Chapter 26 Coagulation Modifier Drugs Copyright 2017 Elsevier

Chapter 26 Coagulation Modifier Drugs Copyright © 2017, Elsevier Inc. All rights reserved.

Hemostasis General term for any process that stops bleeding Coagulation is hemostasis that occurs because of the physiologic clotting of blood Complex relationship between substances that promote clot formation and either inhibit coagulation or dissolve a formed clot Thrombus: technical term for a blood clot Embolus: thrombus that moves through blood vessels Copyright © 2017, Elsevier Inc. All rights reserved. 2

Coagulation System “Cascade” Each activated factor serves as a catalyst that amplifies the next reaction. Result is fibrin, a clot-forming substance Intrinsic pathway and extrinsic pathway Copyright © 2017, Elsevier Inc. All rights reserved. 3

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The fibrinolytic system. Copyright © 2017, Elsevier Inc. All rights reserved. 6

Fibrinolytic System Initiates the breakdown of clots and serves to balance the clotting process Fibrinolysis: mechanism by which formed thrombi are lysed to prevent excessive clot formation and blood vessel blockage Copyright © 2017, Elsevier Inc. All rights reserved. 7

Fibrinolytic System (Cont. ) 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. Copyright © 2017, Elsevier Inc. All rights reserved. 8

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Hemophilia Rare genetic disorder Natural coagulation and hemostasis factors are limited or absent. Patients with hemophilia can bleed to death if coagulation factors are not given. Two types inhibit platelet aggregation Factor VII deficiency Ø Factor VIII and/or factor IX deficiency Ø Copyright © 2017, Elsevier Inc. All rights reserved. 10

Coagulation Modifier Drugs Anticoagulants Inhibit the action or formation of clotting factors Ø Prevent clot formation Ø Antiplatelet drugs Inhibit platelet aggregation Ø Prevent platelet plugs Ø Copyright © 2017, Elsevier Inc. All rights reserved. 11

Coagulation Modifier Drugs (Cont. ) Hemorheologic drugs Ø Thrombolytic drugs Ø Alter platelet function without preventing the platelets from working Lyse (break down) existing clots Antifibrinolytic or hemostatic Ø Promote blood coagulation Copyright © 2017, Elsevier Inc. All rights reserved. 12

Anticoagulants Also known as antithrombotic drugs Have no direct effect on a blood clot that is already formed Prevent intravascular thrombosis by decreasing blood coagulability Used prophylactically to prevent Clot formation (thrombus) Ø An embolus (dislodged clot) Ø Copyright © 2017, Elsevier Inc. All rights reserved. 13

Embolus Thromboembolic events Myocardial infarction (MI): embolus lodges in a coronary artery Ø Stroke: embolus obstructs a brain vessel Ø Pulmonary emboli: embolus in the pulmonary circulation Ø Deep vein thrombosis (DVT): embolus goes to a vein in the leg Ø Copyright © 2017, Elsevier Inc. All rights reserved. 14

Anticoagulants (Cont. ) Heparins Action: inhibit clotting factors IIa (thrombin) and Xa Ø Unfractionated heparin: “heparin” Ø Low-molecular-weight heparins (LMWHs) • enoxaparin (Lovenox) • dalteparin (Fragmin) Ø Copyright © 2017, Elsevier Inc. All rights reserved. 15

Anticoagulants (Cont. ) Heparins (Cont. ) Unfractionated heparin (heparin) Ø Relatively large molecule that is derived from animal sources Ø Frequent laboratory monitoring for bleeding times such as a. PTT Ø Heparin for catheter flush (10 -100 units/m. L): no monitoring is needed Ø Copyright © 2017, Elsevier Inc. All rights reserved. 16

Anticoagulants (Cont. ) Heparins (Cont. ) LMWHs Ø enoxaparin (Lovenox) and dalteparin (Fragmin) Ø Synthetic smaller molecular structure Ø More predictable anticoagulant response Ø Frequent laboratory monitoring of bleeding times using tests such as a. PTT not needed Ø Copyright © 2017, Elsevier Inc. All rights reserved. 17

