Lilley: Chapter 26 Coagulation Modifier Drugs

the degree of anticoagulation (for any of these medications) is monitored by:

PT

Hemorheologic drugs

alter platelet function without preventing the platelets from working

Aspirin

*MI and TIA prevention available in many combinations with other prescription and nonprescription drugs unique contraindication for aspirin is flulike symptoms in children and teenagers. The use of aspirin in this situation is associated with the occurrence of Reye's syndrome, a rare, acute, and sometimes fatal condition involving hepatic and central nervous system damage allergic cross-reactivity between aspirin and other NSAIDs Patients with documented aspirin allergy must not receive NSAIDs. Aspirin is available in both oral and rectal forms. A combination form of aspirin and dipyridamole (Aggrenox) is used for antiplatelet purposes

Antiplatelets: Adverse Effects

*all pose a risk for serious bleeding episodes

Anticoagulants: Adverse Effects

*bleeding (localized or systemic) *heparin-induced thrombocytopenia (HIT) -Type I: more gradual reduction in platelets. In this type, heparin therapy can generally be continued -Type II: an acute fall in the number of platelets (more than 50% reduction from baseline). Heparin therapy must be discontinued in patients with type II HIT *direct thrombin inhibitors lepirudin and argatroban are both specifically indicated for treatment of HIT. Warfarin can cause skin necrosis and "purple toes" syndrome.

Toxicity and Management of Overdose: warfarin

*discontinue warfarin *Vitamin K (because warfarin inactivates the vitamin K-dependent clotting factors and because these clotting factors are synthesized in the liver, it may take 36 to 42 hours before the liver can resynthesize enough clotting factors to reverse the warfarin effects. Giving vitamin K1 (phytonadione) can hasten the return to normal coagulation) High doses of vitamin K (10 mg) given IV will reverse the anticoagulation within 6 hours (the goal is to give the lowest dose possible)

Clopidogrel (Plavix)

*for reduction of atherosclerotic events; acute coronary syndrome without ST segment elevation ADP inhibitor oral only Prasugrel (Effient) and ticagrelor (Brilinta) are similar to clopidogrel black box warning for patients with certain genetic abnormalities, who may have a higher rate of cardiovascular events due to reduced conversion to its active metabolite. effectiveness may be reduced by amiodarone, calcium channel blockers, NSAIDS, and proton pump inhibitors

Eptifibatide (Integrilin)

*for unstable angina, MI, percutaneous coronary procedures GP IIb/IIIa inhibitor, along with tirofiban (Aggrastat) and abciximab (ReoPro) usually administered in intensive care or cardiac catheterization laboratory settings, where continuous cardiovascular monitoring is the norm All are available only for IV use

therapeutic effects of most coagulation modifier drugs include:

*improved circulation *improved tissue perfusion *decreased pain *prevention of further tissue damage *before giving these drugs, a thorough physical assessment must be performed as well as checking of pertinent laboratory values (e.g., INR, aPTT, PT)

thrombolytics are able to break down or lyse preformed clots in blood vessels such as those that supply the heart with blood therapeutic effects for which to monitor include:

*improved tissue perfusion *decreased chest pain *prevention of further myocardial damage

rationale for use of warfarin:

*it works by inhibiting vitamin K-dependent clotting factors *with warfarin, foods high in vitamin K may reduce the drug's ability to prevent clots *increasing and/or decreasing the intake of these vitamin K-containing foods can affect clotting and thus the INR *the average daily allowance for vitamin K is 120 mcg for adult men and 90 mcg for adult women *avoid large amounts of: kale, spinach, Brussels sprouts, collard/mustard greens, lettuce, chard, and green tea. *beverages that may increase the effect of warfarin and are to be avoided include: *cranberry juice and alcohol *herbal products that interact with warfarin and result in increased risk for bleeding include dong quai, garlic, and ginkgo *St. John's wort decreases warfarin's effect *the safest guideline is to avoid dietary supplements unless the prescriber approves

noxaparin (Lovenox)

*low molecular weight heparin large unfractionated heparin molecules into small fragments laboratory monitoring, as done with heparin therapy, is not necessary when enoxaparin is given because of its greater affinity for factor Xa *injection only *All LMWHs have a distinct advantage over heparin in that they do not require any laboratory monitoring and can be given at home. *A potentially deadly medication error is to give heparin in combination with enoxaparin (or any LMWH, dabigatran, rivaroxaban, or apixaban) Always double-check that enoxaparin and other anticoagulants are never given to the same patient. *one exception, however, is that enoxaparin is often used with oral warfarin as overlap treatment for pulmonary embolus or deep vein thrombosis. Enoxaparin is available in prefilled syringes in a range of dosage forms and strengths, for example 40 mg in 0.4 mL. Prefilled syringes and graduated prefilled syringes are for one-time use only and are available with systems that shield the needle after injection **The air bubble should not be expelled from prefilled syringes, as this is designed to remain next to the plunger to ensure the whole dose is administered.

