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Clotting factors

Boris Shenkman, Ivan Budnik, Yulia Einav, Hagit Hauschner, Mykhaylo Andrejchin, Uriel Martinowitz
BACKGROUND: Trauma-induced coagulopathy (TIC) is commonly seen among patients with severe injury. The dynamic process of TIC is characterized by variability of the features of the disease. METHODS: A model of TIC was created. Hemodilution was produced by mixing the blood with 40% TRIS/saline solution, fibrinolysis by treating the blood with 160 ng/mL tPA, acidosis by adding 1.2 mg/mL lactic acid achieving pH 7.0-7.1, and hypothermia by running the assay at 31 °C...
October 25, 2016: Journal of Trauma and Acute Care Surgery
J Lock, H Raat, M Peters, M Scholten, M Beijlevelt, R Oostenbrink, F W G Leebeek, H A Moll, M H Cnossen
BACKGROUND: Transmural support by a haemophilia nurse may improve treatment and may empower parents and patients. AIM: To measure the effect of structured home visits by a haemophilia nurse in (parents of) patient on aspects of prophylactic home treatment. METHODS: A multicentre intervention study in two paediatric haemophilia treatment centres was performed. Primary outcome measures were: adherence to prescribed treatment, health-related quality of life and behavioural scores...
October 25, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
Owain Thomas, Hampus Rein, Karin Strandberg, Ulf Schött
BACKGROUND: The risk of spinal haematoma in patients receiving epidural catheters is estimated using routine coagulation tests, but guidelines are inconsistent in their recommendations on what to do when results indicate slight hypocoagulation. Postoperative patients are prone to thrombosis, and thromboelastometry has previously shown hypercoagulation in this setting. We aimed to better understand perioperative haemostasis by comparing results from routine and advanced tests, hypothesizing that patients undergoing major upper gastrointestinal surgery would be deficient in vitamin K-dependent coagulation factors because of malnutrition, or hypocoagulative because of accumulation of low molecular weight heparin (LMWH)...
2016: Perioperative Medicine
Manasa Reddy, Bernard Tawfik, Chakri Gavva, Sean Yates, Nicole De Simone, Sandra L Hofmann, Siayareh Rambally, Ravi Sarode
Thrombosis is known to occur in patients with rare inherited bleeding disorders, usually in the presence of a thrombotic risk factor such as surgery and/or factor replacement therapy, but sometimes spontaneously. We present the case of a 72-year-old African American male diagnosed with congenital factor VII (FVII) deficiency after presenting with ischemic stroke, presumably embolic, in the setting of atherosclerotic carotid artery stenosis. The patient had an international normalized ratio (INR) of 2.0 at presentation, with FVII activity of 6% and normal Extem clotting time in rotational thromboelastometry...
October 17, 2016: Transfusion and Apheresis Science
H Toinét Cronjé, Cornelie Nienaber-Rousseau, Lizelle Zandberg, Tinashe Chikowore, Zelda de Lange, Tertia van Zyl, Marlien Pieters
Fibrinogen and its functional aspects have been linked to cardiovascular disease. There is vast discrepancy between the heritability of fibrinogen concentrations observed in twin studies and the heritability uncovered by genome wide association studies. We postulate that some of the missing heritability might be explained by the pleiotropic and polygenic co-regulation of fibrinogen through multiple targeted genes, apart from the fibrinogen genes themselves. To this end we investigated single nucleotide polymorphisms (SNPs) in genes coding for phenotypes associated with total and γ' fibrinogen concentrations and clot properties...
October 19, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Gabriel Lima-Oliveira, Dorothy M Adcock, Gian Luca Salvagno, Emmanuel J Favaloro, Giuseppe Lippi
OBJECTIVE: Thus study was aimed to investigate whether the mixing technique could influence the results of routine and specialized clotting tests on post-thawed specimens. METHODS: The sample population consisted of 13 healthy volunteers. Venous blood was collected by evacuated system into three 3.5mL tubes containing 0.109mmol/L buffered sodium citrate. The three blood tubes of each subject were pooled immediately after collection inside a Falcon 15mL tube, then mixed by 6 gentle end-over-end inversions, and centrifuged at 1500g for 15min...
October 18, 2016: Clinical Biochemistry
Dong-Eog Kim, Jeong-Yeon Kim, Su-Kyoung Lee, Ju Hee Ryu, Ick Chan Kwon, Cheol-Hee Ahn, Kwangmeyung Kim, Dawid Schellingerhout
Direct thrombus imaging visualizes the root cause of thromboembolic infarction. Being able to image thrombus directly allows far better investigation of stroke than relying on indirect measurements, and will be a potent and robust vascular research tool. We use an optical imaging approach that labels thrombi with a molecular imaging thrombus marker - a Cy5.5 near-infrared fluorescent (NIRF) probe that is covalently linked to the fibrin strands of the thrombus by the fibrin-crosslinking enzymatic action of activated coagulation factor XIIIa during the process of clot maturation...
