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https://www.readbyqxmd.com/read/28625264/-suppressive-effect-of-corm-2-on-platelet-%C3%AE-granule-exocytosis-in-sepsis-via-snare-munc18b-complex-formation
#1
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
#2
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/28530237/anti-platelet-factor-4-polyanion-antibodies-mediate-a-new-mechanism-of-autoimmunity
#3
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
#4
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...
May 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28446364/clinical-and-laboratory-diagnosis-of-heparin-induced-thrombocytopenia-an-update
#5
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/intravenous-immunoglobulin-for-treatment-of-severe-refractory-heparin-induced-thrombocytopenia
#6
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: 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 HIT patients who had severe thromboembolism and prolonged thrombocytopenia refractory to standard treatment but achieved an immediate and sustained response to intravenous immunoglobulin G (IVIg) therapy...
April 17, 2017: Chest
https://www.readbyqxmd.com/read/28418908/plasma-protein-profiling-in-patients-undergoing-coronary-artery-bypass-grafting-surgery-and-clinical-significance
#7
Zhi-Peng Guo, Hai-Tao Hou, Rui Jing, Zhen-Guo Song, Xiao-Cheng Liu, Guo-Wei He
This study was designed to identify the protein profiling in patients with triple vessel coronary artery disease (CAD) undergoing CABG, in order to detect CAD-related differential proteins in these patients. CABG patients with triple vessel disease with/without left main stenosis (n =160) were compared to normal coronary angiographic subjects (n =160). Plasma samples of 20 males and 20 females in each group were analyzed with iTRAQ technique. ELISA test was used to test the chosen proteins from iTRAQ results in plasma samples from a new cohort of the CABG group (n=120, male/femal=61/59) and control (n =120, male/female=60/60)...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416511/heparin-induced-thrombocytopenia
#8
REVIEW
Gowthami M Arepally
Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate cellular FcγRIIA on platelets and monocytes to propagate a hypercoagulable state culminating in life-threatening thrombosis. It is now recognized that anti-PF4/heparin antibodies develop commonly after heparin exposure, but only a subset of sensitized patients progress to life-threatening complications of thrombocytopenia and thrombosis...
May 25, 2017: Blood
https://www.readbyqxmd.com/read/28407821/-association-between-platelet-activating-factor-acetylhydrolase-gene-polymorphisms-and-gastrointestinal-bleeding-in-children-with-henoch-sch%C3%A3-nlein-purpura
#9
Bao-Xiang Wang, Hong Mei, Han-Ming Peng, Yuan Gao, Yan Ding
OBJECTIVE: To study the association between the single nucleotide polymorphisms (SNPs) of the ninth exon Val279Phe of platelet-activating factor acetylhydrolase (PAF-AH) gene and gastrointestinal bleeding in children with Henoch-Schönlein purpura (HSP). METHODS: A total 516 children with HSP were enrolled, among whom 182 had gastrointestinal bleeding and 334 had no gastrointestinal bleeding. PCR was used to investigate the distribution of genotypes and alleles in the SNPs of Val97Phe...
April 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28391124/performance-characteristics-of-an-automated-latex-immunoturbidimetric-assay-hemosil-%C3%A2-hit-ab-pf4-h-for-the-diagnosis-of-immune-heparin-induced-thrombocytopenia
#10
Theodore E Warkentin, Jo-Ann I Sheppard, Lori-Ann Linkins, Donald M Arnold, Ishac Nazy
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating anti-PF4/heparin antibodies. Given time-sensitive treatment considerations, a rapid and accurate laboratory test for HIT antibodies is needed. AIMS: To determine operating characteristics for the HemosIL(®) HIT-Ab(PF4/H), a rapid, on-demand, fully-automated, latex immunoturbidimetric assay (LIA), for diagnosis of HIT. METHODS: We evaluated LIA sensitivity, specificity, negative (NPV) and positive predictive value (PPV), negative (LR-) and positive likelihood ratio (LR+), using citrated-plasma from 429 patients (prospective cohort study of 4Ts scoring; HIT, n=31), and from consecutive HIT patients (n=125), using reference standard serotonin-release assay (SRA)...