Anticoagulants (Cont. ) Coumarins Action: inhibit vitamin K–dependent clotting factors II, VII, IX, and X Ø Warfarin (Coumadin) Ø Copyright © 2017, Elsevier Inc. All rights reserved. 18

Anticoagulants (Cont. ) Warfarin (Coumadin) Inhibits vitamin K synthesis by bacteria in the gastrointestinal tract Ø Inhibits production of vitamin K–dependent clotting factors II, VII, IX, and X, which are normally synthesized in the liver Ø Final effect prevention of clot formation Ø Copyright © 2017, Elsevier Inc. All rights reserved. 19

Anticoagulants (Cont. ) Direct thrombin inhibitors Action: inhibit thrombin (factor IIa) Ø Human antithrombin III (Thrombate) Ø lepirudin (Refludan) Ø argatroban (Argatroban) Ø bivalirudin (Angiomax) Ø dabigatran (Pradaxa) Ø Copyright © 2017, Elsevier Inc. All rights reserved. 20

Anticoagulants (Cont. ) Selective factor Xa inhibitors Action: inhibit factor Ø fondaparinux (Arixtra) Ø ivaroxaban (Xarelto) Ø apixaban (Eliquis) Ø Copyright © 2017, Elsevier Inc. All rights reserved. 21

Anticoagulants: Mechanism of Action Vary, depending on drug Work on different points of the clotting cascade Prevent intravascular thrombosis by decreasing blood coagulability Do not lyse existing clots Copyright © 2017, Elsevier Inc. All rights reserved. 22

Anticoagulants: Indications Used to prevent clot formation in certain settings in which clot formation is likely MI Ø Unstable angina Ø Atrial fibrillation Ø Indwelling devices, such as mechanical heart valves Ø Major orthopedic surgery Ø Copyright © 2017, Elsevier Inc. All rights reserved. 23

Anticoagulants: Contraindications Drug allergy Any acute bleeding process or high risk for such an occurrence Warfarin is strongly contraindicated in pregnancy. Other anticoagulants are rated in lower pregnancy categories (B or C). LMWHs are contraindicated in patients with an indwelling epidural catheter risk of epidural hematoma. Copyright © 2017, Elsevier Inc. All rights reserved. 24

Anticoagulants: Adverse Effects Bleeding Risk increases with increased dosages Ø May be localized or systemic Ø May also cause: Heparin-induced thrombocytopenia Ø Nausea, vomiting, abdominal cramps, thrombocytopenia, others Ø Copyright © 2017, Elsevier Inc. All rights reserved. 25

Heparin-Induced Thrombocytopenia Type I Gradual reduction in platelets Ø Heparin therapy can generally be continued. Ø Type II Acute fall in the number of platelets (more than 50% reduction from baseline) Ø Discontinue heparin. Ø Copyright © 2017, Elsevier Inc. All rights reserved. 26

Heparin-Induced Thrombocytopenia (Cont. ) Clinical manifestations Thrombosis that can be fatal. Ø Treatment: thrombin inhibitors lepirudin and argatroban Ø Use of warfarin: can cause skin necrosis and “purple toes” syndrome Ø Copyright © 2017, Elsevier Inc. All rights reserved. 27

Treatment: Toxic Effects of Heparin Symptoms: hematuria, melena (blood in the stool), petechiae, ecchymoses, and gum or mucous membrane bleeding Stop drug immediately. Intravenous (IV) protamine sulfate: 1 mg of protamine can reverse the effects of 100 units of heparin. Copyright © 2017, Elsevier Inc. All rights reserved. 28

Treatment: Toxic Effects of Warfarin Discontinue the warfarin. May take 36 to 42 hours before the liver can resynthesize enough clotting factors to reverse the warfarin effects Vitamin K 1 (phytonadione) can hasten the return to normal coagulation. High doses of vitamin K (10 mg) given IV will reverse the anticoagulation within 6 hours. Copyright © 2017, Elsevier Inc. All rights reserved. 29

