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2/22/24, 2:05 PM Realizeit for Student Introduction Drugs given to treat pulmonary embolism (PE) alter multiple aspects of the blood coagulation process. Anticoagulant drugs, which prevent formation of new clots and extension of already existing clots, do not dissolve clots that have already formed....

2/22/24, 2:05 PM Realizeit for Student Introduction Drugs given to treat pulmonary embolism (PE) alter multiple aspects of the blood coagulation process. Anticoagulant drugs, which prevent formation of new clots and extension of already existing clots, do not dissolve clots that have already formed. Thrombolytic drugs are used to dissolve thrombi and limit tissue damage in selected thromboembolic disorders. In this section, you will build on your knowledge of pulmonary emboli by incorporating the pharmacological treatments. Pulmonary Embolism The immediate objective is to stabilize the cardiopulmonary system in the patient with a hemodynamically unstable PE. A sudden increase in pulmonary resistance increases the work of the right ventricle, which can cause acute right-sided heart failure with cardiogenic shock. Emergent measures are initiated to improve respiratory and cardiovascular status (see Chapter 11 for discussion of management of the patient in shock). In patients with PE who do not demonstrate any cardiopulmonary instability (e.g., normotensive, no evidence of hypoxemia) immediate anticoagulation is indicated to prevent recurrence or extension of the thrombus and may continue for 10 days (Tapson, 2019). Long-term anticoagulation is also indicated up to 6 months following the PE and is critical in preventing recurrence of VTE. This duration may be extended indefinitely in patients who are at high risk for recurrence (Weinberger et al., 2019). In patients with stable PE, the initial anticoagulant selected may include an LMWH (e.g., enoxaparin), unfractionated heparin, or a direct oral anticoagulant (DOAC), such as a direct thrombin inhibitor (e.g., dabigatran), or a factor Xa inhibitor (e.g., fondaparinux, rivaroxaban, apixaban, edoxaban) (Tapson & Weinberg, 2020) (see Table 26-2). In select patients with PE who are hemodynamically stable, outpatient therapy can be started by administering the first dose in the emergency department or urgent care center and the remaining doses given at home. Although there are not specific selection criteria for outpatient treatment, the patient is usually at low risk of death, has no respiratory or hemodynamic compromise, does not require opioids for pain control, has no risk factors for bleeding, has no serious comorbid conditions, and has stable baseline mental status with a good understanding of the benefits and risks of treatment (Tapson, 2019). The ideal agent for outpatient administration is not empirically confirmed, although the DOACs are often prescribed. Long-term treatment options include warfarin and the DOACs. An LMWH may also be selected but is usually not prescribed for long-term therapy since it is given via a subcutaneous injection. Warfarin dosing requires regular blood draws for INR monitoring and has a higher bleeding risk, but it has long been the standard of care prior to the development of DOACs. An antidote (vitamin K) is available if the INR is high and there is a risk of bleeding. Warfarin does have interactions with several medications (see Chart 26-10) and has dietary restrictions. DOACs do not require regular blood test monitoring; however, they are more costly than warfarin. The choice of warfarin versus a DOAC is dependent upon risk of bleeding, cost, presence of comorbidities, and provider preference (The Joint Commission [TJC], 2019). Thrombolytic Therapy After emergency measures have been initiated, the treatment goal is to lyse (dissolve) the existing embolus and prevent new ones from forming. Thrombolytic therapy with t-PA or other agents such as reteplase (see Table 26-2) is used in treating unstable PE, particularly in patients who are severely compromised (e.g., those who are hypotensive and have significant hypoxemia despite oxygen supplementation) (Ouellette, 2019). Thrombolytic therapy lyses the thrombi or emboli quickly and restores hemodynamic functioning of the pulmonary circulation, thereby reducing pulmonary hypertension and improving perfusion, oxygenation, and cardiac output. However, the risk of bleeding is significant. Contraindications to thrombolytic therapy include having had a stroke within the past 2 months, other active intracranial processes, active bleeding, surgery within 10 days of the thrombotic event, recent labor and delivery, trauma, or severe hypertension. Consequently, thrombolytic agents are advocated only for PE affecting a significant area of blood flow to the lung and causing hemodynamic instability (Tapson & Weinberg, 2020). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk5… 1/19 2/22/24, 2:05 PM Realizeit for Student Before thrombolytic therapy is started, INR, aPTT, hematocrit, and platelet counts are obtained. Any anticoagulant is stopped prior to administration of a thrombolytic agent. During therapy, all but essential invasive procedures are avoided because of potential bleeding. After the thrombolytic infusion is completed (which varies in duration according to the agent used), maintenance anticoagulation therapy is initiated. Heparins Heparin is a pharmaceutical preparation of the natural anticoagulant produced primarily by mast cells in pericapillary connective tissue, and it is the prototype anticoagulant. Endogenous heparin is found in various body tissues, most abundantly in the liver and lungs. Exogenous heparin is obtained from bovine lung or porcine intestinal mucosa and standardized in units of biologic activity. See later for a discussion of low molecular weight heparins (LMWHs). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk5… 2/19 2/22/24, 2:05 PM Realizeit for Student https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk5… 3/19 2/22/24, 2:05 PM Realizeit for Student Pharmacokinetics It is necessary to give heparin intravenously or subcutaneously, because the gastrointestinal (GI) tract does not absorb the drug. After IV injection, the drug acts immediately. After subcutaneous injection, heparin acts within 20 to 30 minutes. Metabolism takes place in the liver and the reticuloendothelial system. Excretion, primarily in the form of inactive metabolites, occurs in the urine. Hemodialysis does not remove it. Action Heparin combines with antithrombin III (a natural anticoagulant in the blood) to inactivate clotting factors IX, X, XI, and XII; inhibit the conversion of prothrombin to thrombin, and prevent thrombus formation. After thrombosis has developed, heparin can inhibit additional coagulation by inactivating thrombin, preventing the conversion of fibrinogen to fibrin, and inhibiting factor XIII (fibrin-stabilizing factor). Other effects include inhibition of factors V and VIII and platelet aggregation. Use Prophylactically, patients at risk for certain disorders take low doses of heparin prophylactically to prevent DVT and pulmonary embolism. These disorders include the following: Major illnesses (e.g., acute myocardial infarction, heart failure, serious pulmonary infections, stroke) Major abdominal or thoracic surgery A history of thrombophlebitis or pulmonary embolism, including pregnant women Gynecologic surgery, especially in patients who have been taking estrogens or oral contraceptives or have other risk factors for DVT Restrictions such as bed rest or limited activity are expected to last longer than five days Therapeutically, patients receive heparin for management of acute thromboembolic disorders (e.g., DVT, thrombophlebitis, pulmonary embolism). In these conditions, the aim of therapy is to prevent further thrombus formation and embolization. Another use is in disseminated intravascular coagulation (DIC), a life-threatening condition characterized by widespread clotting, which depletes the blood of coagulation factors. The depletion of coagulation factors then produces widespread bleeding. The goal of heparin therapy in DIC is to prevent blood coagulation