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Chapter 9 Agents that Affect Coagulation Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 1 Define terms related to blood coagulation and medications that affect coagulation. Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 1 Anticoagulants Coagulation (clotting) factors A series of twelve factors essential to normal blood clotting Coagulants Agents that inhibit blood clotting Agents that promote, accelerate, or make possible blood coagulation Hemostatics Agents that enhance clot formation and reduce bleeding Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 1 Parenteral Administration route other than the alimentary canal (e.g., intramuscular, intravenous, subcutaneous) Platelet aggregation Clumping together of platelets; part of a sequential mechanism leading to blood clot (thrombus) formation Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 1 Systemic Thrombolytics (fibrinolytics) Pertaining to or affecting the body as a whole Agents that dissolve blood clots Thrombosis Abnormal formation or presence of a blood clot within a blood vessel Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2 Describe the physiology of blood clot formation. Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Blood naturally has Coagulants Anticoagulants Blood must flow smoothly But not from a damaged vessel Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Natural coagulants For small vessels only • Example: paper cut on finger Prevents some blood loss Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Natural anticoagulants Prevent undesired clotting in undamaged vessels Interfere with clotting sequence Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Physiology of clotting is a Cascade in 3 stages Stage 1: thromboplastin Stage 2: thrombin Stage 3: fibrin Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. (pg 198) Objective 2. Physiology of Clotting Stage 1: 2 mechanisms Extrinsic — initiated by • Factors outside blood Intrinsic — initiated by • Factors contained in blood Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Stage 1: extrinsic Damaged tissue releases Factor III (t. thromboplastin) Plus factor VIII and Ca+ = Activated factor X, plus factor V plus Ca+ = thromboplastin Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Stage 1: intrinsic Damaged vessel releases Factor XII activates factor XI Activates factor IX Factor VIII and Ca+ = Activated factor X, plus factor V plus Ca+ = thromboplastin Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting So, Stage 1 is the formation of: Thromboplastin (Prothrombin activator) Two pathways to achieve it Intrinsic Extrinsic Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Stage 2: Thromboplastin converts Prothrombin (factor II) into thrombin Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Stage 3: Thrombin converts Fibrinogen (factor I) into fibrin Fibrin is a mesh of protein threads; a net to form clot. Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting A cascade requires many substances In the correct amount At the correct time Remove 1 substance = no cascade = no clot Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Calcium (Ca+) is required at all stages to enable critical steps. Vitamin K is also required to synthesize several factors. Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 2. Physiology of Clotting Clotting in an intact vessel Thrombosis Arterial requires surgery Venous usually treated medically Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 3 List agents that affect coagulation by category. Presented under the discussion of each category Make drug cards for each Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 4 Identify the category of various agents that effect coagulation. Each category will be presented with discussion. Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 5 State the purpose of each category of medications that effect coagulation. Presented during discussion Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 6 Describe the action of medications that affect coagulation. Presented during discussion of each agent. Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7 List uses, routes of administration, side effects, and contraindications for agents that affect coagulation. – Presented during discussion of each agent. Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Note: all categories/agents These categories and agents do one of two things: Assist natural clotting or Prevent natural clotting Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants Category: (objective 4) Hemostatics Purpose: (objective 5) Promote, accelerate, or make possible blood clotting Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Hemostatics Absorbable gelatin Agents: (objective 3) Action: (objective 6) Primarily mechanical, with pressure to promote clot formation Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Absorbable Gelatin Uses General surgery, otologic, orthopedic, neurosurgery Administration routes Topical only Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Absorbable Gelatin Side effects N/A Contraindications Presence of infection Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Hemostatics Agents: (objective 3) Microfibrillar collagen • Avitene; Instat MCH • Image Pg 203 Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Hemostatics