Treatment: Toxic Effects of Warfarin (Cont. ) Caution: when vitamin K is given, warfarin resistance will occur for up to 7 days. Severe bleeding: transfusions of human plasma or clotting factor concentrates. Life-threatening bleeding from warfarin: Kcentra and Profiline IV vitamin K: risk of anaphylaxis. Risk is diminished by diluting it and giving it over 30 minutes. Copyright © 2017, Elsevier Inc. All rights reserved. 30

Drug Interactions: Anticoagulants Enzyme inhibition of metabolism Displacement of the drug from inactive proteinbinding sites Decrease in vitamin K absorption or synthesis by the bacterial flora of the large intestines Alteration in the platelet count or activity Copyright © 2017, Elsevier Inc. All rights reserved. 31

Heparin Natural anticoagulant obtained from the lungs or intestinal mucosa of pigs 10 to 40, 000 units/m. L DVT prophylaxis: 5000 units subcutaneously two or three times a day; does not need to be monitored when used for prophylaxis When heparin is used therapeutically (for treatment), continuous IV infusion. ØMeasurement of a. PTT (usually every 6 hours until therapeutic effects are seen) is necessary. Copyright © 2017, Elsevier Inc. All rights reserved. 32

Warfarin (Coumadin) Coumadin Most commonly prescribed oral anticoagulant Ø Careful monitoring of the prothrombin time/international normalized ratio (PT/INR) Ø A normal INR (without warfarin) is 1. 0, but 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). Ø Variations in certain genes, CYP 2 CP and VKORC 1 Ø Dietary considerations Ø Copyright © 2017, Elsevier Inc. All rights reserved. 33

Audience Response System Question A patient is receiving an IV infusion of heparin and was started on warfarin therapy the night before. Which statement is most correct? A. The patient is receiving a double dose of anticoagulants. B. The heparin therapy was ineffective, so the warfarin was started. C. The heparin provides anticoagulation until therapeutic levels of warfarin are reached. D. The heparin and warfarin work together synergistically to provide anticoagulation. Copyright © 2017, Elsevier Inc. All rights reserved. 34

Antiplatelet Drugs Prevent platelet adhesion aspirin Ø cilostazol (Pletal) Ø clopidogrel (Plavix) Ø Prasugrel (Effient) Treprostinil (Remodulin) Ø abciximab (Reo. Pro) Ø eptifibatide (Integrilin) Ø tirofiban (Aggrastat) Ø anagrelide (Agrylin) Ø dipyridamole (Persantine) Ø Copyright © 2017, Elsevier Inc. All rights reserved. 35

Relationship between platelets and the clotting cascade Copyright © 2017, Elsevier Inc. All rights reserved. 36

Cyclooxygenase Pathway Copyright © 2017, Elsevier Inc. All rights reserved. 37

Antiplatelet Drugs: Indications and Adverse Effects Antithrombotic effects Adverse effects Ø Vary according to drug Copyright © 2017, Elsevier Inc. All rights reserved. 38

Thrombolytic Drugs that break down, or lyse, preformed clots Older drugs Ø streptokinase and urokinase Current drugs alteplase (Activase, Cathflo Activase) Ø reteplase (Retavase) Ø tenecteplase (TNKase) Ø Copyright © 2017, Elsevier Inc. All rights reserved. 39

Thrombolytic Drugs: Mechanism of Action Activate the fibrinolytic system to break down the clot in the blood vessel quickly Activate plasminogen and convert it to plasmin, which can digest fibrin Reestablish blood flow to the heart muscle via coronary arteries, preventing tissue destruction Copyright © 2017, Elsevier Inc. All rights reserved. 40

Thrombolytic Drugs: Indications Acute MI Arterial thrombolysis DVT Occlusion of shunts or catheters Pulmonary embolus Acute ischemic stroke Copyright © 2017, Elsevier Inc. All rights reserved. 41

