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Continuing education and learning Activity
Unfractionated heparin is an anticoagulant indicated for both the prevention and treatment the thrombotic events such as deep vein thrombosis (DVT) and also pulmonary embolism (PE) as well as atrial fibrillation (AF). Heparin is likewise used to protect against excess coagulation during procedures such together cardiac surgery, extracorporeal circulation, or dialysis, including constant renal instead of therapy. Heparin is also widely provided in the hospital for countless different off-label indications. This task outlines the indications, device of action, dosing, necessary adverse effects, contraindications, monitoring, and also toxicity the heparin and increases practitioners" knowledge about how to approach this medication and also use and monitor it effectively to drive much better patient outcomes.
Review the indications, both approved and also off-label, that heparin.
Identify the potential adverse effects and contraindications of heparin.
Review the security for toxicity, and also any potential reversal actions that may be available.
Explain the importance of improving treatment coordination among the interprofessional team to improve the shipment of care for patients once using heparin together anticoagulation therapy.
Access complimentary multiple choice questions on this topic.
Unfractionated heparin is one anticoagulant suggested for both the prevention and treatment of thrombotic occasions such together deep vein thrombosis (DVT) and also pulmonary embolism (PE) and also atrial fibrillation (AF). Heparin can also be offered to protect against excess coagulation during procedures such together cardiac surgery, extracorporeal circulation, or dialysis, including continuous renal replacement therapy (CRRT).<1><2>
Heparin is widely used in the hospital for countless different off-label indications, because that example, patient who existing with acute coronary syndromes (ACS) and who undergo percutaneous coronary treatment (PCI). Throughout hospitalization, heparin will certainly be supplied to bridge to oral anticoagulation, warfarin for mechanical and also bioprosthetic valves. The American college of Chest physicians (ACCP) recommends making use of heparin for countless other thrombotic states: atrial fibrillation undergoing cardioversion, endocarditis, systemic emboli, or venous thrombosis.<3><4>
Dosing referrals vary for each indication. Many heparin drips will be initiated with a bolus injection of 80 units/kilogram intravenously, adhered to by a continuous infusion rate of 18 units/kilogram/hour. In obese populations, these dosages are capped off at a maximum bolus infusion and also maximum infusion rate. Dosing in some cases is much reduced with different maximum doses. Because that example, in patients with acute coronary syndrome or stroke, the sheep is much lower as result of an enhanced risk because that bleeding. Once heparin is administered and also dosed by indication, there space no dosage adjustments compelled for renal dysfunction.<1><3>
Heparin is also useful in smaller volumes as lock flushes. As result of the rise in adverse effects and also exposure to heparin, these are not used as frequently in clinical practice. These room intended to keep patency for IV lines and also should not be supplied to attain therapeutic anticoagulation. Lock flushes room usually dispensed as a 1 to 5 mL volume syringe used for catheter do the washing up only. A small volume of heparin is instilled into the catheter tip and also flushed daily. Extra caution have to be it was observed in the administration of heparin lock solution generally in a 24 hour period with pediatric patients. Dependent top top the concentration, if instilling a lock flush, this could be close to a therapeutic sheep of heparin in some pediatric patients.<1><2><3>
Mechanism of Action
Once administered, heparin binds to number of proteins; however, that is binding to an antithrombin that is important, as this causes a surface change and inactivates thrombin. Binding come antithrombin blocks numerous different determinants of the clotting cascade, yet two room predominant: thrombin (Factor IIa) and Factor Xa. By inactivating thrombin, it block the conversion of fibrinogen to fibrin; this stays clear of the development of clots and prolongs the clotting time of blood. Heparin walk not influence bleeding time, however it does expand the time that blood takes come clot.<1><2>
Heparin management can be by intravenous (IV) course or subcutaneous SQ) route. Intravenous heparin is repeatedly administered for therapeutic anticoagulation, if intermittent subcutaneous administration is used to stop thromboembolism. Intermittent IV administration is likewise an option. Because that example, heparin is given intermittently by the interventional cardiologist in the cardiac catheterization lab, dependence upon laboratory markers throughout the case. When administered SQ, the onset of action is generally within 1 come 2 hours contrasted to an prompt anticoagulant impact with IV management of heparin. There to be an assessment of intramuscular (IM) injection, however researchers observed an enhanced level the pain, irritation, and hematoma development with ns injections the heparin.<1><3>
Heparin use"s common adverse results include bleeding, thrombocytopenia, injection site reactions, and other adverse impacts only seen v chronic heparin administration. Bleeding is a major complication associated with heparin use. Patients should undergo monitoring for brand-new bleeding the may present in the to pee or stool. Bleeding may also present as bruising, petechial rash, and also nosebleeds.<2>