Rivaroxaban (Xarelto)

*oral factor Xa inhibitor *prevention of strokes in patients with nonvalvular atrial fibrillation, postoperative thromboprophylaxis with knee and hip replacement surgery, and treatment of DVT and PE doses differ for each indication and must be adjusted for renal dysfunction Contraindications: known drug allergy and active bleeding *all of the oral factor Xa inhibitors have black box warnings regarding potential spinal hematomas if the patient has an epidural catheter and regarding the risk for thrombosis if they are discontinued abruptly *adverse effects: peripheral edema, dizziness, headache, bruising, diarrhea, hematuria, and bleeding interactions: decreased effect seen with phenytoin, carbamazepine, rifampin, and St. John's wort. An increased effect is seen with strong CYP3A4 inhibitors (amiodarone, erythromycin, ketoconazole, HIV drugs, diltiazem, verapamil) and grapefruit juice Apixaban (Eliquis) and edoxaban (Savaysa) are similar drugs with similar drug interactions and side effects no routine monitoring is required for either drug, and they may falsely elevate INR. Rivaroxaban or apixaban are not to be given with any other anticoagulant

not technically antifibrinolytic drugs, there are three drugs used for the treatment of hemophilia: y

*produced by recombinant DNA technology which eliminates the risk associated with obtaining them from human blood currently available include: rVII, rVIII, and rIX factors VII, VIII, and IX are important in the coagulation pathway. Warfarin also inhibits these factors. These products are used in patients with hemophilia and are also used in patients with severe bleeding due to warfarin therapy

Antiplatelet: Interactions

*use of dipyridamole with clopidogrel, aspirin, and/or other nonsteroidal antiinflammatory drugs (NSAIDs) produces additive antiplatelet activity and increased bleeding potential *combined use of steroids or nonaspirin NSAIDs with aspirin can increase the ulcerogenic effects of aspirin *combined use of aspirin and heparin with GP IIb/IIIa inhibitors also further enhances antiplatelet activity and increases the likelihood of a serious bleeding episode **in spite of all of these interactions, it is not uncommon to see patients taking daily maintenance doses of aspirin for thrombopreventive purposes, sometimes in combination with other antiplatelet drugs. The most commonly used dose is the "baby aspirin" dose of 81 mg (the standard adult dose is 325 mg)

Three synthetic antifibrinolytics are available:

1. aminocaproic acid 2. tranexamic acid 3. desmopressin

coagulation cascade: extrinsic and intrinsic

1. when blood vessels are damaged by penetration from the outside (e.g., knife or bullet wound), thromboplastin, a substance contained in the walls of blood vessels, is released. This initiates the extrinsic pathway by activating factors VII and X 2. components of the intrinsic pathway are present in the blood in their inactive forms. The intrinsic pathway is activated when factor XII comes in contact with exposed collagen on the inside of damaged blood vessels

some herbals that have potential interactions, especially with warfarin:

capsicum (red pepper), feverfew, garlic, ginger, ginkgo, and St. John's wort

Prothrombin Time (PT)

normal control PT value ranges from 11 to 13 sec target therapeutic level of anticoagulation is 1.5 times the control value, or about 18 sec

Clopidogrel : MOA (Antiplatelet)

ADP inhibitor alters the platelet membrane so that it can no longer receive the signal to aggregate and form a clot. This signal is in the form of fibrinogen molecules, which attach to glycoprotein receptors (GP IIb/IIIa) on the surface of the platelet. Clopidogrel inhibits the activation of this receptor. The combination of aspirin and clopidogrel has been shown to be effective in patients with known cardiovascular disease, but not in patients who only have risk factors.

Mechanism of Action: Antifibrinolytics

Aminocaproic acid and tranexamic acid inhibit the breakdown of fibrin, which prevents the destruction of the formed platelet clot Desmopressin causes a dose-dependent increase in the concentration of plasma factor VIII (von Willebrand factor), along with an increase in the plasma concentration of tissue plasminogen activator overall effect of this is increased platelet aggregation and clot formation

Aspirin : Indication (Antiplatelet)

Aspirin is officially recommended for stroke prevention by the American Stroke Society in daily doses of 50 to 325 mg

Direct thrombin inhibitors (lepirudin, argatroban, bivalirudin, dabigatran): Adverse Effects

Bleeding, dizziness, shortness of breath, fever, urticaria

Heparins (unfractionated heparin, low-molecular-weight heparin) : Adverse Effects

Bleeding, hematoma, anemia, thrombocytopenia

Selective factor Xa inhibitor (fondaparinux, rivaroxaban): Adverse Effects

Bleeding, hematoma, dizziness, rash, gastrointestinal distress, anemia

warfarin (Coumadin): Adverse Effects

Bleeding, lethargy, muscle pain, purple toes

Glycoprotein IIb/IIIa Inhibitors: Adverse Effects (Antiplatelet)

Bradycardia, hypotension, edema, dizziness, bleeding, thrombocytopenia

Clopidogrel: Adverse Effects (Antiplatelet)

Chest pain, edema, Flulike symptoms, headache, dizziness, fatigue, abdominal pain, diarrhea, nausea, epistaxis, rash, and pruritus (itching)

Aspirin: Adverse Effects (Antiplatelet)

Drowsiness, dizziness, confusion, flushing nausea, vomiting, gastrointestinal bleeding Thrombocytopenia, agranulocytosis, leukopenia, neutropenia, hemolytic anemia, bleeding

Xa inhibitors

Fondaparinux (Arixtra) inhibits thrombosis by its specific action against factor Xa alone Rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa) are new oral-acting factor Xa inhibitors

about one third of patients receiving warfarin metabolize it differently than expected, based on variations in certain genes, CYP2CP and VKORC1.

Genetic testing for these genes is helpful in determining the appropriate initial dosage of warfarin

Treatment of severe or large dose heparin (antidote)

IV injection of protamine sulfate Protamine is a specific heparin antidote and forms a complex with heparin, completely reversing its anticoagulant properties reversal occurs in as few as 5 minutes. In general, 1 mg of protamine can reverse the effects of 100 units of heparin.

