (HMMM) model, we observed spontaneous binding of FV-C2 to a phosphatidylserine (PS)-containing membrane within 2-25 ns across twelve independent simulations. FV-C2 interacted with the membrane through three loops (spikes 1-3), achieving a converged, stable orientation. Multiple HMMM trajectories of the spontaneous membrane binding provided extensive sampling and ample data to examine the membrane-induced effects on the conformational dynamics of C2 as well as specific lipid-protein interactions. Despite existing crystal structures representing presumed "open" and "closed" states of FV-C2, our results revealed a continuous distribution of structures between these states, with the most populated structures differing from both "open" and "closed" states observed in crystal environments. Lastly, we characterized a putative PS-specific binding site formed by K23, Q48, and S78 located in the groove enclosed by spikes 1-3 (PS-specificity pocket), suggesting a different orientation of a bound headgroup moiety compared to previous proposals based upon analysis of static crystal structures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
- Published
- 2024
- Full Text
- View/download PDF
64. Structure and function of factor X: properties, activation, and activity in prothrombinase. A retrospective in a historical context.
- Author
-
Jackson, Craig M.
- Abstract
The evolution of our understanding of the formation of thrombin from the postulated thrombokinase of Morawitz to activated Factor X and prothrombinase occurred during a period of nearly 100 years. During this time structure–function relationships have emerged and the roles of phospholipid surfaces, the accessory factor, Factor V and its activated form have been clarified. This paper summarizes this story with particular acknowledgement of the seminal contributions of Haskell Milstone. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
65. Prothrombinase: the paradigm for membrane bound enzyme complexes; a memoir.
- Author
-
Mann, Kenneth G.
- Abstract
This review is a brief summary of the history of the development of the Prothrombinase complex paradigm and its incorporation into the "extrinsic pathway". It summarizes my laboratory's research from 1968 to 2012 and identifies many of the key players in these efforts. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
66. Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia
- Author
-
Norris, JW, Pombo, M, Shirley, E, Blevins, G, and Tablin, F
- Subjects
Veterinary Sciences ,Agricultural ,Veterinary and Food Sciences ,Clinical Research ,Hematology ,Underpinning research ,1.1 Normal biological development and functioning ,Animals ,Blood Platelets ,Blotting ,Western ,Case-Control Studies ,Factor V ,Fibrinogen ,Horse Diseases ,Horses ,Proto-Oncogene Proteins c-akt ,Signal Transduction ,Thrombasthenia ,AKT ,Bleeding Diathesis ,Horse ,Veterinary sciences - Abstract
BackgroundTwo congenital bleeding diatheses have been identified in Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis associated with abnormal platelet function in response to collagen and thrombin stimulation.Hypothesis/objectivesPlatelet dysfunction in horses with this second thrombasthenia results from a secretory defect.AnimalsTwo affected and 6 clinically normal horses.MethodsEx vivo study. Washed platelets were examined for (1) expression of the αIIb-β3 integrin; (2) fibrinogen binding capacity in response to ADP and thrombin; (3) secretion of dense and α-granules; (4) activation of the mammalian target of rapamycin (mTOR)-protein kinase B (AKT) signaling pathway; and (5) cellular distribution of phosphatidylinositol-4-phosphate-3-kinase, class 2B (PIK3C2B) and SH2 containing inositol-5'-phosphatase 1 (SHIP1).ResultsPlatelets from affected horses expressed normal amounts of αIIb-β3 integrin and bound fibrinogen normally in response to ADP, but bound 80% less fibrinogen in response to thrombin. α-granules only released 50% as much Factor V as control platelets, but dense granules released their contents normally. Protein kinase B (AKT) phosphorylation was reduced after thrombin activation, but mTOR Complex 2 (mTORC2) and phosphoinositide-dependent kinase 1 (PDK1) signaling were normal. SH2-containing inositol-5'-phosphatase 1 (SHIP1) did not localize to the cytoskeleton of affected platelets and was decreased overall consistent with reduced AKT phosphorylation.Conclusions and clinical significanceDefects in fibrinogen binding, granule secretion, and signal transduction are unique to this thrombasthenia, which we designate as atypical equine thrombasthenia.
- Published
- 2015
67. Coagulation factor V inhibitors, a review of the case report literature
- Author
-
Hideo Wada, Akitada Ichinose, Katsuya Shiraki, Hideto Shimpo, and Motomu Shimaoka
- Subjects
Factor V ,Inhibitor ,Acquired immune FV deficiency ,Supplement therapy ,Immunosuppressive therapy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Coagulation factor V (FV) inhibitor is a rare disease and few reviews of relevant literature on FV inhibitor have been reported. Methods: A PubMed search identified 1065 reports on factor V inhibitors, in which 150 patients met the criteria for inclusion in this review. Result: One hundred fifty cases with prolonged clotting times and FV inhibitor positivity were selected. The main underlying conditions were the postoperative state, infection, malignant neoplasm, and autoimmune disease; 18.4% showed an idiopathic onset. FV activity was ≤28% in all FV inhibitors and major bleeding (MB) was observed in 48.7% of cases. There were no significant differences in MB or mortality among the underlying conditions. The main therapies for bleeding were fresh frozen plasma and platelet concentrate, and the main immunosuppressive therapies were prednisolone, cyclophosphamide and intravenous immunoglobulin. There were no differences in laboratory data between FV inhibitors with and without MB or between survivors and non-survivors. The mortality rate was 14.8% (23.3% in FV inhibitor with MB vs. 10.0% in FV inhibitor without MB; odds ratio 2.732) and the median survival period was 0.8 months. Conclusion: FV activity was ≤28% in all patients with FV inhibitor. While half of the patients did not have MB, the risk of dying was 2-fold higher in those with MB.
