scholarly journals Characterization and visualization of murine coagulation factor VIII-producing cells in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morisada Hayakawa ◽  
Asuka Sakata ◽  
Hiroko Hayakawa ◽  
Hikari Matsumoto ◽  
Takafumi Hiramoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Factor Viii ◽  
Fluorescent Protein ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Genetically Engineered ◽  
Coagulation Factor Viii ◽  
Liver Sinusoidal Endothelial Cells ◽  
Genetically Engineered Mice

AbstractCoagulation factors are produced from hepatocytes, whereas production of coagulation factor VIII (FVIII) from primary tissues and cell species is still controversial. Here, we tried to characterize primary FVIII-producing organ and cell species using genetically engineered mice, in which enhanced green fluorescent protein (EGFP) was expressed instead of the F8 gene. EGFP-positive FVIII-producing cells existed only in thin sinusoidal layer of the liver and characterized as CD31high, CD146high, and lymphatic vascular endothelial hyaluronan receptor 1 (Lyve1)+. EGFP-positive cells can be clearly distinguished from lymphatic endothelial cells in the expression profile of the podoplanin− and C-type lectin-like receptor-2 (CLEC-2)+. In embryogenesis, EGFP-positive cells began to emerge at E14.5 and subsequently increased according to liver maturation. Furthermore, plasma FVIII could be abolished by crossing F8 conditional deficient mice with Lyve1-Cre mice. In conclusion, in mice, FVIII is only produced from endothelial cells exhibiting CD31high, CD146high, Lyve1+, CLEC-2+, and podoplanin− in liver sinusoidal endothelial cells.

Influence of ABO type on global coagulation assay results: effect of coagulation factor VIII

2015 ◽  
Vol 53 (9) ◽  
Author(s):  
Qute Choi ◽  
Ji-Eun Kim ◽  
Seon Young Kim ◽  
Kyou Sup Han ◽  
Hyun Kyung Kim
Keyword(s):  
Factor Viii ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Blood Type ◽  
Coagulation Factor Viii ◽  
Specific Reference ◽  
Reference Ranges ◽  
Major Contributor ◽  
Time To Peak ◽  
Thrombin Generation Assay

AbstractAs ABO blood type influences the plasma level of coagulation factor VIII (FVIII), it likely also affects activated partial thromboplastin time (aPTT) and thrombin generation assay (TGA) values. Here, we aimed to investigate the effect of ABO type on the normal values of three global coagulation assays: prothrombin time (PT), aPTT, and TGA.PT, aPTT, TGA [1 or 5 pmol/L tissue factor (TF)], coagulation factors, anticoagulation factors, and ABO type were measured in 200 healthy adults.aPTT was significantly prolonged in those with type O compared with those with type non-O, whereas PT was not significantly different between those with type O and type non-O. The time to peak induced by 5 pmol/L TF was significantly prolonged, and the peak thrombin level was decreased in those with type O compared with those with type non-O. FVIII was a major contributor to the ABO-specific reference range of aPTT, 5 pmol/L TF-induced time to peak, and peak thrombin level.The reference ranges of aPTT and TGA (time to peak and peak thrombin level) differed by ABO type. FVIII level is considered a major contributor to ABO type-specific differences with respect to aPTT and TGA.

scholarly journals Congenital hemophilia A with low activity of factor XII: a case report and literature review

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Baoyu Lei ◽  
Chuang Liang ◽  
Haiyan Feng
Keyword(s):  
Genetic Testing ◽  
Factor Viii ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Coagulation Factor Viii ◽  
Factor Xii ◽  
Fviii Activity ◽  
Recombinant Fviii ◽  
Low Activity