March 11, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28384443/effect-of-platelet-derived-%C3%AE-thromboglobulins-on-coagulation
#11
Karl Egan, Johanna P van Geffen, Hui Ma, Barry Kevane, Aine Lennon, Seamus Allen, Elaine Neary, Martin Parsons, Patricia Maguire, Kieran Wynne, Richard O' Kennedy, Johan W M Heemskerk, Fionnuala Ní Áinle
BACKGROUND: β-thromboglobulins are derived from the cleavage of the CXC chemokine platelet basic protein and are released in high concentrations by activated platelets. Platelet-derived β-thromboglobulins (βTG) share 70% homology with platelet factor 4 (PF4), another CXC chemokine released by activated platelets. PF4 modulates coagulation by inhibiting heparin-antithrombin interactions, promoting protein C activation, and attenuating the activity of activated protein C. In contrast, the effect of βTG on coagulation is unknown...
March 30, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28374939/diagnostic-accuracy-of-igg-specific-versus-polyspecific-enzyme-linked-immunoassays-in-heparin-induced-thrombocytopenia-a-systematic-review-and-meta-analysis
#12
H D Husseinzadeh, P A Gimotty, A M Pishko, M Buckley, T E Warkentin, A Cuker
Essentials Immunoassay specificity varies in heparin-induced thrombocytopenia (HIT) testing. This meta-analysis examined 9 studies that tested samples by both IgG and polyspecific methods. IgG-specific assays confer superior diagnostic accuracy compared with polyspecific assays. These results further support recommendations in favor of IgG-specific testing. SUMMARY: Background There are conflicting data on whether the IgG-specific or polyspecific antiplatelet factor 4/heparin (PF4/H) enzyme-linked immunosorbent assay (ELISA) is preferred for the laboratory diagnosis of heparin-induced thrombocytopenia (HIT)...
June 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28369702/the-unique-immunological-features-of-heparin-induced-thrombocytopenia
#13
REVIEW
Phillip Staibano, Donald M Arnold, Dawn M E Bowdish, Ishac Nazy
Heparin-induced thrombocytopenia (HIT) is a serious drug reaction that leads to a decrease in platelet count and a high risk of thrombosis. HIT patients produce pathogenic immunoglobulin G (IgG) antibodies that bind to complexes of platelet factor-4 (PF4) and heparin. HIT immune complexes crosslink Fc-receptors resulting in platelet and monocyte activation. These events lead to the release of procoagulant chemokines and tissue factor, which together create an intensely prothrombotic state. HIT represents an atypical immune response because it has features of both T cell-dependent and T cell-independent mechanisms...
April 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28360858/saponins-from-sanguisorba-officinalis-improve-hematopoiesis-by-promoting-survival-through-fak-and-erk1-2-activation-and-modulating-cytokine-production-in-bone-marrow
#14
Xin Chen, Bogang Li, Yue Gao, Jianxin Ji, Zhongliu Wu, Shuang Chen
Radix Sanguisorbae, the root of Sanguisorba officinalis L. is used as traditional Chinese medicine. In recent decades, it has been reported to be clinically effective against myelosuppression induced by chemotherapy and/ or radiotherapy. However, the underlining mechanism has not been well studied. In this work, we evaluated the hematopoietic effect of total saponins from S. officinalis L. on myelosuppressive mice induced by cyclophosphamide and by(60)Co-γ-irradiation and confirmed the therapeutic effect. Then, we found total saponins and their characteristic constituents Ziyuglycoside I and Ziyuglycoside II can inhibit apoptosis of TF-1 cells caused by cytokine deprivation, and promote survival of mouse bone marrow nuclear cells through focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (Erk1/2) activation in vitro...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28346881/heparin-and-homogeneous-model-heparin-oligosaccharides-form-distinct-complexes-with-protamine-light-scattering-and-zeta-potential-analysis
#15
Cynthia D Sommers, Hongping Ye, Jian Liu, Robert J Linhardt, David A Keire
Large multimolecular complexes of heparin with positively charged proteins such as platelet factor 4 (PF4) or protamine can initiate immune responses associated with heparin use in patients, including the most significant adverse event, heparin-induced thrombocytopenia (HIT). Current evidence suggests that platelet-activating antibodies that recognize large multi-molecular complexes (300-700kDa) of PF4 bound to heparin cause HIT [1] and in very rare cases anti-protamine-heparin antibodies can induce thrombocytopenia [2]...
