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PCC may be either 3 factors (II, IX, and X) or 4 factors (II, VII, IX, and X), but it is unclear what is the superior product.3 Recombinant factor VIIa rapidly normalizes the international normalized ratio (INR) but it is unclear whether it reduces bleeding in patients with hemorrhage.4 The administration of vitamin K overcomes the blockage caused by the vitamin K antagonists and allows the production of normal vitamin K clotting factors. PCC seems superior to fresh frozen plasma because of speed of infusion, routine viral inactivation, lack of need for crossmatching, the small volume to be infused, and the effectiveness of reversal.2 Fresh frozen plasma requires storage in a freezer and requires thawing before use this is not the case for PCC. PCC is a plasma-derived mixture of the vitamin K–dependent clotting factors. Options include fresh frozen plasma or prothrombin complex concentrate (PCC), these replace the deficient clotting factors normalizing coagulation in the time it takes to infuse the product. Immediate reversal of the anticoagulant effect is achieved by the administration of the deficient clotting factors. γ-Carboxylation of the clotting factors is required for their interaction with phospholipids which is in turn required for their action as enzymes. Vitamin K antagonists block vitamin K epoxide reductase preventing the recycling of vitamin K which in turn is involved in the γ-carboxylation of clotting factors II, VII, IX, and X and the natural anticoagulant proteins C and S. The vitamin K antagonists can be reversed although in practice clinicians rarely provide truly effective reversal as a result of their choosing the incorrect type, dose, and route of administration of the reversal agents. Physostigmine to reduce the effect of atropineGlucose in insulin overdoseProthrombin complex concentrate in vitamin K antagonistsĭrugs which block enzymic pathways effect can be reversed by administering the downstream productsĪdministration of vitamin K for those on vitamin K antagonists
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The effects of drugs that reduce certain compounds in the body may be reversed by increasing the levels of these compounds, either by the administration of these compounds or reducing their metabolism/excretion Increasing the drug’s target or increasing the substance that the drugs action reduces Reducing the metabolism of prodrugs before their conversion into the active formĮnhancing the normal excretion of a drug or dialyzing the patient which removes drugs will reduce the level of the drug in the bodyĪlkalization of urine in aspirin poisoningDialysis in lithium poisoningĭrugs may be blocked either by the antidote binding to the drug or the site of actionĭigibind against digoxinNaloxone against the μ-opioid receptor These agents are currently in premarketing studies.ĭrugs that have been recently ingested can be removed by administering emetics or giving activated charcoal that binds drugs and prevents it from being absorbed Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. Dabigatran’s, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Their main disadvantage is currently the absence of a specific reversal agent. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants.
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Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).