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Artículos de revistas sobre el tema "Heparinoid"

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Autor: Grafiati
Publicado: 4 de junio de 2021
Última modificación: 2 de febrero de 2022

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1

Успенская, М. С., М. Г. Ляпина y Е. С. Майстренко. "A heparinoid from peony roots (Paeonia anomala): effects on polymerization and dissolution of fibrin in thrombosis". ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia», n.º 2() (8 de junio de 2020): 80–84. http://dx.doi.org/10.25557/0031-2991.2020.02.80-84.

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Исследование гепаринов и гепариноидов в качестве антитромботических агентов актуально для физиологии и медицины. Многие растения включают гепариноподобные компоненты (гепариноиды), которые препятствуют тромбообразованию. Цель - установление влияния экстракта из корней пиона «Марьин корень» (Paeonia anomala), содержащего гепариноид, на полимеризацию фибрина при процессах тромбообразования ex vivo и определение возможных механизмов его антитромботического действия. Методика. Исследовано влияние гепариноида из пиона (Paeonia anomala) на процессы растворения фибрина в условиях тромбообразования ex vivo. Разработана модель тромбоза (МТ) ex vivo. К плазме крови крыс (объем 0,2 мл) добавляли 2 NIH ед. тромбина (0,05 мл), фибриновый сгусток образовывался в течение 2-3 мин. Экстракт гепариноида из пиона (0,1 мл 0.5%-й) добавляли к предобразованному сгустку через 12 мин после моделирования тромбоза (опыт А), или одновременно с добавлением тромбина к плазме крови (опыт Б). Использовали венозную (из v. jugularis) кровь крыс-самцов Wistar. Полимеризацию фибрина выявляли по тесту фибриндеполимеризационной активности (ФДПА) плазмы крови на нестабилизированном фибрине. В продуктах растворения фибрина под влиянием гепариноида оценивали активность тромбина (по тесту тромбинового времени), cвертывающего фактора XIIIa (по определению активности фактора XIIIa) и ФДПА. Результаты. В опыте А спустя 10 мин после добавления гепариноида к предобразованному сгустку отмечалось появление в нем жидкой фазы, что свидетельствовало о способности исследуемого гепариноида растворять фибрин. В опыте Б сгусток или не образовывался, или же был рыхлым. Полученные данные свидетельствовали об ингибировании процесса полимеризации фибрина под влиянием гепариноида. Выявлены антитромбиновые и антифибринстабилизирующие эффекты гепариноида из пиона при добавлении к фибриновому сгустку. Рассматриваются возможные механизмы действия гепариноида на блокаду полимеризации фибрина. Заключение. Растительный гепариноид препятствовал процессам полимеризации фибрина или растворял образующиеся фибриновые сгустки, что связано с его антитромбиновым и антифибринстабилизирующим действием. Studying heparins and heparinoids as antithrombotic agents is relevant for physiology and medicine. Many plants contain heparin-like components (heparinoids) that prevent thrombosis. The aim of the study was to identify effects of a heparinoid obtained from peony (Maryin root, P. anomala) roots on polymerization of fibrin and fibrinolytic activity of blood plasma and to suggest possible mechanisms of these effects in experimentally induced ex vivo thrombosis in rats. Methods. The effect of peony (Paeonia anomala) root heparinoid on fibrin dissolution was studied in the ex vivo conditions of thrombosis. For ex vivo modeling of thrombosis (MT), 2 NIH units of thrombin (0.05 ml) were added to 0.2 ml of rat plasma. A fibrin clot formed within 2-3 minutes. The peony heparinoid extract (0.5%, 0.1 ml) was added either to the pre-formed clot at 12 min after MT induction (experiment A) or simultaneously with the addition of thrombin to plasma (experiment B). Jugular vein blood from Wistar male rats was used. Fibrin polymerization was detected using a plasma fibrin-depolymerization activity (FDPA) test on non-stabilized fibrin. Thrombin activity (thrombin time test), coagulation factor XIIIa activity, and FDPA were evaluated in products of fibrin dissolution induced by the heparinoid. Results. In experiment A, at 10 min after the addition of heparinoid to the pre-formed clot, a liquid phase emerged, which indicated an ability of the pion heparinoid to dissolve fibrin. In experiment B, the clot either did not form or was liquid. These results indicated inhibition of fibrin polymerization under the action of the heparinoid. Therefore, the peony heparinoid added to the fibrin clot antagonized thrombin and fibrin stabilization. The article addresses possible mechanisms of the heparinoid inhibition of fibrin polymerization. Conclusion. The studied plant heparinoid prevented processes of fibrin polymerization or dissolved formed fibrin clots due to depression of thrombin activity and fibrin stabilization.
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2

Alban, S. y A. Greinacher. "Heparinoide als eine Alternative für die parenterale Antikoagulation bei Patienten mit Heparin-induzierter Thrombozytopenie". Hämostaseologie 16, n.º 01 (enero de 1996): 41–49. http://dx.doi.org/10.1055/s-0038-1656637.

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ZusammenfassungDie Heparin-induzierte Thrombozytopenie (HIT Typ II) ist eine lebensbedrohliche Komplikation der Heparintherapie. Da betroffene Patienten durch diese immunologische, unerwünschte Wirkung der Heparingabe gefährdet sind, neue throm-boembolische Gefäßverschlüsse zu entwickeln, ist bei hinreichendem klinischen Verdacht die sofortige Umstellung auf ein kompatibles Antikoagulans notwendig. Hierfür kommen, neben rekombinantem Hirudin, verschiedene Heparinoide in Betracht. Die Pathophysiologie der HIT Typ II sowie die Struktur und die anti-koagulatorischen Eigenschaften verschiedener Heparinoide werden dargestellt. Der letzte Teil des Artikels faßt den gegenwärtigen Stand der Dosierungsempfehlungen für das Heparinoid Danaparoid (Orgaran®, NV Organon, Niederlande) bei HIT-Typ-Il-Patienten zusammen.
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3

Greinacher, A., I. Michels, V. Kiefel y C. Mueller-Eckhardt. "A Rapid and Sensitive Test for Diagnosing Heparin-Associated Thrombocytopenia". Thrombosis and Haemostasis 66, n.º 06 (1991): 734–36. http://dx.doi.org/10.1055/s-0038-1646493.