- Published
- 2021
- Full Text
- View/download PDF
68. Inherited Bleeding Disorders
- Author
-
Brown, James P. R., Douglas, Joanne, and Mankowitz, Suzanne K. W., editor
- Published
- 2018
- Full Text
- View/download PDF
69. Factor V and Combined Factor V and VIII Deficiency
- Author
-
Brown, James P. R., Douglas, Joanne, and Mankowitz, Suzanne K. W., editor
- Published
- 2018
- Full Text
- View/download PDF
70. Patent Application Titled "COAGULATION FACTOR V (F5) iRNA COMPOSITIONS AND METHODS OF USE THEREOF" Published Online (USPTO 20240218366).
- Subjects
BLOOD coagulation factors ,PATENT applications ,NUCLEOTIDE sequence ,INTERNET publishing ,RNA - Abstract
The USPTO has published a patent application titled "COAGULATION FACTOR V (F5) iRNA COMPOSITIONS AND METHODS OF USE THEREOF." The application proposes iRNA compositions that can inhibit the expression of coagulation Factor V (F5) in cells, potentially improving treatments for thrombosis. Thrombosis is the formation of blood clots in blood vessels, which can lead to serious conditions such as deep vein thrombosis, pulmonary embolism, heart attack, and stroke. The patent application describes specific nucleotide sequences that can be used in the iRNA compositions, including the use of modified nucleotides and the addition of a ligand to the dsRNA agent. For more information, readers are encouraged to refer to the full patent application. [Extracted from the article]
- Published
- 2024
71. Research from National University of Medical Sciences (NUMS) in Military and Defense Provides New Insights (Evaluation of Antithrombin-III Deficiency and Factor V Leiden Mutation in Patients with Stroke in Young Patients).
- Subjects
FACTOR V Leiden ,MEDICAL sciences ,STROKE patients ,DEFENSIVE (Military science) ,BLOOD protein disorders - Abstract
A recent study conducted by the National University of Medical Sciences (NUMS) in Pakistan examined the presence of Antithrombin III deficiency and Factor V Leiden mutation in young stroke patients. The study included 103 individuals with acute ischemic stroke and found that only 1.9% had Antithrombin III deficiency and 0.9% had Factor V Leiden mutation. The researchers concluded that testing for hypercoagulable states in young stroke patients may be useful, particularly in cases with a family history of stroke, smoking, and high-altitude deployment. The study suggests that investigations should be tailored to individual patients to determine the cause of stroke. [Extracted from the article]
- Published
- 2024
72. Findings from Broad Institute in the Area of Blood Coagulation Disorders Described (Thrombosis Risk In Single- and Double-heterozygous Carriers of Factor V Leiden and Prothrombin G20210a In Finngen and the Uk Biobank).
- Subjects
BLOOD coagulation disorders ,FACTOR V Leiden ,THROMBOSIS ,PROTHROMBIN ,BLOOD coagulation factors - Abstract
A recent study conducted by the Broad Institute examined the thrombosis risk in individuals who carry both the factor V Leiden (FVL) and prothrombin G20210A (PTGM) genetic mutations. The study analyzed data from the UK Biobank and FinnGen biorepositories, involving 937,939 individuals. The researchers found that individuals with double heterozygosity (DH) for FVL and PTGM had a significantly elevated risk of venous thromboembolism (VTE) compared to those without the mutations. However, the DH genotype was not associated with a higher risk of arterial thrombosis. These findings suggest that the DH genotype may confer a similar risk of VTE as FVL homozygosity. [Extracted from the article]
- Published
- 2024
73. "COAGULATION FACTOR V (F5) iRNA COMPOSITIONS AND METHODS OF USE THEREOF" in Patent Application Approval Process (USPTO 20240209358).
- Subjects
BLOOD coagulation factors ,PATENT applications ,NUCLEOTIDE sequence ,RNA ,GENE expression - Abstract
A patent application titled "COAGULATION FACTOR V (F5) iRNA COMPOSITIONS AND METHODS OF USE THEREOF" has been made available online. The inventors propose iRNA compositions that can inhibit the expression of coagulation Factor V (F5) in cells, potentially providing more effective treatments for thrombosis. The patent application describes the specific nucleotide sequences of the double-stranded ribonucleic acid (dsRNA) agents that can target F5 expression. These dsRNA agents have the potential to be used in the development of therapies for cardiovascular diseases and conditions related to thrombosis. [Extracted from the article]
- Published
- 2024
74. Abdullah Gul University Researchers Have Published New Data on Factor V (Membrane binding and lipid-protein interaction of the C2 domain from coagulation factor V).
- Abstract
Researchers from Abdullah Gul University in Kayseri, Turkey have conducted a study on factor V, a blood coagulation factor. The study focused on the C2 domain of factor V and its role in anchoring coagulation factors to the membrane. Through molecular dynamics simulations, the researchers observed the spontaneous binding of the C2 domain to a specific lipid-containing membrane. They also identified a putative binding site for phosphatidylserine, suggesting a different orientation compared to previous proposals. The study provides insights into the conformational dynamics and lipid-protein interactions of factor V. [Extracted from the article]
- Published
- 2024
75. Patent Issued for Test strips for determining coagulation factor activities (USPTO 11988678).
- Subjects
BLOOD coagulation factors ,INVENTORS ,BLOOD coagulation factor IX - Abstract
CGT Enterprises LLC has been issued a patent for test strips that can determine the activity of a coagulation factor in a blood sample. The test strip includes a sample inlet port, a reaction area with a blood coagulation reagent, and a support. By measuring the coagulation time, the activity of the specific coagulation factor can be determined. This invention aims to provide a more convenient and efficient method for diagnosing coagulation factor deficiencies, reducing the need for specialized hospitals or laboratories and minimizing the amount of blood required for testing. [Extracted from the article]
- Published
- 2024
76. Jawaharlal Institute of Postgraduate Medical Education and Research Researcher Details Research in Factor V Deficiency (Rare Coagulopathies in Hematologic Spotlight: Isolated Factor V Deficiency and Combined Factor V and VIII Deficiency).