Vorapaxar is administered orally once a day be sure to educate the patient about the contraindications of use with :

NSAIDS, anticoagulants, and strong inhibitors/inducers of CYP3A4

Coagulation Modifiers in general : If doses of medications are omitted, advise the patient to contact the prescriber for further instructions

Oral dosage forms of any of these medications are to be taken with at least 8 ounces of water and/or with food to help minimize stomach upset

Pentoxifylline + Cilostazol : Indications (Antiplatelet)

Pentoxifylline for vascular disease, whereas cilostazol is indicated specifically for intermittent claudication (pain and cramping in the calf muscles associated with walking). Cilostazol has been shown to be superior to pentoxifylline in improving exercise tolerance in older adult patients

Toxicity and Management of Overdose: Anticoagulants

Protamine may also be used to reverse the effects of LMWHs. A 1-mg dose of protamine is administered for each milligram of LMWH given, (e.g., 1 mg protamine for 1 mg enoxaparin). If the heparin overdose has resulted in a large blood loss, replacement with packed red blood cells may be necessary in acute situations in which bleeding is severe, it may be necessary to administer transfusions of human plasma or clotting factor concentrates.

Drugs that affect coagulation are some of the most dangerous drugs used today TRUE or FALSE

TRUE

Heparin may be given by the subcutaneous or IV routes, but not IM : TRUE or FALSE

TRUE

use of Homan's sign is no longer recommended for assessment/evaluation of DVT of the leg due to its lack of reliability: TRUE or FALSE

TRUE

Vitamin K for warfarin overdose

once vitamin K is given, warfarin resistance will occur for up to 7 days; thus the patient cannot be anticoagulated by warfarin during this period In such cases, either heparin or an LMWH may need to be added to provide adequate anticoagulation

with coagulation modifiers in general, advise the patient to report to the prescriber:

unusual bleeding from anywhere on the body severe headache blurred vision vomiting of blood dizziness fainting fever muscular or limb weakness rash nosebleeds excessive vaginal or menstrual bleeding

two prothrombin complex concentrate products (Kcentra and Profiline) that can be used for life-threatening bleeding from warfarin

They also can be used to reverse bleeding seen with the new oral antiXa products. Depending on the clinical situation, oral vitamin K is usually the preferred route. However, when the international normalized ratio (INR) is very elevated and/or the patient is bleeding, vitamin K is given IV. There is a risk for anaphylaxis when it is given by the IV route; the risk is diminished by diluting it and giving it over 30 minutes.

a unique difference between thrombolytics and anticoagulants, which can only prevent the formation of a clot.

Thrombolytic drugs lyse (break down) clots, or thrombi, that have already formed

Anticoagulants : MOA (general)

Vary, depending on drug Work on different points of the clotting cascade Do not lyse existing clots All anticoagulants work in the clotting cascade but do so at different points

Prasugrel (Effient)

a newer antiplatelet drug that is similar to clopidogrel and is used primarily after interventional cardiac procedures and for patients who do not respond to clopidogrel Ticagrelor (Brilinta) is similar to clopidogrel and prasugrel. It is indicated for patients with acute coronary syndrome. It must be avoided in patients taking more than 100 mg of aspirin daily

The nurse is assessing a patient who has a new prescription for vorapaxar (Zontivity). Which of these conditions are considered contraindications to the use of vorapaxar? (Select all that apply.) a. Impaired renal function b. Impaired liver function c. History of myocardial infarction d. Peripheral artery disease e. History of stroke

a. Impaired renal function b. Impaired liver function e. History of stroke

Warfarin: Interactions

acetaminophen (high doses), amiodarone, bumetanide, furosemide: increased anticoagulant effect aspirin, other NSAIDs, broad-spectrum antibiotics: increased coagulant effect Barbiturates, carbamazepine, rifampin, phenytoin: decreased anticoag effect amiodarone, cimetidine, ciprofloxacin, erythromycin, ketoconazole, metronidazole, omeprazole, sulfonamides, macrolides, HMG-CoA reductase inhibitors (statins): increased anticoag effect cholestyramine, sucralfate: decreased effectiveness of warfarin Herbal therapies: dong quai, garlic, ginkgo: increased bleeding St. John's wort: decreased effectiveness of warfarin

Thrombolytics: Indications

activate the conversion of plasminogen to plasmin, the enzyme that breaks down a thrombus. The presence of a thrombus that interferes significantly with normal blood flow on either the venous or the arterial side of the circulation is an indication for the use of thrombolytic therapy. The indications for thrombolytic therapy include acute MI, arterial thrombosis, DVT, occlusion of shunts or catheters, pulmonary embolism, and acute ischemic stroke.

Thrombolytics: MOA

activate the conversion of plasminogen to plasmin, which breaks down, or lyses, the thrombus plasmin is a proteolytic enzyme, which means that it breaks down proteins. It is a relatively nonspecific enzyme that is capable of degrading proteins such as fibrin, fibrinogen, and other procoagulant proteins like factors V, VIII, and XII. In other words, the substances that form clots are destroyed by plasmin. Essentially, thrombolytic drugs work by mimicking the body's own process of clot destruction. Although the individual thrombolytic drugs are somewhat diverse in their actions, they all have this common result.