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SummaryHeparin-associated thrombocytopenia (HAT) is a severe complication of heparin therapy. Its diagnosis is difficult. Conventional assays employ platelet aggregometry (PAA) and/or 14C-serotonin release (SRA) which are either insensitive (PAA) or require radioactive tracers (SRA). We here describe a newly developed sensitive and rapid assay based on visual evaluation of heparin-induced platelet activation (HIPA) in microtiter wells. Using sera of 34 patients with clinically suspected HAT we found the HIPA assay to be as sensitive as the SRA and superior to PAA. The HIPA assay allows investigation of crossreactivity with different types of heparins, low molecular weight (LMW) heparins and heparinoids. Three patients who required further parenteral anticoagulation and in whom the HIPA assay was negative before treatment with the LMW heparinoid Org 10172, were treated with this new heparinoid without adverse reactions. We conclude that the HIPA assay may be a useful tool for differential diagnosis and therapy in patients with HAT.
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4

Ishihara, Masayuki, Shingo Nakamura, Yoko Sato, Tomohiro Takayama, Koichi Fukuda, Masanori Fujita, Kaoru Murakami y Hidetaka Yokoe. "Heparinoid Complex-Based Heparin-Binding Cytokines and Cell Delivery Carriers". Molecules 24, n.º 24 (17 de diciembre de 2019): 4630. http://dx.doi.org/10.3390/molecules24244630.

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Heparinoid is the generic term that is used for heparin, heparan sulfate (HS), and heparin-like molecules of animal or plant origin and synthetic derivatives of sulfated polysaccharides. Various biological activities of heparin/HS are attributed to their specific interaction and regulation with various heparin-binding cytokines, antithrombin (AT), and extracellular matrix (ECM) biomolecules. Specific domains with distinct saccharide sequences in heparin/HS mediate these interactions are mediated and require different highly sulfated saccharide sequences with different combinations of sulfated groups. Multivalent and cluster effects of the specific sulfated sequences in heparinoids are also important factors that control their interactions and biological activities. This review provides an overview of heparinoid-based biomaterials that offer novel means of engineering of various heparin-binding cytokine-delivery systems for biomedical applications and it focuses on our original studies on non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) and polyelectrolyte complex-nano/microparticles (N/MPs), in addition to heparin-coating devices.
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5

&NA;. "Heparin/heparinoid". Reactions Weekly &NA;, n.º 1405 (junio de 2012): 20–21. http://dx.doi.org/10.2165/00128415-201214050-00070.

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6

Mimura, Wataru y Manabu Akazawa. "The Association Between Internet Searches and Moisturizer Prescription in Japan: Retrospective Observational Study". JMIR Public Health and Surveillance 5, n.º 4 (8 de octubre de 2019): e13212. http://dx.doi.org/10.2196/13212.

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Background Heparinoid is a medication prescribed in Japan for skin diseases, such as atopic dermatitis and dry skin. Heparinoid prescription has increased with instances of internet blogs recommending its use as a cosmetic. Objective This study aimed to examine the prescription trends in moisturizer use and analyze their association with internet searches. Methods We used a claims database to identify pharmacy claims of heparinoid-only prescriptions in Japan. Additionally, we used Google Trends to obtain internet search data for the period between October 1, 2007, and September 31, 2017. To analyze the association between heparinoid prescriptions and internet searches, we performed an autoregressive integrated moving average approach for each time series. Results We identified 155,733 patients who had been prescribed heparinoid. The number of prescriptions increased from 2011 onward, and related internet searches increased from 2012 onward. Internet searches were significantly correlated with total heparinoid prescription (correlation coefficient=.25, P=.005). In addition, internet searches were significantly correlated with heparinoid prescription in those aged 20-59 years at –1-month lag in Google Trends (correlation coefficient=.30, P=.001). Conclusions Google searches related to heparinoid prescriptions showed a seasonal pattern and increased gradually over the preceding several years. Google searches were positively correlated with prescription trends. In addition, in a particular age group (20-59 years), prescriptions increased with the increase in internet searches. These results suggest that people obtained health-related information on the internet and that this affected their behavior and prescription requests.
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7

ARGE, E. "Heparinoid and Heparin". Acta Medica Scandinavica 155, n.º 6 (24 de abril de 2009): 469–74. http://dx.doi.org/10.1111/j.0954-6820.1956.tb14396.x.

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8

Preissner, K. T. "Heparinoids and cellular interactions in the vascular system". Hämostaseologie 16, n.º 01 (enero de 1996): 28–34. http://dx.doi.org/10.1055/s-0038-1656635.

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SummaryHeparin and related polysaccharides have long been used for therapautic intervention in different disease states related to thromboembolic complications. The localization and functional availability of heparin-like components in the body is mostly confined to cell surfaces and extracellular matrix/basement membranes. Their strategic position particularly in the vascular system enables heparinoids linked to various core proteins (designated as heparan sulfate proteoglycans) to interact with a variety of heparin-binding proteins such as apolipoproteins, lipases, proteases and protease inhibitors, matrix proteins as well as surface receptors on other cells and microorganisms. The variety in gene expression of respective core proteins and differences in glycosaminoglycan side chains are relevant factors for the selectivity of these interactions. Heparinoid-associated core proteins serve as co-receptors for a number of metabolic properties of vascular cells as well as for the regulation of cellular processes, particular as they relate to cell growth and differentiation in angiogenesis. Moreover, heparan sulfate proteoglycans contribute to the process of lipoprotein retention in the vessel wall and the onset of atherosclerosis. Elucidation of molecular properties, functions and their role in vascular diseases can lead to valuable information for the design of heparinoid analogues to be used for pharmacological intervention.
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9

Muhl, Lars, Etty Zwang, Neta Ilan, Yair Herishanu, Varda Deutsch, Elizabeth Naparstek, Israel Vlodavsky, Klaus Preissner y Ben-Zion Katz. "Heparanase modulates heparinoids anticoagulant activities via non-enzymatic mechanisms". Thrombosis and Haemostasis 98, n.º 12 (2007): 1193–99. http://dx.doi.org/10.1160/th07-04-0256.

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SummaryA key element for the physiological restriction of blood coagulation at the endothelial cell surface is its non-thrombogenic property, mainly attributed to cell surface heparan sulfate proteoglycans. Heparanase is an endo-β-D-glucuronidase with specific heparan sulfate degrading activity, which is produced and stored in platelets, and is released upon their activation. We examined the effects of heparanase pro-enzyme on coagulation functions, predominantly under physiological conditions. While heparanase pro-enzyme does not directly affect coagulation protein activities, it has profound effects on heparinoid-mediated regulation of coagulation responses, apparently via mechanisms that do not involve its enzymatic activity. Heparanase pro-enzyme reverses the anti-coagulant activity of unfractionated heparin on the coagulation pathway as well as on thrombin activity. In addition, heparanase pro-enzyme abrogated the factor X inhibitory activity of low-molecular-weight heparin (LMWH). The pro-coagulant effects of the non-active heparanase were also exerted by its major functional heparin-binding peptide. Finally, the effects of heparanase on the activity of factor VII activating protease that is auto-activated by heparinoids indicated a complete antagonistic action of heparanase in this system. Altogether, heparanase pro-coagulant activities that were also demonstrated in plasma samples from patients under LMWH treatment,point to a possible use of this molecule as antagonist for heparinoid treatment.
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Du, ZhenXing, XueJing Jia, Jing Chen, SiYi Zhou, JianPing Chen, XiaoFei Liu, XiaoHuang Cao, SaiYi Zhong y PengZhi Hong. "Isolation and Characterization of a Heparin-Like Compound with Potent Anticoagulant and Fibrinolytic Activity from the Clam Coelomactra antiquata". Marine Drugs 18, n.º 1 (19 de diciembre de 2019): 6. http://dx.doi.org/10.3390/md18010006.