- Subjects
HEMOPHILIA ,CONTINUING medical education ,MEDICAL research ,BLOOD coagulation disorders ,RESEARCH personnel - Abstract
A recent report from the Jawaharlal Institute of Postgraduate Medical Education and Research in Puducherry, India, highlights the diagnostic challenges posed by rare coagulation disorders. The report presents two cases of isolated factor V deficiency and combined factor V and VIII deficiency. In the first case, a 24-year-old woman was diagnosed with severe factor V deficiency during a routine preoperative evaluation for an ovarian cyst. Despite the absence of bleeding manifestations, a timely diagnosis and appropriate management ensured successful surgical outcomes. The second case involved a 10-year-old male with prolonged gum bleeding, leading to a diagnosis of factor V and VIII deficiency. The researchers aim to contribute valuable insights into the understanding, diagnosis, and management of rare coagulation disorders. [Extracted from the article]
- Published
- 2024
77. Factor-V Leiden G1691A and prothrombin G20210A polymorphisms in Sudanese women with preeclampsia, a case -control study
- Author
-
Nadir A. Ahmed, Ishag Adam, Salah Eldin G. Elzaki, Hiba A. Awooda, and Hamdan Z. Hamdan
- Subjects
Factor V Leiden1691G/A ,prothrombin20210G/A ,Polymorphism ,Factor II ,Factor V ,Preeclampsia ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Preeclampsia can lead to adverse maternal and perinatal outcomes. There are few studies on the association of preeclampsia with thrombophilia in Africa including Sudan. Methods A case –controls study was conducted at Saad Abualila Hospital in Khartoum, Sudan during the period of February through November 2017. The cases were women with preeclampsia and healthy pregnant women were the controls (180 women in each arm of the study). Genotyping for Factor-V Leiden 1691G/A and Prothrombin gene variation 20210G/A was done by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Results There was no significant difference in the age, parity, body mass index (BMI) and the other characteristics between the cases and the controls. Genotypes distribution of Factor V Leiden 1691G/A and prothrombin gene 20210G/A in controls was in accordance with the Hardy–Weinberg equilibrium (P > 0.05). The factor V Leiden-variation was present in 9.6% of the cases compared with 0.6% of the controls, P
- Published
- 2019
- Full Text
- View/download PDF
78. The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V
- Author
-
Juan A. De Pablo-Moreno, Luis Javier Serrano, Luis Revuelta, María José Sánchez, and Antonio Liras
- Subjects
vascular endothelium ,coagulation ,embryo ,von Willebrand factor ,factor VIII ,factor V ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The vascular endothelium has several important functions, including hemostasis. The homeostasis of hemostasis is based on a fine balance between procoagulant and anticoagulant proteins and between fibrinolytic and antifibrinolytic ones. Coagulopathies are characterized by a mutation-induced alteration of the function of certain coagulation factors or by a disturbed balance between the mechanisms responsible for regulating coagulation. Homeostatic therapies consist in replacement and nonreplacement treatments or in the administration of antifibrinolytic agents. Rebalancing products reestablish hemostasis by inhibiting natural anticoagulant pathways. These agents include monoclonal antibodies, such as concizumab and marstacimab, which target the tissue factor pathway inhibitor; interfering RNA therapies, such as fitusiran, which targets antithrombin III; and protease inhibitors, such as serpinPC, which targets active protein C. In cases of thrombophilia (deficiency of protein C, protein S, or factor V Leiden), treatment may consist in direct oral anticoagulants, replacement therapy (plasma or recombinant ADAMTS13) in cases of a congenital deficiency of ADAMTS13, or immunomodulators (prednisone) if the thrombophilia is autoimmune. Monoclonal-antibody-based anti-vWF immunotherapy (caplacizumab) is used in the context of severe thrombophilia, regardless of the cause of the disorder. In cases of disseminated intravascular coagulation, the treatment of choice consists in administration of antifibrinolytics, all-trans-retinoic acid, and recombinant soluble human thrombomodulin.
- Published
- 2022
- Full Text
- View/download PDF
79. A rare case of acquired factor V inhibitor, during treatment with dabigatran for chronic atrial fibrillation, successfully treated with bypassing agents.
