Drug Therapy for Coagulation Disorders

Chapter 9: Drug Therapy for Coagulation Disorders

Learning Objectives

  • After studying this chapter, you should be able to:

    • Describe important elements in the physiology of hemostasis and thrombosis.

    • Discuss possible consequences of blood clotting disorders.

    • Compare and contrast heparin and warfarin in terms of indications for use, onset and duration of action, route of administration, blood tests used to monitor effects, and nursing process implications.

    • Discuss antiplatelet agents in terms of indications for use and effects on blood coagulation.

    • Discuss direct thrombin inhibitors in terms of indications and contraindications for use, routes of administration, and major adverse effects.

    • Discuss direct factor Xa inhibitors in terms of indications and contraindications for use, routes of administration, and major adverse effects.

    • Describe thrombolytic agents in terms of indications and contraindications for use, routes of administration, and major adverse effects.

    • Identify the prototype drug for each drug class.

    • Describe systemic hemostatic agents for treating overdoses of anticoagulant and thrombolytic drugs.

    • Implement the nursing process in the care of patients receiving anticoagulant, antiplatelet, and thrombolytic agents.

Clinical Application Case Study

  • Andrew Oliver, a 45-year-old man, presenting with acute anterior ST elevation myocardial infarction.

    • Received alteplase by continuous intravenous infusion over 3 hours.

    • Received IV bolus of heparin and started on a heparin drip.

    • Nursing responsibilities include monitoring response and side effects.

Key Terms

  • Anticoagulants: drugs that prevent formation of new clots and extension of existing clots; do not dissolve formed clots.

  • Antiplatelet drugs: drugs that prevent steps in prothrombotic activity of platelets.

  • Embolus: object that migrates through circulation and lodges in a blood vessel, causing occlusion.

  • Fibrinolysin: enzyme that breaks down fibrin meshwork stabilizing blood clots; also called plasmin.

  • Hemostasis: prevention or stoppage of blood loss from an injured blood vessel, maintaining vascular integrity.

  • Heparin-induced thrombocytopenia (HIT): immune-mediated adverse effect leading to thrombogenesis and decreased platelet count associated with heparin.

Introduction to Coagulation Disorders

  • Anticoagulant, antiplatelet, and thrombolytic drugs are crucial in managing thrombotic and thromboembolic disorders.

  • Thrombogenesis: normal body mechanism to prevent blood loss; life-saving in hemorrhage, but may lead to life-threatening situations by obstructing blood vessels.

Overview of Coagulation Disorders

Physiology of Hemostasis

  • Hemostasis involves:

    • Vasoconstriction.

    • Formation of a platelet plug.

    • Activation of clotting factors in blood.

    • Growth of fibrous tissue (fibrin).

  • Illustrates complex interactions between activators and inhibitors, including endothelial factors, platelets, and coagulation factors.

Blood Coagulation Process

  • Occurs within 1 to 2 minutes and involves:

    • Release of thromboplastin from platelets and tissue.

    • Conversion of prothrombin to thrombin, requiring thromboplastin and calcium ions.

    • Conversion of fibrinogen to fibrin by thrombin.

  • Two pathways: intrinsic (in blood vessels) and extrinsic (in tissues), leading to the common pathway of thrombin formation.

Clot Lysis

  • Involves plasminogen, which is activated to plasmin (fibrinolysin) to dissolve clots once blood flow is restored and the vessel is repaired.

Etiology of Thrombosis

  • Constant formation and dissolution of thrombi maintain fluid blood.

  • Arterial thrombosis: linked with atherosclerotic plaque, hypertension, and turbulent flow resulting in blockage and ischemia.

  • Venous thrombosis: associated with venous stasis, leading to thrombus formation and potential embolization to the lungs.

Clinical Manifestations

  • Arterial clots can cause diseases like stroke, myocardial infarction, or pulmonary embolism.

  • Venous blood clots may present as DVT, with symptoms including leg swelling and pain, though often asymptomatic.

Drug Therapy for Thrombosis

  • Medications aim to alter blood coagulation processes, classified as:

    • Anticoagulants: prevent new clots and extend existing ones; most effective in venous then arterial thrombosis.

    • Antiplatelet drugs: prevent arterial thrombosis.

    • Thrombolytics: dissolve thrombi to limit tissue damage.

Drug Classes Overview

Drug Class

Prototype Drug

Anticoagulant Drugs

Heparin, Dalteparin, Enoxaparin

Vitamin K antagonists

Warfarin

Direct thrombin inhibitors

Dabigatran, Argatroban

Direct factor Xa inhibitors

Rivaroxaban, Apixaban, Edoxaban

Antiplatelet Drugs

Clopidogrel, Aspirin, Prasugrel, Abciximab

Thrombolytic drugs

Alteplase, Tenecteplase

Anticoagulant Drugs
Heparins

  • Heparin: natural anticoagulant derived from various animal sources; acts quickly when given IV, subcutaneous also possible.

  • Mechanism: inhibits clotting factors IX, X, XI, XII by activating antithrombin III.

  • Indications: prevent DVT, PE, manage acute thromboembolic disorders.

  • Dosage and Administration: IV injection provides immediate action; subcutaneous varies from 20-30 minutes.

Nursing Process for Anticoagulant Therapy

  • Monitoring: Assess aPTT (activated partial thromboplastin time) which should be maintained 1.5 to 2.5 times control, norm 25-35 seconds.

  • Assess for Therapeutic Effects: Reduction in symptoms, absence of thrombus formation.

  • Assess for Adverse Effects: Signs of bleeding should be monitored, including involvement of platelet counts, especially with the risk of HIT.

Warfarin

  • Pharmacokinetics: Absorbed orally, highly protein-bound, metabolism in liver.

  • Mechanism: Inhibits vitamin K-dependent factors II, VII, IX, and X; action takes longer (3-5 days post initiation due to existing factor half-lives).

  • Indications: prevention of thromboembolic disorders. Monitor INR (International Normalized Ratio) for effectiveness, generally between 2.0-3.0.

Antiplatelet Agents

  • Clopidogrel: inhibits ADP receptor on platelet surfaces, used to prevent DVT and in acute coronary syndrome (ACS).

  • Aspirin: inhibits thromboxane A2 synthase, leading to irreversible platelet aggregation inhibition.

  • Indications: Prevention of myocardial infarction and other thromboembolic events.

  • Interactions: Monitor for other medications that may potentiate or reduce effect.

Thrombolytic Agents

  • Alteplase (prototype): fast-acting thrombolytic agent; used for STEMI or PE.

  • Mechanism: catalyzes conversion of plasminogen to plasmin, dissolving clots.

  • Indications: Management of severe thromboembolic disease.

Systemic Hemostatic Agents

  • Protamine sulfate: antidote to heparin, acts quickly if given appropriately.

  • Vitamin K: applicable for warfarin overdose management.

  • Idarucizumab: specific for dabigatran reversal; used for uncontrolled bleeding.

  • Aminocaproic acid and tranexamic acid: treat bleeding from thrombolytics.

Patient Education

  • Emphasize adherence to prescribed medications, monitoring laboratory values, and recognizing signs of bleeding/overmedication.

Nursing Implications

  • Collaborative team-based approach essential for patient management especially in emergencies.

  • Awareness on drug interactions and monitoring parameters critical for safety.

Summary

  • A wide array of coagulation and thrombotic agents exist for management of clotting disorders with specific monitoring requirements and potential adverse effects requiring vigilant nursing oversight.