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Journal of Thrombosis and Haemostasis: JTH

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https://www.readbyqxmd.com/read/30016577/heparin-protamine-balance-after-neonatal-cardiopulmonary-bypass-surgery
#1
J A Peterson, S A Maroney, W Zwifelhofer, J P Wood, K Yan, R S Bercovitz, R K Woods, A E Mast
BACKGROUND: Neonates undergoing cardiopulmonary bypass (CPB) are at risk for excessive bleeding. Blood is anticoagulated with heparin during CPB. Heparin activity is reversed with protamine at the end of CPB. Paradoxically, protamine also inhibits blood coagulation when it is dosed in excess of heparin. OBJECTIVES: To evaluate heparin-protamine balance in neonates undergoing CPB using research and clinical assays and determine their association with post-operative bleeding...
July 17, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/30007118/small-molecule-targeting-the-rac1-nox2-interaction-prevents-collagen-related-peptide-and-thrombin-induced-reactive-oxygen-species-generation-and-platelet-activation
#2
H Akbar, X Duan, R Piatt, S Saleem, A K Davis, N N Tandon, W Bergmeier, Y Zheng
BACKGROUND: Platelets from patients with X-linked chronic granulomatous disease or mice deficient in NADPH oxidase isoform NOX2 exhibit diminished reactive oxygen species (ROS) generation and platelet activation. Binding of Rac1 GTPase to p67phox plays a critical role in NOX2 activation by facilitating the assembly of the NOX2 enzyme complex. OBJECTIVE: We tested the hypothesis that Phox-I, a rationally designed small molecule inhibitor of Rac-p67phox interaction, may serve as an anti-thrombosis agent by suppressing ROS production and platelet activation...
July 14, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/30007116/longitudinal-increase-in-blood-biomarkers-of-inflammation-or-cardiovascular-disease-and-the-incidence-of-venous-thromboembolism
#3
Aaron R Folsom, Pamela L Lutsey, Susan R Heckbert, Kripa Poudel, Saonli Basu, Ron C Hoogeveen, Mary Cushman, Christie M Ballantyne
BACKGROUND: We previously showed that participants in the population-based Atherosclerosis Risk in Communities (ARIC) cohort with elevated blood biomarkers of inflammation or cardiac disease were at increased risk of venous thromboembolism (VTE). OBJECTIVE: We hypothesized now that ARIC participants with larger 6-year increases in three biomarkers - C-reactive protein (CRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), and troponin T - also would have increased subsequent risk of VTE...
July 14, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/30007114/laboratory-criteria-for-antiphospholipid-syndrome-communication-from-the-ssc-of-the-isth-comment
#4
Karl Kackner, Nadine Müller-Calleja
In a recent article the members of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies of the ISTH summarize their consensus on laboratory criteria for antiphospholipid syndrome (APS) [1]. In the section of anticardiolipin (aCL) and beta2-glycoprotein I (aβ2GPI) antibodies they state that "it is mandatory to avoid detection of non-cofactor related aCL associated with infections or several drugs". This statement immediately raises two questions which are not addressed in the article: first, how is detection of non-cofactor related aCL avoided, and second, why should it be avoided at all? Regarding the first question, the authors might want to elaborate more on the technical requirements for avoidance of detection of non-cofactor related aCL...
July 14, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/30007111/laboratory-criteria-for-antiphospholipid-syndrome-reply
#5
Katrien M J Devreese, Thomas L Ortel, Vittorio Pengo, Bas de Laat
We appreciate the comment of Lackner and Müller-Calleja on our recent publication on laboratory criteria of APS (1). In their comment, an advocacy for co-factor independent anticardiolipin antibodies (aCL) is made. In our communication, we recommend testing for β2 glycoprotein I (β2GPI)-dependent aCL as laboratory criteria for antiphospholipid syndrome (APS) primarily to avoid false positive classification of patients as having APS and thereby prevent unnecessary treatment. Our focus on β2GPI-dependent aCL is intended to avoid infectious related aCL that are not associated with clinical symptoms associated to APS...