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Heparin from mollusks with unique sulfated glycosaminoglycan exhibits strong anti-thrombotic activities. This study reports on a purified heparinoid from Coelomactra antiquata, which shows potent anticoagulant and fibrinolytic abilities. Its structure was characterized by infrared spectroscopy, high-performance liquid chromatography, and one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy. Its fibrinolytic activity was determined in vitro and in vivo. Its anticoagulant activity was determined by activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicated that clam heparinoid was a homogeneous glycosaminoglycan with a molecular weight of 30.99 kDa, mainly composed of →4)-α-IdoA2S-(1→4)-α-GlcNS3S6S (or GlcNS6S)-(1→4)-β-GlcA-(1→4)-α-GlcNS6S (or GlcNAC)-(1→. Furthermore, this heparinoid showed a highly anticoagulant titer and fibrinolytic value of 149.63 IU/mg and 1.96 IU/mg, respectively. In summary, clam heparinoid shows great potential for application in the clinic and antithrombotic drugs industry.
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11

Lyapina, M. G., M. S. Uspenkaya, E. S. Maistrenko y M. D. Kalugina. "INFLUENCE OF HEPARINOID FROM PAEONIA LACTIFLORA ON HEMOSTATIC SYSTEM WITHIN CONDITIONS OF PRETHROMBOSIS". Pharmacy & Pharmacology 7, n.º 4 (10 de septiembre de 2019): 208–14. http://dx.doi.org/10.19163/2307-9266-2019-7-4-208-214.

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The search and development of direct and rapid anticoagulants used per os, is an urgent problem in physiological and medical science. A number of plants contain heparin-like components with a positive effect on the hemostatic system, both within normal and in some pathological conditions of the body.The aim of the work was to study the complex effect of fibrin, a heparin-like substance (heparinoid) from the roots of Paeonia lactiflora, on fibrinolytic, anticoagulant systems of the body and polymerization processes, when it is administered per os in animals within normal conditions and when modeling the state of prethrombosis.Materials and methods. To carry out the research, the roots of Paeonia lactiflora growing in the Botanical Garden of Moscow State University, and laboratory animals – male Wistar rats – were used. To study the antithrombotic effects of the extract from roots containing heparinoid, the state of prethrombosis was modeled in rats. The determined parameters of hemostasis were: anticoagulant activity according to the tests of activated partial thromboplastin time and thrombin time, fibrinolytic activity according to the test of total fibrinolytic activity, fibrin polymerization according to the test of fibrindepolymerization activity of blood plasma.Results. With repeated (every 24 hours within 3 days) oral administration of the extract containing heparinoid, in animals within normal conditions and with prethrombosis, the following anticoagulant effects were established in the blood: an increase in anticoagulant, fibrindepolymerization and fibrinolytic plasma activity. Possible mechanisms of the activating effect of heparinoid on fibrinolysis and anticoagulant properties of plasma due to the excretion of tissue plasminogen activator into the bloodstream from the endothelium, thrombin inhibition, and fibrin polymerization are described. Moreover, the anticoagulant effect of the use of the extract from the peony roots was equivalent to that of the reference drug of low molecular weight heparin from Celsus (USA). For the first time, it was revealed that when modeling experimental prethrombosis, the administration of heparinoid in rats at the dose of 37.5 IU/kg МЕ/кг body weight restored impaired hemostasis, which requires a further study.Conclusion. The ability of heparinoid from peony roots to normalize the functional state of the anticoagulant system during the development of prethrombosis in animals has been established. The restriction of fibrin polymerization during oral administration of heparinoid from peony in animals by increasing the enzymatic fibrinolytic and fibrindepolymerization activity of blood plasma was revealed. In the future, heparinoid can be used as an antithrombotic agent.
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12

WESSEL, H. P. "ChemInform Abstract: Heparinoid Mimetics". ChemInform 28, n.º 34 (3 de agosto de 2010): no. http://dx.doi.org/10.1002/chin.199734300.

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13

Ortel, Thomas L., Jon P. Gockerman, Robert M. Califf, Richard L. McCann, Christopher M. O’Connor, Diane M. Metzler y Charles S. Greenberg. "Parenteral Anticoagulation with the Heparinoid Lomoparan (Org 10172) in Patients with Heparin Induced Thrombocytopenia and Thrombosis". Thrombosis and Haemostasis 67, n.º 03 (1992): 292–96. http://dx.doi.org/10.1055/s-0038-1648434.

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SummaryProgressive thrombocytopenia may develop in as many as 5% of patients receiving heparin anticoagulation. In these patients, the risk of thromboembolic complications as well as continued thrombocytopenia necessitates discontinuation of heparin and initiation of an alternative anticoagulant when indicated. The heparinoid Lomoparan (Org 10172) is a mixture of several nonheparin low molecular weight glycosaminoglycans with proven anticoagulant efficacy that is generally non-reactive with platelets in the presence of plasma from patients with heparin induced thrombocytopenia, whereas standard heparin will induce platelet aggregation. We evaluated the role of heparinoid as a potential alternative anticoagulant in patients with heparin induced thrombocytopenia. During a 6 month period, we identified six patients with heparin induced thrombocytopenia who required an alternative parenteral anticoagulant, four as primary treatment for specific medical problem, and two as anticoagulation during a necessary surgical procedure. Heparinoid was used successfully in both medical and surgical patients requiring parenteral anticoagulation. In no case was there an exacerbation of the thrombocytopenia nor thromboembolic complications while on heparinoid therapy. Three of our patients sustained hemorrhagic complications, predominantly in the post-surgical setting in association with elevated anti-factor Xa levels and additional anticoagulant agents. We feel that these results confirm the utility of heparinoid anticoagulation in a select subset of patients with heparin induced thrombocytopenia who require continued parenteral anticoagulation.
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14

Hoek, J. A., M. T. Nurmohamed, K. J. Hamelynck, R. K. Marti, H. C. Knipscheer, H. ten Cate, H. R. Büller, H. N. Magnani y J. W. ten Cate. "Prevention of Deep Vein Thrombosis following Total Hip Replacement by Low Molecular Weight Heparinoid". Thrombosis and Haemostasis 67, n.º 01 (1992): 028–32. http://dx.doi.org/10.1055/s-0038-1648374.

