Hemostasis Drugs Class PDF

Hemostasis Modifier Drugs Chapter 55 Objectives Review the role of certain plasma proteins in the coagulation pathway Review the role of platelets in clot formation Identify the drugs used and their mechanism of action in reducing coagulation Understand how drugs acting on platele...

Hemostasis Modifier Drugs Chapter 55 Objectives Review the role of certain plasma proteins in the coagulation pathway Review the role of platelets in clot formation Identify the drugs used and their mechanism of action in reducing coagulation Understand how drugs acting on platelets reduce platelet activation/aggregation Describe the actions of antifibrinolytic agents (promote clot retension) Understand how thrombolytic agents act Hemostasis Process that halts bleeding after injury to a blood vessel 1. Formation of a platelet plug 2. Production of fibrin end result of the clotting cascade involving a large number of plasma proteins (clotting factors) Platelet Aggregation Blood Clot Hemostasis Modifier Agents Anticoagulants Inhibit the action or formation of clotting factors Prevent clot formation Antiplatelet drugs Inhibit platelet aggregation Prevent platelet plugs Hemostasis Modifier Agents Thrombolytic drugs Lyse (break down) existing clots Hemostatic agents Promote blood coagulation Anticoagulants Patient Thrombosis Information Thrombosis Canada Clotting Cascade Each activated factor serves as a catalyst that amplifies the next reaction Fibrin is final clotting product Coagulation cascade is divided into intrinsic pathway extrinsic pathway Anticoagulants - “Blood thinners” Used prophylactically to prevent Clot formation (thrombus) Emboli (dislodged clot) Do NOT lyse existing clots Anticoagulants: Indications Used to prevent clot formation in certain settings Myocardial infarction Unstable angina Atrial fibrillation DVT eg major orthopedic surgery Indwelling devices, such as mechanical heart valves Pulmonary embolism Anticoagulants All prevent clot formation Heparin and Low-molecular-weight heparins (LMWH) Warfarin – oral Direct-Acting Oral Anticoagulants (DOACs) Direct Factor X & Thrombin inhibitors Anticoagulants: Contraindications Known drug allergy Acute bleeding process Thrombocytopenia Anticoagulants: Adverse Effects Bleeding Risk gums bleed nosebleeds unusual bruising anemia/low Hct (hematocrit) tarry stools Heparin and LMWH Heparin Heparin indirectly inhibits activity of multiple proteins on cascade Thrombin (II) Factor Xa Other factors in intrinsic pathway Natural Heparin From animal sources Anticoagulants - Heparin Heparin - dosage unpredictable Monitored by activated partial thromboplastin times (aPTT) aPTT measure of the intrinsic pathway aPTTs need to be 1.5 – 2.5 x greater than control (40 sec) Anticoagulants - Heparin Heparin Parenteral – IV or SC Effective within minutes Short half-life (1 to 2 hours) Anticoagulants - Heparin Heparin Heparin-induced thrombocytopenia (HIT) 1-5% population (>4 days of administration) stop heparin administration + use alternative Hypersensitivity reactions urticaria, fever, chills Anticoagulant effects reversed by protamine sulfate antidote Anticoagulants - LMWHs Low-molecular-weight heparins (LMWHs) Enoxaparin, tinzaparin and dalteparin More predictable anticoagulant response Do not require frequent laboratory monitoring often given at home SC (every 12 hours) LMWH Anticoagulants - LMWH LMW Heparins indirectly inhibits Factor X only thrombocytopenia (less than heparin?) protamine sulphate antidote Anticoagulants Other drugs Danaparoid structurally distinct from heparin alternative to heparin SC or IV fondaparinux synthetic SC or IV Client Implications: Heparin Doses usually double-checked with another nurse Ensure that SC doses are given SC, NOT IM SC doses should be given in areas of deep subcutaneous fat, prefer abdomen sites rotated (also for LMWH) Protamine sulphate antidote Client Implications: LMWHs Subcutaneously in ABDOMEN ONLY Rotate sites around lower abdomen below umbilicus Protamine sulphate antidote Oral Anticoagulants: Warfarin Anticoagulants - Oral Warfarin (modified coumarin) Winconsin Alumni Research Foundation Cattle fed sweet clover, not corn Epidemic in hemorragic deaths in cattle Contained anticoagulant - very similar to coumarin Anticoagulants - Warfarin Vitamin K “antagonist”  warfarin - Enzyme + Precursors of Vitamin K “Ready for clotting factors action” (II,VII,IX,X) clotting factors Liver Cell Anticoagulants - Warfarin Vitamin K essential for production of several clotting factors (VII, IX, X, pro- thrombin) in liver cells Reduce “ready for action” clotting factors in plasma clotting time extended Anticoagulants - Warfarin Effects depends on clotting factors turnover (protein degradation) Max effect may take 3-5 days start within 24 h Patients may be started on 5 days LMWH + warfarin then LMWH withdrawn Anticoagulants warfarin (Coumadin) Orally only Dosage variable between individuals Monitored by clotting lab test prothrombin time (PT) INR (international normalization reference ratio) Corrects for lab-to-lab variability in test kits PT/INR measure activity of extrinsic pathway Anticoagulants PT to be therapeutic is 1.3 -1.5 times the normal (control) level Normal target INR range 2 to 3 x control Some need to be 2.5 to 3.5 (normal is 0.8 to 1.2) eg mechanical heart valves INR comparable between laboratories Anticoagulants FYI INR = (PTobserved/PTcontrol)ISI ISI = international sensitivity