Thrombocytopenia generally occurs in as much as 30% of patients who receive heparin. Most often, this is no significant; however, there is a form of thrombocytopenia the is an ext serious, recognized as heparin-induced thrombocytopenia (HIT). Thrombocytopenia deserve to be share as kind I or kind II. Kind I is a non-immunogenic interaction with platelets that generally occurs within the very first 48 come 72 hrs of initiation of heparin. The fall in platelet count is generally temporary and will recoup upon cessation the heparin. Form II thrombocytopenia is an ext commonly well-known as heparin-induced thrombocytopenia; this is immune-related thrombocytopenia the occurs when heparin binding to the protein platelet variable 4 (PF4). This facility alerts the immune system and also causes one immune-mediated reaction with platelets. Platelets space activated and consumed by clot development providing a pro-thrombotic atmosphere with a short platelet count. Heparin-induced thrombocytopenia usually occurs about five days right into heparin therapy. Thrombosis can kind and reason severe HITT (heparin-induced thrombocytopenia and thrombosis). Serious events seen v thrombosis incorporate pulmonary embolism, deep vein thrombosis, stroke, myocardial infarction, and thrombosis in main arteries to organs that might lead to significant complications, including limb amputation or death.<5>
Other adverse effects that occur with the usage of heparin encompass injection site reactions, hyperkalemia, alopecia, and also osteoporosis. Osteopenia and also osteoporosis have correlations through chronic heparin use, however not with acute use of heparin.<5>
Therapeutic surveillance for heparin consists of activated partial thromboplastin time (aPTT) and activated coagulation time (ACT). Both of these are aspects of clotting time, i m sorry are prolonged by therapeutic heparin doses. Activated partial thromboplastin time is performed in ~ baseline and also every 6 hours until 2 or more therapeutic values are obtained, climate aPTT can be assessed every 24 hours. Dose titrations space made based on the results of the aPTT. Hospitals have dosing nomograms certain to their target aPTT, which might vary depending on the activities reagent used for your test. Therapeutic aPTT is taken into consideration therapeutic at 1.5 to 2 times control, which likewise varies from basic to facility based upon controls.<1>
ACT is less sensitive than aPTT. Action will only detect abnormalities once there is a 95% abnormality rate in the factors, vice versa, aPTT have the right to detect once there is a 70% abnormality. Action may also be affected when platelets are abnormal, i m sorry can an outcome from the administration of heparin. Action is a allude of care test, which makes trial and error at the bedside more convenient with a quick turnaround. For these reasons, act is generally minimal to use in cardiopulmonary bypass, ECMO (extracorporeal membrane oxygenation), or PCI (percutaneous coronary intervention). Action monitoring throughout bypass is come ensure that the blood is thin sufficient to protect against clotting the the heart and lung machine. Most practitioners will aim because that a score ACT greater than 400 throughout CPB (cardiopulmonary bypass).<6><7>
Another form the monitoring includes anti-factor Xa activity levels. A level is thought about therapeutic in ~ 0.3 to 0.7 global units/milliliter. This surveillance is frequently reserved for use in patients where aPTT security is unreliable, but some institutions have actually protocol-driven titrations based on anti-factor Xa levels.<8>
Monitoring because that adverse effects has hemoglobin, hematocrit, platelet counting (every 2 to 3 days while on therapy), and an essential signs. If hemoglobin, hematocrit, or blood pressure drop, the possibility of hemorrhage should be investigated. If the platelet count falls below 100000/mm3, then the risk and benefit of proceeding heparin must be evaluated, and also an different anticoagulant is the encourage course. A hit 4-T score must be calculated as soon as HIT is suspected.<1>
When heparin toxicity occurs, protamine is recommended for reversal that heparin’s anticoagulant effect. Patients with life-threatening or significant bleeding or patients that undergo surgery might require protamine because that reversal. Neutralization the heparin occurs once protamine binding to the heparin through ionic properties. The protamine-heparin complicated is inactive, and also heparin is can not to act as an anticoagulant. Protamine management should be via slow IV push with no an ext than 50 mg end 10 minutes. Administration of protamine too rapidly has been linked with serious reactions, many commonly, hypotension, pulmonary edema, pulmonary vasoconstriction, and pulmonary hypertension. These effects additionally present through high doses of protamine, repeat doses of protamine, and also previous exposure or present exposure. Anaphylaxis can likewise occur with protamine administration. Because of heparin’s short half-life, time from administration of heparin is used to recognize the initial sheep of protamine necessary for reversal. Every 1mg that protamine administered neutralizes 100 devices of heparin. Heparin neutralization should take place within around 5 minute of protamine administration.<1>
Enhancing medical care Team Outcomes
Heparin enjoys vast use in the hospital setting for several different indications the require specific dosing and management routes. The use of heparin is a balance in between effective anticoagulation to treat or avoid thromboembolism and safety. Follow to ISMP (Institute for for sure Medication Practices), heparin is in the high-risk medication category that correlates with a multitude of patient safety and security errors and has the potential to cause far-reaching harm. Countless factors can contribute to potential errors, including dosing, monitoring, adverse effects, and dispensing logistics. To mitigate these potential errors, major safety surveillance organizations and also several clinical studies have actually been performed to delineate the most effective management criter for hospitals. Collectively, more information available about past errors have the right to influence practice to protect patients in the future.<9>
There are countless documented heparin errors attributed come manufacturer labeling and the countless stock vials and bags available. ~ fatal errors in the pediatric population, a labeling update was instituted in 2013 to display screen the total variety of units in every heparin vial. Limiting existing stock come a typical heparin bag solution and standard vial concentrations for automatically dispensing cabinets might also assist to avoid errors.
