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Thrombosis and Haemostasis

Kristina Busygina, Viola Denzinger, Isabell Bernlochner, Christian Weber, Reinhard Lorenz, Wolfgang Siess
Bruton's tyrosine kinase (Btk) is essential for B cell differentiation and proliferation, but also platelets express Btk. Patients with X-linked agammaglobulinemia due to hereditary Btk deficiency do not show bleeding, but a mild bleeding tendency is observed in high dose therapy of B-cell malignancies with ibrutinib and novel second-generation irreversible Btk inhibitors (acalabrutinib and ONO/GS-4059). This review discusses recent studies that may explain this apparent paradox and gives mechanistic insights that suggest a unique potential of low dose irreversible Btk inhibitors as atherothrombosis-focused antiplatelet drugs...
May 14, 2019: Thrombosis and Haemostasis
Dimitrios Alexopoulos, Stylianos Dragasis, Nikolaos Kafkas
Oral P2Y12 receptor inhibitors represent a mainstay treatment in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. In the setting of ST-elevation myocardial infarction, when early platelet inhibition is highly desirable, the onset of action of oral P2Y12 receptor inhibitors is, however, delayed, likely due to delayed drug absorption. Crushing the tablets, which are to be used for patient loading with an oral P2Y12 receptor inhibitor, has been shown to provide earlier platelet inhibition than standard, integral tablets administration...
May 12, 2019: Thrombosis and Haemostasis
Abdullah Hamadi, Andrew P Grigg, Gasim Dobie, Kate L Burbury, Anthony P Schwarer, Faith A Kwa, Denise E Jackson
Both nilotinib, a second-generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukaemia (CML), and ponatinib, a third-generation TKI used in CML and Philadelphia positive acute lymphocytic leukaemia, have been associated with an increase in arterial occlusive events, in contrast to other TKIs such as imatinib and dasatinib. We have previously demonstrated evidence of a pro-thrombotic state associated with nilotinib, using microvascular and arterial thrombosis C57BL/6 mouse models...
May 12, 2019: Thrombosis and Haemostasis
Jeehoon Kang, Kyung Woo Park, You-Jeong Ki, Jiesuck Park, Taemin Rhee, Chee-Hoon Kim, Jung-Kyu Han, Han-Mo Yang, Hyun-Jae Kang, Bon-Kwon Koo, Masato Nakamura, Toshimitsu Hamasaki, Hiroyoshi Yokoi, David Cohen, Hyo-Soo Kim
BACKGROUND:  The ischemic/bleeding risk of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is still uncertain. We sought to develop a tool to predict ischemic and bleeding events in East Asians receiving 2nd generation drug-eluting stents (DESs) PCI. METHODS:  A pooled cohort of 13,172 East Asian patients receiving PCI with 2nd generation DES (the Grand DES cohort) was analyzed to develop a scoring system. A net score was calculated by subtracting the bleeding score from the ischemic score...
May 12, 2019: Thrombosis and Haemostasis
Joanne I Adamkewicz, David C Chen, Ido Paz-Priel
Emicizumab bridges activated factor IX (FIX) and FX to restore the tenase function mediated by activated FVIII (FVIIIa), which is deficient in people with haemophilia A (PwHA). Unlike FVIII, emicizumab does not require activation to function; thus, in coagulation assays, the behavior of emicizumab may differ from that of FVIII. The objective of this study was to assess the effect of emicizumab on coagulation assays, including potential interference behavior that may produce inaccurate or misleading results...
May 7, 2019: Thrombosis and Haemostasis
Shiro Koizume, Tomoko Takahashi, Mitsuyo Yoshihara, Yoshiyasu Nakamura, Wolfram Ruf, Katsuya Takenaka, Etsuko Miyagi, Yohei Miyagi
Interaction between the transcription factors, hypoxia-inducible factor (HIF1α and HIF2α) and Sp1, mediates hypoxia-driven expression of FVII gene encoding coagulation factor VII (fVII) in ovarian clear cell carcinoma (CCC) cells. This mechanism is synergistically enhanced in response to serum starvation, a condition possibly associated with tumor hypoxia. This transcriptional response potentially results in venous thromboembolism, a common complication in cancer patients by producing procoagulant extracellular vesicles (EVs)...