September 25, 2016: Journal of Visualized Experiments: JoVE
María T Álvarez-Román, Ihosvany Fernández-Bello, Víctor Jiménez-Yuste, Mónica Martín-Salces, Elena G Arias-Salgado, María I Rivas Pollmar, Raúl Justo Sanz, Nora V Butta
Despite their low platelet count some immune thrombocytopenia (ITP) patients seldom bleed, indicating the presence of factors to compensate thrombocytopenia. Moreover, ITP patients may have an increased risk for thrombosis. These facts suggest the presence of procoagulant mechanisms that have not been clarified yet. The aim of this study was to identify these possible factors. Moreover, the utility of rotational thromboelastometry (ROTEM(®) ) to test haemostasis in these patients was also evaluated. Patients with ITP presented a procoagulant profile due to an increased amount of platelet- and red cell-microparticles, an increased resistance to protein C and the formation of a clot more resistant to fibrinolysis due to augmented levels of plasminogen activator inhibitor-1, which might reflect an endothelial damage/activation in ITP patients...
October 21, 2016: British Journal of Haematology
Carol H Miao
Current treatment of hemophilia A (HemA) patients with repeated infusions of factor VIII (FVIII; abbreviated as F8 in constructs) is costly, inconvenient, and incompletely effective. In addition, approximately 25 % of treated patients develop anti-factor VIII immune responses. Gene therapy that can achieve long-term phenotypic correction without the complication of anti-factor VIII antibody formation is highly desired. Lentiviral vector (LV)-mediated gene transfer into hematopoietic stem cells (HSCs) results in stable integration of FVIII gene into the host genome, leading to persistent therapeutic effect...
2016: Thrombosis Journal
Jiaan-Der Wang
As life expectancy greatly increases in persons with hemophilia (PWH), more age-related diseases such as cancer and cardiovascular disease (CVD) emerge among this patient group. The aim of this study was to review the available evidence on the epidemiology of CVD events, and incidence and survival of cancer in PWH. The prevalence of CVD events among PWH seems to be similar to that of the general population. Some known risk factors for the event, including aging, hypertension, and hyperlipidemia, are also associated with its occurrence in PWH...
2016: Thrombosis Journal
Man-Chiu Poon, Adrienne Lee
Prophylaxis is considered optimal care for hemophilia patients to prevent bleeding and to preserve joint function thereby improving quality of life (QoL). The evidence for prophylaxis is irrefutable and is the standard of care in developed nations. Prophylaxis can be further individualized to improve outcomes and cost effectiveness. Individualization is best accomplished taking into account the bleeding phenotype, physical activity/lifestyle, joint status, and pharmacokinetic handling of specific clotting factor concentrates, all of which vary among individuals...
2016: Thrombosis Journal
H Marijke van den Berg
Inhibitors are the most serious side effect of haemophilia treatment; they occur in 25-30 % of all patients with severe haemophilia A. Over the last 2 decades, conflicting data on the impact of clotting products have been published. Due to small studies of selected cases, appreciation of the impact of any particular product has been difficult. Moreover, the emphasis on inhibitor testing has led to increased detection of low-titre inhibitors (to >10 %), while the percentage of high-titre inhibitors is still around 20 %...
2016: Thrombosis Journal
Yuhang Zhou, Shaji Abraham, Stephanie Renna, Leonard C Edelstein, Carol A Dangelmaier, Alexander Y Tsygankov, Satya P Kunapuli, Paul F Bray, Steven E McKenzie
OBJECTIVE: The objective of this study is to investigate the role of T-cell ubiquitin ligand-2 (TULA-2) in the platelet Fc receptor for IgG IIA (FcγRIIA) pathway and in the pathogenesis of heparin-induced thrombocytopenia (HIT). APPROACH AND RESULTS: HIT is a life-threatening thrombotic disease in which IgG antibodies against the heparin-platelet factor 4 complex activate platelets via FcγRIIA. We reported previously differential expression of TULA-2 in human population was linked to FcγRIIA responsiveness...
