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https://www.readbyqxmd.com/read/27863820/b-cell-depleting-therapy-regulates-splenic-and-circulating-t-follicular-helper-cells-in-immune-thrombocytopenia
#1
Sylvain Audia, Marzia Rossato, Malika Trad, Maxime Samson, Kim Santegoets, Alexandrine Gautheron, Cornelis Bekker, Olivier Facy, Nicolas Cheynel, Pablo Ortega-Deballon, Mathieu Boulin, Sabine Berthier, Vanessa Leguy-Seguin, Laurent Martin, Marion Ciudad, Nona Janikashvili, Philippe Saas, Timothy Radstake, Bernard Bonnotte
B cells are involved in immune thrombocytopenia (ITP) pathophysiology by producing antiplatelet auto-antibodies. However more than a half of ITP patients do not respond to B cell depletion induced by rituximab (RTX). The persistence of splenic T follicular helper cells (TFH) that we demonstrated to be expanded during ITP and to support B cell differentiation and antiplatelet antibody-production may participate to RTX inefficiency. Whereas it is well established that the survival of TFH depends on B cells in animal models, nothing is known in humans yet...
November 15, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27842767/drug-hepatotoxicity-newer-agents
#2
REVIEW
Chalermrat Bunchorntavakul, K Rajender Reddy
Idiosyncratic hepatotoxicity is one of the most common reasons for an approved drug being restricted. This article focuses on hepatotoxicity of selected and recently introduced agents, such as, tyrosine kinase inhibitors, monoclonal antibodies, novel oral anticoagulants, newer antiplatelets, antibiotics, anti-diabetics, anti-epileptics, anti-depressants, anti-psychotics and anti-retrovirals. Overall, the incidence of clinically relevant hepatotoxicity from newer agents seems to be lower than that of the older agents...
February 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/27797129/alternative-agents-to-prophylactic-platelet-transfusion-for-preventing-bleeding-in-people-with-thrombocytopenia-due-to-chronic-bone-marrow-failure-a-meta-analysis-and-systematic-review
#3
REVIEW
Michael Desborough, Andreas V Hadjinicolaou, Anna Chaimani, Marialena Trivella, Paresh Vyas, Carolyn Doree, Sally Hopewell, Simon J Stanworth, Lise J Estcourt
BACKGROUND: People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents that could replace, or reduce platelet transfusion, and are effective at reducing bleeding are needed. OBJECTIVES: To compare the relative efficacy of different interventions for patients with thrombocytopenia due to chronic bone marrow failure and to derive a hierarchy of potential alternative treatments to platelet transfusions...
October 31, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27793553/-thrombosis-during-thrombopoietin-receptor-agonist-treatment-for-immune-thrombocytopenia-a-french-multicentric-observational-study
#4
E Weber, G Moulis, M Mahévas, C Guy, B Lioger, I Durieu, M Hunault, M Ramanantsoa, B Royer, A Default, M-C Pérault-Pochat, L Moachon, N Bernard, G Bardy, A-P Jonville-Bera, H Geniaux, B Godeau, P Cathébras
INTRODUCTION: Thrombopoietin-receptor agonists (TPO-RA) are marketed for immune thrombocytopenia (ITP). They have been associated to thrombosis occurrence in randomized controlled trials. However, the characteristics of these thromboses in the real-life practice as well as their management are poorly known. The objectives of this study were to determine the risk factors, circumstances and management of thrombosis occurring during exposure to TPO-RA in ITP. METHODS: We carried out a multicentre retrospective study in France...
October 25, 2016: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/27724926/anti-platelet-therapy-holds-promises-in-treating-adenomyosis-experimental-evidence
#5
Bo Zhu, Yumei Chen, Xiaolu Shen, Xishi Liu, Sun-Wei Guo
BACKGROUND: Recently emerging evidence indicates that endometriotic lesions are wounds undergoing repeated tissue injury and repair (ReTIAR), and platelets induce epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), leading ultimately to fibrosis. Due to the commonality of cyclic bleeding as in endometriosis, adenomyotic lesions are also wounds that undergo ReTIAR, and we have recently provided evidence corroborating platelet-induced EMT, FMT and fibrogenesis in adenomyosis...
