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https://www.readbyqxmd.com/read/28809049/evolution-of-mnc-and-lymphocyte-collection-settings-employing-different-spectra-optia-%C3%A2-leukapheresis-systems
#1
M Punzel, A Kozlova, A Quade, A H Schmidt, R Smith
BACKGROUND AND OBJECTIVES: The Spectra Optia(®) continuous mononuclear cell (CMNC apheresis) system has emerged as the preferred device in peripheral blood stem cell collections over the original two-step Spectra Optia(®) mononuclear cell (MNC apheresis) system. Until now, no comparative data were available for non-stimulated MNC collections that are required for immunotherapy. MATERIALS AND METHODS: We compared collection parameters and product composition for Spectra Optia MNC- as well as CMNC-apheresis systems in non-stimulated MNC collections from 35 registry donors intended for donor lymphocyte infusions...
August 14, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28774196/the-clinical-utility-of-the-heparin-neutralization-assay-in-the-diagnosis-of-heparin-induced-thrombocytopenia
#2
Gang Zheng, Michael B Streiff, Clifford M Takemoto, Jennifer Bynum, Elise Gelwan, Jayesh Jani, Danielle Judge, Thomas S Kickler
Heparin-induced thrombocytopenia (HIT) remains diagnostically challenging. Immunoassays including PF4/heparin enzyme-linked immunosorbent assay (ELISA) have high sensitivity but low specificity. Whether the heparin neutralization assay (HNA) improves the diagnostic accuracy of the PF4/heparin ELISA for HIT is uncertain. In this study, to assess its clinical utility and evaluate whether it improves the diagnostic accuracy for HIT, we implemented HNA in conjunction with PF4/heparin ELISA over a 1-year period...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28771917/5b9-a-monoclonal-anti-platelet-factor-4-heparin-igg-with-a-human-fc-fragment-that-mimics-heparin-induced-thrombocytopenia-antibodies
#3
C Kizlik-Masson, C Vayne, S E McKenzie, A Poupon, Y Zhou, G Champier, Pouplard C, Y Gruel, J Rollin
BACKGROUND: The diagnosis of heparin-induced thrombocytopenia (HIT) is based on clinical and biological criteria, but a standard is lacking for laboratory assays. Moreover, no humanized HIT antibody is available for pathophysiological studies. OBJECTIVE: To characterise 5B9, a chimeric monoclonal antibody, which fully mimics the effects of human HIT antibodies. METHODS/RESULTS: 5B9, a chimeric anti-PF4/H IgG1 antibody was obtained after immunizing specific transgenic mice...
August 3, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28739484/protein-kinase-c%C3%AE-%C3%AE-is-dispensable-for-platelet-function-in-thrombosis-and-hemostasis-in-mice
#4
Sarah Beck, Michael Leitges, David Stegner
Platelet activation at sites of vascular injury is crucial for hemostasis, but it may also cause myocardial infarction or ischemic stroke. Upon platelet activation, cytoskeletal reorganization is essential for platelet secretion and thrombus formation. Members of the protein kinase C family, which includes 12 isoforms, are involved in most platelet responses required for thrombus formation. The atypical protein kinase Cι/λ (PKCι/λ) has been implicated as an important mediator of cell polarity, carcinogenesis and immune cell responses...
July 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28725494/apixaban-for-treatment-of-confirmed-heparin-induced-thrombocytopenia-a-case-report-and-review-of-literature
#5
Daniel E Ezekwudo, Rebecca Chacko, Bolanle Gbadamosi, Syeda Batool, Sussana Gaikazian, Theodore E Warkentin, Jo-Ann I Sheppard, Ishmael Jaiyesimi
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening condition caused by the binding of platelet-activating antibodies (IgG) to multimolecular platelet factor 4 (PF4)/heparin complexes because of heparin exposure. The by-product of this interaction is thrombin formation which substantially increases the risk of venous and/or arterial thromboembolism. Currently, only one anticoagulant, argatroban, is United States Food and Drug Administration-approved for management of HIT; however, this agent is expensive and can only be given by intravenous infusion...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28712066/effect-of-ph-and-ionic-strength-on-the-binding-strength-of-anti-pf4-polyanion-antibodies
#6
Thi-Huong Nguyen, Andreas Greinacher
Antibodies against the chemokine platelet factor 4 (PF4) in complex with heparin cause the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). The current dilemma for laboratory diagnosis of HIT is that only about 50% of these antibodies are pathogenic, but the widely available enzyme immunosorbent assays (EIA), used for diagnosis in the clinical laboratory cannot differentiate between non-pathogenic- and pathogenic (platelet activating) antibodies. It would be highly desirable to improve diagnosis for HIT...
