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https://www.readbyqxmd.com/read/28643538/do-methodological-differences-account-for-the-current-controversy-on-tissue-factor-expression-in-platelets
#1
Marta Brambilla, Laura Rossetti, Chiara Zara, Paola Canzano, Peter L A Giesen, Elena Tremoli, Marina Camera
Tissue factor (TF), the key activator of the blood coagulation cascade and of thrombus formation, is also expressed by circulating human platelets. Despite the documented in-depth characterization of platelet TF carried out in the past 15 years, some authors still fail to identify TF in platelets, especially when assessment in platelet-rich plasma (PRP) or washed platelets is carried out. This study aims to extend the characterization of the subset of TF-positive platelets in PRP from healthy subjects and to verify how different centrifugation forces, used to prepare the PRP, could affect the analysis of TF-positive platelets...
June 23, 2017: Platelets
https://www.readbyqxmd.com/read/28641620/-role-of-microparticles-derived-from-acute-promyelocytic-leukemia-cells-in-coagulopathy
#2
Ying-Mei Zhang, Bo Chen, Long-Yue Wu, Jin-Xiao Hou, Jin-Yue Fu
OBJECTIVE: To evaluate the role of microparticle (MP) derived from acute promyelocytic leukemia (APL) cells and tissue factor (TF) carried by the MP in hypercoagulable state, and the effect of treatment with cytotoxic chemotherapy/differentiating agents on procoagulant activity (PCA) of these MP. METHODS: Bone marrow mononuclear cells (BMMNC) were extracted from 5 APL patients and 5 sex- and age- matched patients with iron deficiency anemia as controls. The cells were cultured in vitro for 48 h, then MP-rich culture medium and MP-free culture medium were harvested and MP was further obtained from certain volume of MP-rich culture medium...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28640323/lys-42-43-44-and-arg-12-of-thrombin-activable-fibrinolysis-inhibitor-comprise-a-thrombomodulin-exosite-essential-for-its-antifibrinolytic-potential
#3
Chengliang Wu, Alan R Stafford, James C Fredenburgh, Jeffrey I Weitz, Ann Gils, Paul J Declerck, Paul Y Kim
The thrombin-thrombomodulin (TM) complex activates thrombin-activable fibrinolysis inhibitor (TAFI) more efficiently than thrombin alone. The exosite on TAFI required for its TM-dependent activation by thrombin has not been identified. Based on previous work by us and others, we generated TAFI variants with one or more of residues Lys 42, Lys 43, Lys 44 and Arg 12 within the activation peptide mutated to alanine. Mutation of one, two, or three Lys residues or the Arg residue alone decreased the catalytic efficiency of TAFI activation by thrombin-TM by 2...
June 22, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28636010/engineering-multi-functional-bacterial-outer-membrane-vesicles-as-modular-nanodevices-for-biosensing-and-bioimaging
#4
Qi Chen, Sharon Rozovsky, Wilfred Chen
Outer membrane vesicles (OMVs) are proteoliposomes derived from the outer membrane and periplasmic space of many Gram-negative bacteria including E. coli as part of their natural growth cycle. Inspired by the natural ability of E. coli to sort proteins to both the exterior and interior of OMVs, we reported here a one-pot synthesis approach to engineer multi-functionalized OMV-based sensors for both antigen binding and signal generation. SlyB, a native lipoprotein, was used a fusion partner to package nanoluciferase (Nluc) within OMVs, while a previously developed INP-Scaf3 surface scaffold was fused to the Z-domain for antibody recruiting...
