Oral Anticoagulant Therapy

Dabigatran metabolism

Not metabolized by the hepatic enzyme system

Which teaching would the nurse provide to Ms. Turner regarding concomitant use of aspirin and dabigatran?

"NSAIDs, including aspirin, can increase the risk for bleeding."

In which time frame does warfarin reach its peak level?

1.5 to 3 days

Dabigatran distribution

35% protein bound

Rivaroxaban dustribution

95% protein bound

What percentage of warfarin is bound to protein?

99%

Rivaroxaban absorption

Bioavailability is 80%-100%. Food increases bioavailability.

Pre-Administration Assessment for Dabigatran and Rivaroxaban: identify high- risk patients

Children: Safety and efficacy is not established in those younger than 18 years. Older adult patients with severe renal impairment (creatinine clearance 15 to 30 mL). Older adult patients who are concurrently using medications that increase the risk for bleeding.

Dabigatran absorption

Absolute bioavailability is 3%-7% after oral administration. Can be taken without regard to food. Although food can slow absorption, it does not reduce the absorption amount of the drug.

Contraindications with Dabigatran and Rivaroxaban

Active major bleeding, patients with mechanical prosthetic heart valves

Side Effects and Adverse Effects of Dabigatran and Rivaroxaban bleeding

Adverse effects related to dabigatran and rivaroxaban are associated with bleeding risk, similar to other anticoagulants. Initiation of bleeding is an indication to discontinue the medication; however, dabigatran and rivaroxaban are less likely than warfarin to cause hemorrhagic stroke and/or other major bleeding events.

Warfarin distribution

Almost 99% of the drug binds to albumin in the blood. The unbound drug can cross cellular membranes, including the placenta and milk-producing glands.

Interactions with Dabigatran and Rivaroxaban drug

Rifampin may decrease drug concentrations. Antacids and proton pump inhibitors may decrease effect of the drugs. Antiplatelets, NSAIDs, other anticoagulants, and thrombolytics may increase risk for bleeding.

A patient taking warfarin asks the nurse what should be done first if bleeding occurs from a small laceration on the arm. Which response would the nurse make?

Apply firm, direct pressure to the cut." If bleeding occurs on the body, firm, direct pressure should be applied to the cut for 5 to 10 minutes. If bleeding does not stop, then the patient should seek emergency health care

Side Effects and Adverse Effects of Dabigatran and Rivaroxaban GI disturbances

As with many other drugs, GI disturbances, such as dyspepsia and/or gastritis-like symptoms, are common side effects. Other common GI symptoms include abdominal pain, esophagitis, and gastroesophageal reflux. Severe disturbances can cause erosive or hemorrhagic gastritis, which would be adverse effects.

For the patient taking an anticoagulant, thorough assessment of the patient by the nurse is vital. The nurse should be aware of the possibility of bleeding-associated risks and plan care accordingly.

Assess for any sign of bleeding (hematuria, melena, bleeding from gums, petechiae, and bruising). Do not obtain blood pressure in lower extremities (possible deep vein thrombosis). Assess for decrease in blood pressure, increase in pulse rate, complaints of abdominal pain, and diarrhea. Obtain a PTT, PT, and platelet count. Question for increase in discharge during menses. Monitor for hematoma. Use care in removing any dressing and tape. Use caution when performing any invasive procedure. Prepare to administer idarucizumab, a reversal drug for dabigatran, for emergent surgery, or for life-threatening or uncontrolled bleeding. Prepare to administer inactivated factor Xa, a reversal drug for rivaroxaban, for uncontrolled or life-threatening bleeding.

Pre-Administration Assessment for Dabigatran and Rivaroxaban determine baseline

Assess the patient for any ecchymosis, petechiae, or bleeding. Assess CBC, including platelet count. Check PT and PTT. Obtain baseline blood pressure. Assess if the patient has any GI problems that would increase the risk for side effects associated with dabigatran.

Dabigatran and rivaroxaban have the same indications, which include the following:

Atrial fibrillation: Prevent stroke and embolism in patients who have nonvalvular atrial fibrillation. Knee or hip replacement: Prevention of VTE and PE following knee or hip replacement surgery. Deep vein thrombosis/pulmonary embolus. Prevention of deep vein thrombosis/pulmonary embolus.

Rivaroxaban mechanism of action

Rivaroxaban selectively inhibits coagulation factor Xa in the clotting cascade. When factor Xa is inhibited, prothrombin is unable to convert to thrombin.

