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Yoshihiro Morino, Tetsuya Tobaru, Satoshi Yasuda, Kazuaki Kataoka, Kengo Tanabe, Atsushi Hirohata, Ken Kozuma, Takeshi Kimura
AIMS: The aim of the study was to investigate the six-month angiographic and nine-month clinical follow-up outcomes in a first-in-man study using the biodegradable polymer-based cobalt-chromium argatroban-eluting stent (JF-04) for treatment of native coronary atherosclerotic lesions. METHODS AND RESULTS: A total of 31 patients with either stable or unstable angina, or silent myocardial ischaemia, exhibiting de novo coronary lesions were enrolled at seven Japanese sites...
November 20, 2016: EuroIntervention
Noémie Despas, Anne-Sophie Larock, Hugues Jacqmin, Jonathan Douxfils, Bernard Chatelain, Marc Chatelain, François Mullier
Traditional anticoagulant agents such as unfractionated heparin (UFH), low molecular weight heparins (LMWHs), fondaparinux, danaparoid and bivalirudine are used in the prevention and treatment of thromboembolic diseases. However, these agents have limitations: their constraining parenteral route of administration and the need for regular coagulation monitoring for HNF. The LMWHs, with their more predictable anticoagulant response, don't require a systematic monitoring. The usefulness of LMWHs monitoring in several clinical situations such as pregnancy, obesity and renal insufficiency is a matter of debate...
December 1, 2016: Annales de Biologie Clinique
Ahmed Aljabri, Yvonne Huckleberry, Jason Karnes, Mahdi Gharaibeh, Hussam I Kutbi, Yuval Raz, Seongseok Yun, Ivo Abraham, Brian Erstad
Despite the availability of multiple non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT), little data is available comparing the cost-effectiveness of these agents. This analysis is particularly important considering differences in risks of adverse effects, routes of administration, requirements for phlebotomy and laboratory monitoring, and overall drug costs. We conducted a cost-effectiveness analysis of argatroban, bivalirudin, and fondaparinux for the treatment of suspected HIT from the institutional perspective...
October 28, 2016: Blood
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
Takuma Maeda, Katsura Nakagawa, Kuniko Murata, Yoshiaki Kanaumi, Shu Seguchi, Shiori Kawamura, Mayumi Kodama, Takeshi Kawai, Isami Kakutani, Yoshihiko Ohnishi, Koichi Kokame, Hitoshi Okazaki, Shigeki Miyata
To diagnose heparin-induced thrombocytopenia (HIT), detection of platelet-activating antibodies (HIT antibodies) is crucial. However, serum platelet activation profiles vary across patients and depend on test conditions. We evaluated the association between clinical outcomes and platelet-activating profiles assessed by a platelet microparticle assay (PMA), which detects activation of washed platelets induced by HIT antibodies, in 401 consecutive patients clinically suspected of having HIT. We made modifications to the assay, such as donor selection for washed platelets that increased sensitivity...
October 13, 2016: Thrombosis and Haemostasis
Cornelius Keyl, Cornelius Lehane, Emanuel Zimmer, Dietmar Trenk
No abstract text is available yet for this article.
November 30, 2016: Thrombosis and Haemostasis
Philippe-Henri Secrétan, Maher Karoui, Mélisande Bernard, Noureddine Ghermani, Fathi Safta, Najet Yagoubi, Bernard Do
Argatroban (ARGA), used as intravenous anticoagulant drug, has been reported to photodegrade under light exposure, requiring specific precautions at handling, storage and administration. Thus, for the first time, aqueous ARGA photodegradation under aerobic conditions has been described in terms of photoproducts, phototransformation processes and potential implications. ARGA significant photoproducts were successfully separated and characterized by gradient reversed-phase liquid chromatography coupled with high-resolution multistage mass spectrometry (LC/HR-MS(n))...
November 30, 2016: Journal of Pharmaceutical and Biomedical Analysis
Rui Xu, Qianqian Feng, Yang He, Fanyong Yan, Li Chen, Yiping Zhao
The present work aims to improve the antifouling properties and anticoagulation of poly(vinylidene fluoride) (PVDF) membrane by dual modification. An amphiphilic copolymer of PVDF-g-(polyacryloylmorpholine-(polyacrylic acid)) [PVDF-g-(PACMO-PAA)] was first prepared by the free radical copolymerization. Then argatroban, a commonly used anticoagulant, was successfully grafted to PVDF-g-(PACMO-PAA). Finally the obtained copolymer was casted into a flat membrane via immersion phase inversion. The as-prepared copolymer membranes show improved hydrophilicity, higher water flux and lower protein adsorption...