index when using an international reference preparation as standard control Anticoagulants: Warfarin What happens to warfarin effectiveness when too much vitamin K in diet? What happens to warfarin effectiveness when too little vitamin K in diet? Warfarin excess? Anticoagulants: Warfarin Vitamin K can be given if excessive PT/ INR IV (slow infusion) 4-8 h effect PO effect within 24 h FYI Vitamin K for newborns within 6 h Prophylaxis of vitamin K deficiency bleeding (VKDB) IM (PO, if IM refused but less effective) Anticoagulants: Warfarin Contraindicated in Pregnancy Risks of fetal bleeding, teratogenicity and spontaneous abortion Use LMWH Client Education: Anticoagulants Maintain intake of vitamin K constant (tomatoes, dark leafy green vegetables) Wearing a medical alert bracelet Consult physician before taking other drugs or OTC products, including natural health/herbal products MANY drug-drug interactions metabolism via CYP enzymes Client Education: Warfarin May be started while the client is still on heparins until prothrombin times/INR indicate adequate anticoagulation Full therapeutic effect takes several days Monitor PT/INR regularly Direct-Acting Oral Anticoagulants (DOACs) Direct-Acting Oral Anticoagulants (DOACs) Advantages over warfarin rapid onset & offset fixed doses no blood test few drug-drug interactions no dietary concerns lower risk of bleeds Anticoagulants Direct thrombin inhibitor Dabigatran po administration 5-10 d LMWH lead-in for DVT GI disturbance N&V, abdominal pain, bloating Anticoagulants - DOACs Direct Factor Xa Inhibitors rivaroxaban apixaban betrixaban edoxaban (5-10 d LMWH lead-in for DVT po administration Anticoagulants - DOACs Antidotes dabigatran - Idarucizumab (antibody) Factor X inhibitors - andexanet alfa (modified Factor X) All DOACs Annual renal function test if below min function, changed to Vit K antagonist Anticoagulants – Adverse Effects Reminder - For all anticoagulants Increased bleeding from mild to life-threatening All Anticoagulants: Client Education Importance of regular lab testing where necessary Signs of abnormal bleeding bleeding of gums while brushing teeth unexplained nosebleeds bruising heavier menstrual bleeding bloody or tarry stools, vomiting blood bloody urine or sputum abdominal pain Antiplatelet Agents Antiplatelet Agents Prevent platelet activation Acetylsalicylic acid (Aspirin) - 81 mg EC Inhibit cyclooxygenase pathway (COX) – what product is important? Irreversible inhibition of COX in platelets Pentoxifylline Antiplatelet Drugs Prevent platelet activation clopidogrel (Plavix), prasugrel, ticlopidine irreversible ADP receptor blocker effect lasts life-time of platelet ticargrelor reversible ADP receptor blocker Antiplatelet Drugs: Indications Antithrombotic effects Reduce MI risk Reduce stroke risk Antiplatelet Agents Aspirin + clopidogrel combination produces additive antiplatelet activity But increased bleeding potential Antiplatelet Agents GPIIb/IIIa Antagonists receptor on platelets activated by TXA2, ADP, 5-HT, others required for fibrinogen cross-linking = platelet aggregation antagonists prevent fibrinogen cross-linking abciximab (antibody - irreversible) tirofiban (reversible) Client Implications: Antiplatelet Drugs Concerns and teaching tips same as for anticoagulants Thrombolytic Agents (fibrinolytic agents) Thrombolytic Drugs Drugs that break down preformed clots Recombinant tissue plasminogen activator (tPA) Alteplase (slow infusion, short T1/2) tenecteplase (single bolus, long T1/2) Reteplase (2xbolus, long T1/2)  Plasminogen (inactive plasma protein) Drug Recombinant tPA tPA (natural substance) eg alteplase Plasmin (active protein) Fibrinolysis Thrombolytic Agents: Mechanism of Action Activate fibrinolytic system to break down clot in blood vessel Activate plasminogen and convert it to plasmin, which can digest fibrin Re-establishes blood flow to heart muscle via coronary arteries (MI) brain (stroke) Thrombolytic Agents: Indications Acute MI Arterial thrombolysis DVT Occlusion of shunts or catheters Pulmonary embolus CONTRAINDICATIONS: Allergy concurrent use of other anticoagulation Thrombolytic Agents: Adverse Effects BLEEDING Internal Intracranial Superficial Other effects Nausea, vomiting, hypotension, anaphylactoid reactions Dysrhythmias Antifibrinolytic Agents Antifibrinolytic Agents Some prevent the lysis of fibrin in an existing clots clot remains Improve clotting factor survival Promote clot formation and / or clot maintenance Antifibrinolytic Agents aminocaproic acid, tranexamic acid (TXA) inhibits fibrinolysis blocks plasminogen activation trauma, antidote to thromolytic agents eg alteplase - aminocaproic acid Antifibrinolytic Agents desmopressin (synthetic pituitary hormone) Similar to vasopressin (ADH) used in the treatment of diabetes insipidus Mild hemophillia A (VIII deficiency) increases plasma concentration of factor VIII (by von Willibrand factor release from endothelial cells) Antifibrinolytic Agents: Indications Prevention and treatment of excessive bleeding Hyperfibrinolysis Surgical complications Excessive oozing from surgical sites such as chest tubes Reducing total blood loss and duration of bleeding in the postoperative period Antifibrinolytic Agents: Contraindications Allergy to agent Never used in DIC (disseminated intravascular coagulation) very rare but critical uncontrolled clotting Antifibrinolytic Agents: Adverse Effects Uncommon and mild Rare reports of thrombotic events