Coagulation Modifying Drugs: Nursing Pharmacology Study Guide

Coagulation Drugs: Generic and Brand Names

• Antiplatelet Agents
  • acetylsalicylic acid (Aspirin, Aspro Clear, Disprin, Bayer Aspirin)
  • cilostazol (Pletal)
  • dipyridamole (Persantine)
  • tirofiban (Aggrastat)
• Anticoagulants
  • warfarin (Coumadin)
  • dabigatran (Pradaxa)
  • rivaroxaban (Xarelto)
• Thrombolytic Agents
  • alteplase (Activase)
  • reteplase (Retavase)
  • tenecteplase (TNKase)
  • urokinase (Abbokinase)
• Low-molecular-weight Heparins
  • dalteparin (Fragmin)
  • enoxaparin (Lovenox)
  • tinzaparin (Innohep)
• Anticoagulant Adjunctive Therapy
  • lepirudin (Refludan)
  • protamine sulfate
  • vitamin K
• Hemorrheologic Agent
  • pentoxifylline (Trental)

Disease Spotlight: Thromboembolic and Hemorrhagic Disorders

Coagulation disorders split into two camps. Thromboembolic disorders (such as CAD) overproduce clots, cutting blood flow and occluding vessels, with hypoxia, anoxia, and even necrosis as the result; they are treated with drugs that interfere with normal coagulation to prevent clots. The less common hemorrhagic disorders feature ineffective clotting and excessive bleeding, and are treated with drugs that promote clotting. They include hemophilia (genetic lack of clotting factors), liver disease (no production of the proteins and clotting factors needed to form a clot), and bone marrow disorders (too few platelets, or ineffective ones).

Antiplatelet Agents

Antiplatelet agents make platelets less responsive to the stimuli that make them clump, so the platelet plug shrinks.

Therapeutic action. Blocking receptor sites on the platelet membrane inhibits platelet adhesion and aggregation and prevents platelets from interacting with each other and with clotting chemicals.

Indications. Mainly cardiovascular disease with a risk of vessel occlusion. Also maintenance of arterial and venous grafts, prevention of cerebrovascular occlusion, and adjunct to thrombolytic therapy for myocardial infarction. One drug, anagrelide, blocks platelet production in the bone marrow.

Contraindications and cautions:

• Allergy to antiplatelet agents. Prevents severe hypersensitivity reactions.
• Known bleeding disorder. Increased risk of excessive blood loss.
• Recent surgery. Increased risk of bleeding in unhealed vessels.
• Closed head injuries. Increased risk of bleeding in injured brain vessels.
• History of thrombocytopenia. Anagrelide decreases bone marrow platelet production.
• Pregnancy, lactation. Generally inadvisable because of potential adverse effects on the fetus or neonate.

Adverse effects. Headache, dizziness, weakness; GI distress, nausea; skin rash; bleeding (often noticed while brushing the teeth).

Interactions. Increased risk of bleeding when combined with another drug that affects clotting.

Anticoagulants

Anticoagulants interrupt the clotting cascade and thrombin formation.

Therapeutic action. Warfarin, the oral agent, reduces vitamin K-dependent clotting factors, which prolongs clotting. Two newer oral agents, dabigatran and rivaroxaban, directly inhibit thrombin (the last step in clotting) and factor Xa, respectively. Heparin and antithrombin block the formation of thrombin from prothrombin.

A note on the adjunctive list: lepirudin (Refludan) was discontinued by its manufacturer in 2012, so it is no longer available. The direct thrombin inhibitors used today for heparin-induced thrombocytopenia (HIT) are argatroban and bivalirudin (Anticoagulation, StatPearls).

Indications. Reduction of stroke and systemic emboli risk, nonvalvular atrial fibrillation, and deep vein thrombosis. Heparin prevents clots in blood samples, dialysis, and venous tubing; because it does not enter breast milk, it is the anticoagulant of choice for lactating women. Antithrombin is a naturally occurring anticoagulant and a built-in safety feature of the clotting system.

Contraindications and cautions:

• Allergy to anticoagulants. Prevents severe hypersensitivity reactions.
• Known bleeding disorder, recent trauma or surgery, indwelling catheters, threatened abortion, GI ulcers. All compromised by increased bleeding tendencies.
• Pregnancy, lactation. Warfarin is contraindicated.

Adverse effects. Warfarin is associated with alopecia, dermatitis, bone marrow depression, and less often prolonged, painful erections. Direct drug toxicity shows as nausea, GI upset, diarrhea, and hepatic dysfunction.

Interactions. Anticoagulants, salicylates, penicillin, and cephalosporin increase bleeding when combined with heparin. Nitroglycerin decreases anticoagulation when combined with heparin. Cimetidine, clofibrate, glucagon, and erythromycin increase bleeding when combined with warfarin. Vitamin K, phenytoin, rifampin, and barbiturates decrease anticoagulation when combined with warfarin. Antifungals, erythromycin, phenytoin, and rifampin alter the metabolism of dabigatran and rivaroxaban.

Thrombolytic Agents

Thrombolytics drive clot resolution by activating the plasmin system to break down a clot that has already formed.