October 20, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Marta Crous-Bou, Laura B Harrington, Christopher Kabrhel
Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism, and a combination of environmental and genetic risk factors contributes to VTE risk. Within environmental risk factors, some are provoking (e.g., cancer, surgery, trauma or fracture, immobilization, pregnancy and the postpartum period, long-distance travel, hospitalization, catheterization, and acute infection) and others are nonprovoking (e.g., age, sex, race/ethnicity, body mass index and obesity, oral contraceptive or hormone therapy use, corticosteroid use, statin use, diet, physical activity, sedentary time, and air pollution)...
October 20, 2016: Seminars in Thrombosis and Hemostasis
Wataru Kikuchi, Motoi Nishimura, Takahisa Kuga, Sachio Tsuchida, Tatsuya Saito, Mamoru Satoh, Kenta Noda, Yoshio Kodera, Takeshi Tomonaga, Fumio Nomura
BACKGROUND: Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9) is a new serum biomarker for chronic hepatitis that was discovered by proteomics analysis. Previous studies have shown that FIC5.9 is derived from the C-terminal region of fibrinogen alpha chain and the serum levels of FIC5.9 decrease in chronic hepatitis. It also have been reported that FIC5.9 cannot be detected in the blood stream of the systemic circulation and it is released from fibrinogen during blood clotting in collecting tube...
2016: Clinical Proteomics
Vamsee D Myneni, Aisha Mousa, Mari T Kaartinen
F13A1 gene, which encodes for Factor XIII-A blood clotting factor and a transglutaminase enzyme, was recently identified as a potential causative gene for obesity in humans. In our previous in vitro work, we showed that FXIII-A regulates preadipocyte differentiation and modulates insulin signaling via promoting plasma fibronectin assembly into the extracellular matrix. To understand the role of FXIII-A in whole body energy metabolism, here we have characterized the metabolic phenotype of F13a1-/- mice. F13a1-/- and F13a1+/+ type mice were fed chow or obesogenic, high fat diet for 20 weeks...
October 19, 2016: Scientific Reports
Leonardo A Moraes, Amanda J Unsworth, Sakthivel Vaiyapuri, Marfoua S Ali, Parvathy Sasikumar, Tanya Sage, Gagan D Flora, Alex P Bye, Neline Kriek, Emilie Dorchies, Olivier Molendi-Coste, David Dombrowicz, Bart Staels, David Bishop-Bailey, Jonathan M Gibbins
OBJECTIVE: Although initially seemingly paradoxical because of the lack of nucleus, platelets possess many transcription factors that regulate their function through DNA-independent mechanisms. These include the farnesoid X receptor (FXR), a member of the superfamily of ligand-activated transcription factors, that has been identified as a bile acid receptor. In this study, we show that FXR is present in human platelets and FXR ligands, GW4064 and 6α-ethyl-chenodeoxycholic acid, modulate platelet activation nongenomically...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Christine C Helms, Shannon Kapadia, Anne C Gilmore, Zhexi Lu, Swati Basu, Daniel B Kim-Shapiro
Fibrin fibers form the structural backbone of blood clots. The structural properties of fibrin clots are highly dependent on formation kinetics. Environmental factors such as protein concentration, pH, salt, and protein modification, to name a few, can affect fiber kinetics through altered fibrinopeptide release, monomer association, and/or lateral aggregation. The objective of our study was to determine the effect of thrombin and fibrinogen exposed to nitric oxide on fibrin clot properties. ProliNONOate (5 μmol/l) was added to fibrinogen and thrombin before clot initiation and immediately following the addition of thrombin to the fibrinogen solution...
October 13, 2016: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Noha A Osman, Nevine El-Abd, Mohamed Nasrallah
Vitamin K is necessary for the carboxylation of clotting factors and matrix Gla protein (MGP). Vitamin K epoxide reductase (VKOR) is the enzyme responsible for recirculation of Vitamin K increasing its tissue availability. Polymorphisms of VKOR may alter the function of MGP, thereby influencing vascular calcification. We conducted this study to investigate the relationship of VKORC1 gene single nucleotide polymorphisms (SNP's) to vascular calcification and clinically overt cardiovascular disease in chronic kidney disease (CKD) patients on hemodialysis (HD)...
September 2016: Saudi Journal of Kidney Diseases and Transplantation
V Gurewich
The interesting article on the antifibrinolytic effect of Factor XIII by Rijken et al [1] was predicated on the assumption that fibrinolysis is mediated only by tPA, since that is what was studied. However, there is evidence that this common assumption should be put into question. In a study published almost thirty years ago, we showed that whereas spontaneous lysis of platelet poor plasma clots was mediated by tPA, that of platelet-rich plasma clots, with which this article was concerned, could not be abolished by tPA antibody, but instead was abolished by the addition of uPA antibody...
October 17, 2016: Journal of Thrombosis and Haemostasis: JTH
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