Toxicity and Management of Overdose: Thrombolytics

acute toxicity primarily causes an extension of the adverse effects of the thrombolytic drug treatment is symptomatic and supportive, because thrombolytic drugs have a relatively short half-life and no specific antidotes

antifibrinolytic drugs

all prevent the lysis of fibrin *fibrin is the substance that helps make a platelet plug insoluble and anchors the clot to the damaged blood vessel *promote clot formation *also called hemostatic drugs *effects are opposite to those of anticoagulant and antiplatelet drugs, which prevent clot formation

Clopidogrel : Indication (Antiplatelet)

and others in its class are given to reduce the risk for thrombotic stroke, and for prophylaxis against transient ischemic attacks (TIAs), as well for post-MI prevention of thrombosis

Vorapaxar (Zontivity) : Indications (Antiplatelet)

antagonist of protease-activated receptor-1 (PAR-1), which inhibits the action of thrombin on the platelet reduce thrombotic cardiovascular events, MI, and stroke in patients with a history of MI or with peripheral arterial disease. It is available as a 2.08-mg tablet and is given once daily in combination with aspirin and/or clopidogrel contraindicated in patients with history of stroke, TIA, intracranial hemorrhage, and active bleeding major risk of this drug is bleeding, and it is not recommended for patients with hepatic or renal impairment should be avoided with anticoagulants, NSAIDS, and strong inhibitors or inducers of CYP3A4 Other side effects include depression, skin rash, and anemia

Pentoxifylline (Trental)

anti platelet drug methylxanthine derivative with properties similar to those of other methylxanthines, such as caffeine and theophylline reduces the viscosity of blood by increasing the flexibility of red blood cells and reducing the aggregation of platelets. sometimes referred to as a hemorheologic drug or a drug that alters the fluid dynamics of the blood antiplatelet effects of pentoxifylline are attributed to its inhibition of ADP, serotonin, and platelet factor IV stimulates the synthesis and release of prostacyclin from blood vessels may have effects on the fibrinolytic system by raising the plasma concentrations of tissue plasminogen activator

Low Molecular Weight Heparins, especially enoxaparin, are also routinely used as

anticoagulant bridge therapy in situations in which a patient must stop warfarin for surgery or other invasive medical procedures. The term bridge therapy refers to the fact that enoxaparin acts as a bridge to provide anticoagulation while the patient must be off of his or her warfarin therapy.

Aminocaproic acid (Amicar)

antifibrinolytic drug used to prevent and control the excessive bleeding that can result from surgery or overactivity of the fibrinolytic system used for excessive bleeding caused by systemic hyperfibrinolysis or urinary fibrinolysis available in oral and parenteral

Cilostazol

antiplatelet inhibits type 3 phosphodiesterase in the platelets and primarily lower-extremity blood vessels effects are to reduce platelet aggregation and promote vasodilation

vorapaxar (Zontivity)

antiplatelet antagonist of protease-activated receptor-1 (PAR-1) inhibits the action of thrombin on the platelet

Heparin, given IV or subcutaneously, prevents clot formation by binding to:

antithrombin III, which turns off certain activating factors.

antiplatelets : interactions

aspirin, NSAIDs rifampin warfarin, heparin, thrombolytics herbal therapies: garlic, ginkgo, kava (all increased bleeding risk)

heparin: Interactions

aspirin, other NSAIDs: increased bleeding Oral anticoagulants, antiplatelet drugs, thrombolytics: increased antocoag effect

heparin sodium contains benzyl alcohol

assess for allergy to this additional component

LMWHs contain sulfites and benzyl alcohol

assess the patient for allergies to these substances

home therapy with parenteral anticoagulants may require injections for a period of time, and LMWHs are generally used If there is a switch from heparin to warfarin (Coumadin), there will be an overlap period of:

at least 5 days during which both drugs are taken to allow therapeutic levels of the oral warfarin to be reached before the heparin is discontinued this process may occur in the hospital or at home provide complete and thorough instructions to the patient, and use return demonstrations to evaluate learning

The nurse is teaching a patient about self-administration of enoxaparin (Lovenox). Which statement will be included in this teaching session? a. "We will need to teach a family member how to give this drug in your arm." b. "This drug is given in the folds of your abdomen, but at least 2 inches away from your navel." c. "This drug needs to be taken at the same time every day with a full glass of water." d. "Be sure to massage the injection site thoroughly after giving the drug."

b. "This drug is given in the folds of your abdomen, but at least 2 inches away from your navel."

A patient is starting warfarin (Coumadin) therapy as part of treatment for atrial fibrillation. The nurse will follow which principles of warfarin therapy? (Select all that apply.) a. Teach proper subcutaneous administration. b. Administer the oral dose at the same time every day. c. Assess carefully for excessive bruising or unusual bleeding. d. Monitor laboratory results for a target INR of 2 to 3. e. Monitor laboratory results for a therapeutic aPTT value of 1.5 to 2.5 times the control value.

b. Administer the oral dose at the same time every day. c. Assess carefully for excessive bruising or unusual bleeding. d. Monitor laboratory results for a target INR of 2 to 3.

A patient has received a double dose of heparin during surgery and is bleeding through the incision site. While the surgeons are working to stop the bleeding at the incision site, the nurse will prepare to take what action at this time? a. Give IV vitamin K as an antidote. b. Give IV protamine sulfate as an antidote. c. Call the blood bank for an immediate platelet transfusion. d. Obtain an order for packed red blood cells.

b. Give IV protamine sulfate as an antidote.