Thrombolytic Drugs: Adverse Effects Bleeding Internal Ø Intracranial Ø Superficial Ø Other effects Nausea, vomiting, hypotension, anaphylactoid reactions Ø Cardiac dysrhythmias; can be dangerous Ø Copyright © 2017, Elsevier Inc. All rights reserved. 42

Audience Response System Question A patient is receiving an IV infusion of a thrombolytic drug during treatment for an acute MI. The nurse notices that there is a slight amount of bleeding from the antecubital area where venous lab work was drawn. What will the nurse do first? A. B. C. D. Monitor the site for further bleeding. Apply pressure to the site with a gauze pad. Slow the rate of infusion of the thrombolytic drug. Stop the infusion of the thrombolytic drug. Copyright © 2017, Elsevier Inc. All rights reserved. 43

Antifibrinolytic Drugs Prevent the lysis of fibrin Result in promoting clot formation Used for prevention and treatment of excessive bleeding resulting from hyperfibrinolysis or surgical complications Treatment of hemophilia or von Willebrand’s disease Copyright © 2017, Elsevier Inc. All rights reserved. 44

Antifibrinolytic Drugs (Cont. ) aminocaproic acid (Amicar) tranexamic acid (Cyklokapron) desmopressin Copyright © 2017, Elsevier Inc. All rights reserved. 45

Antifibrinolytic Drugs: Adverse Effects Uncommon and mild Rare reports of thrombotic events Others include Ø Dysrhythmia, orthostatic hypotension, bradycardia, headache, dizziness, fatigue, nausea, vomiting, abdominal cramps, diarrhea, others Copyright © 2017, Elsevier Inc. All rights reserved. 46

Nursing Implications Assess Patient history, medication history, allergies Ø Contraindications Ø Baseline vital signs, laboratory values Ø Potential drug interactions Ø History of abnormal bleeding conditions Ø Copyright © 2017, Elsevier Inc. All rights reserved. 47

Heparin: Nursing Implications IV doses are usually double checked with another nurse. Ensure that subcutaneous doses are given subcutaneously, not intramuscularly. Subcutaneous doses should be given in areas of deep subcutaneous fat and sites rotated. Copyright © 2017, Elsevier Inc. All rights reserved. 48

Heparin: Nursing Implications (Cont. ) Do not give subcutaneous doses within 2 inches of: Ø The umbilicus, abdominal incisions, open wounds, scars, drainage tubes, or stomas Do not aspirate subcutaneous injections or massage the injection site. Ø May cause hematoma formation Copyright © 2017, Elsevier Inc. All rights reserved. 49

Heparin: Nursing Implications (Cont. ) IV doses may be given by bolus or IV infusions. Anticoagulant effects are seen immediately. Laboratory values are done daily to monitor coagulation effects (a. PTT). Protamine sulfate can be given as an antidote in case of excessive anticoagulation. Copyright © 2017, Elsevier Inc. All rights reserved. 50

LWMHs: Nursing Implications Given subcutaneously in the abdomen Rotate injection sites. Protamine sulfate can be given as an antidote in case of excessive anticoagulation. Copyright © 2017, Elsevier Inc. All rights reserved. 51

Warfarin (Coumadin): Nursing Implications May be started while the patient is still on heparin until PT/INR levels indicate adequate anticoagulation Full therapeutic effect takes several days Monitor PT/INR regularly; keep follow-up appointments. Antidote is vitamin K Copyright © 2017, Elsevier Inc. All rights reserved. 52

Audience Response System Question A 75 -year-old man fell at home and hit his head against a table. His wife reports to their daughter that he does not have cuts or scratches, but there is a small lump on his upper scalp. She does not see any blood. He is taking warfarin and an antidysrhythmic as part of his treatment for chronic atrial fibrillation. What is the main concern at this time? A. Pressure should be applied to the lump for 3 to 5 minutes. B. He will need to take two doses of warfarin tonight to prevent blood clotting. C. He needs to be examined for possible internal bleeding from the fall. D. As long as there is no bleeding, there is no concern. Copyright © 2017, Elsevier Inc. All rights reserved. 53

