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Journal of Thrombosis and Haemostasis: JTH

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https://www.readbyqxmd.com/read/28696568/reproducibility-of-studies-with-genetically-modified-mice
#1
H R Lijnen
In their Editorial in the May issue of JTH, Rosendaal and Reitsma address different factors that may contribute to irreproducible results. They also refer to the Recommendation and Guidelines article by Colin Longstaff where Shiny apps are discussed as a tool to simplify and standardize data analysis for global assays such as thrombin generation and euglobulin clot lysis assays. However, I believe that also for in vivo biomedical studies, in particular with genetically modified mice, the problem of reproducibility of data describing a specific phenotype is becoming a major concern...
July 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28696550/two-novel-variants-of-the-abcg5-gene-cause-xanthelasmas-and-macrothrombocytopenia-a-brief-review-of-hematological-abnormalities-of-sitosterolemia
#2
J M Bastida, R Benito, K Janusz, M Díez-Campelo, J M Hernández-Sánchez, S Marcellini, M Girós, J Rivera, M L Lozano, A Hortal, J M Hernández-Rivas, J R González-Porras
BACKGROUND: Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PS) usually produce xanthomas and premature coronary atherosclerosis, although hematological abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis. OBJECTIVES: To report two novel ABCG5 gene variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL...
July 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28696534/a-fusion-protein-of-interleukin-4-and-interleukin-10-protects-against-blood-induced-cartilage-damage-in-vitro-and-in-vivo
#3
Lize F D van Vulpen, Jelena Popov-Celeketic, Monique E R van Meegeren, Katja Coeleveld, Jacob M van Laar, C Erik Hack, Roger E G Schutgens, Simon C Mastbergen, Floris P J G Lafeber
BACKGROUND: Joint damage still causes significant morbidity in hemophilia. It results from synovial inflammation and direct cartilage-degenerating properties of blood components. Interleukin (IL)-4 and IL-10 have been shown to protect cartilage from blood-induced damage. Recently an IL4-10 fusion protein has been developed to combine the function of IL-4 and IL-10 and increase their bioavailability. OBJECTIVES: In this study it is evaluated whether this IL4-10 fusion protein protects against blood-induced joint damage...
July 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28692141/a-discontinuous-autoinhibitory-module-masks-the-a1-domain-of-von-willebrand-factor
#4
Wei Deng, Yingchun Wang, Samuel A Druzak, John F Healey, Anum K Syed, Pete Lollar, Renhao Li
BACKGROUND: How von Willebrand factor (VWF) senses and responds to shear flow remains unclear. In the absence of shear VWF or its fragments can be induced to bind spontaneously to platelet GPIbα. Objectives To elucidate the auto-inhibition mechanism of VWF. METHODS: Hydrogen-deuterium exchange (HDX) of two recombinant VWF fragments expressed from baby hamster kidney cells were measured and compared. RESULTS: The shortA1 protein contains VWF residues 1261-1472 and binds GPIbα with a significantly higher affinity than the longA1 protein that contains VWF residues 1238-1472...
July 10, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28688221/minimal-factor-xiii-activity-level-to-prevent-major-spontaneous-bleeds
#5
M Menegatti, R Palla, M Boscarino, P Bucciarelli, L Muszbek, E Katona, M Makris, F Peyvandi
BACKGROUND: Congenital factor XIII (FXIII) deficiency is a rare bleeding disorder associated with significant bleeding manifestations. The European Network of Rare Bleeding Disorders (EN-RBD) study, performed from 2007 to 2010, showed a strong association between bleeding severity and FXIII activity in plasma of patients with FXIII deficiency. Among these patients variable levels of FXIII activity, from undetectable to 30%, were associated with a wide range of bleeding severity. Objectives and patients: The present cross-sectional study, in the frame of the PRO-RBDD project, a prospective cohort study, analyzed data of 64 patients with FXIII deficiency and different types of clinical and laboratory severity...
July 8, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28688220/assessment-of-the-protein-interaction-between-coagulation-factor-xii-and-corn-trypsin-inhibitor-by-molecular-docking-and-biochemical-validation
#6
Badraldin K Hamad, Monika Pathak, Rosa Manna, Peter M Fischer, Jonas Emsley, Lodewijk V Dekker
BACKGROUND: Corn trypsin inhibitor (CTI) has selectivity for serine proteases coagulation factor XII (FXII) and trypsin. CTI is in widespread use as a reagent that specifically inhibits the intrinsic pathway of blood coagulation but not the extrinsic pathway. OBJECTIVES: To investigate the molecular basis of FXII inhibition by CTI. METHODS: We performed molecular docking of CTI, using its known crystal structure, with a model of the activated FXII (FXIIa) protease domain...
July 8, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28688133/in-silico-evaluation-of-limited-blood-sampling-strategies-for-individualized-recombinant-factor-ix-prophylaxis-in-hemophilia-b-patients
#7
T Preijers, H C A M Hazendonk, K Fijnvandraat, F W G Leebeek, M H Cnossen, R A A Mathôt
BACKGROUND: Patients with severe hemophilia B regularly administer prophylactic intravenous doses of clotting factor IX (FIX) concentrate to maintain a trough level of at least 0.01 IUmL(-1) in order to prevent joint bleeds. Assessment of individual pharmacokinetic (PK) parameters allows individualization of the recombinant FIX (rFIX) dose. AIM: This in silico study aims to evaluate the predictive performance of limited sampling strategies (LSSs) with 1 to 3 samples to estimate individual PK parameters of rFIX...