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SummaryWe assessed the safety and efficacy of the novel low molecular weight heparinoid Lomoparan (Org 10172) for the prevention of deep-vein thrombosis in patients undergoing elective total hip replacement in a randomized, placebo-controlled, double-blind trial in 197 consecutive patients. The heparinoid (750 anti-factor Xa-units, s. c., b.i.d.) was administered to 97 patients and 99 patients received placebo. Study medication was started preoperatively and continued for 10 days. Efficacy was assessed by bilateral phlebography at day 10, postoperatively.The incidence of deep-vein thrombosis was 56.6% and 15.5% respectively in the placebo and heparinoid treated patients (incidence reduction: 74%; P <0.001). This reduction was observed both for proximal-vein thrombosis (25% to 8%; P <0.005) and isolated calf-vein thrombosis (31% to 7%; P <0001.No major hemorrhage was observed. The number of red-cell units transfused and drain-fluid loss were comparable for the two study groups. Six patients in the heparinoid group and none in the control group developed minor wound hematomas (P <0.05).During an 8-week post-discharge follow-up period three patients with a normal venogram at day 10 developed clinically apparent venous thromboembolism, which was confirmed by objective testing. All three patients belonged to the heparinoid-treated group.We conclude that 750 anti-factor Xa units Org 10172 s.c. twice daily starting preoperatively is safe and effectively reduces early deep-vein thrombosis following elective total hip replacement. Further studies on the incidence of post-discharge thromboembolism are required.
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Maslennikov, А. V., А. G. Yashchuk, G. Kh Gazizova y E. F. Berdigulova. "Effectiveness of using heparinoids in patients with endometrial dysfunction and concomitant undifferentiated connective tissue disease". Voprosy ginekologii, akušerstva i perinatologii 19, n.º 4 (2020): 50–56. http://dx.doi.org/10.20953/1726-1678-2020-4-50-56.

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Objective. To study the effectiveness of heparinoid sulodexide in complex therapy of patients with endometrial dysfunction and concomitant undifferentiated connective tissue disease (UCTD). Patients and methods. We examined 88 patients with UCTD and endometrial dysfunction (the «thin endometrium» phenomenon). The therapeutic regimen of 41 patients (group 1а) additionally to cyclical therapy with 17-b estradiol and didrogesterone was supplemented by continuous heparinoid sulodexide for 3 menstrual cycles (MC), 20 patients (group 1b) in addition to cyclical therapy received the heparinoid from the 5th day of MC until the 7th day after ovulation, 27 patients of the reference group (group 2) received only cyclical therapy without heparinoid supplementation. Results. In patients of groups 1а and 1b, restoration of M-mode echo values ≥7mm was obtained in 71–73% of cases, the median endometrial thickness in group 1а increased by 2.8 mm, in group 1b – by 2.25 mm, in group 2 – only by 1.9 mm. The continuous intake of, including during menstruation, was not associated with an increase in blood loss nor changes in red blood counts. As was also found, in patients with UCTD who had algomenorrhoea with ultrasonic signs of varicose veins of the uterus administration of sulodexide resulted in a decrease of the severity of pain syndrome up to its complete disappearance. Conclusion. The treatment regimen for patients with endometrial dysfunction concomitant with UCTD НДСТ with inclusion of continuous heparinoid sulodexide (without a break during menstruation) enhances the effectiveness of therapy, does not involve a higher menstrual blood loss, and also has a positive effect on the severity of algomenorrhoea. Key words: algomenorrhoea, undifferentiated connective tissue disease, sulodexide, chronic endometritis
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Huhle, G., L. Piazolo, D. L. Heene y J. Harenberg. "Klinischer Einsatz von Heparinoiden". Hämostaseologie 16, n.º 01 (enero de 1996): 50–55. http://dx.doi.org/10.1055/s-0038-1656638.

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ZusammenfassungHeparinoide werden seit nahezu 40 Jahren klinisch eingesetzt. Indikationsge-biete beruhen auf der entzündungshemmenden und antithrombotischen Wir-kung. Bei oraler Verabreichung steht die profibrinolytische Wirkung im Vordergrund. Für Dermatansulfat liegen pharmakokinetische Untersuchungen vor, die eine längere Halbwertszeit aufweisen im Vergleich zu Heparinen. Die Wirksamkeit bei der Hämodialyse 1st belegt. Das Heparinoid Org 10172 ist vielfältig unter-sucht. Seine Wirksamkeit in der postoperativen Thromboembolieprophylaxe und zur Thromboembolieprophylaxe bei Patienten mit Schlaganfall sowie die Wirk-samkeit in der Hämodialyse sind belegt. Eine erste Untersuchung zeigt eine Überlegenheit in der Therapie der frischen Venenthrombose im Vergleich zu unfraktioniertem Heparin. Als Alternative zur Weiterbehandlung bei Heparin-induzierter Thrombozytopenie ist diese Substanz wegweisend. Neue klinische Untersuchungen belegen somit die Wirksamkeit von Heparinoiden zur Prophylaxe und Therapie thromboembolischer Erkrankungen.
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17

Henny, Ch P., H. ten Cate, S. Surachno, P. Stevens, H. R. Büller, M. den Hartog y J. W. ten Cate. "The Effectiveness of a Low Molecular Weight Heparinoid in Chronic Intermittent Haemodialysis". Thrombosis and Haemostasis 54, n.º 02 (1985): 460–62. http://dx.doi.org/10.1055/s-0038-1657872.

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SummaryA new low molecular weight heparinoid, Org 10172 was compared to heparin in a randomized single blind cross-over study in 55 patients with end-stage renal failure undergoing chronic intermittent haemodialysis. The heparinoid administered as a single pre-dialysis i. v. injection of 34.4 anti-Xa units/kg body weight was compared to standard heparin (loading dose 2,500 IU + continuous infusion of 1,800 IU/hr). Mean anti-Xa plasma levels reached were 0.55 and 0.94 anti-Xa units/ml midway dialysis respectively. All 110 dialysis procedures were successfully performed without clotting or bleeding complications. Analysis of the number of clotted hollow-fibres within the dialysers showed a slight statistically calculated advantage in favour of heparin. Clinically no difference was detected. In conclusion, the heparinoid seems to be a good alternative means of anticoagulation in haemodialysis. As it is administered as a single i.v. pre-dialysis injection it will simplify the dialysis procedure.
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Greinacher, A., I. Michels y C. Mueller-Eckhardt. "Heparin-Associated Thrombocytopenia: The Antibody Is Not Heparin Specific". Thrombosis and Haemostasis 67, n.º 05 (1992): 545–49. http://dx.doi.org/10.1055/s-0038-1648491.