July 15, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28708215/changes-in-the-levels-of-beta-thromboglobulin-and-inflammatory-mediators-during-extracorporeal-membrane-oxygenation-support
#7
Jae H Chung, Hye J Yeo, Dohyung Kim, Sun M Lee, Junhee Han, Minseok Kim, Woo H Cho
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been associated with platelet dysfunction, but no markers of platelet dysfunction during ECMO have been identified. METHODS: We investigated the potential uses of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) as markers of platelet activation induced by ECMO in vivo. RESULTS: 13 patients who received ECMO for acute respiratory failure were included. Generalized estimating equations were used to examine the associations between days on ECMO and the plasma levels of beta-TG and PF4 and of proinflammatory markers...
July 5, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28698883/anti-platelet-factor-4-heparin-antibody-formation-occurs-endogenously-and-at-unexpected-high-frequency-in-polycythemia-vera
#8
Sara C Meyer, Eva Steinmann, Thomas Lehmann, Patricia Muesser, Jakob R Passweg, Radek C Skoda, Dimitrios A Tsakiris
BACKGROUND: Myeloproliferative neoplasms (MPN) encounter thromboses due to multiple known risk factors. Heparin-induced thrombocytopenia (HIT) is a thrombotic syndrome mediated by anti-platelet factor 4 (PF4)/heparin antibodies with undetermined significance for thrombosis in MPN. We hypothesized that anti-PF4/heparin Ab might occur in MPN and promote thrombosis. METHODS: Anti-PF4/heparin antibodies were analyzed in 127 MPN patients including 76 PV and 51 ET. Screening, validation testing, and isotype testing of anti-PF4/heparin Ab were correlated with disease characteristics...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28683994/the-effects-of-steroids-on-coagulation-dysfunction-induced-by-cardiopulmonary-bypass-a-steroids-in-cardiac-surgery-sirs-trial-substudy
#9
Domenico Paparella, Alessandro Parolari, Crescenzia Rotunno, Jessica Vincent, Veronica Myasoedova, Pietro Guida, Micaela De Palo, Vito Margari, Philip J Devereaux, Andre Lamy, Francesco Alamanni, Salim Yusuf, Richard Whitlock
Cardiopulmonary bypass (CPB) surgery, despite heparin administration, elicits activation of coagulation system resulting in coagulopathy. Anti-inflammatory effects of steroid treatment have been demonstrated, but its effects on coagulation system are unknown. The primary objective of this study is to assess the effects of methylprednisolone on coagulation function by evaluating thrombin generation, fibrinolysis, and platelet activation in high-risk patients undergoing cardiac surgery with CPB. The Steroids In caRdiac Surgery study is a double-blind, randomized, controlled trial performed on 7507 patients worldwide who were randomized to receive either intravenous methylprednisolone, 250 mg at anesthetic induction and 250 mg at initiation of CPB (n = 3755), or placebo (n = 3752)...
April 2017: Seminars in Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28681377/chronic-periodontitis-is-associated-with-platelet-factor-4-pf4-secretion-a-pilot-study
#10
Mathieu Brousseau-Nault, Jayachandran N Kizhakkedathu, Hugh Kim
AIM: Platelets contribute to chronic inflammation but their role in periodontitis is not well understood. The aim of this study was to compare platelet recruitment and activation in healthy and inflamed periodontium. MATERIALS AND METHODS: Gingival crevicular fluid (GCF) samples were obtained from sites of healthy periodontium, gingivitis and periodontitis. Platelets were quantified in the GCF by staining and microscopy. GCF concentrations of platelet factor 4 (PF4) [PF4]GCF and glycoprotein IIbIIIa ([GPIIbIIIa]GCF ) were determined by ELISA...