January 2017: Journal of Biomedical Materials Research. Part A
Toru Naganuma, Satoru Mitomo, Nobuhide Kin, Sunao Nakamura
We report the first case of transfemoral transcatheter aortic valve implantation with a history of heparin-induced thrombocytopenia that was successfully managed with perioperative argatroban.
October 1, 2016: A & A Case Reports
Megan Y Harada, David M Hoang, Andrea A Zaw, Jason S Murry, Oksana Volod, Beatrice J Sun, Miriam Nuño, Russell Mason, Daniel R Margulies, Eric J Ley
OBJECTIVE: Recent studies reveal a high occurrence of overdiagnosis of heparin-induced thrombocytopenia in surgical patients with critical illness. The optimal criteria for diagnosis of heparin-induced thrombocytopenia remain unclear, contributing to unnecessary treatment. We reviewed patients who were admitted to surgical ICUs and were suspected of heparin-induced thrombocytopenia to identify how often patients were correctly treated. DESIGN: In this clinical prospective study, data were collected including age, sex, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, serotonin release assay, and Warkentin 4Ts scores...
August 4, 2016: Critical Care Medicine
Matej Samoš, Tomáš Bolek, Jela Ivanková, Lucia Stančiaková, František Kovář, Peter Galajda, Peter Kubisz, Ján Staško, Marián Mokáň
Heparin induced thrombocytopenia (HIT) is a life or limb threatening thrombotic thrombocytopenia. HIT is traditionally treated with factor-IIa inhibitors such as bivalirudin, lepirudin or argatroban. However, these agents usually require parenteral administration and are not generally available in all countries. Recently, several experiences with novel oral anticoagulants (NOACs) administration to treat HIT had been reported. NOACs generally offer advantages such as consistent and predictable anticoagulation, oral administration with good patient compliance and a good safety profile...
July 16, 2016: Journal of Cardiovascular Pharmacology
Jane Yu, Elizabeth Brisbois, Hitesh Handa, Gail Annich, Mark Meyerhoff, Robert Bartlett, Terry Major
A biomaterial with both antithrombin and antiplatelet properties is the ideal surface for use in extracorporeal circulation (ECC) as it targets both fibrin generation and platelet adhesion. A hemocompatible surface coating avoids the need for systemic anticoagulation by providing a local anticoagulant effect at the polymer-blood interface. Previous work has demonstrated the potential use of argatroban, a direct thrombin inhibitor, as a nonthrombogenic material for extracorporeal devices. The work reported here focuses on the characterization of argatroban linked to a polyurethane-silicone polymer, CarboSil®...
April 7, 2016: Journal of Materials Chemistry. B, Materials for Biology and Medicine
Jeremy B Chang, Kayla M Quinnies, Ronald Realubit, Charles Karan, Jacob H Rand, Nicholas P Tatonetti
A central challenge in designing and administering effective anticoagulants is achieving the proper therapeutic window and dosage for each patient. The Hill coefficient, nH, which measures the steepness of a dose-response relationship, may be a useful gauge of this therapeutic window. We sought to measure the Hill coefficient of available anticoagulants to gain insight into their therapeutic windows. We used a simple fluorometric in vitro assay to determine clotting activity in platelet poor plasma after exposure to various concentrations of anticoagulants...
2016: Scientific Reports
Martin Beiderlinden, Carsten Brau, Santo di Grazia, Michael Wehmeier, Tanja A Treschan
BACKGROUND: Blood salvage systems help to minimize intraoperative transfusion of allogenic blood. So far no data is available on the use of argatroban for anticoagulation of such systems. We conducted an ex-vivo trial to evaluate the effectiveness of three different argatroban doses as compared to heparin and to assess potential residual anticoagulant in the red cell concentrates. METHODS: With ethical approval and individual informed consent, blood of 23 patients with contraindications for use of blood salvage systems during surgery was processed by the Continuous-Auto-Transfusion-System (C...