October 10, 2016: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/27704162/tnf-alpha-and-annexin-a2-inflammation-in-thrombotic-primary-antiphospholipid-syndrome
#6
REVIEW
Mirjana Bećarević
Antiphospholipid syndrome (APS) is characterized by thromboses and/or pregnancy losses. Laboratory criterion for the diagnosis of APS is the presence of antiphospholipid antibodies (anticardiolipin, anti-beta2-glycoprotein I (aβ2gpI) and lupus anticoagulant). On the one hand, the latest classification criteria for the diagnosis of APS emphasized that thrombotic manifestations of the syndrome should be without any signs of an inflammatory process, while on the other hand, some recent reports have suggested that APS is a "pro-inflammatory state...
December 2016: Rheumatology International
https://www.readbyqxmd.com/read/27702402/development-of-antithrombotic-aptamers-from-recognizing-elements-to-drugs
#7
Elena Zavyalova, Andrey Golovin, Galina Pavlova, Alexey Kopylov
Blood hemostasis is attained with two sophisticated interconnected network systems, a coagulation cascade and a platelet activation system. Multiple inhibitors were developed to various components of both systems to prevent thrombosis-related morbid events that are of extremely high frequency in the human population. Antithrombotic inhibitors possess both positive and negative aspects. One of the essential modern requirements is a controllable mode of action for both anticoagulants and antiplatelets that could be achieved due to the high affinity and specificity of the inhibitor, as well as a possibility to apply an antidote, which quickly annihilates activity of the inhibitor and restores the proper hemostasis...
2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27677394/new-directions-for-pharmacotherapy-in-the-treatment-of-acute-coronary-syndrome
#8
Piotr Adamski, Urszula Adamska, Małgorzata Ostrowska, Marek Koziński, Jacek Kubica
Acute coronary syndromes (ACS) are one of the leading causes of death worldwide. Several landmark trials, followed by a widespread introduction of new agents, have significantly improved ACS outcomes in recent years. However, despite the use of contemporary therapy, a substantial number of ACS patients continue to suffer from cardiovascular events. Areas covered: The aim of this review was to summarize available data on innovative drugs and pharmacological strategies that have potential to amend the current ACS therapy...
October 10, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27671102/eltrombopag-thrombopoietin-receptor-agonist-and-plasmapheresis-as-rescue-therapy-of-acute-post-renal-transplant-immune-thrombocytopenia-in-a-child-with-schimke-immuno-osseous-dysplasia-case-report
#9
Ryszard Grenda, Wioletta Jarmużek, Joanna Latoszyńska, Sylwester Prokurat, Jacek Rubik
SIOD is rare disorder related to SMARCAL1 or SMARCAL2 gene mutation, including (among other comorbidities) T-cell immunodeficiency, nephrotic syndrome, and renal failure. Up to 22% of primary patients may develop various autoimmune disorders. We report the case of 11-year-old male with SIOD, who presented ITP at 2 years after renal transplantation with decrease in platelet count (from normal) to 56 000/μL and then (gradually) to 2000/μL. There was no effect of iv. methylprednisolone/dexamethasone. As the presence of antibodies against GPIIb/IIIa, GPIb, and GPIaIIa platelet glycoproteins was confirmed, patient was given 50 g of IVIG and then was put on plasmapheresis; however, both showed poor direct effect...
September 26, 2016: Pediatric Transplantation
https://www.readbyqxmd.com/read/27616636/antiplatelet-activity-of-flavonoid-and-coumarin-drugs
#10
Cristina Zaragozá Arnaéz, Jorge Monserrat Sanz, Carolina Mantecón Ramiro, Lucinda Villaescusa Castillo, Francisco Zaragozá García, Melchor Álvarez de Mon Soto
Polyphenols are used as phlebotonic drugs, but their mechanism of action remains unknown. Since platelet activity and platelet-endothelial cell interactions are involved in the pathogenesis of cardiovascular disease, this work examines whether different flavonoid and coumarin drugs are able to inhibit platelet aggregation. This specific case of coumarins, the antiplatelet effect is not linked with a possible interaction over blood coagulation since this effect only dicoumarols have it. The antiplatelet capacity of polyphenols was assayed using peripheral blood platelets from healthy controls...