GP IIb/IIIa inhibitors (Antiplatelet)

block the receptor protein by the same name that occurs in the platelet wall membranes This protein plays a role in promoting the aggregation of platelets in preparation for fibrin clot formation currently three available drugs in this class: tirofiban (Aggrastat), eptifibatide (Integrilin), and abciximab (ReoPro) GP IIb/IIIa inhibitors are available only for IV infusion

when taking any of the anticoagulants (oral drugs and/or heparin or LMWHs) or clotting-altering drugs, encourage the patient to avoid

brushing the teeth with a hard-bristled toothbrush, shaving with a straight razor, and/or engaging in any activity that would increase the risk for tissue injury always caution the patient when shaving, nail trimming, gardening, and/or participating in rough or contact sports

A patient is receiving instructions regarding warfarin therapy and asks the nurse about what medications she can take for headaches. The nurse will tell her to avoid which type of medication? a. Opioids b. acetaminophen (Tylenol) c. NSAIDs d. There are no restrictions while taking warfarin.

c. NSAIDs

A patient is receiving dabigatran (Pradaxa), 150 mg twice daily, as part of treatment for atrial fibrillation. Which condition, if present, would be a concern if the patient were to receive this dose? a. Asthma b. Elevated liver enzymes c. Renal impairment d. History of myocardial infarction

c. Renal impairment

anticoagulants : Indications (general)

certain settings in which there is a high likelihood of clot formation: MI unstable angina atrial fibrillation use of indwelling devices such as mechanical heart valves conditions in which blood flow may be slowed and blood may pool such as major orthopedic surgery or prolonged periods of immobilization like hospitalization or even long plane rides

once a clot is formed and fibrin is present, the fibrinolytic system is activated. This system initiates the breakdown of :

clots and serves to balance the clotting process

Thrombolytic Drugs

coagulation modifiers that lyse thrombi in the blood vessels that supply the heart with blood, the coronary arteries. This reestablishes blood flow to the blood-starved heart muscle. If the blood flow is reestablished early, the heart muscle and left ventricular function can be saved. If blood flow is not reestablished early, the affected area of the heart muscle becomes ischemic, and eventually necrotic and nonfunctional thrombolytics have almost completely been replaced by interventional cardiologic procedures, such as percutaneous coronary intervention. Thrombolytics are still a viable option in hospitals that do not offer percutaneous coronary intervention. Currently available thrombolytic drugs include t-PAs (anistreplase [Eminase], alteplase [Activase], reteplase [Retavase], and tenecteplase [TNKase])

to reduce risk factors for cardiovascular disease, the prescriber may recommend :

consumption of a low-fat, low-cholesterol diet; cholesterol-lowering drug therapy; weight reduction; control of blood pressure if hypertension is present; avoidance of smoking; management of stress; and regular exercise

The nurse is monitoring a patient who is receiving antithrombolytic therapy in the emergency department because of a possible MI. Which adverse effect would be of the greatest concern at this time? a. Dizziness b. Blood pressure of 130/98 mm Hg c. Slight bloody oozing from the IV insertion site d. Irregular heart rhythm

d. Irregular heart rhythm

Warfarin sodium (Coumadin)

derivative of the natural plant anticoagulant known as coumarin available oral and IV; used almost exclusively in the oral form *careful monitoring of the prothrombin time/international normalized ratio (PT/INR), which is a standardized measure of the degree to which a patient's blood coagulability has been reduced by the drug. maintenance dosage is determined by the INR significant interactions with many drugs, including amiodarone, fluconazole, erythromycin, metronidazole, sulfonamide antibiotics, and cimetidine (although many more drugs can interact with warfarin, these are the most common) *combining warfarin and amiodarone will lead to a 50% increase in the INR *amiodarone is added to warfarin therapy, it is recommended that the warfarin dose be cut in half herbal products that interact with warfarin and result in increased risk for bleeding include dong quai, garlic, and ginkgo. St. John's wort decreases warfarin's effect

Argatroban

direct thrombin inhibitor indicated both for treatment of active HIT (heparin induced thrombocytopenia) and for percutaneous coronary intervention procedures in patients at risk for HIT (i.e., those with a history of the disorder It is given only by the IV route. lower dosage must be used in patients with severe hepatic dysfunction.

Anticoagulants : Contraindications

drug allergy, any acute bleeding process, or high risk for such an occurrence. Warfarin is strongly contraindicated in pregnancy, whereas the other anticoagulants are rated in lower pregnancy categories (B or C) LMWHs are contraindicated in patients with an indwelling epidural catheter; they can be given 2 hours after the epidural is removed. This is very important to remember, because giving an LMWH with an epidural has been associated with epidural hematoma

coagulation cascade:

each activated clotting factor serves as a catalyst that amplifies the next reaction the result is a large concentration of a clot-forming substance called fibrin the coagulation cascade is typically divided into the intrinsic and extrinsic pathways, and these pathways are activated by different types of injury

educate the patient that a healthy lifestyle is an important part of therapy and will most likely include:

eating the right foods, weight reduction if needed, smoking cessation, control of blood pressure, and stress reduction. Advise the patient to provide a listing of all medications to all possible prescribers (e.g., dentists)

antifibrinolytics : interactions

estrogens or oral contraceptives used concurrently with aminocaproic acid or tranexamic acid, additive effects may occur, resulting in increased coagulation few specific interactions have been reported for desmopressin (but use caution when giving to patients receiving lithium, large doses of epinephrine, heparin, or alcohol) drugs such as chlorpropamide and fludrocortisone may potentiate the antidiuretic response, which may lead to edema

antifibrinolytics prevent the lysis of:

fibrin, thus promoting clot formation, and have an effect opposite to that of the anticoagulants nursing care is very individualized and is based on the characteristics of the patient, thorough assessment data, existing medical conditions, and the specific drug

these drugs inhibit thrombin

five antithrombin drugs that inhibit the thrombin molecules directly, one natural and four synthetic The natural drug is human antithrombin III (Thrombate), which is isolated from the plasma of human donors The synthetic drugs are lepirudin (Refludan), argatroban (Argatroban), bivalirudin (Angiomax), and dabigatran (Pradaxa). Dabigatran is a new oral direct thrombin inhibitor

aminocaproic acid (Amicar) and tranexamic acid (Cyklokapron) : MOA (antifibrinolytic)

form a reversible complex with plasminogen and plasmin by binding to the lysine-binding site of plasminogen,, they displace plasminogen from the surface of fibrin this prevents plasmin from lysing the fibrin clot can work only if a clot has formed

