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https://www.readbyqxmd.com/read/28725494/apixaban-for-treatment-of-confirmed-heparin-induced-thrombocytopenia-a-case-report-and-review-of-literature
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
July 4, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28672052/direct-acting-oral-anticoagulants-for-the-treatment-of-suspected-heparin-induced-thrombocytopenia
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/28418908/plasma-protein-profiling-in-patients-undergoing-coronary-artery-bypass-grafting-surgery-and-clinical-significance
#17
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
#18
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
#19
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
#20
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)...
May 2017: Thrombosis Research
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