- Author
-
Giuffrida, Gaetano, Markovic, Uros, Nicolosi, Daniela, and Calafiore, Valeria
- Subjects
- *
ATRIAL fibrillation , *DABIGATRAN - Abstract
Acquired factor V inhibitor represents a rare condition, described only in case reports. The use of activated bypassing agents in bleeding control could be of aid and improve the survival in symptomatic patients with acquired factor V inhibitor. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
80. A principal component analysis of coagulation after trauma
- Author
-
Kutcher, Matthew E, Ferguson, Adam R, and Cohen, Mitchell J
- Subjects
Hematology ,Physical Injury - Accidents and Adverse Effects ,Clinical Research ,Good Health and Well Being ,Adult ,Antithrombin III ,Blood Coagulation Disorders ,Brain Injuries ,Factor IX ,Factor V ,Factor VII ,Factor VIII ,Factor X ,Fibrin Fibrinogen Degradation Products ,Humans ,Injury Severity Score ,Principal Component Analysis ,Prospective Studies ,Protein C ,Prothrombin ,Wounds and Injuries ,Wounds ,Penetrating ,Coagulopathy ,principal components analysis ,fibrinolysis ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Nursing ,Emergency & Critical Care Medicine - Abstract
BackgroundClotting factor abnormalities underlying acute traumatic coagulopathy are poorly understood, with application of traditional regression techniques confounded by colinearity. We hypothesized that principal components analysis (PCA), a pattern-finding and data reduction technique, would identify clinically predictive patterns in the complex clotting factor milieu after trauma.MethodsPlasma was prospectively collected from 163 critically injured trauma patients. Prothrombin; factors V, VII, VIII, IX, X; D-dimer; activated and native protein C; and antithrombin III levels were assayed and subjected to nonlinear PCA to identify principal components (PCs).ResultsOf 163 patients, 19.0% were coagulopathic on admission. PCA identified 3 significant PCs, accounting for 67.5% of overall variance. PC1 identified global clotting factor depletion; PC2 the activation of protein C and fibrinolysis; and PC3 factor VII elevation and VIII depletion. PC1 score correlated with penetrating injury and injury severity, predicting coagulopathy (odds ratio [OR], 4.67; p < 0.001) and mortality (OR, 1.47; p = 0.032). PC2 score correlated with injury severity, acidosis, and shock, and significantly predicted ventilator-associated pneumonia (OR, 1.59; p = 0.008), acute lung injury (OR, 2.24; p < 0.001), multiorgan failure (OR, 1.83; p = 0.002), and mortality (OR, 1.62; p = 0.006) but was not associated with international normalized ratio (INR)-based or partial thromboplastin time (PTT)-based coagulopathy (p > 0.200). PC3 did not significantly predict outcomes.ConclusionPCA identifies distinct patterns of coagulopathy: depletion coagulopathy predicts mortality and INR/PTT elevation, while fibrinolytic coagulopathy predicts infection, end-organ failure, and mortality, without detectable differences in INR or PTT. While depletion coagulopathy is intuitive, fibrinolytic coagulopathy may be a distinct but often overlapping entity with differential effects on outcomes.
- Published
- 2013
81. Genetic Risk Factors for Perinatal Arterial Ischemic Stroke
- Author
-
Gelfand, Amy A, Croen, Lisa A, Torres, Anthony R, and Wu, Yvonne W
- Subjects
Paediatrics ,Biomedical and Clinical Sciences ,Neurosciences ,Stroke ,Genetics ,Brain Disorders ,Clinical Research ,Pediatric ,Genetic Testing ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Apolipoproteins E ,Arterial Occlusive Diseases ,California ,Case-Control Studies ,Factor V ,Female ,Gene Frequency ,Genetic Predisposition to Disease ,Genotype ,Humans ,Infant ,Lymphotoxin-alpha ,Male ,Polymorphism ,Single Nucleotide ,Pregnancy ,Prothrombin ,Retrospective Studies ,Tumor Necrosis Factor-alpha ,White People ,Young Adult ,Paediatrics and Reproductive Medicine ,Neurology & Neurosurgery - Abstract
The cause of perinatal arterial ischemic stroke is unknown in most cases. We explored whether genetic polymorphisms modify the risk of perinatal arterial ischemic stroke. In a population-based case-control study of 1997-2002 births at Kaiser Permanente Northern California, we identified 13 white infants with perinatal arterial ischemic stroke. Control subjects included 86 randomly selected white infants. We genotyped polymorphisms in nine genes involved in inflammation, thrombosis, or lipid metabolism previously linked with stroke, and compared genotype frequencies in case and control individuals. We tested several polymorphisms: tumor necrosis factor-α -308, interleukin-6, lymphotoxin A, factor V Leiden, methyltetrahydrofolate reductase 1298 and 667, prothrombin 20210, and apolipoprotein E ε2 and ε4 alleles. Patients with perinatal arterial ischemic stroke were more likely than control subjects to demonstrate at least one apolipoprotein E ε4 allele (54% vs 25%, P = 0.03). More patients with perinatal arterial ischemic stroke carried two ε4 alleles than did control subjects (15% vs 2%, P = 0.09), although this finding lacked statistical significance. Proinflammatory and prothrombotic polymorphisms were not associated with perinatal arterial ischemic stroke. The apolipoprotein E polymorphism may confer genetic susceptibility for perinatal arterial ischemic stroke. Larger population-based studies are required to confirm this finding.
- Published
- 2013
82. Characterisation of a novel thrombomodulin c.1487delC,p.(Pro496Argfs*10) variant and evaluation of therapeutic strategies to manage the rare bleeding phenotype.
- Author
-
Morrow, Gael B., Beavis, James, Harper, Sarah, Bignell, Patricia, Laffan, Mike A., and Curry, Nicola
- Subjects
- *
THROMBOMODULIN , *PHENOTYPES , *PROTEIN C , *ANTIFIBRINOLYTIC agents , *HEMORRHAGE , *ACTIVATED protein C resistance , *VON Willebrand disease - Abstract
A novel variant in the thrombomodulin (TM) gene, c.1487delC,p.(Pro496Argfs*10), referred to as Pro496Argfs*10, was identified in a family with an unexplained bleeding disorder. The Pro496Argfs*10 variant results in loss of the transmembrane and intracellular segments of TM and is associated with an increase in soluble TM (sTM) in the plasma. The aim of this study was to characterise the effect of elevated sTM on thrombin generation (TG) and fibrinolysis, and to evaluate therapeutic strategies to manage the patients. Plasma samples were obtained from two patients carrying the variant. TG was triggered using 5 pM tissue factor and measured using the Calibrated Automated Thrombogram. A turbidity clot lysis assay was used to monitor fibrinolysis. TM antigen was quantified by ELISA. Patients with the Pro496Argfs*10 variant had significantly elevated plasma sTM compared to controls (372.6 vs. 6.0 ng/ml). TG potential was significantly lower in patients but was restored by inhibition of activated protein C (APC) or addition of activated Factor VII (FVIIa) or platelet concentrates. In vitro experiments suggested that activated prothrombin complex concentrates (APCC) posed a risk of thrombosis. The time to 50% lysis was significantly prolonged in patients compared to controls, 69.7 vs. 42.3 min. Clot lysis time was shortened by inhibition of activated thrombin activatable fibrinolysis inhibitor (TAFIa). Our data demonstrate that increased sTM enhances APC generation and reduces TG. Simultaneously, the rate of fibrinolysis is delayed due to increased TAFI activation by sTM. Treatment with platelet or FVIIa concentrates may be beneficial to manage this rare bleeding disorder. • Here we report a novel variant in the thrombomodulin (TM) gene, Pro496Argfs*10. • Pro496Argfs*10 is characterised by elevated levels of TM and a bleeding phenotype. • Thrombin generation is significantly lower in patients with the Pro496Argfs*10 variant. • Inhibition of activated protein C restores thrombin generation. • Plasma fibrinolysis is delayed in the Pro496Argfs*10 variant. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