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SummaryIn this study the hypothesis was assessed whether heparin-associated thrombocytopenia (HAT) may be caused by an antibody dependent on polysulfated oligosaccharide epitopes, present not only on heparin but also on different polysulfated substances such as dextran sulfate and pentosan polysulfate. We found that the major factor for eliciting platelet activation with sera of HAT type II patients is neither the structure nor the AT III binding capacity of an oligosaccharide, but rather its grade of sulfation. This was shown by in vitro crossreactivity studies with 40 sera of HAT type II patients using unfractionated heparins, LMW heparins (Fragmin, Fraxiparin), enoxaparin, LMW heparinoid (Org 10172 and its subfractions), de-N-sulfated heparin, dermatan sulfate, dextran sulfate, pentosan polysulfate and dextran. Platelet activation was measured by the heparin induced platelet activation (HIPA) assay and the serotonin release assay (SRA). The platelet activating factor was isolated with the IgG fraction, but did not bind to heparin and dextran sulfate fixed to a solid phase. By isoimmune fixation electrophoresis a monoclonal gammopathy was ruled out in the three sera assessed. The in vivo effect of different LMW heparins and the heparinoid Org 10172 was observed in 10 patients with HAT type II. In a prospective study, a compatible heparin-like anticoagulant was selected for 10 HAT patients for whom further parenteral anticoagulation was required. The only substance that showed no crossreactivity in vitro was the LMW heparinoid Org 10172, which differs from heparin and LMW heparins by its low-grade sulfation. Upon treatment with the heparinoid, all 10 patients had a good clinical outcome, even if they had previously developed thromboembolic complications under LMW heparin administration. As Org 10172 contains a small amount of a LMW heparin-like substance (3%) this heparinoid should not be used in HAT patients without prior in vitro testing. We conclude that heparin-associated thrombocytopenia is not caused by a heparin-specific antibody and that a major factor contributing to the pathomechanism is the high grade of sulfation present in a variety of polysulfated oligosaccharides.
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19

Hajjar, D. P., D. B. Boyd, P. C. Harpel y R. L. Nachman. "Histidine-rich glycoprotein inhibits the antiproliferative effect of heparin on smooth muscle cells." Journal of Experimental Medicine 165, n.º 3 (1 de marzo de 1987): 908–13. http://dx.doi.org/10.1084/jem.165.3.908.

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Histidine-rich glycoprotein (HRGP), an alpha-glycoprotein in human plasma that is also present in platelets and macrophages, binds heparin with high affinity and neutralizes its anticoagulant activity. We now report that HRGP specifically inhibits the antiproliferative effect of heparin on arterial smooth muscle cells while other heparinoid-binding proteins do not influence mitogenesis. The multicellular inflammatory response to endothelial injury characterized, in part, by the influx of platelets and macrophages, may be associated with HRGP release into the arterial microenvironment. This release of HRGP may allow smooth muscle cell proliferation and atherogenesis by inhibiting the action of endothelial cell-derived heparinoid substances.
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20

Kumar, Neeraj, A. Bentolila y A. Domb. "Structure and Biological Activity of Heparinoid". Mini-Reviews in Medicinal Chemistry 5, n.º 5 (1 de mayo de 2005): 441–47. http://dx.doi.org/10.2174/1389557053765538.

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21

TSUJI, Hajime. "Proper use of heparin and heparinoid". Japanese Journal of Thrombosis and Hemostasis 19, n.º 2 (2008): 187–90. http://dx.doi.org/10.2491/jjsth.19.187.

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22

Stopschinski, Barbara E., Talitha L. Thomas, Sourena Nadji, Eric Darvish, Linfeng Fan, Brandon B. Holmes, Anuja R. Modi et al. "A synthetic heparinoid blocks Tau aggregate cell uptake and amplification". Journal of Biological Chemistry 295, n.º 10 (23 de enero de 2020): 2974–83. http://dx.doi.org/10.1074/jbc.ra119.010353.

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Tau aggregation underlies neurodegeneration in Alzheimer's disease and related tauopathies. We and others have proposed that transcellular propagation of pathology is mediated by Tau prions, which are ordered protein assemblies that faithfully replicate in vivo and cause specific biological effects. The prion model predicts the release of aggregates from a first-order cell and subsequent uptake into a second-order cell. The assemblies then serve as templates for their own replication, a process termed “seeding.” We have previously observed that heparan sulfate proteoglycans on the cell surface mediate the cellular uptake of Tau aggregates. This interaction is blocked by heparin, a sulfated glycosaminoglycan. Indeed, heparin-like molecules, or heparinoids, have previously been proposed as a treatment for PrP prion disorders. However, heparin is not ideal for managing chronic neurodegeneration, because it is difficult to synthesize in defined sizes, may have poor brain penetration because of its negative charge, and is a powerful anticoagulant. Therefore, we sought to generate an oligosaccharide that would bind Tau and block its cellular uptake and seeding, without exhibiting anticoagulation activity. We created a compound, SN7–13, from pentasaccharide units and tested it in a range of assays that measured direct binding of Tau to glycosaminoglycans and inhibition of Tau uptake and seeding in cells. SN7–13 does not inhibit coagulation, binds Tau with low nanomolar affinity, and inhibits cellular Tau aggregate propagation similarly to standard porcine heparin. This synthetic heparinoid could facilitate the development of agents to treat tauopathy.
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23

Chong, BH, F. Ismail, J. Cade, AS Gallus, S. Gordon y CN Chesterman. "Heparin-induced thrombocytopenia: studies with a new low molecular weight heparinoid, Org 10172". Blood 73, n.º 6 (1 de mayo de 1989): 1592–96. http://dx.doi.org/10.1182/blood.v73.6.1592.1592.