Fibrinolysis is the reverse of the clotting process. It is the mechanism by which :

formed thrombi are lysed (broken down) to prevent excessive clot formation and blood vessel blockage Fibrin in the clot binds to a circulating protein known as plasminogen. This binding converts plasminogen to plasmin. Plasmin is the enzymatic protein that eventually breaks down the fibrin thrombus into fibrin degradation products. This keeps the thrombus localized to prevent it from becoming an embolus that can travel to obstruct a major blood vessel in the lung, heart, or brain

An important caution for heparin use is pregnancy or lactation

however, if there is a need for an anticoagulant during pregnancy, heparin is the drug of choice, not warfarin

The overall effect of Heparin is to:

inactivate the coagulation pathway and prevent clots from forming Heparin does not lyse (break down) a clot.

desmopressin (DDAVP) : MOA (Antifibrinolytic)

increases the level of factor VII (von Willebrand factor), which anchors platelets to damaged vessels via the glycoprotein Ib platelet receptor desmopressin acts as a general endothelial stimulant, promoting the release of factor VIII, prostaglandin I2, and plasminogen activator

Dipyridamole: MOA (Antiplatelet)

inhibit platelet aggregation by preventing the release of ADP, platelet factor IV, and TXA2, all substances that stimulate platelets to aggregate or form a clot may also directly stimulate the release of prostacyclin and inhibit the formation of TXA2

Anticoagulants action

inhibit the action or formation of clotting factors and therefore prevent clots from forming.

warfarin prevents clot formation by:

inhibiting vitamin K-dependent clotting factors (factors II, VII, IX, and X) and is used prophylactically to prevent clots from forming; it cannot lyse preformed clots

Aspirin : MOA

inhibits cyclooxygenase in the platelet irreversibly so that the platelet cannot regenerate this enzyme. the effects of aspirin last the lifespan of a platelet, or 7 days irreversible inhibition of cyclooxygenase in the platelet prevents the formation of TXA2, a substance that causes blood vessels to constrict and platelets to aggregate by preventing TXA2 formation, aspirin prevents these actions, which results in dilation of the blood vessels and prevention of platelets from aggregating or forming a clot

warfarin: MOA (anticoagulant)

inhibits vitamin K synthesis by bacteria in the gastrointestinal tract. this inhibits production of clotting factors II, VII, IX, and X. these four factors are normally synthesized in the liver and are known as vitamin K-dependent clotting factors as with heparin, the final effect is the prevention of clot formation

Thrombolytics: Adverse Effects

internal, intracranial, and superficial bleeding hypersensitivity, anaphylactoid reactions, nausea, vomiting, and hypotension. These drugs can also induce cardiac dysrhythmias

Dipyridamole : Indication (Antiplatelet)

is used to decrease platelet aggregation in various other thromboembolic disorders.

antifibrinolytics: contraindications

known drug allergy disseminated intravascular coagulation (DIC)

Antiplatelets: Contraindications

known drug allergy to a specific product, thrombocytopenia, active bleeding, leukemia, traumatic injury, gastrointestinal ulcer, vitamin K deficiency, and recent stroke

Thrombolytics: Contraindications

known drug allergy to the specific product and any preservatives, and concurrent use of other drugs that alter clotting

because warfarin inhibits vitamin K-dependent clotting factors, foods that are high in vitamin K may reduce warfarin's ability to prevent clots. Common foods rich in vitamin K include

leafy green vegetables (e.g., kale, spinach, collard greens) Patients do not need to completely cut these foods out. Once their maintenance warfarin dose is established, patients may still eat greens, but they need to be consistent in their intake of green vegetables, because increasing or decreasing their intake can affect the INR

Dalteparin is another anticoagulant with comparable pharmacology and indications as

lovenox

Antiplatelet drugs: MOA

many of the antiplatelet drugs affect the cyclooxygenase pathway, which is one of the common final enzymatic pathways in the complex arachidonic acid pathway that operates within platelets and on blood vessel walls

with dabigatran (Pradaxa), educate the patient to protect the original bottle from:

moisture *once a bottle is opened, it must be used within 60 days; this needs to be written on the bottle/label with the date of expiration *instruct the patient to remove only 1 capsule from the opened bottle at the time of use and that the bottle needs to be immediately and tightly closed *encourage the patient to take the medication with food if dyspepsia occurs *capsules are not to be repackaged or placed in other pillboxes/organizers

specific handling instructions for dabigatran

must be stored in and dispensed from its original bottle. This is important because if not stored properly and with the desiccant-drying agent (which absorbs moisture) in the packaging cap, the substance in the drug is easily broken down and a loss of potency occurs discard the drug after 30 days of opening the original container, recent data suggest that it can maintain its potency for up to 60 days if the cap is closed tightly after each use and the bottle is kept away from excessive moisture, heat, and/or cold