83. Inpatient thrombophilia workup; does hematology consult prevent unnecessary testing?
- Author
-
Anderson Z, Ahsan M, Aguirre C, Ramirez M, and Plowman K
- Subjects
- Humans, Inpatients, Blood Coagulation, Anticoagulants, Risk Factors, Thrombophilia complications, Thrombophilia diagnosis, Venous Thromboembolism diagnosis, Hematology
- Abstract
Hypercoagulable disorders are best described as a group of acquired and hereditary conditions that increase the risk for the development of thrombi within veins or arteries. In the setting of an unprovoked venous thromboembolism, common practice in the inpatient setting has been further investigation via a thrombophilia workup to establish an underlying cause. Current Hematology-Oncology guidelines argue against inpatient workup as the results rarely influence inpatient management. Following American Society of Hematology guidelines (Middledorp), the current study found that only 15% (11/72) of patients met appropriate criteria for thrombophilia testing. There was no relationship between appropriate thrombophilia testing and diagnosis of thrombophilia or initiation of anticoagulation. There was a relationship between appropriate thrombophilia testing and Hematology-Oncology consultation. This demonstrates the need for expert consultation if thrombophilia testing is being considered. The current study provides more evidence that a strong recommendation against inpatient testing should be made as testing does not aid in diagnosis or change management and is an overutilization of healthcare resources., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
- Full Text
- View/download PDF
84. Age-related variation in coagulation factors in non-valvular atrial fibrillation patients receiving direct oral anticoagulants.
- Author
-
Kumano O, Suzuki S, Yamazaki M, An Y, Yasaka M, and Ieko M
- Subjects
- Humans, Middle Aged, Rivaroxaban adverse effects, Warfarin, Anticoagulants, Hemorrhage drug therapy, Dabigatran adverse effects, Factor X therapeutic use, Factor VII therapeutic use, Prothrombin, Factor V, Pyridones therapeutic use, Administration, Oral, Stroke etiology, Stroke prevention & control, Atrial Fibrillation complications, Atrial Fibrillation drug therapy, Atrial Fibrillation chemically induced, Pyridines, Thiazoles
- Abstract
Age is a significant risk factor for ischemic stroke. However, the influence of aging on coagulation parameters in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOACs) remains unclear. A total of 775 samples were collected from 224 NVAF patients receiving apixaban, edoxaban or rivaroxaban. The samples were categorized into three age groups: (i) ≤ 64 years, (ii) 65-74 years, and (iii) ≥ 75 years (apixaban: N = 48, 108, 119; edoxaban: N = 63, 68, 126; rivaroxaban: N = 115, 90, 38, respectively). Coagulation parameters including fibrinogen (Fbg), factor II, factor V, factor VII, factor X, and D-dimer, were compared between the three age groups for each drug. The slopes in the correlation between drug concentrations and modified diluted prothrombin time (mdPT) were also assessed. Fbg and factor V increased with age, while factor II and factor X decreased. Factor VII and D-dimer showed no significant differences across age categories. The slope in response to drug concentrations was similar between the age groups. In NVAF patients treated with apixaban, edoxaban and rivaroxaban, some coagulation parameters exhibited age-related variation. However, the response of mdPT to drug concentration was consistent across age categories., (© 2024. Japanese Society of Hematology.)
- Published
- 2024
- Full Text
- View/download PDF
85. Acquired factor V and factor X Deficiency coexisting with acquired dysfibrinogenaemia in a patient with light chain myeloma.
- Author
-
Jeffrey S, Hamilton C, and Ames PRJ
- Subjects
- Aged, Female, Humans, Factor V, Fibrinogen, Afibrinogenemia complications, Factor X Deficiency, Multiple Myeloma complications
- Abstract
An elderly woman with light chain myeloma presented with prolonged epistaxis and extensive cutaneous haematomas: her kappa/lambda ratio was high at 395, her coagulation screen, thrombin and reptilase times were abnormal, her FV and FX were in the low range in the absence of specific inhibitors, her Clauss fibrinogen was low at 0.95 g/l but antigenic FNG was 1.58 g/l. The patient denied treatment and died of progressive renal failure. We wish to describe the unusual association of FX and FV deficiency co-existing with an acquired dysfibrinogenaemia., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
