PMC:6723693 / 677-3009
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/6723693","sourcedb":"PMC","sourceid":"6723693","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6723693","text":"In healthy individuals, blood freely circulates along arteries and veins throughout the entire human body, in which the normal vascular endothelium acts as an overall antithrombotic surface. Yet, it becomes immediately active if the hemostatic system is triggered by the coagulation cascade. As we know, when a blood vessel is damaged platelets and fibrin quickly engage in an aggregation process leading to hemorrhage prevention. This is beneficial in avoiding blood loss, at the same time excessive clotting can lead to life-threatening thrombotic complications. Such a physiological situation might disgracefully happen during different clinical practices, such as large surgeries, blood transfusions, or dialysis treatments; accordingly, a delicate balance between thromboembolism risk and excessive bleeding prevention must be carefully optimized for each patient. Heparin, a linear polysaccharide consisting of repeating units of 2-O-sulfated iduronic acid and 6-O-sulfated, N-sulfated glucosamine (IdoA(2S)-GlcNS(6S) (Figure 1a), is one of the most charged dense naturally occurring polyanion in biological systems [1] and, equally, one of the most widely used clinical anticoagulants worldwide [2]. Once the clinical treatment requiring coagulation control is over, reversal of the administered heparin anticoagulant activity is obviously required. Protamine, a small, nuclear, basic, arginine-rich protein (Figure 1b), is the only FDA (Food and Drug Administration) approved molecule employed to that purpose. In fact, by virtue of its high positive charge, protamine binds to heparin via strong electrostatic interaction thereby removing the polysaccharide from the bloodstream and ultimately re-enabling clotting. Unfortunately, protamine is associated with several, important side-effects, including immunological and inflammatory alterations, and anaphylactic responses characterized by hypotension, bradycardia, pulmonary vasoconstriction, and allergy if not exactly administered [3]. Hence, the development of new, protamine-alternative heparin-rescue agents, which could stably bind the polyanion so that excretion of their intact complexes can easily and quantitatively occur, but at the same time, could safely degrade into non-toxic components if administered in excess, is a current hot need in medical practice.","tracks":[{"project":"2_test","denotations":[{"id":"31434309-29661409-7261660","span":{"begin":1995,"end":1996},"obj":"29661409"}],"attributes":[{"subj":"31434309-29661409-7261660","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#9393ec","default":true}]}]}}