June 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28632925/a-kallikrein-targeting-rna-aptamer-inhibits-the-intrinsic-pathway-of-coagulation-and-reduces-bradykinin-release
#5
K-A Steen-Burrell, J Layzer, B A Sullenger
BACKGROUND: Plasma kallikrein is a serine protease that plays an integral role in many biological processes including coagulation, inflammation, and fibrinolysis. The main function of kallikrein in coagulation is the amplification of activated factor XIIa (FXIIa) generation which ultimately leads to thrombin generation and fibrin clot formation. Kallikrein is generated by FXIIa-mediated cleavage of the zymogen, prekallikrein which is usually complexed with the nonenzymatic cofactor, high-molecular-weight kininogen (HK)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28605123/in-vitro-effects-of-dalteparin-on-thrombin-generation-in-canine-plasma
#6
Carolyn Gara-Boivin, Jérôme R E Del Castillo, Marilyn E Dunn, Christian Bédard
BACKGROUND: The calibrated automated thrombogram (CAT) is a functional thrombin generation (TG) assay that may provide a new approach for monitoring anticoagulant therapy in dogs. The effects of dalteparin on TG variables in dogs are unknown. OBJECTIVES: Objectives were to establish normal TG variable ranges in dogs and measure the in vitro TG variables in canine pooled platelet-poor plasma (PPP) spiked with different dalteparin concentrations. METHODS: In the first experiment, plasma samples from 25 adult healthy Beagle dogs and 11 client-owned healthy dogs of multiple breeds was measured individually for obtaining normal TG values...
June 12, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28602694/prolonged-targeted-temperature-management-compromises-thrombin-generation-a-randomised-clinical-trial
#7
Anni Nørgaard Jeppesen, Anne-Mette Hvas, Christophe Henri Valdemar Duez, Anders Morten Grejs, Susanne Ilkjær, Hans Kirkegaard
AIM: To investigate whether prolonged compared with standard duration of targeted temperature management (TTM) compromises coagulation. METHODS: Comatose survivors after out-of-hospital cardiac arrest (n=82) were randomised to standard (24hours) or prolonged (48hours) duration of TTM at 33±1°C. Blood samples were drawn 22, 46 and 70hours after attaining the target temperature. Samples were analysed for rotational thromboelastometry (ROTEM(®) (EXTEM(®), INTEM(®), FIBTEM(®) and HEPTEM(®))) and thrombin generation using the Calibrated Automated Thrombogram(®) assay...
June 7, 2017: Resuscitation
https://www.readbyqxmd.com/read/28602219/tranexamic-acid-leads-to-paradoxical-coagulation-changes-during-cardiac-surgery-a-pilot-rotational-thromboelastometry-study
#8
Rajiv Sharma, Hayley L Letson, Samuel Smith, Geoffrey P Dobson
BACKGROUND: Tranexamic acid (TXA) is increasingly used during major surgery with the goal to reduce excessive bleeding, transfusion requirements, and reexploration. Our aim was to examine the effect of TXA on coagulation at different times during cardiac surgery using rotational thromboelastometry. MATERIALS AND METHODS: Nineteen adult males (EuroSCORE 4-5) were recruited consecutively for first-time cardiopulmonary bypass (CPB) surgery. Ten patients received TXA at anesthesia and nine received no TXA...
May 8, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28600979/circulating-microvesicle-number-function-and-small-rna-content-vary-with-age-gender-smoking-status-lipid-and-hormone-profiles
#9
Anoop K Enjeti, Anita Ariyarajah, Angel D'Crus, Michael Seldon, Lisa F Lincz
BACKGROUND: Characterization of circulating microvesicles (MV) in healthy subjects in relation to various biological factors is not well studied. OBJECTIVES: We evaluated the influence of age, gender, smoking status, lipid and hormone profiles on circulating MV in healthy subjects. METHODS: Platelet free plasma from 143 volunteer blood donors (males=80, females=63) was evaluated by standardized flow cytometry for MV expressing CD41 (platelet-derived), CD105 (endothelial-derived), CD235 (red cell-derived), TF (tissue factor) and phosphatidylserine (PS) MV...
April 20, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28600123/multifunctional-and-redundant-roles-of-leptospira-interrogans-proteins-in-bacterial-adhesion-and-fibrin-clotting-inhibition
#10
Priscila R M Pereira, Luis G V Fernandes, Gisele O de Souza, Silvio A Vasconcellos, Marcos B Heinemann, Eliete C Romero, Ana L T O Nascimento
Pathogenic Leptopira is the etiological agent of leptospirosis, the most widespread zoonotic infection in the world. The disease represents a major public health problem, especially in tropical countries. The present work focused on two hypothetical proteins of unknown function, encoded by the genes LIC13059 and LIC10879, and predicted to be surface-exposed proteins. The genes were cloned and the proteins expressed using E. coli as a host system. We report that the recombinant proteins interacted with extracellular matrix (ECM) laminin, in a dose-dependent fashion and are novel potential adhesins...