Dosing the heparin varies from indication, and dosage is by weight. Weight-based dosing offers another area because that potential errors through calculations. Whether the initial sheep is ordered together a unit/kilogram/hour price versus a unit/hour matches milliliters/hour deserve to significantly influence the initial dose. Present recommendations are that hospitals have a standard initiation protocol pushed by dosing data for each indication.
Monitoring aPTT levels throughout heparin treatment can additionally offer one area because that errors. Protocols space in place to instruct nursing employee on titration accuse based exclusively on the aPTT level. However, at the time, a brand-new rate should be calculated and also titrated based on the accuse on the protocol. This protocols have correlated with an increase in the quantity of time the the aPTT is in ~ the therapeutic range, which would enhance the outcomes of patients v thromboembolism.<10><11>
The heparin prescribing details states that dosing and titration regularly require an interprofessional dual check come ensure the exactly dose and indication. One examine evaluated the use of pharmacist monitoring of heparin the showed considerably fewer errors in the hospitals where pharmacologists were controlling anticoagulation.
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In conclusion, heparin is a high-risk medication that requires many safety obstacles to stop errors and also protect patients; this bring away an interprofessional team approach in the hospitals consists of clinicians (MDs, DOs, NPs, PAs), nurses, and also pharmacists.
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Mulloy B, Hogwood J, Gray E, bar R, web page CP. Pharmacology the Heparin and Related Drugs. Pharmacol Rev. 2016 Jan;68(1):76-141.
Hirsh J, Anand SS, Halperin JL, Fuster V., American heart Association. AHA scientific Statement: overview to anticoagulant therapy: heparin: a statement because that healthcare specialists from the American heart Association. Arterioscler Thromb Vasc Biol. 2001 Jul;21(7):E9-9.
Hemker HC. A century of heparin: past, present and also future. J Thromb Haemost. 2016 Dec;14(12):2329-2338.
Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia: diagnosis and also management update. Postgrad Med J. 2007 Sep;83(983):575-82.
De Waele JJ, van Cauwenberghe S, Hoste E, Benoit D, Colardyn F. The use of the triggered clotting time for security heparin therapy in critically ok patients. Intensive care Med. 2003 Feb;29(2):325-8.
Atallah S, Liebl M, Fitousis K, Bostan F, Masud F. Evaluation of the set off clotting time and also activated partial thromboplastin time because that the monitoring of heparin in adult extracorporeal membrane oxygenation patients. Perfusion. 2014 Sep;29(5):456-61.
Vandiver JW, Vondracek TG. Antifactor Xa level versus set off partial thromboplastin time for surveillance unfractionated heparin. Pharmacotherapy. 2012 Jun;32(6):546-58.
Barclay CA, Vonderhaar KJ, Clark EA. The advance of evidence-based care recommendations to improve the safe use of anticoagulants in children. J Pediatr Pharmacol Ther. 2012 Apr;17(2):155-8.
Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The weight-based heparin dosing nomogram compared with a "standard care" nomogram. A randomized regulated trial. Ann Intern Med. 1993 Nov 01;119(9):874-81.
Raschke RA, Gollihare B, Peirce JC. The efficiency of implementing the weight-based heparin nomogram as a exercise guideline. Arch Intern Med. 1996 Aug 12-26;156(15):1645-9.
Bond CA, Raehl CL. Pharmacist-provided anticoagulation administration in United states hospitals: death rates, length of stay, Medicare charges, bleeding complications, and also transfusions. Pharmacotherapy. 2004 Aug;24(8):953-63.