July 14, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/30007049/factor-xi-promotes-hemostasis-in-factor-ix-deficient-mice
#6
Bassem M Mohammed, Qiufang Cheng, Anton Matafonov, Dougald M Monroe, Joost C M Meijers, David Gailani
BACKGROUND: In humans, deficiency of coagulation factor XI (FXI) may be associated with a bleeding disorder, but until recently FXI-deficient mice did not appear to have a hemostatic defect. A recent study, however, indicated that FXI-deficient mice display a moderate hemostatic defect in a saphenous vein bleeding (SVB) model. OBJECTIVES: To study the effect of FXI on bleeding in mice with normal levels of the FXI-substrate factor IX (FIX) and in mice lacking FIX (a murine model of hemophilia B)...
July 14, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/30007048/assessment-of-whole-blood-coagulation-with-a-microfluidic-dielectric-sensor
#7
Debnath Maji, Maria De La Fuente, Erdem Kucukal, Ujjal D S Sekhon, Alvin H Schmaier, Anirban Sen Gupta, Umut A Gurkan, Marvin T Nieman, Evi X Stavrou, Pedram Mohseni, Michael A Suster
BACKGROUND: Rapid point-of-care (POC) assessment of hemostasis is clinically important in patients with a variety of coagulation factor and platelet defects who have bleeding disorders. OBJECTIVE: To evaluate a novel dielectric microsensor, termed ClotChip, which is based on the electrical technique of dielectric spectroscopy for rapid, comprehensive assessment of whole blood coagulation. METHODS: The ClotChip is a three-dimensional, parallel-plate, capacitive sensor integrated into a single-use microfluidic channel with miniscule sample volume (<10 μL)...
July 14, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/30007042/nano-evidence-for-joint-microbleeds-in-hemophilia-patients
#8
LETTER
John Puetz
The concept of joint microbleeding in hemophilia patients was first proposed over 10 years ago. This was based on unexpected abnormalities found in medical imaging studies of asymptomatic joints. Since then, there have been no published studies confirming the presence of joint microbleeds. This critique will review the evidence for and against joint microbleeding in hemophilia patients and the potential implications. This article is protected by copyright. All rights reserved.
July 14, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29993188/the-chaperone-like-sodium-phenylbutyrate-improves-factor-ix-intracellular-trafficking-and-activity-impaired-by-the-frequent-p-r294q-mutation
#9
S Pignani, A Todaro, M Ferrarese, S Marchi, S Lombardi, D Balestra, P Pinton, F Bernardi, M Pinotti, A Branchini
BACKGROUND: Missense mutations often impair protein folding and intracellular processing, which can be improved by small compounds with chaperone-like activity. However, little has been done in coagulopathies, where even modest increases of functional levels could have therapeutic implications. OBJECTIVES: To rescue the expression of factor IX (FIX) variants affected by missense mutations associated with type I Haemophilia B (HB) through chaperone-like compounds...
July 11, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29984467/mechanisms-and-mitigating-factors-for-venous-thromboembolism-in-chronic-kidney-disease-the-regards-study
#10
K L Cheung, N A Zakai, P W Callas, G Howard, B K Mahmoodi, C A Peralta, S E Judd, M Kurella Tamura, M Cushman
BACKGROUND: Chronic kidney disease (CKD) is associated with venous thromboembolism (VTE) risk via unknown mechanisms. Whether factors associated with reduced VTE in the general population might also be associated with reduced risk in CKD is unknown. OBJECTIVES: To determine whether thrombosis biomarkers attenuate VTE risk and if factors associated with reduced VTE are similarly effective in CKD. METHODS: Baseline biomarkers were measured in a case-cohort (294 VTE cases, 939 non-cases) from the REGARDS study, a nationwide prospective cohort of 30,239 persons age ≥45 with 4...
July 8, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29983001/pdk1-governs-thromboxane-generation-and-thrombosis-in-platelets-by-regulating-activation-of-raf1-in-the-mapk-pathway-comment
#11
Pravin Patel, Kalyan Golla, Ulhas P Naik
PDK1 has gained interest in the field as a potential target for antithrombotic therapies [1]; however, the role of PDK1 downstream of the P2Y1/12 receptors remained unknown. We therefore read with great interest a recent report published in the Journal of Thrombosis and Haemostasis, by Manne et al. [2] describing the role of PDK1 in regulating platelet activation and TxA2 generation downstream of the P2Y1/12 receptors. In their study, Manne et al. used both pharmacological and genetic methods to conclusively show that targeting PDK1 can significantly attenuate pulmonary thromboembolism-induced mortality in an in vivo murine model...