86. Rel Family Transcription Factor NFAT5 Upregulates COX2 via HIF-1α Activity in Ishikawa and HEC1a Cells.
- Author
-
Okumura T, Raja Xavier JP, Pasternak J, Yang Z, Hang C, Nosirov B, Singh Y, Admard J, Brucker SY, Kommoss S, Takeda S, Staebler A, Lang F, and Salker MS
- Subjects
- Humans, Female, Cyclooxygenase 2 genetics, NFATC Transcription Factors, Signal Transduction, Dinoprostone, Factor V, Transcription Factors, Gene Expression Regulation, Endometrial Neoplasms genetics
- Abstract
Nuclear factor of activated T cells 5 (NFAT5) and cyclooxygenase 2 (COX2; PTGS2 ) both participate in diverse pathologies including cancer progression. However, the biological role of the NFAT5-COX2 signaling pathway in human endometrial cancer has remained elusive. The present study explored whether NFAT5 is expressed in endometrial tumors and if NFAT5 participates in cancer progression. To gain insights into the underlying mechanisms, NFAT5 protein abundance in endometrial cancer tissue was visualized by immunohistochemistry and endometrial cancer cells (Ishikawa and HEC1a) were transfected with NFAT5 or with an empty plasmid. As a result, NFAT5 expression is more abundant in high-grade than in low-grade endometrial cancer tissue. RNA sequencing analysis of NFAT5 overexpression in Ishikawa cells upregulated 37 genes and downregulated 20 genes. Genes affected included cyclooxygenase 2 and hypoxia inducible factor 1α ( HIF1A ). NFAT5 transfection and/or treatment with HIF-1α stabilizer exerted a strong stimulating effect on HIF-1α promoter activity as well as COX2 expression level and prostaglandin E2 receptor (PGE2) levels. Our findings suggest that activation of NFAT5-HIF-1α-COX2 axis could promote endometrial cancer progression., Competing Interests: The authors declare that they have no conflicts of interests.
- Published
- 2024
- Full Text
- View/download PDF
87. A Novel Variant of the LMAN1 Gene in Combined Factor V and Factor VIII Deficiency in a Saudi Female Child: A Case Report.
- Author
-
Alasmari BG, Alpakra M, Rayees S, Hassanien SS, and Almakki ZE
- Abstract
Combined factor V and factor VIII deficiency (F5F8D) is an exceedingly rare autosomal recessive disease that causes concomitantly low levels of factor V and factor VIII, leading to mild to moderate bleeding tendencies. Within this disorder, mutations manifest in the lectin mannose-binding protein (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) genes. This report presents a case of a five-year-old Saudi female child who was referred from an otolaryngology clinic, with an incidental finding of prolonged prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) detected during routine preoperative investigations for tonsillectomy, prompting further investigations. There was no prior history of bleeding symptoms in the patient. She was discovered to have low assays of factor V and factor VIII on subsequent investigations. Whole exome sequencing revealed the novel homozygous mutation c.604C>T in the LMAN1 gene, validating the diagnosis of F5F8D., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Alasmari et al.)
- Published
- 2024
- Full Text
- View/download PDF
88. Successful hip arthroplasty in a patient with combined deficiency of factor V and factor FVIII.
- Author
-
Yang W, Mu H, Zhou F, Wang J, Bi H, and Zhou Z
- Subjects
- Humans, Factor V, Factor VIII, Arthroplasty, Replacement, Hip, Factor V Deficiency, Hemophilia A
- Published
- 2024
- Full Text
- View/download PDF
89. Structural architecture of the acidic region of the B domain of coagulation factor V.
- Author
-
Mohammed BM, Basore K, Summers B, Pelc LA, and Di Cera E
- Subjects
- Humans, Protein Domains, Microscopy, Electron, Factor V metabolism, Blood Coagulation
- Abstract
Background: Coagulation factor (F)V features an A1-A2-B-A3-C1-C2 domain organization and functions as the inactive precursor of FVa, a component of the prothrombinase complex required for rapid thrombin generation in the penultimate step of the coagulation cascade. An intramolecular interaction within the large B domain (residues 710-1545) involves the basic region (BR, residues 963-1008) and acidic region (AR, residues 1493-1537) and locks FV in its inactive state. However, structural information on this important regulatory interaction or on the separate architecture of the AR and BR remains elusive due to conformational disorder of the B domain., Objectives: To reveal the structure of the BR-AR interaction or of its separate components., Methods: The structure of FV is solved by cryogenic electron microscopy., Results: A new 3.05 Å resolution cryogenic electron microscopy structure of FV confirms the overall organization of the A and C domains but resolves the segment 1507 to 1545 within a largely disordered B domain. The segment contains most of the AR and is organized as recently reported in FV short, a spliced variant of FV with a significantly shorter and less disordered B domain., Conclusion: The similar architecture of the AR in FV and FV short provides structural context for physiologically important interactions of this region with the BR in FV and with the basic C-terminal end of tissue factor pathway inhibitor α in FV short., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
90. Recovery of factor V activity is delayed with reperfusion injury after liver transplant.
- Author
-
Thakkar M, Saini S, Stoll J, Kulkarni S, Wilson DB, Khan A, Doyle M, and Fields ME
- Subjects
- Humans, Liver, Factor V, Liver Transplantation adverse effects, Reperfusion Injury etiology
- Published
- 2024
- Full Text
- View/download PDF
91. Thrombin generation abnormalities in Quebec platelet disorder.
- Author
-
Brunet, Justin G., Sharma, Tanmya, Tasneem, Subia, Liang, Minggao, Wilson, Michael D., Rivard, Georges E., and Hayward, Catherine P. M.