Rivaroxaban Pharmacodynamic Profile

RivaroxabanOnset: UnknownPeak: 2-4 hoursDuration: UnknownHalf-Life: 5-9 hours

Warfarin mechanism of action

Clotting factors, including prothrombin, require the active form of vitamin K to make them. Warfarin prolongs clotting time by interfering with the synthesis of vitamin K-dependent clotting factors II, VII, IX, and X. It also depletes functional vitamin K reserves. Anticoagulant effects of warfarin begin after 24 hours, but a steady state may take 3 to 4 days. With any dosage change, the process is repeated. It also takes 4 to 5 days after discontinuation for warfarin to clear from the body.

Determine Baseline Data for Warfarin

Collect a complete medical history, including all current drugs and alternative therapies (prescription, herbal, and over the counter [OTC]). Discuss history that is associated with abnormal clotting, such as severe alcoholism or liver or renal disease. Perform a full physical assessment. Be especially aware of the presence of bleeding or bruising. Obtain baseline laboratory values, including a complete blood count (CBC) and coagulation levels (specifically PT and INR). Adhere to organizational policy for administration of high-alert medications.

Common side effects of warfarin

Common side effects include bleeding and GI distress, such as nausea and abdominal cramps. Bleeding is associated with the drug dosage and patient's comorbid conditions. Adverse drug effects include intracranial and retroperitoneal bleeding and hypersensitivity reaction (dermatitis, urticaria), especially in those sensitive to aspirin.

NOACs include direct thrombin and direct factor Xa inhibitors. These drugs are used to treat the following:

Complications due to atrial fibrillation in which the atria are not pumping blood in an organized manner; these complications can result in blood clots that can be ejected into the systemic circulation, causing a stroke. Venous thromboembolism (VTE) in which blood clots form in the venous system (usually the lower leg) because of immobility or venous dysfunction and are at risk for breaking loose and entering the pulmonary system (pulmonary emboli), resulting in a potentially life-threatening situation. Any other condition that requires long-term alteration in the coagulation system to reduce the risk for clotting-related dysfunction.

Warfarin disadvantages

Delayed onset Frequent blood tests required No fixed dosage; adjusted according to PT/INR Many drug-food interactions

Dabigatran mechanism of action

Dabigatran inhibits thrombin that is free in the blood and thrombin that is bound to a clot. When thrombin is inhibited, it stops the conversion of fibrinogen into fibrin and prevents the activation of special clotting factors (specifically factor XIII). This process prevents clots from occurring.

Dabigatran Pharmacodynamic Profile

DabigatranOnset: UnknownPeak: 1 hourDuration: UnknownHalf-Life: 12-17 hours

Warfarin advantages

Decades of clinical experience Precise dosage timing not critical because of long duration

Warfarin mechanism

Decreased synthesis of vitamin K-dependent clotting factors (factors II, VII, IX, X, and prothrombin)

Rivaroxaban mechanism

Direct inhibition of factor Xa. Prevents the conversion of prothrombin to thrombin

Dabigatran mechanism

Direct inhibition of thrombin. Prevents the conversion of fibrinogen to fibrin

Dabigatran disadvantages

Dosing on time is important because of short duration Limited clinical experience GI disturbances are common

Rivaroxaban disadvantages

Dosing same time each day Limited clinical experience Risk for bleeding similar to warfarin except less risk for intracranial bleeds Not dialyzable

Interactions with Warfarin drug to drug

Drugs that increase the effects of warfarin include aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), other types of antiinflammatory drugs, sulfonamides, cimetidine, and allopurinol. Phenytoin and oral sulfonylureas increase the risk of toxicity when given with warfarin.

before administering warfarin, check the

INR and assess for any bleeding.

Warfarin is administered orally. Tablets are available in 1-mg to 10-mg tablets. Dosage is patient specific and is dependent on laboratory values. A parenteral anticoagulant, such as unfractionated heparin, is usually administered with warfarin until a therapeutic INR level is reached; then the parenteral anticoagulant is discontinued. Additional administration considerations for warfarin are as follows:

It can be administered without regard to food intake. If GI upset occurs, administer with a meal or a snack. Administer at the same time each day. Acetaminophen for pain and fever should be used instead of aspirin or ibuprofen.

Warfarin interventions

Examine the patient's mouth, nose, urine, and skin for bleeding. Watch older adults closely for bleeding, because their skin is thin, and their capillary beds are fragile; this puts them at higher risk for bleeding. Be alert to complaints of abdominal/back pain and severe headache (may be a sign of hemorrhage). Note any excessive bleeding from minor cuts and scratches. Check stools periodically for occult blood. Hold warfarin if INR is greater than 3.