July 7, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29982998/targeting-platelet-epcr-for-better-therapeutic-factor-viia-activity
#12
Sean X Gu, Steven R Lentz
Management of patients with inhibitory antibodies to factor VIII or factor IX remains one of the most challenging aspects of modern hemophilia care. Control of bleeding in patients with high titer inhibitors often relies on the use of bypassing agents such as activated prothrombin complex concentrates or recombinant factor VIIa (rFVIIa). The mechanism of action of pharmacologically dosed rFVIIa has been contentious [1]. Unlike endogenous FVIIa, which binds to tissue factor (TF) at sites of vascular injury to promote the activation of factors X and IX, high dose rFVIIa appears to function via TF-independent activation of factor X on the surface of activated platelets [2, 3]...
July 7, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29981270/anti-c1-domain-antibodies-that-accelerate-factor-viii-clearance-contribute-to-antibody-pathogenicity-in-a-murine-hemophilia-a-model
#13
G Batsuli, J Ito, R Mercer, W H Baldwin, C Cox, E T Parker, J F Healey, P Lollar, S L Meeks
BACKGROUND: The development of neutralizing anti-factor VIII (fVIII) antibodies remains a challenging complication of modern hemophilia A care. In vitro assays are the primary method used for quantifying inhibitor titers, predicting bleeding risk, and determining bleeding management. However, other mechanisms of inhibition are not accounted for in these assays, which may result in discrepancies between the inhibitor titer and clinical bleeding symptoms. OBJECTIVES: We evaluated fVIII clearance in vivo as a potential mechanism for antibody pathogenicity and whether increased fVIII dosing regimens corrected the associated bleeding phenotype...
July 7, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29981269/flavin-monooxygenase-3-the-host-hepatic-enzyme-in-the-metaorganismal-trimethylamine-n-oxide-generating-pathway-modulates-platelet-responsiveness-and-thrombosis-risk
#14
W Zhu, J A Buffa, Z Wang, M Warrier, R Schugar, D M Shih, N Gupta, J C Gregory, E Org, X Fu, L Li, J A DiDonato, A J Lusis, J M Brown, S L Hazen
BACKGROUND: Gut microbes play a critical role in the production of trimethylamine N-oxide (TMAO), an atherogenic metabolite that impacts platelet responsiveness and thrombosis potential. Involving both microbe and host enzymatic machinery, TMAO generation utilizes a metaorganismal pathway, beginning with ingestion of trimethylamine (TMA)-containing dietary nutrients such as choline, phosphatidylcholine and carnitine, which are abundant in a Western diet. Gut microbial TMA lyases use these nutrients as substrates to produce TMA, which upon delivery to the liver via the portal circulation, is converted into TMAO by host hepatic flavin monooxygenases (FMOs)...
July 7, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29981265/pdk1-governs-thromboxane-generation-and-thrombosis-in-platelets-by-regulating-activation-of-raf1-in-the-mapk-pathway-reply
#15
Bhanu Kanth Manne, Matthew T Rondina
We appreciate the letter from Dr. Pravin Patel and colleagues[1] regarding our recent studies to determine how phosphoinositide 3-kinase (PDK1) regulates thromboxane generation[2], a mechanism that had not previously been known. We also examined the downstream signaling cascades, reporting that PDK1-regulated thromboxane generation is controlled through the Raf1-ERK1/2 pathway. This article is protected by copyright. All rights reserved.