Therapeutic action. The conversion of plasminogen to plasmin is the body's natural anticlotting system. Thrombolytics activate it, breaking down fibrin threads and dissolving formed clots to prevent vessel occlusion and restore blood flow.

Indications. Acute MI, pulmonary embolism, and acute ischemic stroke. Also clearing occluded IV catheters and central venous access devices.

Contraindications and cautions:

• Allergy to thrombolytics. Prevents severe hypersensitivity reactions.
• Known bleeding disorder, recent trauma or surgery, acute liver disease, cerebrovascular accident within 2 months, GI ulcers. All affect normal clotting factors and plasminogen production.
• Pregnancy, lactation. Potential adverse effects on the fetus or neonate.

Adverse effects. Cardiac arrhythmias, hypotension; bleeding (most common); uncommon hypersensitivity reaction with rash, flushing, and bronchospasm.

Interactions. Anticoagulants and antiplatelets increase the risk of bleeding.

Pharmacokinetics

Antiplatelet Agents

Anticoagulants

Thrombolytic Agents

Coagulation Drugs Across Age Groups

In children, only heparin and warfarin are indicated for the antiplatelet and anticoagulant uses, and both demand careful dose calculation; thrombolytics are not indicated for this age group. Adults need injury-prevention teaching (electric razor, soft-bristled toothbrush), instruction on what to do if bleeding occurs (apply firm pressure) and which bleeding signs to watch for, and documentation of all other drugs because interactions are heavy; emphasize that periodic blood tests track the therapy. In pregnancy, these drugs are inadvisable unless the benefit to the mother clearly outweighs the risk to the fetus, and they are generally inadvisable during lactation. Older adults are more susceptible to drug toxicity and drug-to-drug interactions, so monitor liver and kidney function and start at the lowest possible level, adjusting accordingly.

Nursing Considerations

Nursing Assessment

Screen for the contraindications above (hypersensitivity, acute liver disease, pregnancy, and for thrombolytics a CVA within 2 months). Do a thorough baseline physical assessment. Obtain baseline complete blood count and clotting studies, plus a fecal occult blood test (FOBT) before thrombolytic therapy, to catch potential adverse effects.

Nursing Diagnoses

• Disturbed sensory perception related to CNS effects (antiplatelet)
• Acute pain related to CNS and GI effects (antiplatelet)
• Ineffective tissue perfusion related to blood loss (anticoagulant)
• Disturbed body image related to drug toxicity with rash and alopecia (anticoagulant)
• Decreased cardiac output related to arrhythmias and bleeding potential (thrombolytic)
• Risk for injury related to bleeding tendencies, bone marrow depression, or clot-dissolving effects

Implementation with Rationale

Give antiplatelet drugs with meals to ease GI upset, and treat headache because the pain can cut compliance. Across all three classes, teach safety habits (electric razor, soft-bristled toothbrush, cautious movement) because any injury can precipitate bleeding, and assess for signs of blood loss (petechiae, bruises, dark stools). Establish safety precautions: raise side rails, ensure adequate lighting, and pad the bed sides.

For anticoagulants, keep antidotes at the bedside: protamine sulfate for heparin, vitamin K for warfarin. The direct oral anticoagulants have their own reversal agents for life-threatening bleeding: idarucizumab (Praxbind) reverses dabigatran, and andexanet alfa (Andexxa) reverses the factor Xa inhibitors apixaban and rivaroxaban (Reversal of Direct Oral Anticoagulants, Anticoagulation Forum). Monitor effectiveness with prothrombin time (PT) and international normalized ratio (INR) for warfarin, and whole blood clotting time (WBCT) and activated partial thromboplastin time (APTT) for heparin. For thrombolytics, monitor coagulation studies and adjust the dose accordingly. Educate every patient on the drug name, indication, and adverse effects to watch for.

Evaluation

Monitor the response to therapy (increased bleeding time, prevention of occlusive events, dissolution of the clot and return of blood flow) and for adverse effects (bleeding, bone marrow depression, alopecia, anemia, hypotension). Confirm the patient can name the drug, its indication, and the adverse effects to watch for, and monitor compliance.

Frequently Asked Questions

What is the antidote for heparin, and for warfarin? Protamine sulfate reverses heparin; vitamin K (phytonadione) reverses warfarin. Keep the matching agent on hand whenever a patient is anticoagulated.

How are the newer oral anticoagulants reversed? They have specific reversal agents for serious bleeding: idarucizumab (Praxbind) for dabigatran, and andexanet alfa (Andexxa) for the factor Xa inhibitors apixaban and rivaroxaban. Vitamin K and protamine do not reverse these drugs.

Which labs monitor warfarin versus heparin? Warfarin is followed with PT and INR. Unfractionated heparin is followed with aPTT (and whole blood clotting time). Low-molecular-weight heparins like enoxaparin usually need no routine monitoring.

Why is lepirudin no longer used? Its manufacturer discontinued it in 2012. Argatroban and bivalirudin are the direct thrombin inhibitors now used to anticoagulate patients with heparin-induced thrombocytopenia.

What is the headline risk across all of these drugs? Bleeding. Whether the patient is on an antiplatelet, an anticoagulant, or a thrombolytic, you are watching for petechiae, bruising, dark or bloody stools, and bleeding gums, and you know where the reversal agent lives.