May 5, 2019: Thrombosis and Haemostasis
Kelly Njine Mouapi, Lucille J Wagner, Chad A Stephens, Mohammed M Hindi, Daniel W Wilkey, Michael L Merchant, Muriel C Maurer
Fibrinogen (Fbg) levels and extent of fibrin polymerization have been associated with various pathological conditions such as cardiovascular disease, arteriosclerosis, and coagulation disorders. Activated factor XIII (FXIIIa) introduces γ-glutamyl-ε-lysinyl isopeptide bonds between reactive glutamines and lysines in the fibrin network to form a blood clot resistant to fibrinolysis. FXIIIa crosslinks the γ-chains and at multiple sites in the αC region of Fbg. Fbg αC contains a FXIII binding site involving αC (389-402) that is located near three glutamines whose reactivities rank Q237 > Q366 ≈ Q328...
May 5, 2019: Thrombosis and Haemostasis
Thita Chiasakul, Benjaporn Akkawat, Ponlapat Rojnuckarin
No abstract text is available yet for this article.
April 30, 2019: Thrombosis and Haemostasis
Terence J Quinn, Deirdre A Lane
No abstract text is available yet for this article.
April 30, 2019: Thrombosis and Haemostasis
Valentina Paloschi, Hanna Winter, Joana Viola, Oliver Soehnlein, Lars Maegdefessel
Inflammation plays a pivotal role in the chronicity of atherosclerotic lesion development and progression. Myeloid cells are involved in all stages of atherosclerosis development: they contribute in early phases to endothelial dysfunction and create a pro-inflammatory environment responsible for disease progression. Numerous studies over the last decade have repeatedly provided evidence for the crucial importance for different classes of non-coding ribonucleic acids (RNAs) in regulating gene expression, as well as messenger RNA and protein stability...
April 29, 2019: Thrombosis and Haemostasis
Martina Olsson Lindvall, Lena Hansson, Sofia Klasson, Marcela Davila Lopez, Christina Jern, Tara M Stanne
OBJECTIVE:  Elucidating the genetic basis underlying hepatic hemostatic gene expression variability may contribute to unraveling genetic factors contributing to thrombotic or bleeding disorders. We aimed to identify novel cis -regulatory variants involved in regulating hemostatic genes by analyzing allele-specific expression (ASE) in human liver samples. STUDY DESIGN:  Biopsies of human liver tissue and blood were collected from adults undergoing liver surgery at the Sahlgrenska University Hospital ( n  = 20)...
April 29, 2019: Thrombosis and Haemostasis
Gesa König, Tobias Obser, Olivier Marggraf, Sonja Schneppenheim, Ulrich Budde, Reinhard Schneppenheim, Maria A Brehm
The platelet receptor glycoprotein (GP) IIb/IIIa, formed by integrins αIIb and β3 , plays an important role in platelet adhesion and aggregation. Its major binding site is the arginine-glycine-aspartic acid (RGD) sequence present in several adhesive proteins. Upon platelet activation, inside-out signaling activates the complex permitting binding to RGD motif containing proteins, such as von Willebrand factor (VWF). VWF is a large multidomain plasma GP essential to primary hemostasis, which can directly interact with platelets because it exhibits binding sites for GPIbα and GPIIb/IIIa in its A1 and C4 domain, respectively...
April 29, 2019: Thrombosis and Haemostasis
Anne Hollerbach, Nadine Müller-Calleja, Svenja Ritter, Friederike Häuser, Antje Canisius, Carolin Orning, Kerstin Jurk, Karl J Lackner
Antiphospholipid antibodies (aPL) have been reported to activate platelets. This is considered to be one of the pathogenic properties of aPL. Even though aPL heterogeneity is quite well established, little is known, if the ability to activate platelets is common to all aPL or depends on antigen specificity. To further study this issue, we analyzed the ability of three human monoclonal aPL with distinctly different antigenic specificities to activate platelets in vitro. The results obtained with human monoclonal aPL were validated with immunoglobulin G (IgG) fractions obtained from patients with antiphospholipid syndrome (APS)...