- Subjects
- *
BLOOD platelet disorders , *GENETIC mutation , *THROMBIN , *THROMBOPLASTIN , *PLATELET-rich plasma , *TRANEXAMIC acid , *DISEASE risk factors - Abstract
Introduction: Calibrated automated thrombograms (CAT) with platelet‐poor (PPP) and platelet‐rich plasma (PRP) have provided useful insights on bleeding disorders. We used CAT to assess thrombin generation (TG) in Quebec platelet disorder (QPD)—a bleeding disorder caused by a PLAU duplication mutation that increases platelet (but not plasma) urokinase plasminogen activator (uPA), leading to intraplatelet (but not systemic) plasmin generation that degrades α‐granule proteins and causes platelet (but not plasma) factor V (FV) deficiency. Methods: Calibrated automated thrombograms was used to test QPD (n = 7) and control (n = 22) PPP and PRP, with or without added tranexamic acid (TXA). TG endpoints were evaluated for relationships to platelet FV and uPA, plasma FV and tissue factor pathway inhibitor (TFPI) levels, and bleeding scores. Results: Quebec platelet disorder PPP TG was normal whereas QPD PRP had reduced endogenous thrombin potential and peak thrombin concentrations (P values <.01), proportionate to the platelet FV deficiency (R2 ≥ 0.81), but unrelated to platelet uPA, plasma FV, or bleeding scores. QPD TG abnormalities were not associated with TFPI abnormalities and were not reproduced by adding uPA to control PRP. TXA increased QPD and control PRP TG more than PPP TG, but it did not fully correct QPD PRP TG abnormalities or improve TG by plasminogen‐deficient plasma. Conclusion: Quebec platelet disorder results in a platelet‐specific TG defect, proportionate to the loss of platelet FV, that is improved but not fully corrected by TXA. Our study provides an interesting example of why it is important to assess both PRP and PPP TG in bleeding disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
92. Recurrent bleeding after posthemorrhoidectomy caused by factor V deficiency: a case report and review of the literature
- Author
-
Jun Seong Chung, Han Deok Kwak, and Jae Kyun Ju
- Subjects
Excessive Bleeding ,medicine.medical_specialty ,Factor V Deficiency ,Blood transfusion ,biology ,business.industry ,medicine.medical_treatment ,Gastroenterology ,Factor V ,medicine.disease ,Hemorrhagic disorder ,Surgery ,Hemorrhoids ,Coagulation ,biology.protein ,medicine ,Fresh frozen plasma ,business - Abstract
Congenital factor V (FV) deficiency is a rare hemorrhagic disorder that can cause excessive bleeding during and after surgery in the affected patient. This report is the case of a patient who had FV deficiency with recurrent posthemorrhoidectomy bleeding treated with the hemostatic procedure and fresh frozen plasma (FFP) transfusions. A 45-year-old male patient had previously undergone hemorrhoidectomy for multiple hemorrhoids at a local hospital. Hemorrhoidectomy was successful; however, he was transferred to our hospital for evaluation of the origin of the recurrent posthemorrhoidectomy bleeding and underwent a hemostatic procedure. This bleeding was treated with coagulation using electrocautery, multiple sutures, and FFP transfusion (1,600 mL/day) for 7 consecutive days. The patient’s plasma FV activity was 23%. Early detection of clotting factor deficiency in patients with hemorrhagic events after surgical treatments may prevent unnecessary procedures such as reoperations and minimize the cost of replacement therapy such as large-volume FFP transfusion.
- Published
- 2022
93. Platelet-Derived Factor V Is an Important Determinant of the Metastatic Potential of Circulating Tumor Cells
- Author
-
Xin Deng, Ziqian Feng, Luochen Zhu, Ni Chen, Yifei Deng, Yongjie Li, Rong Li, Liqun Wang, Mao Luo, and Jianbo Wu
- Subjects
platelets ,factor V ,tissue factor pathway inhibitor ,metastasis ,coagulation cascade ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Factor V (FV) is a critical component in the blood coagulation cascade. In patients, FV inhibitors have been reported to be associated with malignancy. FV is present in plasma and platelets, which exhibit physical and functional differences. However, the functions of FV in cancer progression remain poorly understood. We evaluated the impact of different levels of FV in plasma and platelets on the haematogenous mouse pulmonary metastasis model to determine whether FV determines the metastatic potential of circulating tumor cells. The role of platelet-derived FV was evaluated using a murine B16F10 pulmonary metastasis model, an assay of tumor cell adhesion to endothelial cells, and western blotting. By combining genetic models and FV inhibitory antibody, the transgenic mice with lower platelet FV expression showed significant increases in metastases compared with mice with higher platelet FV expression. In vitro, labeled B16F10 melanoma cells appeared to exhibit increased adhesion to endothelial cells that were treated with lower levels of platelet FV, but not platelet-poor plasma. Furthermore, platelets from mice with lower platelet FV levels expressed TFPIα at lower levels than with mice with higher platelet FV expression. Based on these findings, platelet-derived FV contributes to haematogenous pulmonary metastasis and is associated with the regulation of tumor cell adhesion to the vessel wall.
- Published
- 2020
- Full Text
- View/download PDF
94. A Case of Acquired Factor V Deficiency in Patient with Bleeding
- Author
-
Davide Vetri, Giovanni Lumera, Salvatore Tarascio, Salvatore Scuto, Elisa Marino, Giuliana Barcellona, and Salvatore Santo Signorelli
- Subjects
coagulation ,acquired inhibitors ,factor v ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Low frequency of rare diseases origins from missed diagnosis addressing to poor prognosis. Acquired factor V inhibitor is a very low frequent bleeding condition (prevalence: 0.09/100,000,000–0.29/1,000,000 per year). Antibiotics, surgery, bacterial infections, malignancies, and autoimmune diseases are predisposing factors; however, no predisposing factor was found often. Authors reported a case of bleeding originating from an acquired factor V deficiency because they wish to draw attention to unfrequented or rare clinical situations rarely diagnosed in internal medicine unit.