July 8, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28688113/assessing-clinical-probability-of-pulmonary-embolism-prospective-validation-of-the-simplified-geneva-score-in-outpatients
#8
H Robert-Ebadi, K Mostaguir, M M Hovens, M Kare, F Verschuren, P Girard, M V Huisman, F Moustafa, P W Kamphuisen, H R Buller, M Righini, G Le Gal
BACKGROUND: Pretest probability assessment by a clinical prediction rule (CPR) is an important step in the management of patients with suspected pulmonary embolism (PE). A limitation to the use of CPR is that their constitutive variables and corresponding number of points are difficult to memorize. A simplified version of the Geneva score (i.e. attributing one point to each variable) has been proposed but never been prospectively validated. AIMS: Prospective validation of the simplified Geneva score (SGS) and comparison with the previous version of the Geneva score (GS)...
July 8, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28682499/high-dose-dexamethasone-or-all-trans-retinoic-acid-restores-the-balance-of-macrophage-toward-m2-in-immune-thrombocytopenia
#9
Q Feng, M Xu, Y Y Yu, Y Hou, X Mi, Y X Sun, S Ma, X Y Zuo, L L Shao, M Hou, X H Zhang, J Peng
Immune thrombocytopenia (ITP) is an autoimmune disorder. Deficiency of immune-tolerance in antigen-presenting cells (APCs) and cross-communication between APCs and T cells are involved in the pathogenesis of ITP. Macrophages can polarize into pro-inflammatory M1 or anti-inflammatory M2 phenotypes in response to different environmental stimuli, and possess diverse immunological functions OBJECTIVES: To investigate the imbalance of M1/M2 in ITP and whether high-dose dexamethasone (HD-DXM) or all-trans retinoic acid (ATRA) could restore this imbalance METHODS: Numbers of M1 and M2 in the spleens of ITP patients and patients with traumatic spleen rupture were analyzed by immunofluorescence...
July 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28682477/preclinical-safety-and-efficacy-of-andexanet-alfa-in-animal-models
#10
G Lu, S J Hollenbach, D C Baker, S Tan, A Hutchaleelaha, J T Curnutte, P B Conley
BACKGROUND: Andexanet is a recombinant modified form of factor Xa (FXa), designed to bind to and reverse the anticoagulant activity of FXa inhibitors. OBJECTIVES: To evaluate the ability of andexanet to reverse the anticoagulant activity of rivaroxaban, and assess its pharmacokinetics (PK) and toxicity in animal models. METHODS: The effects of andexanet on blood loss, anti-FXa activity, rivaroxaban unbound plasma concentrations, and other coagulation parameters were assessed in a rabbit liver laceration 'treatment' model...
July 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28677246/factor-xi-deficient-mice-exhibit-increased-bleeding-after-injury-to-the-saphenous-vein
#11
C Ay, Y Hisada, B Cooley, N Mackman
BACKGROUND: Factor XI (FXI) is a key component of the intrinsic pathway of coagulation. It can be activated by either FXIIa or thrombin and amplifies thrombin generation during clot formation. Congenital FXI deficiency in humans (known as hemophilia C) is associated with bleeding after hemostatic challenge. However, to date there are no reports of excess bleeding in FXI deficient mice. OBJECTIVES: To determine if the absence of FXI in mice prolongs bleeding in different models...
July 4, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28667788/altered-%C3%AE-2-glycoprotein-i-expression-on-microparticles-in-the-presence-of-antiphospholipid-antibodies
#12
Fariborz Mobarrez, Iva Gunnarsson, Elisabet Svenungsson
BACKGROUND: Antiphospholipid antibodies (aPL) together with thrombosis and/or pregnancy morbidities characterize the antiphospholipid syndrome. β2-glycoprotein-I (β2 GPI), the most important antigen for aPL, is a scavenger molecule that specifically binds to phosphatidylserine (PS), expressed on microparticles (MPs). OBJECTIVES: We evaluated β2 GPI-expressing MPs in patients with systemic lupus erythematosus (SLE) stratified for aPL status, and healthy controls...
July 1, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28662310/thrombotic-thrombocytopenic-purpura-pathogenesis-diagnosis-and-potential-novel-therapeutics
#13
REVIEW
Manish Saha, Jenny K McDaniel, X Long Zheng
Thrombotic thrombocytopenic purpura (TTP), a potentially fatal clinical syndrome, is primarily caused by autoantibodies against the von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS13. In general, severe deficiency of plasma ADAMTS13 activity (<10 IU/dL) with or without detectable inhibitory autoantibodies against ADAMTS13 supports the diagnosis of TTP if a patient presents with thrombocytopenia and microangiopathic hemolytic anemia (i.e. schistocytes, elevated serum lactate dehydrogenase, decreased hemoglobin and haptoglobin) without other known etiologies that cause thrombotic microangiopathy (TMA)...