Microfibrillar collagen Action: (objective 6) Attracts platelets; triggers platelet aggregation Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Microfibrillar Collagen Uses General surgery, otologic, orthopedic, neurosurgery Administration routes Topical only Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Microfibrillar Collagen Side effects N/A Contraindications presence of infection Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Hemostatics Agents: (objective 3) Oxidized cellulose • Surgicel, Oxycel Action: (objective 6) Serves as a nucleus for clotting Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Oxidized Cellulose Uses Neurosurgery, otorhinolaryngology Administration routes Topical only Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Oxidized Cellulose Side effects N/A Contraindications Presence of infection Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Hemostatics Agents: (Objective 3) Absorbable collagen sponge • Hemopad, Helistat, Collastat Action: (Objective 6) Promotes platelet aggregation Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Absorbable Collagen Sponge Uses General surgery Administration routes Topical only Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Absorbable Collagen Sponge Side effects N/A Contraindications Not used on bone when using cement Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Absorbable Collagen Sponge Agent: Superstat Contains calcium Action: Activates body’s coagulation mechanism Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Absorbable Collagen Sponge Uses Route Topical Side effects General surgery N/A Contraindications Neurosurgery Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Hemostatics Agents: (Objective 3) Thrombin Action: (Objective 6) Catalyzing the conversion of fibrinogen to fibrin Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Thrombin Uses General surgery Administration routes Topical ONLY Can cause systemic clotting if injected! Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Thrombin Side effects N/A Contraindications – hypersensitivity Pg 204 Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Hemostatics Agents: (objective 3) Bone wax Action: (objective 6) Mechanical only, physical plug Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Bone Wax Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. (pg 205) Objective 7. Bone Wax Uses Administration routes Topical Side effects Orthopedics, neurosurgery N/A Contraindications Hypersensitivity Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Hemostatics Agents: (Objective 3) Chemical Hemostatics • Tannic acid • Silver nitrate Action: (Objective 6) Cauterization Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Chemical Hemostatics Uses Tannic acid (in combination) • Tonsillectomy Silver nitrate • Remove warts Admin route Topical Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Chemical Hemostatics Side effects N/A Contraindications Not for use near eyes Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Hemostatics Agents: (Objective 3) Chemical Hemostatics • Monsel’s solution Action: (Objective 6) Cauterization Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Monsel’s Solution Uses Admin route Topical Side effects Hemostasis for cervical cone biopsy N/A Contraindications N/A Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Chemical Hemostatics CAUTION: Do NOT confuse Monsel’s solution with Lugol’s solution, which is a staining agent Both are iodine-based and brown in color Both may be on back table for cervical conization Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants Category: (Objective 4) Systemic coagulants Purpose: (Objective 5) Replace deficiencies in natural clotting mechanism Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Systemic Agents: (Objective 3) Calcium salts Action: (Objective 6) Promotes clotting in all 3 stages of cascade Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Calcium salts Uses Replace deficiency Preoperative or intraoperative Administration routes Surgery — IV Medical — oral or IM Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Calcium salts Side effects N/A Contraindications MH susceptible patients Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Systemic Agents: (Objective 3) Vitamin K Action: (Objective 6) synthesis of prothrombin by liver Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Vitamin K Uses: replace deficiency Preoperative Administration routes Subcutaneous RARE: IV Side effects N/A Contraindications N/A Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Coagulants: Systemic Agents: (Objective 3) Coagulation factors VIII (AHF) & IX complex Action: (Objective 6) Vital links in cascade Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Coagulation factors Uses: replace deficiency Administration routes IV Side effects Preoperative N/A Contraindications N/A Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Anticoagulants Category: (Objective 4) Parenteral anticoagulants Purpose: (Objective 5) Prevent or interfere with clotting Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Anticoagulants: Parenteral Agents: (Objective 3) Heparin Action: (Objective 6) Inhibits factor X and thrombin Inhibits platelet aggregation Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Heparin Uses All vascular and cardiac surgery Administration routes IV, subq Topical (at surgical site) Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Heparin Side effects risk hemorrhage Thrombocytopenia Contraindications Existing thrombocytopenia Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Heparin Note: heparin strengths must be labeled Image pg 212 Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Anticoagulants: Parenteral Agents: (Objective 3) Enoxaparin (Lovenox) A LMW form of heparin Action: (Objective 6) Inhibits factor X and thrombin Inhibits platelet aggregation Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Lovenox Uses Prevent DVT following hip or knee replacement Medical, not surgical use Administration routes Subcutaneous Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Lovenox Side effects Local irritation, pain Fever, nausea Contraindications Active major bleeding Hypersensitivity Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Anticoagulants Category: (Objective 4) Oral anticoagulants Purpose: (Objective 5) Long-term management of thromboembolic disease • PE, DVT, CVA Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Anticoagulants: Oral Agents: (Objective 3) Warfarin (Coumadin) Action: (Objective 6) Inhibits vitamin K activity in liver Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Warfarin Uses Long-term management of • DVT, PE, CVA Administration routes Oral Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Warfarin Side effects Epistaxis, hematuria, bleeding gums Contraindications Do not use concurrently with aspirin Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Warfarin and Aspirin Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. (pg 27) Anticoagulants: Oral Agents: (Objective 3) Aspirin Action: (Objective 6) Inhibits platelet aggregation Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. aspirin Uses (pertaining to clotting) Post-MI, post-TIA: prevent additional clot formation Administration routes Oral Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Aspirin Side effects Normal bleeding time may be doubled Contraindications Not for use concurrent with warfarin therapy Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Anticoagulants Category: (Objective 4) Thrombolytics Purpose: (Objective 5) Break down existing blood clots Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Anticoagulants: Thrombolytics Agents: (Objective 3) Streptokinase, urokinase, antistreplase Action: (Objective 6) Activate plasminogen Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Thrombolytics Uses Acute MI w/coronary artery thrombosis Treatment of DVT, PE Administration routes IV Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Thrombolytics Side effects Hemorrhage, skin rash, itching, nausea, headache Contraindications Hypersensitivity Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Anticoagulants: Thrombolytics Agents: (Objective 3) Alteplase (Activase) Action: (Objective 6) Human enzyme; tissue-type plasminogen activator (tPA) Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Alteplase Uses Acute MI w/coronary artery thrombosis Treatment of DVT, PE, CVA Administration route IV Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 7. Alteplase Side effects Fewer due to human origin of enzyme Contraindications N/A Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 8 Describe the impact of preoperative oral anticoagulant therapy on the surgical patient. Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 8 Bleeding times will be prolonged. Meticulous hemostasis is necessary Have additional hemostatic aids available Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 9 List examples of surgical procedures in which agents that affect coagulation may be administered. Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 9 General surgery Cholecystectomy (liver bed) Liver resection/trauma Spleen or kidney repair Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 9 Orthopedics Total hip/knee arthroplasty Spinal fusion Neurosurgery Craniotomy Spinal surgery Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 9 Peripheral vascular AAA Carotid endarterectomy Femoral embolectomy Venous access procedures Dialysis graft insertion Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 9 Cardiovascular CABG Valve replacement/repair Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 10 Compare and contrast administration route, onset of action, antagonist, and purpose of parenteral and oral anticoagulants. Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 10 Compare and contrast Ask yourself: How are these alike? How are they different? Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 10: Administration route Different Parenteral anticoagulants IV, subq, topical Oral anticoagulants Oral only Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 10 Onset of action: Different Parenteral anticoagulants Heparin = 5 minutes Oral anticoagulants Warfarin = 12-72 hours Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 10 Antagonist Different Parenteral anticoagulants Protamine sulfate Oral anticoagulants Vitamin K (for warfarin) Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc. Objective 10 Purpose: Similar purpose but different indications Both prevent clots Parenteral anticoagulants Short-term treatment/surgery Oral anticoagulants Long-term management Elsevier items and derived items © 2006 by Saunders, an imprint of Elsevier Inc.