May 31, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28598864/advances-in-vascular-thiol-isomerase-function
#11
Robert Flaumenhaft
PURPOSE OF REVIEW: The present review will provide an overview of several recent advances in the field of vascular thiol isomerase function. RECENT FINDINGS: The initial observation that protein disulfide isomerase (PDI) functions in thrombus formation occurred approximately a decade ago. At the time, there was little understanding regarding how PDI or other vascular thiol isomerases contribute to thrombosis. Although this problem is far from solved, the past few years have seen substantial progress in several areas that will be reviewed in this article...
June 8, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28597369/first-report-of-real-time-monitoring-of-coagulation-function-potential-and-igg-subtype-of-anti-fviii-autoantibodies-in-a-child-with-acquired-hemophilia-a-associated-with-streptococcal-infection-and-amoxicillin
#12
Masahiro Takeyama, Keiji Nogami, Takahiro Kajimoto, Kenichi Ogiwara, Tomoko Matsumoto, Midori Shima
We describe an 8-year-old boy with acquired hemophilia A (AHA) associated with streptococcal infection and amoxicillin. Laboratory data revealed low factor VIII activity (FVIII:C, 1.5 IU/dl), and FVIII inhibitor (15.9 BU/ml). Comprehensive coagulation function assays, including rotation thromboelastometry (ROTEM(®)), revealed a markedly prolonged clotting time. Thrombin and plasmin generation (TG/PG) appeared to be moderately impaired. The inhibitor epitope of his anti-FVIII autoantibody recognized light and heavy chains...
June 8, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28594467/biochemical-characterization-of-lr769-a-new-recombinant-factor-viia-bypassing-agent-produced-in-the-milk-of-transgenic-rabbits
#13
G Chevreux, N Tilly, Y Leblanc, C Ramon, V Faid, M Martin, F Dhainaut, N Bihoreau
BACKGROUND: The bypassing agent factor VII (FVIIa) is a first-line therapy for the treatment of acute bleeding episodes in patients with haemophilia and high-titre inhibitors. FVIIa is a highly post-translationally modified protein that requires eukaryotic expression systems to produce a fully active molecule. A recombinant FVIIa was produced in the milk of transgenic rabbits to increase expression and provide an efficient, safe and affordable product after purification to homogeneity (LR769)...
June 8, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28594458/concizumab-an-anti-tissue-factor-pathway-inhibitor-antibody-induces-increased-thrombin-generation-in-plasma-from-haemophilia-patients-and-healthy-subjects-measured-by-the-thrombin-generation-assay
#14
E K Waters, J Sigh, U Friedrich, I Hilden, B B Sørensen
AIMS: Concizumab, a humanized monoclonal antibody against tissue factor pathway inhibitor (TFPI), is being developed as a subcutaneously (s.c.) administered treatment for haemophilia. It demonstrated a concentration-dependent procoagulant effect in functional TFPI assays; however, global haemostatic assays, such as the thrombin generation assay (TGA), offer a more complete picture of coagulation. We investigated how concizumab affects thrombin generation following ex vivo spiking in plasma from haemophilia patients using the TGA, and if the assay can detect the effect of multiple s...
June 8, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28594360/rapid-complexation-of-aptamers-by-their-specific-antidotes
#15
Heidi Stoll, Heidrun Steinle, Nadja Wilhelm, Ludmilla Hann, Silju-John Kunnakattu, Miwako Narita, Christian Schlensak, Hans P Wendel, Meltem Avci-Adali
Nucleic acid ligands, aptamers, harbor the unique characteristics of small molecules and antibodies. The specificity and high affinity of aptamers enable their binding to different targets, such as small molecules, proteins, or cells. Chemical modifications of aptamers allow increased bioavailability. A further great benefit of aptamers is the antidote (AD)-mediated controllability of their effect. In this study, the AD-mediated complexation and neutralization of the thrombin binding aptamer NU172 and Toll-like receptor 9 (TLR9) binding R10-60 aptamer were determined...