long enough for clotting factors to be replenished and thus be able to control hemorrhage. In addition, clinicians use heparin to prevent clotting during cardiac and vascular surgery, extracorporeal circulation, hemodialysis, and blood transfusions and in blood samples to be used in laboratory tests. Heparin does not cross the placental barrier and is not secreted in breast milk, making it the anticoagulant of choice for use during pregnancy and lactation. Key aPTT activated partial thromboplastin time DIC disseminated intravascular coagulation DVT deep vein thrombosis INR international normalized ratio PE pulmonary embolism PTCA percutaneous transluminal coronary angioplasty or atherectomy; sec, seconds Use in Children Little information about the use of anticoagulants in children is available. When children take heparin for systemic anticoagulation, weight is the basis for determination of dosage (~50 units/kg). It is essential to use extreme caution to ensure that the vial concentration of heparin is https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk5… 4/19 2/22/24, 2:05 PM Realizeit for Student correct. Fatalities in infants involving heparin overdoses have occurred. In addition, premature infants should not take heparin solutions containing benzyl alcohol as a preservative; fatal reactions have resulted. QSEN Alert: Technology Several major adverse events have resulted from the use of heparin, and it is classified as a high-alert drug. Nurses demonstrate consistent practic heightened individual awareness of the risks and by advocating for systems to account for human error such as bar coding and “smart” pumps. Eff safety and quality include special safeguards to reduce the risk of errors that may harm the patient. Use in Older Adults Older adults often have atherosclerosis and thrombotic disorders, including myocardial infarction, thrombotic stroke, and peripheral arterial insufficiency, for which they receive an anticoagulant drug. They are more likely than younger adults to experience bleeding and other complications associated with this therapy. With standard heparin, general principles for safe and effective use apply. With LMWHs, elimination may be delayed in older adults with renal impairment, and the drugs should be used cautiously. Use in Patients With Renal Impairment People with renal impairment may take heparin in usual dosages. However, the half-life of the drug may increase. Use in Patients With Hepatic Impairment Likewise, people with hepatic impairment may take heparin in usual dosages. However, the half-life of the drug may increase or decrease. Use in Patients With Critical Illness Heparin is often used in patients who are critically ill. However, the risk of bleeding is increased in the presence of other coexisting conditions. People who are critically ill have a high risk of DVT and pulmonary embolism, as well as a higher morbidity and mortality, including an increase in length of hospital stay, the need and duration of mechanical ventilation, and death. Effective prevention and treatment of thrombosis is necessary and typically includes LMWHs. In addition, it is essential to consider intermittent pneumatic compression devices and other measures to prevent DVT or pulmonary embolism. Use in Patients Receiving Home Care Patients may take standard heparin at home using the subcutaneous route, and use of LMWHs for home management of venous thrombosis has become standard practice. Daily visits by a home care nurse may be necessary if the patient or a family member is unable or unwilling to inject the medication. It is essential to take platelet counts before therapy begins and every 2 to 3 days during heparin therapy. If the platelet count falls below 100,000 platelets per microliter of blood or to less than half the baseline value, it is necessary to discontinue the heparin. Adverse Effects Hemorrhage is the major side effect of heparin therapy, hypersensitivity to the drug has occurred, and local irritation with subcutaneous injections of heparin can cause erythema and mild pain. Heparin-induced thrombocytopenia (HIT) (type II) is a potentially life-threatening complication of heparin administration, leading to a decrease in platelet count and detectable HIT antibodies. This condition occurs in 1% to 3% of people receiving heparin at therapeutic levels for 4 to 14 days, sometimes sooner in those who have previously received heparin. HIT is one of the most common immune-mediated adverse drug reactions. All patients exposed to any heparin at therapeutic or prophylactic doses or minute amounts in heparin flushes or on heparin-coated catheters, as well as those receiving LMWH, are at risk. If HIT occurs, it is necessary to discontinue all heparin and manage anticoagulation with a DTI such as argatroban. Contraindications Contraindications include GI ulcerations (e.g., peptic ulcer disease, ulcerative colitis), intracranial bleeding, dissecting aortic aneurysm, blood dyscrasias, severe kidney or liver disease, severe hypertension, polycythemia vera, and recent surgery of the eye, spinal cord, or brain. Caution is necessary in patients with hypertension, renal or hepatic disease, alcoholism, history of GI ulcerations, drainage tubes (e.g., nasogastric tubes, indwelling urinary catheters), threatened abortion, endocarditis, and any occupation with high risks of traumatic injury. Nursing Implications Preventing Interactions Many medications interact with heparin, increasing or decreasing its effect. Some herbs and foods increase the effects of the drug. No herbs or foods that decrease the effects of heparin have been identified. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk5… 5/19 2/22/24, 2:05 PM Realizeit for Student Drug Interactions: Heparin Drugs That Increase the Effects of Heparin Alteplase, direct thrombin inhibitors, platelet inhibitors Increase the risk of bleeding Antithrombin Increases pharmacologic effects Cephalosporins Lead to potential coagulopathies and risk of bleeding Penicillins (parenteral) Lead to altered platelet aggregation and increased risk of bleeding Warfarin May prolong and possibly invalidate the PT; if receiving both heparin and warfarin, draw blood for the PT at least 5 hours after the last IV heparin d Drugs That Decrease the Effects of Heparin Antihistamines, digoxin, nicotine, nitroglycerin (IV), tetracycline Decrease the anticoagulant effect IV, intravenous; PT, prothrombin time. Herb and Dietary Interactions: Heparin Herbs and Foods That Increase the Effects of Heparin Chamomile, garlic, ginger, ginkgo, ginseng, high-dose vitamin E Administering the Medication Traditional anticoagulants have two major limitations: a narrow therapeutic window of adequate anticoagulation without bleeding and a highly variable individual dose–response that requires monitoring by laboratory testing. Prescribers use the activated partial thromboplastin time (aPTT), which is sensitive to changes in blood clotting factors, except factor VII, to regulate heparin dosage. Thus, normal or control values of aPTT indicate normal blood coagulation, and therapeutic values of adequate anticoagulation indicate low levels of clotting factors and delayed blood coagulation. During heparin therapy, the aPTT should be maintained at approximately 1.5 to 2.5 times the control or baseline value. The normal control value is 25 to 35 seconds; therefore, therapeutic values of adequate anticoagulation are 45 to 70 seconds, approximately. With continuous IV infusion, blood for the aPTT may be drawn at any time; with intermittent administration, blood for the aPTT should be drawn approximately 1 hour before a dose of heparin is scheduled. It is not necessary to monitor aPTT with lowdose standard heparin given subcutaneously for prophylaxis of thromboembolism or with the LMWHs (e.g., enoxaparin). The nurse should be aware that heparin has disadvantages: parenteral injection is necessary, and the drug has a short duration of action, which means that there is a need for frequent administration. Assessing for Therapeutic Effects The nurse assesses for the absence or reduction of signs and symptoms of thrombotic disorders (e.g., less edema and pain with DVT, less chest pain and respiratory difficulty with pulmonary embolism, absence of uncontrolled bleeding). It is also necessary to ensure that aPTT values are within the therapeutic range. Assessing for Adverse Effects The nurse assesses the patient for signs of overt bleeding or HIT. Protamine sulfate, which is discussed in more detail later in the chapter, is an antidote for standard heparin and LMWHs. Protamine is typically given for bleeding that may not respond to merely withdrawing the heparin or when hemorrhaging is present. Patient Teaching Education related to bleeding risk is essential for patients receiving heparin. The nurse reinforces instructions for safe use of the drug and related anticoagulants, reminding patients to obtain laboratory tests, and teaching how to observe for signs and symptoms of bleeding. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk5… 6/19 2/22/24, 2:05 PM Realizeit for Student Patient Teaching Guidelines for Anticoagulants General Considerations Anticoagulant drugs are given to people who have had, or who are at risk of having, a heart attack, stroke, or other problems from blood clots. Fo thrombosis, which usually occurs in the legs, you are likely to be given heparin injections for a few days, followed by warfarin for long-term thera blood clot from getting larger, traveling to your lungs, or recurring later. All anticoagulants can increase the risk of bleeding, so you need to take safety precautions to prevent injury. To help prevent blood clots from forming and decreasing blood flow through your arteries, you need to reduce risk factors that contribute to card low-fat, low-cholesterol diet (and medication if needed) to lower total cholesterol to below 200 mg/dL and low-density lipoprotein cholesterol to b overweight; control of blood pressure if hypertensive; avoidance of smoking; stress reduction techniques; and regular exercise. To help maintain a steady level of anticoagulation with warfarin, do not change your intake of foods that are high in vitamin K, which decreases th broccoli, brussels sprouts, cabbage, cauliflower, chives, collard greens, kale, lettuce, mustard greens, peppers, spinach, tomatoes, turnips, and w To help prevent blood clots from forming in your leg veins, avoid or minimize situations that slow blood circulation, such as wearing tight clothing prolonged sitting or standing, and bed rest. For example, on automobile trips, stop and walk around every 1 to 2 hours; on long plane trips, exerc walk around when you can. Following instructions regarding these medications is extremely important. Too little medication increases your risk of problems from blood clot f bleeding. While taking any of these medications, you need regular medical supervision and periodic blood tests. The blood tests can help your health care maintain your safety. Notify your health care provider if you suddenly stop tobacco smoking, because this may result in a reduced clearance of warfarin. A dosage cha With enoxaparin, you need an injection, usually every 12 hours. You or someone close to you may be instructed in injecting the medication, or a v necessary. You need to take the drugs as directed. Avoid taking other drugs without the health care provider’s knowledge and consent, inform any health ca are taking an anticoagulant drug before any invasive diagnostic tests or treatments are begun, and keep all appointments for continuing care. With warfarin therapy, you need to avoid walking barefoot; avoid contact sports; use an electric razor; avoid injections when possible; and carry a bracelet (e.g., MedicAlert) stating the name of the drug and the health care provider’s name and telephone number. A routine blood test is necessary to ensure that your warfarin dose is appropriate. The results of this test determine your daily dose of warfarin. O blood tests are done less often (e.g., every 2 weeks). Report any sign of bleeding (e.g., excessive bruising of the skin, blood in urine or stool). If superficial bleeding occurs, apply direct pressure to th necessary. Self-Administration With enoxaparin, wash hands and cleanse skin to prevent infection; inject deep under the skin, around the navel, upper thigh, or buttocks; and c bruising occurs at the injection site, rubbing an ice cube over an area before the injection may be helpful. With warfarin as with all medications, take as prescribed. Because the prescriber may set a dosing schedule that could vary from one day to the written record of the date and the amount of medication taken. Other Drugs in the Class LMWHs are synthetic heparins, have smaller molecular structures, and efficiently inactivate factor Xa via antithrombin. The drugs are as effective as IV heparin in treating thrombotic disorders and provide a more predictable anticoagulant response at recommended doses. The drugs do not cross the placenta. Indications for their use include prevention or management of thromboembolic complications associated with surgery or ischemic complications of unstable angina and myocardial infarction. The currently available LMWHs, dalteparin (Fragmin) and enoxaparin (Lovenox), differ from standard heparin and each other and are not interchangeable. LMWHs are typically given subcutaneously in fixed or weight-based dosing without monitoring of blood coagulation. These characteristics simplify outpatient anticoagulant therapy and safety. Enoxaparin may be administered intravenously in specific situations but should not be given intramuscularly. The drugs are also associated with less thrombocytopenia than is standard heparin. However, monitoring of platelet counts during therapy is necessary. With significant bleeding, protamine sulfate may be considered although it does not completely neutralize LMWHs; clinical bleeding may be reduced. The Institute for Safe Medication Practices (ISMP) classifies the LMWHs as high-alert drugs because there is a possible risk of significant harm when the drugs are used in error. Fondaparinux (Arixtra) indirectly and selectively inhibits factor Xa by mechanisms identical to LMWHs but without affecting thrombin activity. As a synthetic pentasaccharide, the drug binds to antithrombin and is administered for prophylaxis of DVT in people undergoing hip or knee surgery. It is administered subcutaneously and has a longer half-life than LMWHs, necessitating only a once-daily dose. The ISMP classifies fondaparinux as a high-alert drug because there is a possible risk of significant harm when the drug is used in error. Fondaparinux has no effect on prothrombin time, aPTT, platelet aggregation, or bleeding time, so it does not require routine coagulation monitoring. As with other anticoagulants, bleeding is a concern particularly in patients with renal dysfunction, because fondaparinux is primarily eliminated by the kidneys. Currently, no agent for reversal of fondaparinux is available. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk5… 7/19 2/22/24, 2:05 PM Realizeit for Student Vitamin K Antagonists Warfarin (Coumadin) is the most commonly used oral anticoagulant and is the prototype vitamin K antagonist. Table 9.2 presents dosage information for warfarin. Pharmacokinetics Warfarin is well absorbed after oral administration. Administration with food may delay the rate but not the extent of absorption. The drug is highly bound to plasma proteins (98%), mainly albumin. Metabolism takes place in the liver. Excretion, primarily as inactive metabolites, occurs in the kidneys. Renal impairment does not affect drug metabolism but may decrease excretion of the drug. Action Warfarin acts in the liver to prevent synthesis of vitamin K–dependent clotting factors (i.e., factors II, VII, IX, and X). Similar to vitamin K in structure, warfarin therefore acts as a competitive antagonist to hepatic use of vitamin K. Conversely, vitamin K serves as the antidote for warfarin. Warfarin has no effect on circulating clotting factors or on platelet function, so the anticoagulant effects do not occur for 3 to 5 days after warfarin is started because clotting factors already in the blood follow their normal pathway of elimination. Use Warfarin is most useful in long-term prevention