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https://www.readbyqxmd.com/read/27913490/heparin-induced-thrombocytopenia-research-and-clinical-updates
#1
Oluwatoyosi Onwuemene, Gowthami M Arepally
Heparin-induced thrombocytopenia (HIT) remains an important diagnosis to consider in hospitalized patients developing thrombocytopenia. HIT is an immune-mediated prothrombotic disorder caused by antibodies to platelet factor 4 (PF4) and heparin. Recent basic scientific studies have advanced our understanding of disease pathogenesis through studies of the PF4/heparin structure, immune mechanisms, and cellular basis of thrombosis. Clinical advances have also occurred in areas of HIT prevention, description of disease variants, and diagnostic strategies...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27829148/pf4-promotes-platelet-production-and-lung-cancer-growth
#2
Ferdinando Pucci, Steffen Rickelt, Andita P Newton, Christopher Garris, Ernesto Nunes, Charles Evavold, Christina Pfirschke, Camilla Engblom, Mari Mino-Kenudson, Richard O Hynes, Ralph Weissleder, Mikael J Pittet
Co-option of host components by solid tumors facilitates cancer progression and can occur in both local tumor microenvironments and remote locations. At present, the signals involved in long-distance communication remain insufficiently understood. Here, we identify platelet factor 4 (PF4, CXCL4) as an endocrine factor whose overexpression in tumors correlates with decreased overall patient survival. Furthermore, engineered PF4 over-production in a Kras-driven lung adenocarcinoma genetic mouse model expanded megakaryopoiesis in bone marrow, augmented platelet accumulation in lungs, and accelerated de novo adenocarcinogenesis...
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27812736/integrative-analysis-for-identification-of-shared-markers-from-various-functional-cells-tissues-for-rheumatoid-arthritis
#3
Wei Xia, Jian Wu, Fei-Yan Deng, Long-Fei Wu, Yong-Hong Zhang, Yu-Fan Guo, Shu-Feng Lei
Rheumatoid arthritis (RA) is a systemic autoimmune disease. So far, it is unclear whether there exist common RA-related genes shared in different tissues/cells. In this study, we conducted an integrative analysis on multiple datasets to identify potential shared genes that are significant in multiple tissues/cells for RA. Seven microarray gene expression datasets representing various RA-related tissues/cells were downloaded from the Gene Expression Omnibus (GEO). Statistical analyses, testing both marginal and joint effects, were conducted to identify significant genes shared in various samples...
November 3, 2016: Immunogenetics
https://www.readbyqxmd.com/read/27785869/probing-functional-heteromeric-chemokine-protein-protein-interactions-through-conformation-assisted-oxime-ligation
#4
Stijn M Agten, Rory R Koenen, Hans Ippel, Veit Eckardt, Philipp von Hundelshausen, Kevin H Mayo, Christian Weber, Tilman M Hackeng
Protein-protein interactions (PPIs) govern most processes in living cells. Current drug development strategies are aimed at disrupting or stabilizing PPIs, which require a thorough understanding of PPI mechanisms. Examples of such PPIs are heteromeric chemokine interactions that are potentially involved in pathological disorders such as cancer, atherosclerosis, and HIV. It remains unclear whether this functional modulation is mediated by heterodimer formation or by the additive effects of mixed chemokines on their respective receptors...
November 21, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27772839/pf4-induced-apoptosis-in-breast-cancer-in-vivo-study-the-role-of-the-caspases-family
#5
Tengku Ahmad Damitri Al Astani Tengku Din, Azman Seeni, Muhamad Saiful Bahri Yusoff, Shaharum Shamsuddin, Hasnan Jaafar
No abstract text is available yet for this article.
February 2016: Pathology
https://www.readbyqxmd.com/read/27734602/recurrent-heparin-induced-thrombocytopenia-due-to-heparin-rinsing-before-priming-the-machine-in-a-hemodialysis-patient-a-case-report
#6
Jin Han Lim, Kyung Pyo Kang, Sik Lee, Sung Kwang Park, Won Kim
Heparin has remained the most commonly used anticoagulant for patients undergoing hemodialysis. It is usually safe to use but can have severe adverse effects in some cases. Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of exposure to heparin. It results from an autoantibody directed against endogenous platelet factor 4 (PF4) in complex with heparin, which activates platelets and can cause catastrophic arterial and venous thromboses. Here, we present the case of an 80-year-old woman with a recent diagnosis of chronic renal failure who developed acute HIT (platelet count nadir, 15 × 10(9) /L) on day 7 of hemodialysis performed with routine heparin anticoagulation, who despite subsequent heparin-free hemodialysis (with argatroban and warfarin) developed recurrent HIT (complicated by acute cerebral infarction) on day 11 that we attributed to "rinsing" of the circuit with heparin-containing saline (3,000 units of unfractionated heparin, with subsequent saline washing) performed pre-dialysis as per routine...
