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Ruconest, conestat alfa. European public assessment report (EPAR). Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/medicines\/001223\/human_med_001382.jsp&mid=WC0b01ac058001d124\" xlink:type=\"simple\">http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/medicines\/001223\/human_med_001382.jsp&amp;mid=WC0b01ac058001d124<\/ext-link>. Accessed 7 July 2016."},{"key":"ref20","unstructured":"European Medicines Agency (EMA). Firazyr, icatibant. European public assessment report (EPAR). Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/medicines\/000899\/human_med_000793.jsp&mid=WC0b01ac058001d124\" xlink:type=\"simple\">http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/medicines\/000899\/human_med_000793.jsp&amp;mid=WC0b01ac058001d124<\/ext-link>. Accessed 7 July 2016."},{"key":"ref21","unstructured":"Ottawa (ON): Canadian Agency for Drugs and Technologies in Health. C1 Esterase Inhibitor for Prophylaxis against Hereditary Angioedema Attacks: A Review of the Clinical Effectiveness, Cost-Effectiveness, and Guidelines. CADTH Rapid Response Reports. 2015; 24 April 2015 26180896."},{"issue":"4","key":"ref22","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1159\/000381341","article-title":"Home Therapy with Plasma-Derived C1 Inhibitor: A Strategy to Improve Clinical Outcomes and Costs in Hereditary Angioedema","volume":"166","author":"A Petraroli","year":"2015","journal-title":"International archives of allergy and immunology"},{"issue":"5","key":"ref23","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.anai.2016.03.008","article-title":"Real-life experience with long-term prophylactic C1 inhibitor concentrate treatment of patients with hereditary angioedema: Effectiveness and cost","volume":"116","author":"ER Rasmussen","year":"2016","journal-title":"Annals of allergy, asthma & immunology"},{"issue":"1","key":"ref24","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/cc9304","article-title":"Bench-to-bedside review: the role of C1-esterase inhibitor in sepsis and other critical illnesses","volume":"15","author":"M Singer","year":"2011","journal-title":"Critical Care"},{"key":"ref25","article-title":"Myocardial infarction induces atrial inflammation that can be prevented by C1-esterase inhibitor","author":"MP Begieneman","year":"2016","journal-title":"Journal of clinical pathology"},{"issue":"2","key":"ref26","first-page":"264","article-title":"Potentiation of C1-esterase inhibitor activity by heparin","volume":"23","author":"R Rent","year":"1976","journal-title":"Clinical and Experimental Immunology"},{"issue":"4","key":"ref27","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0022-5223(99)70302-8","article-title":"Heparin-coated cardiopulmonary bypass equipment. 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US 7008931-B2 (07.03.2006), EP1337261-B1 (21.03.2007)."},{"issue":"2","key":"ref43","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1021\/bm010032u","article-title":"Partial Synthetic Glucan Sulfates as Potential New Antithrombotics: A Review","volume":"2","author":"S Alban","year":"2001","journal-title":"Biomacromolecules"},{"issue":"1","key":"ref44","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3390\/md13010076","article-title":"Sulfated Galactofucan from the Brown Alga Saccharina latissima-Variability of Yield, Structural Composition and Bioactivity","volume":"13","author":"K Ehrig","year":"2015","journal-title":"Marine drugs"},{"issue":"11","key":"ref45","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1021\/bm900501g","article-title":"Optimized and standardized isolation and structural characterization of anti-inflammatory sulfated polysaccharides from the red alga Delesseria sanguinea (Hudson) Lamouroux (Ceramiales, Delesseriaceae)","volume":"10","author":"N Gr\u00fcnewald","year":"2009","journal-title":"Biomacromolecules"},{"key":"ref46","unstructured":"Alban S, Scriba GKE. Comment on monograph \u201cDanaparoid sodium\u201d Ph. Eur. 5.5, 2090. 26th ed. Eschborn: Govi; 2007."},{"issue":"12","key":"ref47","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1111\/j.1538-7836.2007.02770.x","article-title":"The plasma kallikrein-kinin system: its evolution from contact activation","volume":"5","author":"AH Schmaier","year":"2007","journal-title":"Journal of Thrombosis and Haemostasis"},{"issue":"1","key":"ref48","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/jth.13194","article-title":"The contact activation and kallikrein\/kinin systems: pathophysiologic and physiologic activities","volume":"14","author":"AH Schmaier","year":"2016","journal-title":"Journal of Thrombosis and Haemostasis"},{"issue":"29","key":"ref49","doi-asserted-by":"crossref","first-page":"21100","DOI":"10.1074\/jbc.M700841200","article-title":"C1 inhibitor serpin domain structure reveals the likely mechanism of heparin potentiation and conformational disease","volume":"282","author":"L Beinrohr","year":"2007","journal-title":"The Journal of Biological Chemistry"},{"issue":"2","key":"ref50","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1042\/BJ20090198","article-title":"Modulation of the proteolytic activity of the complement protease C1s by polyanions: implications for polyanion-mediated acceleration of interaction between C1s and SERPING1","volume":"422","author":"TA Murray\u2011Rust","year":"2009","journal-title":"Biochemical Journal"},{"issue":"1","key":"ref51","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bbagen.2011.10.008","article-title":"Potentiation of C1-esterase inhibitor by heparin and interactions with C1s protease as assessed by surface plasmon resonance","volume":"1820","author":"M Rajabi","year":"2012","journal-title":"Biochimica et Biophysica Acta\u2014General Subjects"},{"issue":"2","key":"ref52","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0161-5890(82)90342-X","article-title":"A postulated mechanism for heparin&apos;s potentiation of C1 inhibitor function","volume":"19","author":"GB Caughman","year":"1982","journal-title":"Molecular Immunology"},{"issue":"12","key":"ref53","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.2174\/138161208784246135","article-title":"Pharmacological strategies for inhibition of thrombin activity","volume":"14","author":"S Alban","year":"2008","journal-title":"Current Pharmaceutical Design"},{"issue":"5","key":"ref54","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1182\/blood-2013-07-515726","article-title":"Polyphosphate suppresses complement via the terminal pathway","volume":"123","author":"JM Wat","year":"2014","journal-title":"Blood"},{"key":"ref55","article-title":"Polyphosphate is a novel cofactor for regulation of complement by the serpin, C1-inhibitor","author":"LC Wijeyewickrema","year":"2016","journal-title":"Blood"},{"issue":"24","key":"ref56","doi-asserted-by":"crossref","first-page":"7277","DOI":"10.1021\/jp4030766","article-title":"On the initial binding of alginate by calcium ions. 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