or management of venous thromboembolic disorders, including DVT, pulmonary embolism, and embolization associated with atrial fibrillation and prosthetic heart valves. In addition, warfarin therapy after myocardial infarction may decrease reinfarction, stroke, venous thromboembolism, and death. The smaller doses used now are equally effective as ones used formerly, with similar antithrombotic effects and decreased risks of bleeding. Use in Children After cardiac surgery, children receive warfarin to prevent thromboembolism, but there are no established doses and guidelines for safe, effective use. Accurate drug administration, close monitoring of blood coagulation tests, safety measures to prevent trauma and bleeding, avoiding interacting drugs, and informing others in the child's environment (e.g., teachers, babysitters, health care providers) are necessary. Use in Older Adults Warfarin metabolism may be altered in older adults. As patient age increases, a lower dose of warfarin is usually required to produce a therapeutic effect. Use in Patients With Hepatic Impairment Warfarin is more likely to cause bleeding in patients with hepatic disease because of decreased synthesis of vitamin K and decreased plasma proteins. In addition, only the liver eliminates warfarin; thus, it may accumulate in people with hepatic impairment, and dosage adjustment may be necessary. Use in Patients With Critical Illness Because the anticoagulant and antithrombotic effects of warfarin take several days to occur, patients who are critically ill require concurrent treatment with other anticoagulants, such as heparin or LMWHs. Heparin is usually continued until the international normalized ratio (INR) is the therapeutic range. Use in Patients Receiving Home Care For prevention of DVT, warfarin is usually self-administered at home, with periodic office or clinic visits for blood tests and other follow-up care. For home management of DVT, warfarin may be self-administered, but a nurse usually visits, performs a fingerstick INR, and notifies the prescriber, who then prescribes the appropriate dose of warfarin. Precautions to decrease risks of bleeding are necessary. However, the risk of bleeding has decreased in recent years because lower doses of warfarin are now used. In addition, medical conditions other than anticoagulation may cause bleeding during warfarin therapy. Adverse Effects The primary adverse effect associated with warfarin therapy is hemorrhage. Additionally, nausea, vomiting, abdominal pain, alopecia, urticaria, dizziness, and joint or muscle pain may occur. Contraindications Contraindications to warfarin include GI ulcerations, blood disorders associated with bleeding, severe kidney or liver disease, severe hypertension, and recent surgery of the eye, spinal cord, or brain. Caution is warranted in patients with mild hypertension, renal or hepatic disease, alcoholism, history of GI ulcerations, drainage tubes (e.g., nasogastric tubes, indwelling urinary catheters), or occupations with high risks of traumatic injury. Warfarin, a pregnancy category X medication, is contraindicated during pregnancy because it crosses the placenta https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk5… 8/19 2/22/24, 2:05 PM Realizeit for Student and may produce fatal fetal hemorrhage. The US Food and Drug Administration (FDA) has issued a BLACK BOX WARNING ♦ for warfarin because of the risk of its causing major or fatal bleeding. Nursing Implications Preventing Interactions Many medications and herbs interact with warfarin, increasing or decreasing its effect. Drug Interactions: Warfarin Drugs That Increase the Effects of Warfarin Acetaminophen (high dose), allopurinol, amiodarone Increase the anticoagulant effect Alteplase, androgens, aspirin and other nonsteroidal anti-inflammatory drugs, azithromycin, bismuth subsalicylate, carbamazepine, chloral hydra ciprofloxacin and other quinolone antibiotics, cisapride, clarithromycin, clofibrate, cotrimoxazole, direct thrombin inhibitors, heparin, macrolide an propranolol, quinidine, ranitidine, ritonavir, sertraline, simvastatin, sulfinpyrazone, sulfonamide, tamoxifen, tetracyclines, thyroid hormones, tricyc Increase the risk of bleeding Antithrombin Increases the pharmacologic effect Cephalosporins Result in potential coagulopathies and risk of bleeding Drugs That Decrease the Effects of Warfarin Chlordiazepoxide, haloperidol, intravenous lipid emulsions (contains soybean oil), isotretinoin, meprobamate, spironolactone Cause effects by various mechanisms Chlorthalidone May diminish warfarin's ability to cause blood clots to form Ethchlorvynol, trazodone Cause effects by unknown mechanism Etretinate May induce anticoagulant's hepatic microsomal enzyme Herb and Dietary Interactions: Warfarin Herbs and Foods That Increase the Effects of Warfarin Angelica, cat's claw, chamomile, chondroitin, cranberry juice, feverfew, garlic, ginkgo, goldenseal, grape seed extract, green tea, psyllium, turme Herbs and Foods That Decrease the Effects of Warfarin Ginseng, St. John's wort, vitamin K, foods high in vitamin K (broccoli, brussels sprouts, cabbage, cauliflower, chives, collard greens, kale, lettuce tomatoes, turnips, and watercress) Administering the Medication Vitamin K antagonists such as warfarin have a narrow therapeutic window of adequate anticoagulation without bleeding and a highly variable individual dose–response that requires monitoring by laboratory testing. QSEN Alert: Safety When warfarin therapy begins, daily evaluation of INR is necessary until a stable daily dose is reached (the dose that maintains the prothrombin tim and does not cause bleeding). A therapeutic PT value is approximately 1.5 times control, or 18 seconds. Thereafter, a patient’s INR values require c duration of oral anticoagulant drug therapy. If a prescriber changes the warfarin dose, more frequent INR measurements are necessary until a stable nurse should administer warfarin after ensuring that laboratory values are within therapeutic parameters. QSEN Alert: Safety https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk5… 9/19 2/22/24, 2:05 PM Realizeit for Student Institutions often have protocol for the therapeutic range of INR. In the absence of a protocol, the nurse holds the dose if the INR is above 3.0 and n Assessing for Therapeutic Effects As with heparin, the nurse assesses for the absence or reduction of signs and symptoms of thrombotic disorders (e.g., less edema and pain with DVT, less chest pain and respiratory difficulty with pulmonary embolism, absence of uncontrolled bleeding, hematuria or blood in the stools). It is also necessary to ensure that PT and INR values are within the therapeutic range. Assessing for Adverse Effects The nurse assesses for signs of bleeding, including excessive bruising of the skin, bleeding from IV sites or the gum line, and blood in urine or stool. As previously stated, vitamin K is the antidote for warfarin and may be administered if the INR level is five or more and signs of bleeding are present. Additionally, prothrombin complex concentrate (PCC), human (Kcentra) is used for urgent warfarin reversal with major or life-threatening hemorrhage. Patient Teaching The nurse reinforces instructions for safe use of warfarin, assists patients to obtain required laboratory tests, and teaches how to observe for signs and symptoms of bleeding. Direct Thrombin Inhibitors Both parenteral and oral DTIs are available. The original prototype of the bivalent type, hirudin, is not commercially available; however, its discovery led to the development through recombinant technology of parenteral derivatives, bivalirudin, desirudin, argatroban, and one oral DTI, dabigatran. Lepirudin, another derivative, was discontinued and is no longer on the market. In this discussion, the only oral DTI, dabigatran etexilate (Pradaxa), serves as the prototype. Table 9.2 presents dosage information for the DTIs. Pharmacokinetics Dabigatran etexilate is an inactive prodrug that is rapidly and hydrolyzed to dabigatran, its active form, in the body by plasma and hepatic esterases. The drug is excreted in the urine, and the systemic elimination is proportional to