June 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28593927/laboratory-characterization-of-leukemic-cell-procoagulants
#16
Renáta Hudák, Ildikó Beke Debreceni, Ivett Deák, Gabriella Gál Szabó, Zsuzsanna Hevessy, Péter Antal-Szalmás, Bjarne Osterud, János Kappelmayer
BACKGROUND: In acute myeloid leukemias, there is an increased chance to develop thrombotic disorders. We hypothesized that in addition to leukemic promyelocytes, monocytic leukemia cells may also have a higher procoagulant activity. METHODS: Fibrin formation was assessed by a one-stage clotting assay using a magnetic coagulometer. The thrombin generation test (TGT) of magnetically isolated normal human monocytes, intact leukemic cells and their isolated microparticles was performed by a fluorimetric assay...
May 5, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28587383/mechanism-of-the-protective-effects-of-the-combined-treatment-with-rhynchophylla-total-alkaloids-and-sinapine-thiocyanate-against-a-prothrombotic-state-caused-by-vascular-endothelial-cell-inflammatory-damage
#17
Yunlun Li, Xinya Zhang, Wenqing Yang, Chao Li, Yanjun Chu, Haiqiang Jiang, Zhenzhen Shen
The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS) associated with the tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury of vascular endothelial cells (VECs). A TNF-α-induced VEC inflammatory injury model was established, and cell morphology of VECs was evaluated using scanning electron microscopy. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression of coagulation-related factors, including nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), tissue factor (TF), plasminogen activator inhibitor (PAI-1), protease-activation receptors (PAR-1) and protein kinase C (PKC-α) in VECs...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28584295/membrane-ballooning-in-aggregated-platelets-is-synchronised-and-mediates-a-surge-in-microvesiculation
#18
Ejaife O Agbani, Christopher M Williams, Ingeborg Hers, Alastair W Poole
Human platelet transformation into balloons is part of the haemostatic response and thrombus architecture. Here we reveal that in aggregates of platelets in plasma, ballooning in multiple platelets occurs in a synchronised manner. This suggests a mechanism of coordination between cells, previously unrecognised. We aimed to understand this mechanism, and how it may contribute to thrombus development. Using spinning-disc confocal microscopy we visualised membrane ballooning in human platelet aggregates adherent to collagen-coated surfaces...
June 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28580443/reduced-prothrombinase-inhibition-by-tissue-factor-pathway-inhibitor-contributes-to-the-factor-v-leiden-hypercoagulable-state
#19
Jeremy P Wood, Lisa M Baumann Kreuziger, Paul E R Ellery, Susan A Maroney, Alan E Mast
Activated factor V (FVa) and factor X (FXa) form prothrombinase, which converts prothrombin to thrombin. The α isoform of tissue factor (TF) pathway inhibitor (TFPI) dampens early procoagulant events, partly by interacting with FV. FV Leiden (FVL) is the most common genetic thrombophilia in Caucasians. Thrombosis risk is particularly elevated in women with FVL taking oral contraceptives, which produce acquired TFPIα deficiency. In mice, FVL combined with 50% reduction in TFPI causes severe thrombosis and perinatal lethality...
February 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/28569922/thrombin-is-a-selective-inducer-of-heparanase-release-from-platelets-and-granulocytes-via-protease-activated-receptor-1
#20
Mifleh Tatour, Ma'anit Shapira, Elena Axelman, Shourouk Ghanem, Anat Keren-Politansky, Lilach Bonstein, Benjamin Brenner, Yona Nadir
Heparanase, known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of factor Xa. Platelets and granulocytes contain abundant amounts of heparanase that may enhance the coagulation system upon discharge. It was the aim of this study to identify the inducer and pathway of heparanase release from these cells. Platelets and granulocytes were purified from pooled normal plasma and were incubated with ATP, ADP, epinephrine, collagen, ristocetin, arachidonic acid, serotonin, LPS and thrombin...
June 1, 2017: Thrombosis and Haemostasis
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