June 29, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28662299/thrombotic-risk-stratification-by-platelet-count-in-patients-with-antiphospholipid-antibodies-a-longitudinal-study
#14
Ryo Hisada, Masaru Kato, Eri Sugawara, Yuichiro Fujieda, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Shinsuke Yasuda, Tatsuya Atsumi
BACKGROUND: Thrombocytopenia is a non-criteria clinical manifestation of antiphospholipid syndrome (APS). However, it remains to be elucidated whether thrombocytopenia increases thrombotic risk in antiphospholipid antibody (aPL) carriers. OBJECTIVES: To investigate the impact of platelet count in terms of predicting thrombotic events in aPL carriers and to stratify the thrombotic risk by combining platelet count and antiphospholipid score (aPL-S), which represents a quantification of aPL varieties and titres PATIENTS/METHODS: A single centre retrospective, longitudinal study comprising 953 consecutive patients who were suspected to have autoimmune disease between January 2002 and December 2006...
June 29, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28639418/clinical-course-of-isolated-distal-deep-vein-thrombosis-in-patients-with-active-cancer-a-multicenter-cohort-study
#15
F Dentali, S Pegoraro, S Barco, M N D di Minno, D Mastroiacovo, F Pomero, C Lodigiani, F Bagna, M Sartori, G Barillari, N Mumoli, M Napolitano, S M Passamonti, R Benedetti, W Ageno, M Di Nisio
Essentials Isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer. No study has specifically evaluated the long-term clinical course of cancer-associated IDDVT. Patients with cancer-associated IDDVT are at very high risk of symptomatic recurrence and death. We observed low rates of major bleeding during anticoagulation. SUMMARY: Background Although isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer, no study has specifically evaluated the long-term clinical course of IDDVT in this setting...
June 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28632940/characterization-of-the-i4399m-variant-of-apolipoprotein-a-implications-for-altered-prothrombotic-properties-of-lipoprotein-a
#16
Corey A Scipione, Jackson T McAiney, Daniel J Simard, Zainab A Bazzi, Matthew Gemin, Rocco Romagnuolo, Fraser L Macrae, Robert A Ariëns, Robert A Hegele, Janeen Auld, James W Gauld, Michael B Boffa, Marlys L Koschinsky
BACKGROUND: Lipoprotein(a) (Lp(a)) is a causal risk factor for a variety of cardiovascular diseases. Apolipoprotein(a) (apo(a)), the distinguishing component of Lp(a), is homologous to plasminogen, suggesting that Lp(a) can interfere with the normal fibrinolytic functions of plasminogen. This has implications for the persistence of fibrin clots in the vasculature and hence to atherothrombotic diseases. A single nucleotide polymorphism (rs3798220) in the gene encoding apo(a) has been reported that results in an Ile to Met substitution in the protease-like domain (I4399M variant)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28632925/a-kallikrein-targeting-rna-aptamer-inhibits-the-intrinsic-pathway-of-coagulation-and-reduces-bradykinin-release
#17
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/28622439/clinical-effectiveness-of-a-bayesian-algorithm-for-the-diagnosis-and-management-of-heparin-induced-thrombocytopenia
#18
Robert A Raschke, Tyler Gallo, Steven C Curry, Tonya Whiting, Angela Padilla-Jones, Theodore E Warkentin
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by anti-platelet factor 4/heparin (anti-PF4/H) antibodies. Commercial tests to detect these antibodies have limitations. We previously developed a diagnostic algorithm for HIT that incorporated "four Ts" (4Ts) scoring and a stratified interpretation of an anti-PF4/H enzyme-linked immunosorbent assay (ELISA) and yielded a discriminant accuracy of 0.97 (95% CI: 0.93-1.00). OBJECTIVES: The purpose of this study was to validate the algorithm in an independent patient population and quantitate effects that algorithm adherence could have on clinical care...
June 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28618141/mortality-caused-by-intracranial-bleeding-in-non-severe-hemophilia-a-patients-reply
#19
J I Loomans, K Fijnvandraat
With great interest we read the letter of Dr. Patil et al. (1) in which they present the number and percentage of hemophilia patients registered in the Mumbai hemophilia center who died from (intracranial) bleeding between 2002 and 2015. We thank Dr. Patil et al. for sharing their data and for providing essential insight into fatal intracranial bleeding in nonsevere hemophilia A patients from a large hemophilia center in India. This article is protected by copyright. All rights reserved.
June 15, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28608988/should-the-dosing-algorithms-for-vitamin-k-antagonists-be-centered-around-only-vkorc1-and-cyp2c9-genotypes
#20
Tejasvita Gaikwad, Kanjaksha Ghosh, Shrimati Shetty
We read with interest the recent report by Baranova et al. [1] in which authors have carried out secondary analysis of European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) data by evaluating the performance of different dosing algorithms and time intervals of outcome assessment across VKORC1- CYP2C9 genetic sub groups. This article is protected by copyright. All rights reserved.
June 13, 2017: Journal of Thrombosis and Haemostasis: JTH
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