- Published
- 2020
- Full Text
- View/download PDF
95. ASSOCIATION BETWEEN FACTOR V LEIDEN (FV G1691A) MUTATION AND CORONARY ARTERY DISEASE DEVELOPMENT IN GAZA STRIP - PALESTINE
- Subjects
Factor V Leiden ,Factor V ,Coronary Artery Disease ,Polymerase Chain Reaction-Restriction Fragment Length Polymorphism ,Medicine (General) ,R5-920 - Abstract
Introduction: Coronary Artery Disease(CAD) is multi-factorial and usually results from a combination of acquired environmental and inherited factors with a change in lifestyle. One of these inherited factors is the G1691A factor V. Factor V Leiden (FVL) is the most common heritable thrombophilic disorder. It is concomitant with an increased the risk of thrombosis and may lead to CAD. The aim of this study is to investigate the relation of this mutation with CAD in Gaza strip population. Methods: it is a retrospective study which includes 180 samples; patients with CAD, n=90 and control group, n=90. An interview with questionnaire was applied. EDTA samples were collected for DNA extraction. The FVL mutation was identified by PCR-RFLP. Results: The frequency of FVL genotypes were: wild type 83.2%, heterozygous16.7% and complete absence of mutant homozygous in control group, whereas in CAD patients were: 70%,26.7% and 3.3%. The FVL G and A alleles frequencies of the participants were: for case group 0.833 and 0.167 while 0.917 and 0.083 were in control group. Furthermore, the distribution of FVL heterozygote and mutant(AA) genotypes were not significantly different between the study and control groups. The GA and AA genotypes increase the risk of developing CAD in patients by 1.9 and 8.3 times respectively. The presence of FVL A allele increases the risk of exposure to heart attack among CAD patient (OR =1.7). The frequency of A allele among diabetic patients increases the risk of developing CAD 1.5 fold. Conclusion: Factor V Leiden A allele is associated with the development CAD.
- Published
- 2020
- Full Text
- View/download PDF
96. Coagulation factor V is a marker of tumor-infiltrating immune cells in breast cancer
- Author
-
Mari Tinholt, Benedicte Stavik, Xavier Tekpli, Øystein Garred, Elin Borgen, Vessela Kristensen, Kristine Kleivi Sahlberg, Per Morten Sandset, and Nina Iversen
- Subjects
blood coagulation ,factor v ,breast neoplasm ,survival ,cellular immune response ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Factor (F) V is an essential cofactor in blood coagulation, however, F5 expression in breast tumors has also been linked to tumor aggressiveness and overall survival. The specific role of FV in breast cancer is yet unknown. We therefore aimed at dissecting the biological relevance of FV in breast cancer. Methods Gene expression data from a Scandinavian breast cancer cohort (n = 363) and the cancer genome atlas (TCGA) (n = 981) and 12 replication cohorts were used to search for F5 co-expressed genes, followed by gene ontology analysis. Pathological and bioinformatic tools were used to evaluate immune cell infiltration and tumor purity. T cell activation, proliferation and migration were studied in FV treated Jurkat T cells. Results F5 co-expressed genes were mainly associated with immune system processes and cell activation. Tumors with high expression of F5 were more infiltrated with both lymphoid (T cells, NK cells, and B cells) and myeloid cells (macrophages and dendritic cells), and F5 expression was negatively correlated with tumor purity (ρ = −0.32). Confirming a prognostic role, data from the Kaplan-Meier plotter showed that high F5 expression was associated with improved relapse-free survival. The strongest association was observed in basal-like breast cancer (HR = 0.55; 95% CI, 0.42–0.71). Exogenous FV did not substantially affect activation, proliferation or migration of human T cells. Conclusions F5 was identified as a novel marker of immune cell infiltration in breast cancer, and the prognostic role of F5 was verified. FV emerge as an interesting immunological biomarker with potential therapeutic relevance for the cancer-inflammation-thrombosis circuit.
- Published
- 2020
- Full Text
- View/download PDF
97. Successful Outcome of Severe Intra-cerebral Bleeding Associated with Acquired Factor V Inhibition: Utilization of Multiple Therapeutic Agents
- Author
-
Panagiotis Andreadis, Katerina Kafantari, Aleka Agapidou, Sofia Vakalopoulou, and Efthymia Vlachaki
- Subjects
Haemophilia ,factor V ,rituximab ,inhibitor ,cephalosporin ,Medicine - Abstract
A 78-year-old male presented to the emergency department due to repeated episodes of syncope over the last 3 days. Physical examination during admission revealed pallour and extensive ecchymosis in his left hemithorax and left thigh. The rest of the clinical and neurological examination revealed no pathological findings
- Published
- 2018
- Full Text
- View/download PDF
98. Investigators from St. Louis University Zero in on Factor V (Structural Architecture of the Acidic Region of the B Domain of Coagulation Factor V).
- Abstract
A recent report from St. Louis University discusses new research on the structural architecture of Factor V, a blood coagulation protein. Factor V is the precursor of Factor Va, which is necessary for thrombin generation in the coagulation cascade. The study used cryogenic electron microscopy to reveal the structure of Factor V, specifically focusing on the acidic region of the B domain. The research provides insight into the interactions of this region with other components and may have implications for understanding blood clotting disorders. The study was funded by various institutions, including the National Institutes of Health. [Extracted from the article]
- Published
- 2024
99. Data on Factor V Deficiency Detailed by Researchers at Yonsei University College of Medicine (Acquired Factor V Deficiency After Carbapenem Administration: A Case Report).
- Published
- 2024
100. Researchers from Maastricht University Provide Details of New Studies and Findings in the Area of Antibiotics (in Vitro And Ex Vivo Rescue of a Nonsense Mutation Responsible for Severe Factor V).
- Subjects
NONSENSE mutation ,RESEARCH personnel ,BLOOD coagulation factors ,ANTIBIOTICS ,BLOOD proteins - Abstract
A recent report from Maastricht University in the Netherlands discusses the use of readthrough therapy to treat coagulation factor V (FV) deficiency, a rare bleeding disorder. The researchers investigated the effectiveness of five readthrough agents in in vitro and ex vivo models of the F5 p.Arg1161Ter mutation, which causes severe FV deficiency. The study found that G418, ELX-02, and 2,6-diaminopurine (2,6-DAP) were effective in increasing FV activity, while PTC-124 and Amlexanox were not. The findings suggest that readthrough therapy could be a potential treatment for this mutation. [Extracted from the article]
- Published
- 2024
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.