June 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28344423/anti-platelet-factor-4-heparin-antibody-plays-a-significant-role-in-progression-of-arterial-stiffness-among-hemodialysis-patients
#16
Chieh Kuo, Chiang-Chin Tsai, Chien-An Chen, Yueh-Feng Tsai, Yen-Hsun Chen
BACKGROUND: Arterial stiffness is a determinant of cardiovascular disease in end stage renal disease. Hemodialysis patients may develop anti-platelet factor 4/heparin antibody (PF4-H Ab) because of heparin treatment in dialysis. We tested whether PF4-H Ab was associated with progression of arterial stiffness in a 3-year follow-up. METHODS: We enrolled 74 hemodialysis patients and studied their clinical, biochemical and arterial stiffness measurement with brachial-ankle pulse wave velocity (baPWV) over 3 years...
March 2017: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/28302997/platelets-cellular-and-functional-characteristics-in-patients-with-atrial-fibrillation-a-comprehensive-meta-analysis-and-systematic-review
#17
REVIEW
Alexander Weymann, Sadeq Ali-Hasan-Al-Saegh, Anton Sabashnikov, Aron-Frederik Popov, Seyed Jalil Mirhosseini, Luis Nombela-Franco, Luca Testa, Mohammadreza Lotfaliani, Mohamed Zeriouh, Tong Liu, Hamidreza Dehghan, Senol Yavuz, Michel Pompeu Barros de Oliveira Sá, William L Baker, Jae-Sik Jang, Mengqi Gong, Umberto Benedetto, Pascal M Dohmen, Fabrizio D'Ascenzo, Abhishek J Deshmukh, Giuseppe Biondi-Zoccai, Hugh Calkins, Gregg W Stone, Integrated Meta-Analysis Of Cardiac Surgery And Cardiology-Group Imcsc-Group
BACKGROUND This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of platelet cellular and functional characteristics including platelet count (PC), MPV, platelet distribution width (PDW), platelet factor 4, beta thromboglobulin (BTG), and p-selectin with the occurrence of atrial fibrillation (AF) and consequent stroke. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating platelet characteristics in patients with paroxysmal, persistent and permanent atrial fibrillations...
March 17, 2017: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/28296751/serum-platelet-factor-4-is-a-reliable-activity-parameter-in-adult-patients-with-inflammatory-bowel-disease-a-pilot-study
#18
Lei Ye, Yu-Ping Zhang, Na Yu, Ya-Xu Jia, Shu-Jun Wan, Fang-Yu Wang
To investigate the diagnostic utility of serum platelet factor 4 (PF4) levels and to assess its accuracy in detecting inflammatory bowel disease activity.This study included 45 patients with ulcerative colitis (UC), 45 patients with Crohn disease (CD), and 30 control subjects at Jinling Hospital between May 2014 and July 2015. Laboratory tests measured white blood count, C-reactive protein, erythrocyte sedimentation rate, and platelet count. PF4 was examined by enzyme-linked immunosorbent assays. Patients were divided into 2 groups according to disease activity: active and inactive...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28287032/new-platelet-functional-method-for-identification-of-pathogenic-antibodies-in-hit-patients
#19
M L Guarino, I Massimi, S Mardente, A Lappa, S Donfrancesco, G P Visentin, F M Pulcinelli
Heparin-induced thrombocytopenia (HIT) is a thrombotic complication of heparin therapy. The most used functional method for HIT diagnosis is serotonin release assay (SRA). A different functional method based on ATP release with luciferin/luciferase long-life and stable luminescent signal is used here, which is shown to be comparable for accuracy with SRA in both negative (patients 4Ts ≤3, and negative for both anti-PF4/heparin immunoassay and SRA) and positive (4Ts >3, and positive for both PF4/heparin antibodies and SRA) patients...
March 13, 2017: Platelets
https://www.readbyqxmd.com/read/28271738/profile-of-instrumentation-laboratory-s-hemosil%C3%A2-acustar-hit-ab-pf4-h-assay-for-diagnosis-of-heparin-induced-thrombocytopenia
#20
REVIEW
Michael Nagler, Adam Cuker
Immunoassays play an essential role in the diagnosis of heparin-induced thrombocytopenia (HIT). The objective of this article is to review HemosIL® AcuStar HIT-Ab(PF4-H) (Instrumentation Laboratory, Bedford, MA, USA), a new chemiluminescent immunoassay for HIT. Areas covered: The authors searched the published literature for evaluation studies of HemosIL® AcuStar HIT-Ab(PF4-H) and sought information from the manufacturer. In this paper, the authors discuss the analytical principle and technical aspects of the assay; describe its diagnostic performance in validation studies; report on its reproducibility, cost-effectiveness, and regulatory status; and discuss the implications of the assay on clinical practice and means of integrating it in diagnostic pathways...
May 2017: Expert Review of Molecular Diagnostics
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