Abstract Background Congenital hemophilia A is a recessive inherited hemorrhagic disorder. According to the activity of functional coagulation factors, the severity of hemophilia A is divided into three levels: mild, moderate and severe. The first bleeding episode in severe and moderate congenital hemophilia A occurs mostly in early childhood and mainly involves soft tissue and joint bleeds. At present, there are limited reports on severe congenital hemophilia A with low factor XII (FXII) activity during the neonatal period. Case presentation A 13-day-old neonate was admitted to the hospital with hematoma near the joints of both upper arms. Coagulation tests showed he had low activity of factor VIII (FVIII) and FXII. He was diagnosed with congenital hemophilia A and treated with human coagulation factor VIII (recombinant FVIII). Although the hematoma became smaller, FVIII activity was only increased to a certain extent and FXII activity decreased gradually. Unfortunately, the child responded poorly to recombinant human coagulation factor VIII and his guardian rejected prophylactic inhibitors and genetic testing and refused further treatment. Three months later, the child developed intracranial hemorrhage (ICH) due to low FVIII activity. Conclusions In hemophilia A, the presence of FVIII inhibitors, drug concentration and testing are three important aspects that must be considered when FVIII activity does not reach the desired level. Early positive disease treatment and prophylaxis can decrease the frequency of bleeding and improve quality of life. We recommend that pregnant women with a family history of hemophilia A undergo early prenatal and neonatal genetic testing.

scholarly journals A Macroglobulin with Inhibitory Activity Against Coagulation Factor VIII

Blood ◽  
1970 ◽  
Vol 35 (3) ◽  
pp. 370-376 ◽  
Author(s):  
P. A. CASTALDI ◽  
R. PENNY
Keyword(s):  
Factor Viii ◽  
Specific Activity ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Clotting Factor ◽  
Factor Deficiency ◽  
Spontaneous Correction ◽  
Characteristic Features

Abstract Deficiency of coagulation factor VIII occurred in a patient with a monoclonal gamma-M protein and characteristic features of Waldenström’s macroglobulinemia. The protein, found to contain lambda light chains, had specific activity against normal factor VIII that was reversible by reduction with 2-mercaptoethanol. Spontaneous correction of the clotting factor deficiency occurred during treatment. It is suggested that the macroglobulin in this patient removed or masked factor VIII by adsorption and that alteration of the protein in vitro by mercaptoethanol and in vivo by treatment removed this capacity.

scholarly journals Oncostatin M induces IL-33 expression in liver endothelial cells in mice and expands ST2+CD4+lymphocytes

2015 ◽  
Vol 309 (7) ◽  
pp. G542-G553 ◽  
Author(s):  
Muhammad Imran Arshad ◽  
Pierre Guihard ◽  
Yannic Danger ◽  
Gregory Noel ◽  
Jacques Le Seyec ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fluorescent Protein ◽  
Vascular Endothelial Cells ◽  
Oncostatin M ◽  
Dependent Manner ◽  
Liver Sinusoidal Endothelial Cells ◽  
Liver Endothelial Cells ◽  
Green Fluorescent

Interleukin (IL)-33 is crucially involved in liver pathology and drives hepatoprotective functions. However, the regulation of IL-33 by cytokines of the IL-6 family, including oncostatin M (OSM) and IL-6, is not well studied. The aim of the present study was to determine whether OSM mediates regulation of IL-33 expression in liver cells. Intramuscular administration in mice of an adenovirus encoding OSM (AdOSM) leads to increase in expression of OSM in muscles, liver, and serum of AdOSM-infected mice compared with control mice. The increase of circulating OSM markedly regulated mRNA of genes associated with blood vessel biology, chemotaxis, cellular death, induction of cell adhesion molecules, and the alarmin cytokine IL-33 in liver. Steady-state IL-33 mRNA was upregulated by OSM at an early phase (8 h) following AdOSM infection. At the protein level, the expression of IL-33 was significantly induced in liver endothelial cells [liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells] with a peak at 8 days post-AdOSM infection in mice. In addition, we found OSM-stimulated human microvascular endothelial HMEC-1 cells and human LSEC/TRP3 cells showed a significant increase in expression of IL-33 mRNA in a dose-dependent manner in cell culture. The OSM-mediated overexpression of IL-33 was associated with the activation/enrichment of CD4+ST2+cells in liver of AdOSM-infected mice compared with adenovirus encoding green fluorescent protein-treated control mice. In summary, these data suggest that the cytokine OSM regulates the IL-33 expression in liver endothelial cells in vivo and in HMEC-1/TRP3 cells in vitro and may specifically expand the target CD4+ST2+cells in liver.