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Abstract Studies were performed to determine the cross-reaction rate of the heparin-dependent antibody with Org 10172, a new low molecular weight heparinoid, and to investigate the effect of Org 10172 on platelet activation induced by the antibody. The plasmas of 17 patients with thrombocytopenia induced by standard heparin were shown, by platelet aggregation studies, to contain the heparin-dependent antibody. Of these 17 patient plasmas, only three cross-reacted with the heparinoid, producing a cross-reaction rate of 18%. When Org 10172 was added to a reaction mixture containing normal platelet-rich plasma, patient plasma, and standard heparin with non-cross-reacting plasmas, it inhibited platelet aggregation and thromboxane B2 production induced by the antibody, provided that the ratio of Org 10172 concentration (anti- Xa U/mL) to standard heparin concentration (IU/mL) exceeded 2.5 to 5.0. This inhibitory effect was observed only with platelet activation mediated by the antibody, but not by collagen (2 micrograms/mL) or ADP (5.0 mumol/L). Additionally, three of 17 patients with serious thrombosis, whose plasma showed no cross-reaction with the heparinoid, received Org 10172 treatment with a good response in each case. These findings suggest that Org 10172 may be a useful drug for the treatment of heparin-induced thrombocytopenia.
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24

Chong, BH, F. Ismail, J. Cade, AS Gallus, S. Gordon y CN Chesterman. "Heparin-induced thrombocytopenia: studies with a new low molecular weight heparinoid, Org 10172". Blood 73, n.º 6 (1 de mayo de 1989): 1592–96. http://dx.doi.org/10.1182/blood.v73.6.1592.bloodjournal7361592.

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Studies were performed to determine the cross-reaction rate of the heparin-dependent antibody with Org 10172, a new low molecular weight heparinoid, and to investigate the effect of Org 10172 on platelet activation induced by the antibody. The plasmas of 17 patients with thrombocytopenia induced by standard heparin were shown, by platelet aggregation studies, to contain the heparin-dependent antibody. Of these 17 patient plasmas, only three cross-reacted with the heparinoid, producing a cross-reaction rate of 18%. When Org 10172 was added to a reaction mixture containing normal platelet-rich plasma, patient plasma, and standard heparin with non-cross-reacting plasmas, it inhibited platelet aggregation and thromboxane B2 production induced by the antibody, provided that the ratio of Org 10172 concentration (anti- Xa U/mL) to standard heparin concentration (IU/mL) exceeded 2.5 to 5.0. This inhibitory effect was observed only with platelet activation mediated by the antibody, but not by collagen (2 micrograms/mL) or ADP (5.0 mumol/L). Additionally, three of 17 patients with serious thrombosis, whose plasma showed no cross-reaction with the heparinoid, received Org 10172 treatment with a good response in each case. These findings suggest that Org 10172 may be a useful drug for the treatment of heparin-induced thrombocytopenia.
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25

Hoek, Jaap A., Ch Pieter Henny, Haye C. Knipscheer, Hugo ten Cate, Michael T. Nurmohamed y Jan W. ten Cate. "The Effect of Different Anaesthetic Techniques on the Incidence of Thrombosis following Total Hip Replacement". Thrombosis and Haemostasis 65, n.º 02 (1991): 122–25. http://dx.doi.org/10.1055/s-0038-1647468.

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SummaryWe performed a retrospective analysis on the influence of three types of anaesthesia on the incidence of deep vein thrombosis (DVT) following total hip replacement (THR) in consecutive patients randomized to either the low molecular weight heparinoid Otg 10172 (97 patients), of placebo (99 patients). Ninety patients were operated under epidural anaesthesia, 77 patients under psoas compartment block with additional inhalation anaesthesia, and 29 patients under general anaesthesia. DVT assessment was performed by bilateral venography between days 8 and 12 postoperatively. The overall incidence of DVT in the 196 patients was 37% in the epidural anaesthasia group, 35% in the psoas compartment block group, and 36% in the general anaesthesia group. Although the incidence of DVT in patients randomuedto placebo was similar in the two anaesthesia groups (53%), there was an important reduction of the occurrence of proximal DVT by the heparinoid in the psoas compartment block group (from 20 to 0%), compared to the epidural anaesthesia group (from 27 to l8%) (p <0.0061). Significant y more minor wound hematomas occurred in the psoas compartment block group as compared to the epidural anaesthesia group (p <0.05). Synergrsm of thrombin generation inhibition by the heparinoid and inhibition of plateletlggregation at the damaged vessel wall, by high local concentrations of bupivacaine in the psoas compartment block technique, is proposed as a possible mechanism behind this observation.
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26

Rele, Shyam M., Suri S. Iyer, Subramanian Baskaran y Elliot L. Chaikof. "Design and Synthesis of Dimeric Heparinoid Mimetics". Journal of Organic Chemistry 69, n.º 26 (diciembre de 2004): 9159–70. http://dx.doi.org/10.1021/jo049092r.

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27

Korsan-Bengtsen, Kristoffer, Walter Berg y Gunnar Aspenström. "A Clinical Study of a New Heparinoid". Acta Medica Scandinavica 173, n.º 1 (24 de abril de 2009): 107–14. http://dx.doi.org/10.1111/j.0954-6820.1963.tb16511.x.

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28

Ockelford, Paul A., C. J. Carter y J. Hirsh. "In vivo activity of a new heparinoid". Pathology 17, n.º 1 (1985): 78–81. http://dx.doi.org/10.3109/00313028509063731.

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29

ITO, Y., Y. IGUCHI y Y. IMANISHI. "Synthesis and non-thrombogenicity of heparinoid polyurethaneureas". Biomaterials 13, n.º 3 (1992): 131–35. http://dx.doi.org/10.1016/0142-9612(92)90060-2.

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30

Borawski, Jacek, Beata Naumnik, Miroslaw Dubowski y Michal Mysliwiec. "Full-Length TFPI Release by Heparinoid Sulodexide". Clinical and Applied Thrombosis/Hemostasis 16, n.º 4 (19 de julio de 2010): 485–87. http://dx.doi.org/10.1177/1076029609338048.

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31

Alban, Susanne, Roland Kaufmann, Edelgard Lindhoff-Last, Wolf-Henning Boehncke, Ralf J. Ludwig y Marc Schindewolf. "Molecular weight determines the frequency of delayed type hypersensitivity reactions to heparin and synthetic oligosaccharides". Thrombosis and Haemostasis 94, n.º 12 (2005): 1265–69. http://dx.doi.org/10.1160/th05-05-0318.