Heparin

natural anticoagulant obtained from the lungs or intestinal mucosa of pigs *when used for flushing purposes, there is no need for monitoring *commonly used for DVT prophylaxis in a dose of 5000 units two or three times a day given subcutaneously, and it does not need to be monitored when used for prophylaxis. *when used therapeutically (for treatment), it is given by continuous IV infusion *because the dosage is based on the patient's weight in kilograms, ensure that the appropriate weight is recorded and that only kilograms are used, and not pounds A potential double-dose medication error can occur if pounds and kilograms are mixed This is also true for enoxaparin, because it is dosed on body weight when used therapeutically When heparin is given by IV infusion, monitoring by frequent measurement of aPTT (usually every 6 hours until therapeutic effects are seen) is necessary. *other drugs that affect the coagulation cascade can have additive effects with heparin, which may lead to bleeding even though warfarin can cause additive effects, it is combined with IV heparin therapy-usually started within the first day or two of heparin infusion available only in injectable form in multiple strengths ranging from 10 to 40,000 units/mL

hemophilia is a rare genetic disorder in which

natural coagulation and hemostasis factors are limited or absent. Hemophilia is categorized into two main types depending on which of the coagulation factors is absent (factor VII, factor VIII, and/or factor IX). Patients with hemophilia can bleed to death if coagulation factors are not given

Always double-check that enoxaparin and heparin are

never given to the patient simultaneously

Dabigatran (Pradaxa)

oral direct thrombin inhibitor approved for prevention of strokes and thrombosis in patients with nonvalvular atrial fibrillation prodrug that becomes activated in the liver. specifically and reversibly binds to both free and clot-bound thrombin excreted extensively in the kidneys, and the dose is dependent upon renal function most common and serious side effect: bleeding, with an increased in GI bleeding as compared to warfarin. **no coagulation monitoring is required for dabigatran Drug interactions include phenytoin, carbamazepine, rifampin, and St. John's wort (which cause a decreased effect) and strong CYP3A4 inhibitors such as amiodarone, quinidine, erythromycin, verapamil, azole antifungals, and HIV protease inhibitors (which cause an increased effect) other anticoagulants are not to be given with dabigatran

The greatest risk to the patient with heparin-induced thrombocytopenia is the

paradoxical occurrence of thrombosis, something that heparin normally prevents or alleviates. Thrombosis that occurs in the presence of HIT can be fatal

normal INR (without warfarin) is 1 whereas a therapeutic INR (with warfarin) ranges from 2 to 3.5, depending on the indication for use of the drug (e.g., atrial fibrillation, thromboprevention, prosthetic heart valve)

patients older than 65 years of age may have a lower INR threshold for bleeding complications and may need to be monitored accordingly

substances that promote coagulation include

platelets, von Willebrand factor, activated clotting factors, and tissue thromboplastin

Antiplatelet drugs action

prevent platelet plugs from forming by inhibiting platelet aggregation, which can be beneficial in preventing heart attacks and strokes

antiplatelet drugs prevent clot formation by:

preventing platelet involvement in clot formation

coagulation modifiers work by :

preventing/promoting clot formation, lysing a preformed clot, and/or reversing the action of anticoagulants coagulation modifiers include: anticoagulants antiplatelets thrombolytics antifibrinolytics and reversal drugs

Antifibrinolytics: Indications

prevention and treatment of excessive bleeding resulting from systemic hyperfibrinolysis or surgical complications stop excessive oozing from surgical sites such as chest tubes as well as in reducing the total blood loss and the duration of bleeding in the postoperative period Desmopressin may also be used in patients who have hemophilia A or type I von Willebrand disease. Recombinant factors VII, VIII, and IX are used to treat hemophilia or to stop the bleeding from excessive warfarin therapy

Antifibrinolytic drugs, also known as hemostatic drugs, have the opposite effect of these other classes of drugs; they

promote blood coagulation

Substances that inhibit coagulation include

prostacyclin, antithrombin III, and proteins C and S. In addition, tissue plasminogen activator is a natural substance that dissolves clots that are already formed

with coagulation modifiers in general:

report any decrease in urine output; constant ringing in the ears; swelling of the feet, ankles, or legs; dark urine; clay-colored stools; abdominal pain; rash (use needs to be discontinued as ordered if rash occurs); and/or blurred vision to the prescriber immediately

Fondaparinux (Arixtra)

selective inhibitor of factor Xa, which is indicated for prophylaxis or treatment of DVT or PE. *contraindicated with known allergy or in patients with a creatinine clearance less than 30 mL/min or a body weight of less than 50 kg Bleeding is the most common and serious adverse reaction. *thrombocytopenia has also been reported, and therapy should be stopped if platelet count falls below 100,000 *DO NOT give for at least 6 to 8 hours after surgery and should be used with caution in conjunction with warfarin side effects include anemia, increased wound drainage, postoperative hemorrhage, hematoma, confusion, urinary tract infection, hypotension, dizziness, and hypokalemia. There is no antidote for fondaparinux, and its effect cannot be measured by standard anticoagulant tests. Fondaparinux is given only by subcutaneous injection Fondaparinux has a black box warning regarding potential spinal hematomas if the patient has an epidural catheter.

teach the patient about clot-preventive measures, including :

situations to minimize sluggish circulation (e.g., avoid tight-fitting clothing, minimize sitting for prolonged periods of time, avoid crossing the legs at the knees and wearing of tight-fitting socks/stockings, avoid prolonged bed rest, make stops during long trips to walk around every 1 to 2 hours, keep well hydrated)

with patients, emphasize the rationale for use of the coagulation-modifying drugs to prevent serious complications related to clotting such as :

stroke heart attack clot formation (deep vein thrombosis of the legs) with heart valve replacements mini-strokes/TIAs (transient ischemic attacks) need for frequent and close monitoring