September 8, 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27603334/bilateral-sudden-sensorineural-hearing-loss-as-a-presenting-feature-of-systemic-lupus-erythematosus-case-report-and-brief-review-of-other-published-cases
#11
Sylvain Chawki, Jessie Aouizerate, Selim Trad, Jacques Prinseau, Thomas Hanslik
INTRODUCTION: Sudden sensorineural hearing loss is an unusual presenting clinical feature of systemic lupus erythematosus. CASE REPORT: We report the case of a young woman who was admitted to hospital for sudden sensorineural hearing loss and hemophagocytic syndrome which was attributed to systemic lupus erythematosus on the basis of specific renal involvement, thrombocytopenia, and consistent autoantibodies. Favorable outcome was obtained on high-dose corticosteroids, and the hearing fully recovered...
September 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27567293/pathways-linked-to-internuclear-ophthalmoplegia-on-diffusion-tensor-imaging-in-a-case-with-midbrain-infarction
#12
Haruka Takeshige, Yuji Ueno, Koji Kamagata, Fuyuko Sasaki, Kazuo Yamashiro, Ryota Tanaka, Shigeki Aoki, Nobutaka Hattori
BACKGROUND: Midbrain infarction shows diverse patterns of ophthalmoplegia; however, the association of ophthalmoplegia with a precise microanatomy has not been fully studied. Here, we report a patient with characteristic ophthalmoplegia and explore the associated pathologic fiber tracts using diffusion-tensor imaging (DTI). METHODS: A 21-year-old woman with an 11-year history of mixed connective tissue disease (MCTD) abruptly developed bilateral internuclear ophthalmoplegia (INO) with upward gaze and convergence palsies...
August 24, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/27496152/prevention-treatment-of-obstetrical-complications-in-aps-is-hydroxychloroquine-the-holy-grail-we-are-looking-for
#13
Pier Luigi Meroni
Pregnancy morbidity is part of the clinical spectrum of the anti-phospholipid syndrome (APS), with an important social and economical cost. Antiplatelet and anticoagulant agents are effective in preventing the clinical manifestations in the majority of the patients. However, a consistent proportion of the pregnant women present recurrences in spite of the standard therapy. Observational studies and anecdotal reports raised the issue of additional therapeutic strategies in these refractory cases. Among these, anti-malarials (AMs) and in particular hydroxychloroquine (HCQ) are becoming more and more popular in APS as well as in other systemic autoimmune rheumatic conditions...
August 2, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27457513/eular-recommendations-for-women-s-health-and-the-management-of-family-planning-assisted-reproduction-pregnancy-and-menopause-in-patients-with-systemic-lupus-erythematosus-and-or-antiphospholipid-syndrome
#14
L Andreoli, G K Bertsias, N Agmon-Levin, S Brown, R Cervera, N Costedoat-Chalumeau, A Doria, R Fischer-Betz, F Forger, M F Moraes-Fontes, M Khamashta, J King, A Lojacono, F Marchiori, P L Meroni, M Mosca, M Motta, M Ostensen, C Pamfil, L Raio, M Schneider, E Svenungsson, M Tektonidou, S Yavuz, D Boumpas, A Tincani
OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes...
July 25, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27312155/t-cells-in-the-pathogenesis-of-immune-thrombocytopenia
#15
Yu Wei, Ming Hou
Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disease characterized by both increased platelet destruction and reduced platelet production. ITP involves complicated upstream immune dysregulations in which T-cell subsets are supposed to take the center stage. Survival of autoreactive T cells is prolonged. Th-cell polarization is observed in Th1, Th17, and Th22 subsets with a positive correlation, whereas Tregs, a protective subset, is deficient in both frequency and function. Restoration of the imbalanced Th1/Th17/Tregs may correct the abnormal autoimmunity...
April 2016: Seminars in Hematology
https://www.readbyqxmd.com/read/27310493/unraveling-the-pharmacokinetic-interaction-of-ticagrelor-and-medi2452-ticagrelor-antidote-by-mathematical-modeling
#16
J Almquist, M Penney, S Pehrsson, A-S Sandinge, A Janefeldt, S Maqbool, S Madalli, J Goodman, S Nylander, P Gennemark
The investigational ticagrelor-neutralizing antibody fragment, MEDI2452, is developed to rapidly and specifically reverse the antiplatelet effects of ticagrelor. However, the dynamic interaction of ticagrelor, the ticagrelor active metabolite (TAM), and MEDI2452, makes pharmacokinetic (PK) analysis nontrivial and mathematical modeling becomes essential to unravel the complex behavior of this system. We propose a mechanistic PK model, including a special observation model for post-sampling equilibration, which is validated and refined using mouse in vivo data from four studies of combined ticagrelor-MEDI2452 treatment...