July 6, 2017: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/28677022/performance-of-4t-score-and-heparin-platelet-factor-4-antibody-in-the-diagnosis-of-heparin-induced-thrombocytopenia-hit-in-cancer
#11
Myra Wong, Thein Hlaing Oo, Wei Qiao, Naveen Garg, Cristhiam M Rojas-Hernandez
Cancer patients have characteristics which significantly influence the 4T score and heparin-platelet factor 4 antibody (H-PF4 ab). Our aim was to determine among cancer patients the correlation of the 4T score and H-PF4 ab with the serotonin release assay (SRA). We performed a retrospective analysis of records of cancer patients in whom H-PF4 polyclonal (IgG, IgM and IgA) enzyme-linked immunosorbent assay (ELISA) and SRA were evaluated. Cases were defined as heparin induced thrombocytopenia (HIT) when SRA confirmed the diagnosis...
August 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28672052/direct-acting-oral-anticoagulants-for-the-treatment-of-suspected-heparin-induced-thrombocytopenia
#12
Kyle A Davis, Daphne O Davis
OBJECTIVE: To evaluate the efficacy and safety of direct oral anticoagulant (DOAC) therapy in hospitalized patients with suspected heparin induced thrombocytopenia (HIT). METHODS: Retrospective cohort study of adult patients prescribed apixaban, dabigatran, or rivaroxaban for the treatment of acute HIT from January 1 2013 to January 1 2017. Eligibility requirements included an intermediate or high pretest probability for HIT (4T score ≥ 4) and a positive IgG-specific anti-PF4/ heparin complex assay...
July 3, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28663252/glucose-transporter-3-potentiates-degranulation-and-is-required-for-platelet-activation
#13
Trevor P Fidler, Elizabeth Middleton, Jesse W Rowley, Luc H Boudreau, Robert A Campbell, Rhonda Souvenir, Trevor Funari, Nicolas Tessandier, Eric Boilard, Andrew S Weyrich, E Dale Abel
OBJECTIVE: On activation, platelets increase glucose uptake, glycolysis, and glucose oxidation and consume stored glycogen. This correlation between glucose metabolism and platelet function is not well understood and even less is known about the role of glucose metabolism on platelet function in vivo. For glucose to enter a cell, it must be transported through glucose transporters. Here we evaluate the contribution of GLUT3 (glucose transporter 3) to platelet function to better understand glucose metabolism in platelets...
June 29, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28646118/direct-oral-anticoagulants-for-treatment-of-hit-update-of-hamilton-experience-and-literature-review
#14
Theodore E Warkentin, Menaka Pai, Lori-Ann Linkins
Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, Canada, since January 1, 2015 (when we completed our prospective rivaroxaban for HIT study) using rivaroxaban for serologically-confirmed HIT (4Ts score ≥4 points, PF4/heparin immunoassay-positive, serotonin-release assay positive). We also performed a literature review of HIT treatment using a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28625264/-suppressive-effect-of-corm-2-on-platelet-%C3%AE-granule-exocytosis-in-sepsis-via-snare-munc18b-complex-formation
#15
Mingfeng Zhuang, Bingwei Sun, Dadong Liu, Yuan Shi
OBJECTIVE: To investigate the suppressive effect of carbon monoxide-releasing molecule II (CORM-2) on LPS induced platelet α-granule exocytosis in sepsis via soluble N-ethylmaleimide-sensitive factor attached protein receptor/mammalian uncoordinated 18b (SNARE/Munc18b) complex formation. METHODS: Blood was collected from healthy volunteers' cubital vein, then platelets were isolated by differential centrifugation. Platelets were randomly divided into 5 groups. The control group did not undergo any treatment, the LPS group received 10 mg/L LPS simulation, the CORM-2 group and iCORM-2 group underwent LPS simulation and immediate administration of CORM-2 (10 μmol/L and 50 μmol/L) or iCORM-2 (50 μmol/L), respectively...