October 13, 2016: Hemodialysis International
https://www.readbyqxmd.com/read/27720587/composition-of-growth-factors-and-cytokines-in-lysates-obtained-from-fresh-versus-stored-pathogen-inactivated-platelet-units
#7
Felix Sellberg, Erik Berglund, Martin Ronaghi, Gabriel Strandberg, Helena Löf, Pehr Sommar, Norbert Lubenow, Folke Knutson, David Berglund
BACKGROUND: Platelet lysate is a readily available source of growth factors, and other mediators, which has been used in a variety of clinical applications. However, the product remains poorly standardized and the present investigation evaluates the composition of platelet lysate obtained from either fresh or stored pathogen-inactivated platelet units. MATERIALS AND METHODS: Platelet pooled units (n = 10) were obtained from healthy blood donors and tested according to standard procedures...
September 28, 2016: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/27716443/a-discrete-cluster-of-urinary-biomarkers-discriminates-between-active-systemic-lupus-erythematosus-patients-with-and-without-glomerulonephritis
#8
Carolina Landolt-Marticorena, Stephenie D Prokopec, Stacey Morrison, Babak Noamani, Dennisse Bonilla, Heather Reich, James Scholey, Carmen Avila-Casado, Paul R Fortin, Paul C Boutros, Joan Wither
BACKGROUND: Management of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN. METHODS: Urine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels...
October 4, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27714919/the-association-of-anti-platelet-factor-4-heparin-antibodies-with-early-and-delayed-thromboembolism-after-cardiac-surgery
#9
I J Welsby, E F Krakow, J A Heit, E C Williams, G M Arepally, S Bar-Yosef, D F Kong, S Martinelli, I Dhakal, W W Liu, J Krischer, T L Ortel
: Essentials We evaluated antibody status, thromboembolism and survival after cardiac surgery. Positive antibody tests are common - over 50% are seropositive at 30 days. Seropositivity did not increase thromboembolism or impair survival after cardiac surgery. Results show heparin induced thrombocytopenia antibody screening after surgery is not warranted. SUMMARY: Background Heparin-induced thrombocytopenia (HIT) is a prothrombotic response to heparin therapy with platelet-activating, anti-platelet factor 4 (PF4)/heparin antibodies leading to thrombocytopenia associated with thromboembolism...
October 7, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27658429/biophysical-tools-to-assess-the-interaction-of-pf4-with-polyanions
#10
Mihaela Delcea, Andreas Greinacher
The antigen in heparin-induced thrombocytopenia (HIT) is expressed on platelet factor 4 (PF4) when PF4 complexes with polyanions. In recent years, biophysical tools (e. g. circular dichroism spectroscopy, atomic force microscopy, isothermal titration calorimetry, x-ray crystallography, electron microscopy) have gained an important role to complement immunological and functional assays for better understanding the interaction of heparin with PF4. This allowed identification of those features that make PF4 immunogenic (e...
October 28, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27631372/the-role-of-cytokine-pf4-in-the-antiviral-immune-response-of-shrimp
#11
Yulei Chen, Jiao Cao, Xiaobo Zhang
During viral infection in vertebrates, cytokines play important roles in the host defense against the virus. However, the function of cytokines in invertebrates has not been well characterized. In this study, shrimp cytokines involved in viral infection were screened using a cytokine antibody microarray. The results showed that three cytokines, the Fas receptor (Fas), platelet factor 4 (PF4) and interleukin-22 (IL-22), were significantly upregulated in the white spot syndrome virus (WSSV)-challenged shrimp, suggesting that these cytokines played positive regulatory roles in the immune response of shrimp against the virus...
2016: PloS One
https://www.readbyqxmd.com/read/27609736/utilization-of-4t-score-to-determine-the-pretest-probability-of-heparin-induced-thrombocytopenia-in-a-community-hospital-in-upstate-new-york
#12
Yazan Samhouri, Mohammad Telfah, Ruth Kouides, Timothy Woodlock
BACKGROUND: Thrombocytopenia is common in hospitalized patients. Heparin-induced thrombocytopenia (HIT) is a life-threatening condition which can lead to extensive thrombosis. Diagnosis of HIT relies on clinical suspicion determined by 4T score and immunoassays through testing for anti-PF4/heparin antibodies. Clinical practice guidelines published by the American Society of Hematology in 2013 recommended use of the 4T score before ordering the immunoassays as a measure of pretest probability...
2016: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/27597121/acute-intraoperative-heparin-induced-thrombocytopenia-hit-and-thrombosis-during-coronary-artery-bypass-grafting-two-case-reports-providing-evidence-for-the-role-of-preoperative-lmwh-in-triggering-sensitization
#13
M Khoury, A Pitsis, H Poumpouridou-Kioura, G Soufla, C Kanthou, N Matoula, A Angelidis, E Melissari
INTRODUCTION: Systemic anticoagulation is necessary during cardiac surgery. To date, the only well established anticoagulation protocol involves the use of heparin. However, heparin can cause heparin-induced thrombocytopenia (HIT) a potentially life threatening immune-mediated thromboembolic syndrome. Until now, devastating consequences of HIT syndrome in patients undergoing heart surgery have been described, but only postoperatively. Here we report the development of HIT syndrome during cardiac revascularization by intra-operative heparin administration in two patients previously exposed to LMWH...