Interactions with Dabigatran and Rivaroxaban herb

Feverfew, ginkgo biloba, green tea, and red clover may increase the risk for bleeding. St. John's wort may decrease concentration/effect of the drugs.

Interactions with Warfarin food

Foods high in vitamin K decrease warfarin's effectiveness. The patient should avoid or limit foods that contain high levels of vitamin K, or work with a nutritionist who can serve as a resource regarding how much to eat. Because vitamin K is typically in dark, leafy vegetables, advise the patient to avoid large amounts of these. They should also be advised to avoid broccoli, legumes, soybean oil, green tea, excessive alcohol, and certain herbs and nutritional supplements. Other vitamin K sources include green apples, chamomile tea, egg yolk, algae, seaweed, and mint.

Which products, if taken by Ms. Wang, would concern the nurse because they increase the effects of warfarin?

Garlic ibuprofen allopurinol gingko

Interactions with Dabigatran and Rivaroxaban food

Grapefruit and cranberry juices can increase anticoagulant effect.

Rivaroxaban metabolism

HEPATIC enzyme system

The nurse should be knowledgeable of anticoagulants and evaluate for drug effectiveness while minimizing side and adverse drug effects. Also, the nurse should ensure the patient understands what to report to the health care provider. Expected outcomes are as follows:

Hemoglobin and hematocrit will remain stable. Blood pressure and heart rate will remain in normal range. Active bleeding does not occur. Patient will understand to report complications related to anticoagulant drug therapy.

Cautions for warfarin

Hemophilia and other bleeding disorders that are not controlled Severe hypertension Malignancy Increased capillary permeability Cerebrovascular disease Traumas GI ulcer and GI bleeding Cardiovascular disease Renal insufficiency Dissecting aneurysm Age 65 and older High anticoagulation factor INR greater than 4 Abortion, therapeutic, spontaneous Patient with genotype variances specific to warfarin metabolism

The nurse is preparing to administer warfarin to a patient whose international normalized ratio (INR) is 5.2. Which action would the nurse take?

Hold the warfarin. The therapeutic range for INR in a patient who is on warfarin is 2 to 3. Because 5.2 is above the therapeutic range, the nurse should hold the dose.

Interactions with Warfarin herbal

Increasing effects of warfarin: garlic and ginkgo Decreasing effects of warfarin: green tea, ginseng, and St. John's wort, which decrease the effects of warfarin Increasing bleeding risks: licorice, parsley, and horseradish

Patient Teaching for Dabigatran and Rivaroxaban side and adverse drug effects

Inform the patient to contact the health care provider if any of these side or adverse drug effects are experienced: Red or dark urine Red or dark bowel movements Heartburn, indigestion, or nausea Stomach pain Diarrhea Numbness, tingling, or weakness to the extremities

Which laboratory value is used to adjust the dosage of warfarin?

International normalized ratio (INR) Patients taking warfarin should obtain frequent laboratory work assessing the INR. The dosage of warfarin is adjusted accordingly. The therapeutic range is 2 to 3 seconds.

Anticoagulants, such as warfarin, increase the risk for bleeding. Therefore nurses should evaluate the therapeutic effects while minimizing side and adverse drug effects.

Monitor PT/INR for warfarin's therapeutic effect. INR should be 2 to 3. Monitor platelet count (anticoagulants can decrease platelet count). Keep anticoagulant antagonists (vitamin K for warfarin) available when drug dose is increased or there are indications of frank bleeding. Fresh-frozen plasma may be needed for transfusion. Question women about an increase in the amount of menstrual discharge.

Warfarin ongoing assessment

Monitor vital signs. An increased pulse rate, followed by a decreased systolic blood pressure, can indicate a fluid volume deficit, resulting from external or internal bleeding. Monitor for any ecchymosis or bleeding. Monitor laboratory values, such as CBC and PT/INR.

warfarin pharmacodynamic profile

Onset: 36-48 hours Peak: 1.5-3 days Duration: 2-5 days Half-Life: 20-60 hours and is patient specific

Dabigatran elimination

Primarily in the kidneys

Rivaroxaban advantages

Rapid onset Fixed dosage Routine monitoring of PT/INR not needed As effective as warfarin Decreased risk for intracranial bleeds than with warfarin