Streptokinase

substance used to break down fibrin clots (thrombolytic)

Desmopressin (DDAVP)

synthetic polypeptide -antifibrinolytic structurally similar to vasopressin, which is antidiuretic hormone, the natural human posterior pituitary hormone (because of these physical characteristics, it is most often used to increase the resorption of water by the collecting ducts in the kidneys to prevent or control polydipsia, polyuria, and dehydration in patients with diabetes insipidus due to a deficiency of endogenous posterior pituitary vasopressin or in patients with polyuria and polydipsia resulting from trauma or surgery in the pituitary region) *also causes a dose-dependent increase in plasma factor VIII (von Willebrand factor), along with an increase in tissue plasminogen activator, which results in increased platelet aggregation and clot formation; thus it is often used to stop bleeding. *contraindicated in patients with a known hypersensitivity to it and in those with nephrogenic diabetes insipidus. *available in both injectable and intranasal dosage forms. *nasal spray is used for primary nocturnal enuresis

International Normalized Ratio (INR)

target levels of INR range from 2 to 3 or an average of 2.5 for individuals taking warfarin for treatment of recurring systemic clots or emboli and those with mechanical heart valves, the target INR may be 2.5 to 3.5, with a middle value of 3

Anticoagulant drugs: In (continued)

the ultimate consequence of a clot can be a stroke or a heart attack, DVT, or PE prevention of these serious events is the ultimate benefit of these drugs anticoagulants are used for both prevention and treatment of clots Patients at risk for clots are given DVT prophylaxis while in the hospital and after major surgery.

Alteplase (Activase)

thrombolytic *t-PA *fibrin specific and therefore does not produce a systemic lytic state *because it is present in the human body in a natural state, its administration for therapeutic use does not induce an antigen-antibody reaction-it can be re-administered immediately in the event of reinfarction *has a very short half-life of 5 minutes *opens the clogged artery rapidly, but its action is short-lived *given with heparin to prevent reocclusion of the affected blood vessel *available only in parenteral form. *a smaller dosage form known as Cathflo Activase that is used to flush clogged IV or arterial lines *also used for ischemic stroke *Tenecteplase (TNKase) is a newer form of alteplase that is given by IV push after MI

antifibrinolytics: adverse effects

thrombotic events, such as acute cerebrovascular thrombosis and acute MI dysrhythmias, orthostatic hypotension, bradycardia headache, dizziness, fatigue, hallucinations, convulsions, nausea, vomiting, abdominal cramps, diarrhea

withdraw warfarin (as with all drugs altering bleeding/clotting)—as ordered—before the patient undergoes any dental procedures or if there is any evidence of

tissue necrosis, gangrene, diarrhea, intestinal flora imbalances, or steatorrhea

direct the patient to take all of the clotting-altering drugs exactly as prescribed because:

too little of the drug may lead to clot formation and too much of the drug may lead to bleeding

there are also hemostatic drugs that are used topically (on the skin or tissue surface) in surgical settings to stop excessive bleeding these include:

topical thrombin, microfibrillar collagen, absorbable gelatin, and oxidized cellulose

Toxicity and Management of Overdose: Anticoagulants

toxic effects of all anticoagulants are hemorrhagic in nature, the management is different for each drug S/S: hematuria, melena (blood in the stool), petechiae, ecchymoses, and gum or mucous membrane bleeding *stop the drug immediately *for heparin, stopping the drug alone may be enough to reverse the toxic effects because of the drug's short half-life (1 to 2 hours)

GP IIb/IIIa inhibitors : Indication (Antiplatelet)

used to treat acute unstable angina and MI, and are given during percutaneous coronary intervention procedures, such as angioplasty. Their purpose is to prevent the formation of thrombi. This is known as thromboprevention. This treatment approach is based on the fact that prevention of thrombus formation is easier and less risky overall from a pharmacologic standpoint than is lysing a formed thrombus.

Lab values : activated partial thromboplastin time (aPTT), partial thromboplastin time (PTT) (with heparin therapy)

values need to fall between 1.5 and 2.5 times the control or baseline value normal control values are 25 to 35 seconds (sec) target therapeutic level of anticoagulation is between 45 and 70 sec

Route: anticoagulants

warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban are used orally. The rest are given by IV and/or subcutaneous injection only. Intramuscular (IM) injection of these drugs is contraindicated due to their propensity to cause large hematomas at the site of injection.

heparin : MOA (anticoagulant)

works by binding to a substance called antithrombin III, which turns off three main activating factors: 1.activated factor II (also called thrombin) 2.activated factor X 3.activated factor IX (Factors XI and XII are also inactivated but do not play as important a role as the other three factors) thrombin is the most sensitive to the actions of heparin *turns off the coagulation pathway

Anticoagluants: Interactions (4 main mechanisms)

• Enzyme inhibition of metabolism • Displacement of the drug from inactive protein-binding sites • Decrease in vitamin K absorption or synthesis by the bacterial flora of the large intestine • Alteration in the platelet count or activity *although both aspirin and warfarin increase the risk for bleeding when given with heparin, they are commonly given together in clinical practice. *when a patient is placed on IV heparin, it is recommended that warfarin be started at the same time *recommendations are to continue overlap therapy of the heparin and warfarin for at least 5 days; the heparin is stopped after 5 days when the INR is above 2