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SummaryEczematous lesions, resulting from type IV sensitizations are well-known and relatively frequent cutaneous adverse effects of s.c. heparin therapy. If anticoagulation is further required intravenous heparin, heparinoids or lepirudin may be used as a substitute. However, these alternatives are not optimal in terms of practicability and/or safety-profiles. As molecular weight of different heparin preparations has repetitively been implied to determine the frequency of sensitization, we hypothesized, that due to its low molecular weight the pentasaccharide fondaparinux may provide a practicable and safe anticoagulant therapy in patients with delayed type hypersensitivity reactions (DTH) to heparin and other oligosaccharides. To test this concept, patients referred for diagnosis of cutaneous reactions after s.c. anticoagulant treatment underwent a series of in vivo skin allergyand challenge-tests with unfractionated heparin, a series of low molecular weight heparins (nadroparin, dalteparin, tinzaparin, enoxaparin and certoparin), the heparinoid danaparoid and the synthetic pentasaccharide fondaparinux. In total, data from twelve patients was evaluated. In accordance with previously published data, we report a high crossreactivity among heparins and heparinoids. In contrast – and in support of our initial hypothesis – sensitization towards the synthetic pentasaccharide fondaparinux was rarely observed. Plotting the cumulative incidence against the determined molecular weight of the individual anticoagulant preparations, shows that molecular weight generally is a key determinant of sensitization towards heparins and other oligosaccharides (r2=0.842, p=0.009). Hence, fondaparinux may be used as a therapeutic alternative in patients with cutaneous DTH relations towards heparin and other polysaccharides.
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32

Newton, Faith, Kimberly Glaser, Jennifer Reeves, Lyndsay Sheperd y Bappaditya Ray. "Refractory Heparin-Induced Thrombocytopenia in a Patient With Subarachnoid Hemorrhage—A Clinical Conundrum". Neurohospitalist 11, n.º 4 (15 de febrero de 2021): 360–64. http://dx.doi.org/10.1177/1941874421995377.

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Heparin induced thrombocytopenia (HIT) often resolves with discontinuation of heparin/ heparinoid products. Severe HIT with platelet counts <20,000/µL and disseminated intravascular coagulation is frequently associated with consumptive coagulopathy and systemic thrombosis. Management of severe HIT in patients who fail to improve on discontinuing heparinoid products and argatroban infusion is not well established. We describe a patient admitted with aneurysmal subarachnoid hemorrhage (SAH) who developed severe autoimmune HIT, failed conventional anticoagulation therapy with argatroban and progressed to develop extensive deep venous thrombosis and limb ischemia. She was successfully treated using bivalirudin, immunomodulation with 2 cycles of intravenous immunoglobulin and immunosuppression with methylprednisolone. Refractory severe HIT among SAH patients is rare and pose several therapeutic challenges. We report successful treatment using alternate anticoagulant and immune suppression and modulation.
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33

Boehncke, Wolf-Henning, Lutz Weber y Helmut Gall. "Tolerance to intravenous admiration of heparin and heparinoid in a patient with delayed-type hypersensitivity to heparins and heparinoids". Contact Dermatitis 35, n.º 2 (agosto de 1996): 73–75. http://dx.doi.org/10.1111/j.1600-0536.1996.tb02293.x.

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34

SCHWARZ, ANKE. "New Aspects of the Treatment of Nephrotic Syndrome". Journal of the American Society of Nephrology 12, suppl 1 (febrero de 2001): S44—S47. http://dx.doi.org/10.1681/asn.v12suppl_1s44.

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Abstract.The nephrotic syndrome, caused by glomerulonephritis, diabetes mellitus, or amyloidosis, is still a therapeutic challenge. Newer therapeutic approaches may be sought in the fields of immunosuppression, nonspecific supportive measures, heparinoid administration, and removal of a supposed glomerular basement membrane toxic factor. In immunosuppression, the newer drugs now used in organ transplantation (cyclosporine, tacrolimus, and mycophenolate mofetil) can also be used in the treatment of glomerulonephritis. In nonspecific supportive treatment, angiotensin II receptor antagonists are now used in addition to angiotensin-converting enzyme inhibitors. Positive effects of hydroxymethylglutaryl coenzyme A reductase inhibitors on the nephrotic syndrome have not yet been proven. Cyclooxygenase II inhibitors must be tested but probably have too many renal side effects, similar to those of nonsteroidal anti-inflammatory drugs. Heparinoids or glycosaminoglycans serve as polyanions and thus have protective effects on the negative charge of the glomerular basement membrane. They can now be administered as oral medications. The removal of a supposed glomerular basement membrane toxic factor that induces proteinuria has been attempted for 20 yr and now is usually performed using immunoadsorption. Especially in cases of recurrent nephrotic syndrome after renal transplantation for patients with glomerulonephritis, this approach has been successful in decreasing proteinuria, although in most cases its effect is not lasting but must be continuously renewed.
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35

ten Cate, Hugo, Ch Pieter Henny, Jan W. ten Cate, Harry R. Büller y Nosjir F. Dabhoiwala. "Randomized Double-Blind, Placebo Controlled Safety Study of a Low Molecular Weight Heparinoid in Patients Undergoing Transurethral Resection of the Prostate". Thrombosis and Haemostasis 57, n.º 01 (1987): 092–96. http://dx.doi.org/10.1055/s-0038-1651069.

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SummaryIn preparation for an efficacy study, the effect of the low molecular weight heparinoid Org 10172 on postoperative blood loss was assessed in a randomized double-blind, placebo controlled study in patients undergoing transurethral resection of the prostate (TURP). Org 10172 and placebo were given twice daily as i.v. injection for three postoperative days starting one hour preoperatively. Three doses of Org 10172 (800, 1600, and 2400 anti-Xa units b.d.) were evaluated against placebo in three consecutive patient blocks respectively. Each block consisted of 20 patients, 15 receiving Org 10172 and 5 patients placebo. The study was discontinued after 9 patients of the third block had completed the protocol because of excessive urinary blood loss. Data analysis showed a dose-dependent increase in postoperative haemoglobin loss, this was not significant for the 800 anti-Xa units b. d. dosage but was significant in those patients treated with 1600 (p <0.05) and 2400 anti-Xa units b.d. (p <0.01).It was concluded that the heparinoid Org 10172 caused a dose dependent increase in urinary blood loss following TURP.
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36

Nielsen, Vance G. y Brian T. Geary. "Hepatoenteric ischemia-reperfusion increases circulating heparinoid activity in rabbits". Journal of Critical Care 15, n.º 4 (diciembre de 2000): 142–46. http://dx.doi.org/10.1053/jcrc.2000.19230.

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37

Koya, Madhusudan P., Murugesan Manoharan, Sandy S. Kim y Mark S. Soloway. "Venous thromboembolism in radical prostatectomy: is heparinoid prophylaxis warranted?" BJU International 96, n.º 7 (noviembre de 2005): 1019–21. http://dx.doi.org/10.1111/j.1464-410x.2005.05783.x.

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38

Shimada, Shigeki, Hideto Yamada, Tatsuya Atsumi, Takashi Yamada, Noriaki Sakuragi y Hisanori Minakami. "Intravenous immunoglobulin therapy for aspirin-heparinoid-resistant antiphospholipid syndrome". Reproductive Medicine and Biology 9, n.º 4 (15 de junio de 2010): 217–21. http://dx.doi.org/10.1007/s12522-010-0056-3.