April 24, 2019: Thrombosis and Haemostasis
Søren Paaske Johnsen, Lars Frost
No abstract text is available yet for this article.
April 23, 2019: Thrombosis and Haemostasis
Shana A Shaya, Dhulfiha Muzafar Gani, Jeffrey I Weitz, Paul Y Kim, Peter L Gross
BACKGROUND:  Deep vein thrombosis (DVT) can lead to pulmonary embolism (PE), but the mechanisms responsible for this progression are unknown. Previously, we showed that inhibition of thrombin-mediated activation of factor (F) XIII promotes venous thrombus stability in a murine model. AIM:  In this study, we investigate the consequence of attenuating fibrinolysis, using FXIII, α2 -antiplasmin (α2 -AP) or ε-aminocaproic acid (EACA) supplementation, on clot lysis and venous thrombus stability using the same mouse model...
April 20, 2019: Thrombosis and Haemostasis
Stéphanie Roullet, Sylvie Labrouche, Geneviève Freyburger
BACKGROUND:  During liver transplantation (LT), thrombin generation (TG) is altered. The most frequently used assay for TG is the Calibrated Automated Thrombogram (CAT). It is designed for series of plasmas and is semi-automated. Complete automation has led to a new device, the ST-Genesia, enabling quantitative standardized TG evaluation. OBJECTIVE:  The aim of this observational study was to compare the TG results of the CAT and the ST-Genesia on frozen-thawed plasma samples prepared from the blood of LT patients...
April 20, 2019: Thrombosis and Haemostasis
Katharina Trabold, Stephanie Makhoul, Stepan Gambaryan, Joanne van Ryn, Ulrich Walter, Kerstin Jurk
The direct thrombin inhibitor (DTI) dabigatran is a non-vitamin K antagonist oral anticoagulant for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. In addition to its anti-thrombotic efficacy, dabigatran has been suggested to exert some pro-thrombotic effect due to fostering the ligation of thrombin to its high affinity platelet receptor glycoprotein (GP) Ibα in patients with atrial fibrillation. On the other hand, we provided evidence that a member of another class of DTIs, lepirudin, stimulates the inhibitory cyclic guanosine monophosphate (cGMP)/soluble guanylate cyclase pathway in human platelets...
April 20, 2019: Thrombosis and Haemostasis
Madeleine Hui, Jo-Ann I Sheppard, Na Li, Theodore E Warkentin
BACKGROUND:  Heparin-induced thrombocytopenia (HIT) antibodies activate platelets, monocytes and neutrophils. Despite these findings, it is unknown whether white blood cell (WBC) counts, including neutrophils and monocytes, are altered during HIT. MATERIALS AND METHODS:  We evaluated changes in total WBC counts (including WBC subsets), in 50 post-cardiac surgery patients with serologically confirmed HIT (30 patients with HIT-associated thrombosis). Daily leukocyte counts were compared with those measured one day prior to HIT onset; WBC increases were classified as mild (20...
April 20, 2019: Thrombosis and Haemostasis
Julie Brogaard Larsen, Mathies Appel Laursen, Christine Lodberg Hvas, Kim Michael Larsen, Steffen Thiel, Anne-Mette Hvas
BACKGROUND:  Activation of the complement system is part of the dysregulated immune response in sepsis. The mannose-binding lectin-associated serine proteases (MASP)-1 and -2 activate the lectin pathway of the complement system. Besides, these proteins can activate coagulation in vitro. However, the role of the lectin pathway proteins in the development of sepsis-related disseminated intravascular coagulation (DIC) is only sparsely investigated. AIM:  This article investigates the association between lectin pathway proteins and coagulation disturbances in septic shock patients...
April 15, 2019: Thrombosis and Haemostasis
David Keire
No abstract text is available yet for this article.
April 9, 2019: Thrombosis and Haemostasis
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