June 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27307776/long-term-safety-and-efficacy-of-romiplostim-for-treatment-of-immune-thrombocytopenia
#17
REVIEW
Prakash Vishnu, David M Aboulafia
Inhibition of platelet production and mediated by antiplatelet antibodies is a well-known mechanism causing low platelet counts in immune thrombocytopenia (ITP). Use of thrombopoietin receptor agonists increases platelet counts and decreases the risk of bleeding in patients with ITP. Two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are approved by the US Food and Drug Administration to treat thrombocytopenia in adults, and most recently, children with persistent or chronic ITP. This review focuses on the efficacy data and safety analysis of the pooled data from the clinical trials evaluating romiplostim for treatment of adults with ITP...
2016: Journal of Blood Medicine
https://www.readbyqxmd.com/read/27297331/association-of-anticardiolipin-antiphosphatidylserine-anti-%C3%AE-2-glycoprotein-i-and-antiphosphatidylcholine-autoantibodies-with-canine-immune-thrombocytopenia
#18
Yu-Chen Chen, Lang-Ming Chi, Kuan-Chih Chow, Shiow-Her Chiou, Yi-Hsin Fan, Shu-Peng Ho, Yu-Chen Hsu, Yu-Chyi Hwang, Meng-Xing Wu, Wei-Ming Lee, Shiun-Long Lin, Chau-Loong Tsang, Frank Chiahung Mao
BACKGROUND: In humans, the presence of antiphospholipid antibodies (aPL) is frequently found in immune thrombocytopenia. The present study investigated whether aPL and any aPL subtypes are associated with canine thrombocytopenia, in particular, immune-mediated thrombocytopenia (immune thrombocytopenia) that usually manifests with severe thrombocytopenia. RESULTS: Sera were collected from 64 outpatient dogs with thrombocytopenia (Group I, platelet count 0 - 80 × 10(3)/uL), and 38 of which having severe thrombocytopenia (platelet count < 30 × 10(3)/uL) were further divided into subgroups based on the presence of positive antiplatelet antibodies (aPLT) (subgroup IA, immune thrombocytopenia, n =20) or the absence of aPLT (subgroup IB, severe thrombocytopenia negative for aPLT, n =18)...
2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27291997/olaratumab-and-doxorubicin-versus-doxorubicin-alone-for-treatment-of-soft-tissue-sarcoma-an-open-label-phase-1b-and-randomised-phase-2-trial
#19
RANDOMIZED CONTROLLED TRIAL
William D Tap, Robin L Jones, Brian A Van Tine, Bartosz Chmielowski, Anthony D Elias, Douglas Adkins, Mark Agulnik, Matthew M Cooney, Michael B Livingston, Gregory Pennock, Meera R Hameed, Gaurav D Shah, Amy Qin, Ashwin Shahir, Damien M Cronier, Robert Ilaria, Ilaria Conti, Jan Cosaert, Gary K Schwartz
BACKGROUND: Treatment with doxorubicin is a present standard of care for patients with metastatic soft-tissue sarcoma and median overall survival for those treated is 12-16 months, but few, if any, novel treatments or chemotherapy combinations have been able to improve these poor outcomes. Olaratumab is a human antiplatelet-derived growth factor receptor α monoclonal antibody that has antitumour activity in human sarcoma xenografts. We aimed to assess the efficacy of olaratumab plus doxorubicin in patients with advanced or metastatic soft-tissue sarcoma...
July 30, 2016: Lancet
https://www.readbyqxmd.com/read/27229722/antiphospholipid-antibody-mediated-thrombotic-mechanisms-in-antiphospholipid-syndrome-towards-pathophysiology-based-treatment
#20
REVIEW
Md Asiful Islam, Fahmida Alam, Teguh Haryo Sasongko, Siew Hua Gan
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by a persistently high titer of antiphospholipid antibodies (aPLs). In addition to pregnancy morbidity, arterial and/or venous thrombosis is another clinical feature of APS. Regardless of the type of APS, the thrombi formed by the induction of aPLs can lead to deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke and gangrene. Although the concept of APS was introduced approximately 32 years ago, its thrombogenic pathophysiology is still unclear...
2016: Current Pharmaceutical Design
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