October 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27583400/aspirin-but-not-tirofiban-displays-protective-effects-in-endotoxin-induced-lung-injury
#14
Jessica Tilgner, Klaus Thilo von Trotha, Alexander Gombert, Michael J Jacobs, Maik Drechsler, Yvonne Döring, Oliver Soehnlein, Jochen Grommes
BACKGROUND: Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Recruitment of neutrophils into the lungs, regarded as a key mechanism in progression of ALI, depends on signaling between neutrophils and platelets. Consequently we explored the effect of platelet-targeted aspirin and tirofiban treatment in endotoxin induced acute lung injury. METHODS: C57Bl/6 mice were exposed to aerosolized LPS (500μg/ml) for 30min and treated with Aspirin (100μg/g bodyweight via intraperitoneal injection, 30 min before or 1 hour after LPS inhalation) or Tirofiban (0...
2016: PloS One
https://www.readbyqxmd.com/read/27576282/-heparin-induced-thrombocytopenia-new-therapeutical-options
#15
Carina E Seculini Patiño, Aldo H Tabares
Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications...
2016: Medicina
https://www.readbyqxmd.com/read/27558507/reduced-induction-of-anti-pf4-heparin-antibody-in-ra-patients-after-total-knee-arthroplasty
#16
Masahiro Izumi, Tatsuya Sakai, Atsunori Shirakawa, Hideko Kozuru, Yuka Jiuchi, Yasumori Izumi, Tomohiko Asahara, Kenji Kumagai, Masaaki Mawatari, Makoto Osaki, Satoru Motokawa, Kiyoshi Migita
BACKGROUND: Heparin-induced thrombocytopenia is caused by antibodies (Abs) specific to platelet factor 4 (PF4)/heparin complexes. In this study, we evaluated the rates of seroconversion of anti-PF4/heparin Ab between patients with rheumatoid arthritis (RA) and with osteoarthritis (OA) who underwent total knee arthroplasty. METHODS: The subjects of this randomized controlled trial were 124 patients who underwent total knee arthroplasty (TKA) and received edoxaban with or without a foot pump as thromboprophylaxis...
2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27556645/modification-of-pulsed-electric-field-conditions-results-in-distinct-activation-profiles-of-platelet-rich-plasma
#17
Andrew L Frelinger, Anja J Gerrits, Allen L Garner, Andrew S Torres, Antonio Caiafa, Christine A Morton, Michelle A Berny-Lang, Sabrina L Carmichael, V Bogdan Neculaes, Alan D Michelson
BACKGROUND: Activated autologous platelet-rich plasma (PRP) used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF) to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF) pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin...
2016: PloS One
https://www.readbyqxmd.com/read/27534900/rapamycin-and-bafilomycin-a1-alter-autophagy-and-megakaryopoiesis
#18
Qi Wang, Tao You, Hongqiong Fan, Yinyan Wang, Tinatian Chu, Mortimer Poncz, Li Zhu
Autophagy is an effective strategy for cell development by recycling cytoplasmic constituents. Genetic deletion of autophagy mediator Atg7 in hematopoietic stem cells (HSCs) can lead to failure of megakaryopoiesis and enhanced autophagy has been implicated in various hematological disorders such as immune thrombocytopenia and myelodysplastic syndrome. Here, we examined the hypothesis that optimal autophagy is essential for megakaryopoiesis and thrombopoiesis by altering autophagy using pharmacological approaches...
August 18, 2016: Platelets
https://www.readbyqxmd.com/read/27501998/treatment-of-heparin-induced-thrombocytopenia-before-and-after-the-implementation-of-a-hemostatic-and-antithrombotic-stewardship-program
#19
Brianne M Ritchie, Katelyn W Sylvester, David P Reardon, William W Churchill, Nancy Berliner, Jean M Connors
In October 2013, we implemented a hemostatic and antithrombotic (HAT) stewardship program with the primary focus of ensuring appropriate use of intravenous direct thrombin inhibitors (DTI) in patients with heparin-induced thrombocytopenia (HIT). We sought to compare the duration and cost of DTI therapy for the management of HIT before and after implementation of the HAT stewardship program. Following institutional review board approval, we conducted a single center, retrospective chart review of all patients with a suspected diagnosis of HIT as assessed by an anti-heparin-PF4 enzyme-linked immunosorbent assay 6 months pre-HAT and post-HAT implementation...
November 2016: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/27487857/role-of-monocytes-and-endothelial-cells-in-heparin-induced-thrombocytopenia
#20
Daria Madeeva, Douglas B Cines, Mortimer Poncz, Lubica Rauova
Heparin-induced thrombocytopenia (HIT) is an autoimmune disorder characterised by thrombocytopenia and thrombosis. The mechanisms leading to platelet destruction are complex and the thrombotic complications of HIT appear to be due to multiple different intravascular targets. The dual binding of HIT antibodies to platelet surface PF4/GAG complexes and to FcγRIIA likely leads to both platelet clearance and to their direct activation. Monocytes and endothelial cells bind PF4 with higher avidity than platelets and are more resistant to competitive removal of surface-bound PF4 in the presence of heparin...
August 4, 2016: Thrombosis and Haemostasis
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