2016: BMC Anesthesiology
Sixten Selleng, Kathleen Selleng
Thrombocytopenia as well as anti-platelet factor 4/heparin (PF4/H) antibodies are common in cardiac surgery patients and those treated in the intensive care unit. In contrast, heparin-induced thrombocytopenia (HIT) is uncommon in these populations (~1 % and ~0.5 %, respectively). A stepwise approach where testing for anti-PF4/H antibodies is performed only in patients with typical clinical symptoms of HIT improves diagnostic specificity of the laboratory assays without losing sensitivity, thereby helping to avoid overdiagnosis and resulting HIT overtreatment...
October 28, 2016: Thrombosis and Haemostasis
Patricia J Ho, Juan A Siordia
Heparin-induced thrombocytopenia (HIT) is a serious, immune mediated complication of exposure to unfractionated or low-molecular-weight heparin. Though rare, it is a condition associated with high morbidity and mortality that requires immediate change to alternative anticoagulants for the prevention of life-threatening thrombosis. The direct thrombin inhibitors lepirudin and argatroban are currently licensed for the treatment of HIT. Dabigatran, a novel oral anticoagulant (NOAC) with a similar mechanism of action and effective use in other indications, has recently been proposed as another therapeutic option in cases of HIT...
June 2016: Blood Research
Theodore E Warkentin, Andreas Greinacher
PURPOSE OF REVIEW: The purpose of this review is to summarize recent findings on heparin-induced thrombocytopenia (HIT), a prothrombotic disorder caused by platelet-activating IgG targeting platelet factor 4 (PF4)/polyanion complexes. RECENT FINDINGS: HIT can explain unusual clinical events, including adrenal hemorrhages, arterial/intracardiac thrombosis, skin necrosis, anaphylactoid reactions, and disseminated intravascular coagulation. Sometimes, HIT begins/worsens after stopping heparin ('delayed-onset' HIT)...
September 2016: Current Opinion in Hematology
Adam B King, Anne E O'Duffy, Avinash B Kumar
We report a challenging case of cerebral venous sinus thrombosis (multiple etiologic factors) that was complicated by heparin resistance secondary to suspected antithrombin III (ATIII) deficiency. A 20-year-old female previously healthy and currently 8 weeks pregnant presented with worsening headaches, nausea, and decreasing Glasgow Coma Scale/Score (GCS), necessitating mechanical ventilatory support. Imaging showed extensive clots in multiple cerebral venous sinuses including the superior sagittal sinus, transverse, sigmoid, jugular veins, and the straight sinus...
July 2016: Neurohospitalist
Calvin H Yeh, Alan R Stafford, Beverly A Leslie, James C Fredenburgh, Jeffrey I Weitz
Thrombin is a highly plastic molecule whose activity and specificity are regulated by exosites 1 and 2, positively-charged domains that flank the active site. Exosite binding by substrates and cofactors regulates thrombin activity by localizing thrombin, guiding substrates, and by inducing allosteric changes at the active site. Although inter-exosite and exosite-to-active-site allostery have been demonstrated, the impact of active site ligation on exosite function has not been examined. To address this gap, we used surface plasmon resonance to determine the effects of dabigatran and argatroban, active site-directed inhibitors, on thrombin binding to immobilized γA/γA-fibrin or glycoprotein Ibα peptide via exosite 1 and 2, respectively, and thrombin binding to γA/γ'-fibrin or factor Va, which is mediated by both exosites...
2016: PloS One
K Asanuma, T Yoshikawa, K Yoshida, T Okamoto, Y Asanuma, T Hayashi, N Akita, T Oi, A Nishimura, M Hasegawa, A Sudo
The purpose of this study was to clarify the precise effect of argatroban on the inhibition of cytokine secretion induced by thrombin on synovial cells. The efficiency of thrombin inactivation by thrombin inhibitors was evaluated in human synovial fluids (SFs). In SFs from 13 osteoarthritis (OA) and 11 rheumatoid arthritis (RA) patients, thrombin, Factor Xa (FXa), plasmin activity, IL-6, MMP-3, VEGF, and D-dimer concentrations were measured. Tissue factor (TF) activity or IL-6, MMP-3, and VEGF secretion of human synovial cells with or without thrombin and argatroban were measured...
2016: Cellular and Molecular Biology
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