Dabigatran advantages

Rapid onset Fixed dosage Routine monitoring of PT/INR not needed Less bleeding and hemorrhagic stroke Few drug-food interactions Dialyzable

Dabigatran and Rivaroxaban cautions

Renal impairment (creatinine clearance 15 to 30 mL/min), moderate hepatic impairment, invasive procedures, spinal anesthesia, major surgery, those with congenital or acquired bleeding disorders, older adults, and concurrent use of medication that increases risk for bleeding

warfarin general teaching

Suggest that patients carry medical identification card or wear medical alert bracelet that lists the patient's name, telephone number, and drug taken. Warn patients not to smoke. Smoking increases drug metabolism, so warfarin dose may need to be increased. If patient insists on smoking, notify the health care provider; offer smoking cessation program information. To reduce venous stasis and reduce the risk for thrombosis, advise patients to avoid prolonged immobility, elevate the legs when sitting, avoid garments that can restrict blood flow in the legs, exercise, and wear support hose. Instruct patients to take the drug at the same time of day and not to skip doses to prevent drop in blood level. Teach patients to avoid large amounts of foods or drinks that include green, leafy vegetables (spinach, kale, and broccoli) because these are high in vitamin K and can inhibit the effect of warfarin. Warn women to avoid pregnancy while taking this drug. Warfarin is teratogenic.

Warfarin bleeding prevention

Teach patients to inform the dentist when taking an anticoagulant. Advise patients to use a soft toothbrush to prevent gums from bleeding with routine oral hygiene. Warn patients to shave with an electric razor because this can be less likely to cause cuts. Bleeding from cuts caused by shaving may be difficult to control. Teach patients how to control bleeding from accidents or injuries. This includes applying firm, direct pressure to the bleeding area for at least 5 to 10 minutes with a clean, dry, absorbent material (e.g., gauze, towel). Inform patients about reporting signs of bleeding, which include abdominal pain; dark, tarry stools; and bruising. Inform patients that many herbal products interact with anticoagulants and may increase bleeding.

Before administering warfarin, the nurse would ensure that which antidote is on hand in case of an overdose?

Vitamin K

Interactions with Dabigatran and Rivaroxaban laboratory values

They may increase activated partial thromboplastin time (aPTT), PT, and INR.

Identify High-Risk Patients for warfarin

Thorough medical history and physical assessment are needed to identify patients who are at high risk for hematologic complications. Patients with renal dysfunction may be at risk for bleeding. Anticoagulants are eliminated in the kidneys. Nurses should be familiar with administration protocol and side and adverse drug effects.

Absolute Contraindications for warfarin

Thrombocytopenia or uncontrollable bleeding Patients undergoing lumbar puncture; regional anesthesia; or surgery of the eye, brain, or spinal cord Presence of vitamin K deficiency, liver disease, and alcoholism—these are conditions that can disrupt hepatic synthesis of clotting factors Pregnancy (unless treating mechanical heart valves) and lactation

Warfarin therapeutic uses

To continue anticoagulation for 3 to 6 months after heparin therapy for a thrombus or embolus To prevent thromboembolic conditions (pulmonary embolism [PE] or stroke) in persons with long-term risks (e.g., atrial fibrillation or mitral valve replacement) To reduce risk for transient ischemic attacks (TIAs) and myocardial infarction (MI) In general, patients taking warfarin should have an INR of 2 to 3. However, those with mechanical heart valve should have an INR of 2.5 to 3.5.

Warfarin excretion

Warfarin is excreted primarily in the urine and some in the feces.

Warfarin metabolism

Warfarin is metabolized in the liver.

Warfarin absorption

Warfarin is well absorbed orally.

Rivaroxaban antidote available

Yes (factor XA, inactivated)

Dabigatran antidote available

Yes (idarucizumab)

Warfarin dosage

adjusted based on inr

Because warfarin is highly protein bound, it is affected by

numerous drug interactions. Other drugs can displace warfarin from the protein-bound site. This displacement causes more free-circulating anticoagulants. Because drug-drug interactions occur, a complete assessment of all drugs should be done before starting warfarin. Dosage may need to be adjusted, and teaching about drug interaction should be done.

Warfarin is a vitamin K what

antagonist, which means that it decreases the synthesis of vitamin K. Clotting factors, including prothrombin, require the active form of vitamin K to make them. When these clotting factors are decreased, blood is not able to clot as easily. In the event of overdose, warfarin can be counteracted with vitamin K.