Warfarin (Coumadin): Nursing Implications Many herbal products have potential interactions; increased bleeding may occur Capsicum pepper Ø Garlic Ø Ginger Ø Ginkgo Ø St. John’s wort Ø Feverfew Ø Copyright © 2017, Elsevier Inc. All rights reserved. 54

Audience Response System Question A 72 -year-old woman is taking an over-the-counter multivitamin that contains ginkgo. Her physician has recommended that she start taking low-dose aspirin therapy as part of her treatment for transient ischemic attacks. The concern with taking these two drugs together is A. increased risk of gastric ulcer. B. decreased action of the aspirin because of the interaction with the ginkgo. C. increased risk of bleeding because of the ginkgo. D. antagonism of the action of the aspirin because of the multivitamins. Copyright © 2017, Elsevier Inc. All rights reserved. 55

Anticoagulants: Patient Education should include: Importance of regular laboratory testing Ø Signs of abnormal bleeding Ø Measures to prevent bruising, bleeding, and tissue injury Ø Copyright © 2017, Elsevier Inc. All rights reserved. 56

Anticoagulants: Patient Education (Cont. ) Education should include: (Cont. ) Wearing a medical alert bracelet Ø Avoiding foods high in vitamin K (tomatoes, dark leafy green vegetables) Ø Consulting physician before taking other drugs or over -the-counter products, including herbals Ø Copyright © 2017, Elsevier Inc. All rights reserved. 57

Antiplatelet Drugs: Nursing Implications Concerns and teaching tips same as for anticoagulants Drug–drug interactions Adverse reactions to report Monitoring for abnormal bleeding Copyright © 2017, Elsevier Inc. All rights reserved. 58

Thrombolytic Drugs: Nursing Implications Follow strict manufacturer’s guidelines for preparation and administration. Monitor IV sites for bleeding, redness, and pain. Monitor for bleeding from gums, mucous membranes, nose, and injection sites. Observe for signs of internal bleeding (decreased blood pressure, restlessness, increased pulse). Copyright © 2017, Elsevier Inc. All rights reserved. 59

Case Study The nurse is caring for a patient receiving IV heparin therapy for treatment of a pulmonary embolus. The patient is being converted to warfarin (Coumadin) therapy. The following questions relate nursing considerations when caring for this patient. Copyright © 2017, Elsevier Inc. All rights reserved. 60

Case Study (Cont. ) 1. Nursing considerations for conversion of IV heparin to oral warfarin (Coumadin) therapy will include: A. immediate discontinuation of IV heparin and administration of oral warfarin (Coumadin) therapy only. B. overlapping therapy of IV heparin and warfarin are for at least 5 days. C. monitoring the INR and stopping the IV heparin when the INR is 1. 0. Copyright © 2017, Elsevier Inc. All rights reserved. 61

Case Study (Cont. ) 2. When converting from IV heparin to oral warfarin (Coumadin) therapy, the prescriber monitors which of the following to determine the next appropriate dose of warfarin? A. B. C. D. Platelet levels a. PTT Red blood cell count PT/INR Copyright © 2017, Elsevier Inc. All rights reserved. 62

Case Study (Cont. ) 3. Which of the following should the nurse include when providing dietary teaching for the patient receiving warfarin (Coumadin) therapy? A. Avoid drinking large amounts of green tea. B. Cranberry juice will provide you with needed nutrients while taking Coumadin. C. You must never eat spinach. D. You can only eat lettuce once a month. Copyright © 2017, Elsevier Inc. All rights reserved. 63

Case Study (Cont. ) 4. The patient accidentally takes too much of the prescribed warfarin (Coumadin) and is readmitted to the hospital with bleeding. The nurse anticipates administration of A. B. C. D. protamine sulfate. alteplase (Activase, Cathflo Activase). reteplase (Retavase). vitamin K. Copyright © 2017, Elsevier Inc. All rights reserved. 64