scholarly journals A von Willebrand factor fragment containing the D′D3 domains is sufficient to stabilize coagulation factor VIII in mice

Blood ◽  
2014 ◽  
Vol 124 (3) ◽  
pp. 445-452 ◽  
Author(s):  
Andrew Yee ◽  
Robert D. Gildersleeve ◽  
Shufang Gu ◽  
Colin A. Kretz ◽  
Beth M. McGee ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Key Points ◽  
Von Willebrand ◽  
Willebrand Factor

Key Points The D′D3 domains of VWF are sufficient to stabilize FVIII in vivo. The prolongation of VWF D′D3 survival in vivo by Fc fusion elevates FVIII levels in the setting of VWF but not FVIII deficiency.

RECOVERY TEST AND ITS ROLE IN ASSESSMENT OF LONG-TERM PROPHYLAXIS EFFECTIVENESS IN HEMOPHILIA A PATIENTS

2017 ◽  
Author(s):  
Т. Андреева ◽  
И. Лавриченко ◽  
В. Константинова ◽  
А. Ким ◽  
О. Крашенинникова ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Recombinant Factor Viii ◽  
Coagulation Factor Viii ◽  
Recovery Test ◽  
Fviii Activity ◽  
In Vivo Recovery

Введение. Гемофилия А (ГФА) — сцепленное с Х-хромосомой рецессивное врожденное заболевание, обусловленное недостаточностью VIII фактора свертывания крови (FVIII). Главным признаком заболевания является склонность к кровотечениям. Клинические проявления ГФА, как правило, коррелируют с уровнем активности FVIII. Единственным эффективным лечением гемофилии в настоящее время является заместительная терапия препаратами дефицитного фактора. Материалы и методы. Проведен ретроспективный анализ результатов обследования 28 пациентов (14 детей в возрасте от 3 до 17 лет и 14 взрослых в возрасте от 21 до 57 лет) с тяжелой формой ГФА. Все пациенты находились на длительной профилактической терапии препаратами FVIII — как рекомбинантными, так и плазматическими. Для подбора оптимального режима профилактики пациенту с ГФА проводили тест восстановления (in vivo recovery) — определение активности FVIII в двух пробах крови; определяли также прирост показателя восстановления (incremental recovery), активированное частичное тромбопластиновое время и каолиновое время. Результаты. Проведена оценка теста восстановления фактора свертывания VIII при применении плазматических и рекомбинантного препаратов фактора VIII у пациентов с тяжелой гемофилией А; изучена корреляция теста восстановления с фармакодинамическими показателями, характеризующими состояние коагуляции. Заключение. Ввиду наличия внутрииндивидуальных и межиндивидуальных колебаний фармакокинетических показателей препаратов фактора свертывания VIII у пациентов с ГФА рекомендуется проведение теста восстановления как при назначении препарата фактора свертывания VIII, так и в процессе длительной профилактики с целью контроля за терапией и ее оптимизации в случае необходимости. Introduction. Hemophilia A (HРA) is a recessive X-linked congenital disease caused by the defi ciency of VIII coagulation factor (FVIII). Hemorrhagic tendency is the main sign of the disease. As a rule, clinical manifestations of HPA correlate with level of FVIII activity. At present time substitution therapy with medication of defi cit factor is the only eff ective treatment for hemophilia. Materials and methods. We performed a retrospective study analysis of 28 patients (14 children aged from 3 to 17 years and 14 adults aged from 21 to 57 years) examination with severe HРA. All patients received prolonged preventive therapy with recombinant factor VIII products. To select the optimal prophylaxis mode for patients with HPA we performed a recovery test (in vivo recovery), determination of FVIII activity in two blood samples, determined index of incremental recovery, activated partial thromboplastin time and kaolin time. Results. We assessed recovery test for coagulation factor VIII using plasma and recombinant factor VIII products in patients with severe haemophilia A and studied correlation of recovery test with pharmacodynamic parameters that characterized coagulation state. Conclusion. Due to intra-individual and inter-individual fl uctuations in pharmacokinetic parameters of recombinant factor VIII products in patients with HPA we recommend to perform a recovery test both at appointment of coagulation factor VIII product and also during of long-term prophylaxis for monitoring and optimization of therapy.

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