July 7, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29978544/risk-factors-for-bleeding-including-platelet-count-threshold-in-newly-diagnosed-immune-thrombocytopenia-adults
#16
Marie-Léa Piel-Julian, Matthieu Mahévas, Johanne Germain, Laetitia Languille, Thibault Comont, Maryse Lapeyre-Mestre, Bernard Payrastre, Odile Beyne-Rauzy, Marc Michel, Bertrand Godeau, Daniel Adoue, Guillaume Moulis
BACKGROUND: The aim of this cross-sectional study was to assess risk factors of bleeding in ITP adults, including the determination of platelet count thresholds. METHODS: We selected all newly diagnosed ITP adults included in the CARMEN register and at the French referral center for autoimmune cytopenias. Frequencies of any bleeding, mucosal bleeding and severe bleeding (gastro-intestinal, intracranial or macroscopic hematuria) at ITP onset were assessed. Platelet count thresholds were assessed using receiver-operating characteristics curves...
July 6, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29975003/acquired-platelet-antagonism-off-target-antiplatelet-effects-of-malignancy-treatment-with-tyrosine-kinase-inhibitors
#17
REVIEW
Bibian M E Tullemans, Johan W M Heemskerk, Marijke J E Kuijpers
Platelets can contribute to tumour progression and metastasis. Cancer patients are at increased risk of thrombosis, while advanced stages of cancer associate with thrombocytosis or increased platelet reactivity. Tyrosine kinase inhibitors (TKIs) are widely used as a targeted strategy for cancer treatment, aiming to prolong progression-free survival of the patients. Because of their broad kinase target spectrum, most TKIs inevitably have off-target effects. Platelets rely on tyrosine kinase activity for their activation...
July 5, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29974611/less-abnormal-uterine-bleeding-with-dabigatran-than-warfarin-in-women-treated-for-acute-venous-thromboembolism
#18
Menno V Huisman, Melanie Ferrreira, Martin Feuring, Mandy Fraessdorf, Frederikus A Klok
INTRODUCTION: While Direct Oral Anticoagulants (DOACs) are associated with a better safety profile than warfarin in patients with acute venous thromboembolism (VTE), direct factor Xa-inhibitors involve a higher risk of abnormal uterine bleeding (AUB). We aimed to determine the risk of AUB during anticoagulation with dabigatran compared to warfarin. METHODS: Post-hoc analysis of the pooled RE-COVER studies and the RE-MEDY trial. Incidences of AUB, based on a defined preferred terms search in adverse events, in female patients aged 18-50 years treated with dabigatran were compared with those treated with warfarin...
July 5, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29974610/alcohol-consumption-and-the-risk-of-incident-pulmonary-embolism-in-u-s-women-and-men
#19
L B Harrington, K A Hagan, K J Mukamal, J H Kang, J Kim, M Crous-Bou, S Lindström, E B Rimm, C Kabrhel, M K Jensen
BACKGROUND: Moderate alcohol consumption has been variably associated with hemostatic and fibrinolytic factor levels, but the association between alcohol consumption and risk of incident pulmonary embolism (PE) remains uncertain. OBJECTIVE: To evaluate alcohol consumption amount and frequency in relation to PE risk. METHODS: Nurses' Health Study (NHS), NHS II, and Health Professionals Follow-Up Study participants free of venous thromboembolism (VTE) at baseline (n=217,442) reported alcohol consumption by type, quantity, and frequency, every 2-4 years...
July 5, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29971917/leukocytes-as-a-reservoir-of-circulating-oncogenic-dna-and-regulatory-targets-of-tumor-derived-extracellular-vesicles
#20
S Chennakrishnaiah, B Meehan, E D'Asti, L Montermini, T-H Lee, N Karatzas, M Buchanan, N Tawil, D Choi, M Divangahi, M Basik, J Rak
BACKGROUND: Tumor-derived extracellular vesicles (EVs) and free nucleosomes (NSs) carry into the circulation a wealth of cancer-specific, bioactive and poorly understood molecular cargo, including genomic DNA (gDNA). OBJECTIVE: Here we investigated the distribution of extracellular oncogenic gDNA sequences (HRAS and HER2) in the circulation of tumor-bearing mice. METHODS AND RESULTS: Surprisingly, circulating leukocytes (WBCs), especially neutrophils, contained the highest levels of mutant gDNA, which exceeded the amount of this material recovered from soluble fractions of plasma, circulating EVs, platelets, red blood cells (RBCs), and peripheral organs as quantified by digital droplet PCR (ddPCR)...
July 3, 2018: Journal of Thrombosis and Haemostasis: JTH
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