the glomerular filtration rate. Typically, the elimination half-life is 12 to 17 hours, which can be extended in the elderly and those with renal failure. Action As an inactive prodrug, dabigatran etexilate lacks anticoagulant activity. With conversion to the active form in the body, dabigatran has been shown to specifically and reversibly inhibit both free and fibrin-bound thrombin, the key enzyme in the coagulation cascade, thereby inhibiting coagulation. DTIs have no known antagonists. Given orally, the drug peaks in 1 hour. Use Dabigatran etexilate is used to prevent strokes and systemic embolization in individuals with nonvalvular atrial fibrillation. In addition, it is given for the treatment and prevention of deep venous thrombosis and pulmonary embolism. Therapeutic drug monitoring is not necessary. Use in Older Adults Dabigatran etexilate is identified in the Beers Criteria as a potentially inappropriate medication; it should be used with caution in older adults who have a creatinine clearance less than 30 mL/min or those 75 years and older. However, no dosage adjustment of dabigatran etexilate is needed in elderly patients with normal renal function. But the risk of bleeding, a common side effect, increases with age. Use in Patients With Renal Impairment Because dabigatran etexilate is cleared by the kidneys, it accumulates in patients with renal insufficiency, and dosage adjustments may be required based on creatinine clearance calculations. The use of the drug is not recommended in patients receiving hemodialysis. Adverse Effects The most common adverse effects associated with the administration of dabigatran etexilate are bleeding, dyspepsia, abdominal pain, gastritis, and anemia. Contraindications Contraindications include a known hypersensitivity to any of the components of dabigatran etexilate and in patients with active pathologic bleeding or with a mechanical prosthetic heart valve. Use in pregnancy and lactation requires caution. Nursing Implications https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk… 10/19 2/22/24, 2:05 PM Realizeit for Student The ISMP classifies dabigatran etexilate as a high-alert drug because of the possible risk of significant harm that results when it is used in error. Preventing Interactions Many medications interact with dabigatran etexilate, altering its effect. No foods decrease the drug's bioavailability, although the drug's peak plasma concentration is delayed 2 hours if taken with food. Drug Interactions: Dabigatran Etexilate Drugs That Increase the Effects of Dabigatran Etexilate Anticoagulants, apixaban, aspirin, antiplatelet agents (especially clopidogrel), collagenase, dasatinib, defarasirox, deoxycholic acid, edoxaban, h inflammatory agents, pentosanpolysulfate sodium, prostacyclin analogs, salicylates, sugammadex, sulfinpyrazone, thrombolytics, tibolone, ticag Increase the risk of bleeding Amiodarone, clarithromycin, dronedarone, ketoconazole P-glycoprotein/ABCB1 inhibitors, quinidine, verapamil May increase serum concentration Drugs That Decrease the Effects of Dabigatran Etexilate Antacids, atorvastatin, lumacaftor, P-glycoprotein/ABCB1 inducers, proton pump inhibitors May decrease serum concentration Estrogen derivatives, progestins May decrease the anticoagulant effects Herb and Dietary Interactions: Dabigatran Etexilate Herbs and Foods That Increase the Effects of Dabigatran Etexilate Alfalfa, anise, bilberry, omega-3 fatty acids, vitamin E Administering the Medication The drug capsules should be administered intact with a full glass of water without regard to meals. If the capsules are open or chewed, absorption is increased, and the risk of adverse drug effects is enhanced. Assessing for Therapeutic Effects The nurse assesses for the absence of signs and symptoms of thrombotic disorders, including HIT, and for laboratory values within normal range. A therapeutic range has not been established for tests of anticoagulant activity. Assessing for Adverse Effects The most common adverse effect associated with the administration of dabigatran etexilate is bleeding; therefore, assessing for signs of bleeding is a priority. Additionally, the nurse assesses for other adverse effects, including GI and hematologic effects. The anticoagulant effects of dabigatran can be reversed by idarucizumab (Praxbind). Patient Teaching Patients need to understand that stopping the drug without provider instruction could increase the risk of blood clots. Patients should notify other health care providers about taking dabigatran etexilate, particularly with spinal or epidural procedures that increase the risk of bleeding around the spine, because paralysis may occur. Direct Factor Xa Inhibitors Direct factor Xa inhibitors inactivate circulating and clot-bound factor Xa. Unlike fondaparinux, which acts indirectly, this class of drugs binds directly and, by doing so, inhibits the production of thrombin. These direct oral anticoagulants, along with dabigatran, are at least as https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk… 11/19 2/22/24, 2:05 PM Realizeit for Student effective as the vitamin K antagonists but are associated with less life-threatening bleeding. Currently, three orally acting direct factor Xa inhibitors are approved, rivaroxaban, apixaban, and edoxaban; no direct factor Xa inhibitors are available for intravenous infusion. Rivaroxaban serves as the prototype. Pharmacokinetics Rivaroxaban is rapidly absorbed and is highly bound to protein. The drug undergoes partial metabolism by CYP3A4 (an isozyme of the cytochrome P-450 system) and is excreted in the urine (36% as unchanged drug) and feces (7% as unchanged drug). Peak plasma levels are reached in 2 to 4 hours, and the half-life is 5 to 9 hours. Actions Rivaroxaban inhibits platelet activation and formation of fibrin clotting by inhibition of factor Xa in both intrinsic and extrinsic coagulation pathways. Use Rivaroxaban is used in the treatment and secondary prevention of venous thromboembolism and in stroke prevention in patients with nonvalvular atrial fibrillation. Use in Children The safety of rivaroxaban in children has not been established. Use in Older Adults According to the Beers Criteria, dosage adjustment is indicated in older adults with creatinine clearance between 30 and 50 mL/min. Rivaroxaban is a potentially inappropriate medication in older adults with a creatinine clearance less than 30 mL/min because of increased risk of bleeding. Use in Patients With Renal Impairment Rivaroxaban is metabolized in the kidney and the liver. Therefore, the drug should not be used in individuals with a creatinine clearance of less than 15 mL/min; with delayed excretion of the drug, there may be increased risk of bleeding. Use in Patients With Hepatic Impairment Rivaroxaban should not be used in individuals with moderate to severe hepatic impairment. Use in Patients With Critical Illness Individuals who are critically ill may have complications that may necessitate the use of rivaroxaban, including treatment and secondary prevention of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. The critically ill have a high risk of DVT and pulmonary embolism, as well as an increased risk of bleeding in the presence of other coexisting conditions, particularly those involving the kidneys or liver. Use in Patients Receiving Home Care Rivaroxaban for home use following knee or hip surgery for the prevention of venous thrombosis or management of nonvalvular atrial fibrillation has become common practice as the drug requires no INR monitoring. Additionally, rivaroxaban has fixed dosing schedule, a lower bleeding risk, and few drug interactions as compared to heparin. Regular home care by the nurse, particularly in the older adult, can enhance the safe use of the drug and recognition of signs and symptoms of bleeding before serious bleeding occurs. Adverse Effects Bleeding is the most common adverse effect of rivaroxaban, and this risk increases if the is drug taken with other agents that alter hemostasis. Intracranial, gastric, and retinal bleeding has been reported. Additionally, the possibility of spinal or epidural hematoma exists in patients undergoing