February 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28622439/clinical-effectiveness-of-a-bayesian-algorithm-for-the-diagnosis-and-management-of-heparin-induced-thrombocytopenia
#16
R A Raschke, T Gallo, S C Curry, T Whiting, A Padilla-Jones, T E Warkentin, A Puri
Essentials We previously published a diagnostic algorithm for heparin-induced thrombocytopenia (HIT). In this study, we validated the algorithm in an independent large healthcare system. The accuracy was 98%, sensitivity 82% and specificity 99%. The algorithm has potential to improve accuracy and efficiency in the diagnosis of HIT. SUMMARY: Background Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by antiplatelet factor 4/heparin (anti-PF4/H) antibodies...
June 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28530237/anti-platelet-factor-4-polyanion-antibodies-mediate-a-new-mechanism-of-autoimmunity
#17
Thi-Huong Nguyen, Nikolay Medvedev, Mihaela Delcea, Andreas Greinacher
Antibodies recognizing complexes of the chemokine platelet factor 4 (PF4/CXCL4) and polyanions (P) opsonize PF4-coated bacteria hereby mediating bacterial host defense. A subset of these antibodies may activate platelets after binding to PF4/heparin complexes, causing the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). In autoimmune-HIT, anti-PF4/P-antibodies activate platelets in the absence of heparin. Here we show that antibodies with binding forces of approximately 60-100 pN activate platelets in the presence of polyanions, while a subset of antibodies from autoimmune-HIT patients with binding forces ≥100 pN binds to PF4 alone in the absence of polyanions...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28467728/the-pf4-ppbp-cxcl5-gene-cluster-is-associated-with-periodontitis
#18
A Shusterman, M Munz, G Richter, S Jepsen, W Lieb, B Krone, P Hoffman, M Laudes, J Wellmann, K Berger, T Kocher, S Offenbacher, K Divaris, A Franke, S Schreiber, H Dommisch, E Weiss, A S Schaefer, Y Houri-Haddad, F A Iraqi
Periodontitis is a common dysbiotic inflammatory disease with an estimated heritability of 50%. Due to the limited sample size of available periodontitis cohorts and the underlying trait heterogeneity, genome-wide association studies (GWAS) of chronic periodontitis (CP) have been unsuccessful in discovering susceptibility factors. A strategy that combines agnostic GWAS with a well-powered candidate-gene approach has the potential to discover novel loci. We combined RNA-seq data from gingival tissues with quantitative trait loci (QTLs) that were identified in a F2-cross of mice resistant and susceptible to infection with oral bacterial pathogens...
July 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28446364/clinical-and-laboratory-diagnosis-of-heparin-induced-thrombocytopenia-an-update
#19
REVIEW
Emmanuel J Favaloro, Georgia McCaughan, Leonardo Pasalic
Heparin remains a commonly used anticoagulant in prophylaxis and treatment of venous and arterial thrombosis, in addition to ensuring patency of artificial blood circuits such as cardiopulmonary bypass (CPB). Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy that results from production of polyclonal antibodies to heparin in complex, usually with platelet factor 4 (PF4). In a proportion of patients, this causes platelet activation and thrombin generation, which may result in thrombosis...
June 2017: Pathology
https://www.readbyqxmd.com/read/28427966/ivig-for-treatment-of-severe-refractory-heparin-induced-thrombocytopenia
#20
Anand Padmanabhan, Curtis G Jones, Shannon M Pechauer, Brian R Curtis, Daniel W Bougie, Mehraboon S Irani, Barbara J Bryant, Jack B Alperin, Thomas G Deloughery, Kevin P Mulvey, Binod Dhakal, Renren Wen, Demin Wang, Richard H Aster
BACKGROUND: Heparin-induced thrombocytopenia (HIT) complicated by severe thrombocytopenia and thrombosis can pose significant treatment challenges. Use of alternative anticoagulants in this setting may increase bleeding risks, especially in patients who have a protracted disease course. Additional therapies are lacking in this severely affected patient population. METHODS: We describe three patients with HIT who had severe thromboembolism and prolonged thrombocytopenia refractory to standard treatment but who achieved an immediate and sustained response to IVIg therapy...
April 17, 2017: Chest
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