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39

Jackson, Mark R., Christopher A. Danby y Barbara M. Alving. "Heparinoid Anticoagulation and Topical Fibrin Sealant in Heparin-Induced Thrombocytopenia". Annals of Thoracic Surgery 64, n.º 6 (diciembre de 1997): 1815–17. http://dx.doi.org/10.1016/s0003-4975(97)01065-5.

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40

Hayama, Koremasa, Yusaku Takano, Jin Tamura, Hachiro Tagami y Tadashi Terui. "Effectiveness of a heparinoid-containing moisturiser to treat senile xerosis". Australasian Journal of Dermatology 56, n.º 1 (10 de octubre de 2014): 36–39. http://dx.doi.org/10.1111/ajd.12179.

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41

Massey, E. W., J. Biller, J. N. Davis, H. P. Adams, J. R. Marler, L. B. Goldstein, M. Alberts y A. Bruno. "Large-dose infusions of heparinoid ORG 10172 in ischemic stroke." Stroke 21, n.º 9 (septiembre de 1990): 1289–92. http://dx.doi.org/10.1161/01.str.21.9.1289.

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42

Herzog, S., W. Rath y W. Kuhn. "Erfolgreiche Therapie einer heparinassoziierten Thrombozytopenie mit einem niedrig-sulfatierten Heparinoid". Geburtshilfe und Frauenheilkunde 55, n.º 03 (marzo de 1995): 164–66. http://dx.doi.org/10.1055/s-2007-1022797.

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43

Vannas, Salme y Ulf Krause. "A TRIAL WITH A PHYSIOLOGICAL HEPARINOID* IN SOME SCLEROTIC CHORIORETINOPATHIES". Acta Ophthalmologica 39, n.º 3 (27 de mayo de 2009): 466–74. http://dx.doi.org/10.1111/j.1755-3768.1961.tb00876.x.

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44

Wessel, H. P., A. Chucholowski, J. Fingerle, N. Iberg, H. P. Marki, R. Muller, M. Pech et al. "ChemInform Abstract: From Glycosaminoglycans to Heparinoid Mimetics with Antiproliferative Activity". ChemInform 30, n.º 21 (15 de junio de 2010): no. http://dx.doi.org/10.1002/chin.199921293.

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45

Kumokawa, Tadao, Kazumasa Hirata, Keiichi Sato y Satoshi Kano. "Dermal absorption of mucopolysaccharide polysulfate (heparinoid) in human and minipig". Arzneimittelforschung 61, n.º 02 (28 de noviembre de 2011): 85–91. http://dx.doi.org/10.1055/s-0031-1296172.

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46

Scott-Burden, T. y F. R. Bühler. "Regulation of smooth muscle proliferative phenotype by heparinoid-matrix interactions". Trends in Pharmacological Sciences 9, n.º 3 (marzo de 1988): 94–98. http://dx.doi.org/10.1016/0165-6147(88)90175-7.

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47

ten Cate, H., Ch P. Henny, J. W. ten Cate, H. R. Büller y N. Dabhoiwala. "Heparinoid ORG 10172 in patients undergoing turp: a safety, study". Thrombosis Research 41 (enero de 1986): 84. http://dx.doi.org/10.1016/0049-3848(86)91513-6.

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48

Deryck, Y. L. J. M., R. M. Schepp, R. J. van Krugten y B. Mochtar. "Heparinoid ORG 10172 anticoagulation for cardiopulmonary bypass : A case report". Journal of Cardiothoracic Anesthesia 4, n.º 6 (diciembre de 1990): 40. http://dx.doi.org/10.1016/0888-6296(90)90111-r.

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49

Utsunomiya, R., H. Okazaki, X. Dai, M. Murakami, K. Masuda, H. Mori, K. Shiraishi, M. Tohyama y K. Sayama. "449 Novel function of heparinoid as an anti-inflammatory agent". Journal of Investigative Dermatology 137, n.º 10 (octubre de 2017): S269. http://dx.doi.org/10.1016/j.jid.2017.07.645.

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50

Seto, Stephanie L., Megan E. Barra, Russel J. Roberts y Rachel P. Rosovsky. "Incidence and Outcomes of Heparin-Induced Thrombocytopenia Associated with a Heparin Shortage at a Large Academic Medical Center". Blood 136, Supplement 1 (5 de noviembre de 2020): 10. http://dx.doi.org/10.1182/blood-2020-141282.

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Heparin-induced thrombocytopenia (HIT) is a life-threatening complication associated with significant morbidity and mortality in hospitalized patients. The 2019 African swine fever outbreak in China resulted in a critical national shortage of porcine-derived heparin products in the United States. As a result, our institution implemented a multitude of mitigation strategies to reduce heparin utilization by &gt;80% and optimize safe and effective alternative therapies. The aim of this study was to determine whether this change in clinical practice impacted the incidence of HIT and associated outcomes. A single-center, retrospective cohort study was performed on patients admitted to Massachusetts General Hospital who were ≥ 18 years of age and had a positive platelet factor 4 (PF4) drawn between February 2019 and January 2020. Patient demographics, comorbidities, baseline labs, serotonin release assay results, timing and magnitude of platelet count fall, and characteristics of heparinoid and non-heparinoid anticoagulant use were collected from the medical record. Thrombotic and hemorrhagic outcomes were characterized. Seventy-five patients were included in the final analysis, of which 56 (75%) were critically-ill. Baseline characteristics were similar between groups including median age 66.8 years, 49% male, 80% Caucasian. Forty-four (59%) patients underwent surgery, 23 (31%) required continuous renal replacement therapy, and 13 (17%) underwent extracorporeal membrane oxygenation. Incidence of HIT with any exposure to heparinoid product was 0.3% and 0.15% (p=0.002) in the pre-shortage and shortage periods, respectively. In those who received therapeutic dose unfractionated heparin, incidence of HIT was 1.26% and 1.05% (p=0.63) in the pre-shortage and shortage groups, respectively. Thrombotic complications were observed in 19 (41%) patients in the pre-shortage group and 11 (38%) in the post-shortage group (p=0.77). Bleeding events were observed in 8 (17%) and 5 (17%) (p=0.99). We observed a lower incidence of HIT resulting from our institution's efforts to conserve unfractionated heparin supply and utilize alternative anticoagulants during a critical national drug shortage. There were no significant differences in associated thrombotic and bleeding events. Disclosures Rosovsky: Bristol-Myers Squibb, Dova, Janssen, Portola: Consultancy; Bristol-Myers Squibb, Janssen: Research Funding.
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