It may cause major or fatal bleeding. Consider cardiac/hepatic function, age, nutritional status, concurrent medications, and risk for bleeding when dosing for what

arfarin. Genetic variations have been identified as factors associated with dosage and bleeding risk. Genotyping tests are available.

As with other anticoagulants, dabigatran and rivaroxaban can cause

bleeding

Oral anticoagulants that are vitamin K antagonists, such as warfarin, prolong

clotting times. Dosage for warfarin depends on achieving a therapeutic level. Dosage is adjusted according to the international normalized ratio (INR).

Warfarin onset

delayed (days)

Dabigatran drug food interactions

few

Rivaroxaban drug- food interactions

few

Dabigatran dosage

fixed

Rivaroxaban dosage

fixed

Dabigatran and rivaroxaban are used to prevent stroke related to nonvalvular atrial fibrillation; the discontinuation of these drugs should only be considered if

ife-threatening bleeding occurs or if it is determined that the risk of taking the drug is greater than its benefit. Anticoagulants should be not be abruptly

The antidote for dabigatran

is idarucizumab. Idarucizumab can be used to reverse the effects of dabigatran when an emergent surgery is needed or if there is life-threatening or uncontrolled bleeding. Rivaroxaban does not have an antidote.

Dabigatran and rivaroxaban are anticoagulants that can cause

life-threatening complications, usually related to bleeding. Any condition that delays the metabolism or excretion of the drugs, or increases the anticoagulant properties, should be considered a contraindication for its use. In addition, any accidental trauma or procedure that breaks the skin could place the patient at risk for serious bleeding.

Warfarin drug-food

many

Dabigatran inr testing needed

no

Rivaroxaban inr testing needed

no

Dabigatran is the only

oral direct thrombin inhibitor and will therefore be the prototype drug for this class. Factor Xa inhibitors include rivaroxaban, apixaban, and edoxaban. Rivaroxaban will be the prototype drug for this class.

Historically, vitamin K antagonists, such as warfarin, have been the standard of care fo

oral treatment for thromboembolism. Many limitations are associated with warfarin, despite its widespread use. Warfarin has a narrow therapeutic window; requires frequent laboratory monitoring; and is affected by diet, genetics, and illnesses. Direct thrombin and direct factor Xa inhibitors are relatively new and offer many of these potential benefits.

Vitamin K is usually administered

orally. It can be administered intramuscularly, subcutaneously, and intravenously. The IV route can cause anaphylactic responses such as flushing, hypotension, and even circulatory collapse. To combat this risk, oral administration is preferred. If used intravenously, vitamin K should be diluted and administered slowly, not to exceed 1 mg/min. Smaller doses of vitamin K are preferred because large doses can cause long-term resistance to warfarin. If vitamin K does not control bleeding, whole blood or fresh-frozen plasma can be used to rapidly increase clotting factors.

Warfarin is administered

orally. The drug can be taken with food to decrease gastrointestinal (GI) distress.

Warfarin duration

prolonged

Patient Teaching for Dabigatran and Rivaroxaban general teaching

provide the following information to the patient. Do not chew, crush, open, or divide capsules. Take drug with a glass of water. Use an electric razor and soft toothbrush to prevent bleeding. Do not abruptly stop taking the drug. Do not use OTC drugs without consulting with the health care provider. Laboratory tests may be required during treatment.

Dabigatran onset

rapid (hours)

Rivaroxaban onset

rapid (hours)

The role of the nurse when administering direct thrombin and direct factor Xa inhibitors is based on

safely administering drugs and providing patient education. A thorough assessment of the patient and the patient's laboratory work is critical. The baseline data described below assesses key indicators of patient stability. These data are used to determine whether the drug is working as intended, as well as identifying potential complications, such as bleeding, shock, or serious side effects.

Dabigatran duration

short

Rivaroxaban duration

short

INR is a laboratory test that measure

the time it takes for blood to clot in the presence of certain clotting factors. INR is typically performed immediately before administering each warfarin dose until the therapeutic level has been attained. INR is a ratio between a patient's prothrombin time (PT) and a standardized value.

Rivaroxaban elimination

urine and feces

Dabigatran and rivaroxaban are available in varied doses for oral administration. Both are generally well tolerated

with or without food. However, rivaroxaban at doses higher than 10 mg should be taken with food. Use caution in administering dabigatran or rivaroxaban in patients with renal or hepatic impairment. Anticoagulants should not be abruptly discontinued without another blood thinner in the system. Follow the protocol when switching from one type of anticoagulant to another.

Warfarin inr testing needed

yes

Warfarin antidote available

yes vitamin k