epidural anesthesia or spinal puncture with procedures or trauma that can lead to permanent paralysis. Dosage adjustment is recommended with anticipated procedures involving the spine. Contraindications Contraindications to rivaroxaban include a known hypersensitivity to the drug. The drug appears unsafe during pregnancy; it is associated with pregnancy-related hemorrhage and risk to the fetus. Benefits of therapy in pregnancy should outweigh risks. Nursing Implications Preventing Interactions https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk… 12/19 2/22/24, 2:05 PM Realizeit for Student Numerous drugs and some herbs are known to interact with rivaroxaban, increasing or decreasing its effect. Drug Interactions: Rivaroxaban Drugs That Increase the Effects of Rivaroxaban Anticoagulants, apixaban, aspirin, antiplatelet agents, collagenase, dasatinib, edoxaban, hemin, ibrutinib, limaprost, nonsteroidal anti-inflammato prostacyclin analogues, salicylates, sugammadex, thrombolytics, tibolone, tipranavir, vorapaxar, vitamin E Increase the risk of bleeding Clarithromycin, osimertinib May increase serum concentration Drugs That Decrease the Effects of Rivaroxaban Bosentan, CYP3A4 inducers, deferasirox, estrogen derivatives, fusidic acid, nevirapine, progestins, siltuximab May decrease serum concentration Estrogen derivatives, progestins May decrease the anticoagulant effects Herb and Dietary Interactions: Rivaroxaban Herbs and Foods That Increase the Effects of Rivaroxaban Alfalfa, anise, bilberry, grapefruit juice Herbs and Foods That Decrease the Effects of Rivaroxaban St. John's wort Administering the Medication Rivaroxaban is generally given at a fixed-dose. Although 10-mg tablets can be administered without regard to food, 15- and 20-mg tablets should be taken with food. The drug should be administered with the evening meal for nonvalvular atrial fibrillation. Assessing for Therapeutic Effects The nurse should assess for absence of DVT or other unanticipated clotting. No routine monitoring of INR or other coagulation parameters is required. Assessing for Adverse Effects As with all anticoagulants, the nurse should observe for signs of bleeding, for any change in baseline renal or hepatic function that could enhance the risk of bleeding, and for concurrent administration of drugs known to interact with rivaroxaban. Patient Teaching Education related to bleeding risk is essential for patients receiving rivaroxaban. The nurse reinforces instructions for safe use of the drug and related anticoagulants and teaching how to observe for signs and symptoms of bleeding. Patients should notify other health care providers about taking rivaroxaban, particularly before spinal or epidural procedures that increase the risk of bleeding around the spine, because paralysis may occur. Other Drugs in the Class Apixaban (Eliquis) and edoxaban (Savaysa) are additional oral direct factor Xa inhibitors. A major advantage of these drugs is fixed dosing, less variability in drug effect for a given dose, and the lack of required monitoring. Although the overall risks of bleeding are similar to vitamin K antagonists, the risks for intracranial bleeding are less with the direct factor Xa inhibitors. These drugs carry the same risks in spinal or epidural procedures as rivaroxaban; the risk of paralysis may occur. As with rivaroxaban, and other anticoagulants, premature discontinuation of the direct factor Xa inhibitors without adequate alternative anticoagulation increases the risk of thrombosis. All drugs in the class pose a risk of hemorrhage and are classified as high-alert drugs by the ISMP because the drugs carry a heightened risk of causing significant patient harm when used in error. No drug that reverses the effects of the direct factor Xa inhibitors is currently available, and the drugs are not removed with dialysis. Should a patient experience hemorrhaging, oral activated charcoal may be given if the timing of administration would prove beneficial. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk… 13/19 2/22/24, 2:05 PM Realizeit for Student Thrombolytic Drugs Alteplase is the prototype recombinant tissue plasminogen activator (rtPA). However, tenecteplase is the thrombolytic of choice in the United States and Canada; it is just as effective as alteplase but results in a decreased risk of noncerebral bleeding. Pharmacokinetics Administration of alteplase is by IV infusion. Metabolism occurs predominately in the liver. Following discontinuation of the infusion, more than 50% of the drug is cleared, with more than 80% clearance within 10 minutes. Excretion takes place in the urine. Whether alteplase crosses the placenta or is excreted into breast milk is unknown. Action Alteplase is a protein that lyses unwanted fibrin blood clots by catalyzing the conversion of plasminogen to plasmin. Use Indications for alteplase include lysis of acute coronary arterial thromboembolism associated with evolving transmural myocardial infarction or acute pulmonary thromboembolism. Clinicians also considered it as first-line therapy for the treatment of acute ischemic stroke in selected people. Use in Older Adults Caution is warranted in older patients (65–80 years of age). Alteplase is not recommended in people older than 80 years of age. Use in Patients With Hepatic Impairment Caution is necessary in patients with significant hepatic impairment. Adverse Effects As with other anticoagulants and antiplatelet agents, bleeding is the main adverse effect of alteplase. To minimize this risk, it is important to select recipients carefully, avoid invasive procedures when possible, and omit anticoagulant or antiplatelet drugs (except for aspirin) while thrombolytics are being given. The major risk of rtPA therapy is symptomatic brain hemorrhage, and when rtPA treatment is chosen, the prescriber should obtain informed consent signed by the stroke patient or family member. There is a 3% mortality rate and a 6% to 8% risk of symptomatic hemorrhage associated with its use. In rtPA overdose, aminocaproic acid serves as an antidote. Contraindications Due to an increased risk of bleeding, alteplase is contraindicated in patients with uncontrolled severe hypertension, aneurysm, arteriovenous malformation, known coagulopathy or internal bleeding, intracranial or intraspinal surgery or trauma within the past three months, intracranial mass, recent major surgery, or current use of oral anticoagulants. Alteplase can increase the risk of cerebral embolism in people with atrial fibrillation or atrial flutter. QSEN Alert: Evidence-Based Practice The likelihood of improved neurologic outcomes is greater with earlier treatment of an acute ischemic stroke with intravenous recombinant tissue p thrombectomy. In 2018, the American Heart Association (AHA)/American Stroke Association (ASA) Guidelines for the Early Management of Patients the previous recommended upper time limit of 3 to 4.5 hours after onset of symptoms. In a review of six clinical trials of patients who underwent me suggested that the therapeutic benefit of thrombolytic treatment is greatest when given very early after ischemic stroke and declines throughout the treatment of acute ischemic stroke can maximize a patient's return to baseline neurologic function. Teaching of high-risk patients should emphasize help as soon as neurologic symptoms develop to increase the magnitude of benefit from early treatment. Nursing Implications Only experienced personnel in an emergency department, a critical care unit, or diagnostic/interventional setting with cardiac and other monitoring devices in place should perform thrombolytic therapy. It is necessary to minimize intramuscular injections in patients who are receiving systemic thrombolytic therapy, because bleeding, bruising, or hematomas may develop. The nurse assesses patients for cardiac dysrhythmias, including sinus bradycardia, premature ventricular contractions, and ventricular tachycardia resulting from reperfusion following coronary thrombolysis. He or she must promptly identify and report any evidence of bleeding. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk… 14/19 2/22/24, 2:05 PM Realizeit for Student Preventing Interactions Many medications and herbs interact with alteplase, increasing its effect. No herbs or foods appear to decrease its effect. Drug Interactions: Alteplase Drugs That Increase the Effects of Alteplase Aspirin or other salicylates, abciximab, cilostazol, clopidogrel, dalteparin, dipyridamole, enoxaparin, eptifibatide, fondaparinux, heparin, nonstero tirofiban, warfarin Increase the risk of bleeding Herb and Dietary Interactions: Alteplase Herbs and Foods That Increase the Effects of Alteplase Cat's claw, dong Quai, evening primrose, feverfew, garlic, ginkgo, ginseng, green tea, horse chestnut, red clover Administering the Medication Before a thrombolytic agent is begun, it is essential to check INR, aPTT, platelet count, and fibrinogen to establish baseline values and to determine whether a blood coagulation disorder is present. Two or three hours after thrombolytic therapy is started, the nurse must ensure that the fibrinogen level is measured to determine that fibrinolysis is occurring. Alternatively, he or she can check INR or aPTT for increased values because the breakdown products of fibrin exert anticoagulant effects. During and following alteplase administration, the nurse monitors blood pressure frequently and ensures that it is well controlled. The ISMP lists alteplase as a high-alert drug because of its potential risk of causing significant harm when used in error. Administration is IV as a bolus injection or infusion. The nurse administers all infusions using an IV infusion device. It is necessary to reconstitute alteplase as indicated and not to shake it. Assessing for Therapeutic Effects The goal is to minimize total ischemic time and restore blood flow. Therapeutic effects include For cardiac revascularization—stabilization of the patient, reversal of symptoms, stabilization of cardiac rhythm, decrease of the STsegment elevations by 50% of the initial height, and absence of bleeding complications For cerebral revascularization—stabilization of the patient, reversal of symptoms, normal mentation, and absence of bleeding complications Assessing for Adverse Effects The nurse assesses for evidence of bleeding. In addition, it is necessary to determine that the condition leading to initiation of thrombolytic therapy is reversed and that there is a return of function. If bleeding does occur, it is most likely from a venipuncture or invasive procedure site, and local pressure may control it. If bleeding cannot be controlled or involves a vital organ, it is necessary to stop the thrombolytic drug and replace fibrinogen with whole blood plasma or cryoprecipitate. Giving aminocaproic acid or tranexamic acid may also be appropriate. When the drugs are used in acute myocardial infarction, cardiac dysrhythmias may occur when blood flow is reestablished. Therefore, antidysrhythmic drugs should be readily available. Patient Teaching The nurse instructs patients and significant others regarding the purpose of the drug, the underlying condition, and the increased risk of bleeding. Patients should take special care brushing their teeth to reduce bleeding at the gum line. Discharge planning emphasizes managing the complications of the underlying disease (myocardial infarction or stroke) and seeking timely professional help if symptoms recur. Other Drugs in the Class All of the available agents are effective with recommended uses. Thus, the choice of a thrombolytic agent depends mainly on risks of adverse effects and costs. All of the drugs may cause bleeding. Tenecteplase (TNKase) is the other rtPA drug used mainly in acute myocardial infarction to dissolve clots obstructing coronary arteries and reestablish perfusion of tissues beyond the thrombotic area. The most common adverse effect is bleeding, which may be internal (e.g., intracranial, GI, genitourinary) or external (e.g., venous or arterial https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk… 15/19 2/22/24, 2:05 PM Realizeit for Student puncture sites, surgical incisions). Tenecteplase causes less noncerebral bleeding than alteplase, is easier to administer, and lacks antigenicity. Streptokinase, the original thrombolytic enzyme, and urokinase, a naturally occurring product, are no longer available in the United States. These drugs have been removed from the market because they were not fibrin specific, which enhanced the risk of bleeding. In addition, reteplase has also been removed from the market, but attempts by the manufacturer to seek new drug approval from the FDA are ongoing. Drugs Used to Control Bleeding Reversal of Heparin and Low Molecular Weight Heparins Protamine sulfate is an antidote for standard heparin and LMWHs. Because heparin is an acid and protamine sulfate is a base, protamine neutralizes heparin activity. Protamine dosage depends on the amount of heparin administered during the previous four hours. Each milligram of protamine neutralizes approximately 100 units of heparin or dalteparin and 1 mg of enoxaparin. The FDA has issued a BLACK BOX WARNING ♦ with the use of protamine sulfate because of the risk of severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension with its use. A single dose should not exceed 50 mg because of the risk of severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension with its use. The drug is given by slow IV infusion over at least 10 minutes (to prevent or minimize adverse effects of hypotension, bradycardia, and dyspnea). Its effects occur immediately and last for approximately 2 hours. A second dose may be required because heparin activity lasts approximately 4 hours. Severe hypotensive and anaphylactoid reactions may result from protamine administration. Thus, the drug should be given in settings with equipment and personnel for resuscitation and management of anaphylactic shock. Reversal of Vitamin K Antagonists Vitamin K (Mephyton) is an antidote for warfarin overdosage. An oral dose of 10 to 20 mg usually stops minor bleeding and returns the INR to a normal range within 24 hours. INR serum levels less than 5 with no significant bleeding may be managed with withholding of the warfarin based on protocols; INR levels greater than 5 may require the use of oral vitamin K. Decisions about management of a patient with an INR above the therapeutic range are based on the degree of elevation of the INR serum level, the clinical status of the patient with regard to bleeding, thrombogenic potential, as well as risk factors such as age and presence of concurrent disease. Urgent reversal of warfarin overdosage in adults with acute major bleeding or in need of emergent surgery can be accomplished with PCC (Kcentra). The drug, collected from pooled human plasma, contains therapeutic levels of all four vitamin K–dependent coagulation factors (II, VII, IX, and X) and the antithrombotic proteins C and S. Dosing is based on the most current predose INR value and body weight. The drug should be administered concurrently with vitamin K to maintain factor levels once the effects of PCC have diminished. Resumption of anticoagulation should occur once the risk of thromboembolism outweighs the risk of acute bleeding. Unlike plasma, PCC does not require blood group typing or thawing, so it can be administered more quickly than frozen plasma and at recommended doses is administered in a significantly lower volume than plasma. The FDA has issued a BLACK BOX WARNING ♦ with the use of PCC because reversal of an anticoagulant state in patients being treated with vitamin K–antagonist therapy may predispose the patient to a thromboembolic complication. Benefits of reversal must be weighed against potential risk of a subsequent thromboembolic event. Reversal of Oral Direct Thrombin Inhibitors Idarucizumab (Praxbind), a humanized monoclonal antibody fragment, is the antidote for dabigatran, currently the only oral DTI. The drug reverses the anticoagulant effects of dabigatran for uncontrolled or life-threatening bleeding or for emergency surgery or procedures. In adults, the drug is given intravenously, administered as two separate doses no more than 15 minutes apart. The drug’s half-life is about 45 minutes in individuals with normal renal function and the duration of the effect is about 24 hours. However, if coagulation parameters reelevate within 12 hours of administration, a second dose may be considered. Reversing the effects of dabigatran will subject a patient to an elevated risk of thrombosis, so it is necessary to resume anticoagulant therapy after 24 hours of administering idarucizumab, as appropriate. Reversal of Thrombolytic Agents https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk… 16/19 2/22/24, 2:05 PM Realizeit for Student Aminocaproic acid (Amicar) and tranexamic acid (Cyklokapron) are used to stop bleeding caused by overdoses of thrombolytic agents. Aminocaproic acid also may be used in other bleeding disorders caused by hyperfibrinolysis (e.g., in cardiac surgery, blood disorders, hepatic cirrhosis, prostatectomy, neoplastic disorders). Tranexamic acid also is used for short periods (2–8 days) in patients with hemophilia to prevent or decrease bleeding from tooth extraction or menorrhagia. Depending on the indication for administration, aminocaproic acid may be infused as a loading dose over 15 to 60 minutes to reduce the risk of hypotension and dysrhythmias with a rapid bolus. A continuous infusion may be required. Tranexamic acid can be administered orally or intravenously. Tablets should be swallowed whole. A rapid IV bolus can be given, but the drug is usually administered diluted and administered intravenously over 5 to 30 minutes. Dosage of the drug should be reduced in the presence of moderate or severe renal impairment. Example Video: YouTube: Pulmonary Embolism | Nursing Care for PE Patient for NCLEX RNpedia. Anticoagulants, Antiplatelets, Thrombolytics Drugs Nursing Considerations & Management. Retrieved from: https://www.rnpedia.com/nursing-notes/pharmacology-drug-studynotes/anticoagulants-antiplatelets-thrombolytics-drugs/ Straight Nursing. Blood Thinners: What You Need to Know. Retrieved from: https://www.straightanursingstudent.com/blood-thinners/ Try Its Question: A client is receiving thrombolytic treatment for a pulmonary embolism. Which of the following is the most frequent undesirable effect of this treatment? A: Irregular dysrhythmias B: Nausea, vomiting, and anorexia C: Anaphylactic reaction https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk… 17/19 2/22/24, 2:05 PM Realizeit for Student D: Internal and superficial bleeding Answer: D: Bleeding, both internal and superficial, as well as intracranial, is the most common undesirable effect of thrombolytic therapy. The other options list possible adverse effects of thrombolytic drugs, but they are not the most common effects. Summary For people with massive pulmonary embolism, the goal of fibrinolytic therapy is to restore pulmonary artery perfusion. Thrombolytic drugs are used to dissolve thrombi and limit tissue damage in selected thromboembolic disorders. Anticoagulant drugs, which prevent formation of new clots and extension of already existing clots, do not dissolve clots that have already formed. Anticoagulant therapy accompanies thrombolytic therapy either before or following initiation. All of the medications given to treat PE modify and/or interrupt the blood coagulation process, thereby placing clients at a high risk of bleeding. Bleeding precautions should be taken and serum laboratory studies must be closely monitored. References Agency for Healthcare Quality and Research (AHRQ), www.ahrq.gov American Association for Respiratory Care (AARC), www.aarc.org American College of Chest Physicians (ACCP), www.chestnet.org American Lung Association, www.lung.org American Thoracic Society (ATS), www.thoracic.org Baglin, T., Hillarp, A., Tripodi, A., Elalamy, I., Bueller, H., & Ageno, W. (2013). Measuring oral direct inhibitors of thrombin and factor Xa: A recommendation from the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Journal of Thrombosis and Haemostasis, 11(4), 756–760. Karch, A. M. (2014). Lippincott’s nursing drug guide. Philadelphia, PA: Lippincott Williams & Wilkins. Kearon, C., Akl, E. A., Comerota, A. J., Prandoni, P., Bounameaux, H., Goldhaber, S. Z., et al. (2012). Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 141(2 Suppl), e419S–e494S. Porth, C. M. (2013). Pathophysiology: Concepts of altered health states (9th ed.). Philadelphia, PA: Lippincott Williams & Wilkins. Centers for Disease Control and Prevention (CDC), National Institute for Occupational Safety and Health and Safety (NIOSH), www.cdc.gov/niosh/ Hull, R. D., & Lip G. Y. H. (2016). Venous thromboembolism: Anticoagulation after initial management. UpToDate. Last updated April 12, 2016. Retrieved on 6/7/2016 at: www.uptodate.com/contents/venous-thromboembolism-anticoagulation-after-initial-management? source=search_result&search=Venous+thromboembolism%3A+Anticoagulation+after+initial+management&selectedTitle=1∼150 Kearon, C., Aki, E. A., Omelas, J, et al. (2016). Antithrombotic therapy for VTE diseases: Chest guideline, Chest, 2015.11.026 National Heart, Lung, and Blood Institute (NHLBI), www.nhlbi.nih.gov Respiratory Nursing Society (RNS), www.respiratorynursingsociety.org Tapson, V. F. (2016). Overview of the treatment, prognosis, and follow-up of acute pulmonary embolism in adults. UpToDate. Last updated April 7, 2016. Retrieved on 6/7/2016 at: www.uptodate.com/contents/overview-of-the-treatment-prognosis-and-follow-up-of-acutepulmonary-embolism-in-adults?source=search_result&search=Tapson+Overview+of+the+treatment%2C+prognosis%2C+and+followup+of+acute+pulmonary+embolism+in+adults&selectedTitle=1∼150 https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk… 18/19 2/22/24, 2:05 PM Realizeit for Student Weinberger, S. E., Cockrill, B. A., & Mandel, J. (2014). Principles of pulmonary medicine (6th ed.). Philadelphia, PA: Elsevier Saunders. Review Anticoagulant drugs are given to prevent formation of new clots and extension of clots already present. Thrombolytic agents are used to dissolve thrombi and limit tissue damage in selected thromboembolic disorders. Heparin anticoagulant effect begins immediately with IV administration. When anticoagulation is required during pregnancy, heparin is used because it does not cross the placenta. Currently available LMWHs (dalteparin, enoxaparin) differ from standard heparin and each other and are not interchangeable. During heparin therapy, the aPTT should be maintained at approximately 1.5 to 2.5 times the control or baseline value. Monitoring of aPTT is not necessary with low-dose standard heparin given subcutaneously for prophylaxis of thromboembolism or with the LMWHs. Protamine sulfate is the antidote for standard heparin and LMWHs. The FDA has issued a BLACK BOX WARNING with the use of protamine sulfate because of the risk of severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension with its use. Warfarin dosage is regulated according to the INR (derived from prothrombin time [PT]), for which a therapeutic value is between 2.0 and 3.0 in most conditions; a therapeutic PT value is approximately 1.5 times the control, or 18 seconds. Vitamin K (Mephyton) and prothrombin complex concentrate can reverse the effects of warfarin. The FDA has issued a BLACK BOX WARNING with warfarin because of its risk of causing major or fatal bleeding. The FDA has issued a BLACK BOX WARNING with the use of prothrombin complex concentrate because reversal of an anticoagulant state in patients being treated with vitamin K–antagonist therapy may predispose the patient to a thromboembolic complication. The FDA has issued a BLACK BOX WARNING with the use of clopidogrel in people who are reduced metabolizers of the drug; these people may remain at risk for heart attack, stroke, and cardiovascular death because of the drug's reduced effect on platelet function. The FDA has issued a BLACK BOX WARNING with the use of cilostazol as it is contraindicated in patients with heart failure of any severity. When the thrombolytic agents are used in acute myocardial infarction, cardiac dysrhythmias may likely occur when blood flow is reestablished; antidysrhythmic drugs should be readily available. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zSNYYvz6N%2bxRwegtqPK%2fJ7UsPJxuq7nE1D4sTAvq22Nk… 19/19