Drugs Affecting Coagulation Objectives p2b3f

DRUGS AFFECTING COAGULATION OBJECTIVES 1. Define the following :  Anticoagulant – substances that keep blood from clotting; prevent blood blots from forming or extending; don’t break down existing clots; given IV, SC, or PO  Clot – thrombus; results from excessive coagulation (hypercoagulation)  Clotting cascade – series of steps initiated by tissue damage and platelet activation, which mobilize clotting factors that are circulating in the blood. Active clotting factors work with Ca++ to form fibrin, which signals completion of blood coagulation and end of blood loss. End result is formation of a stable blood clot. Occurs over 2 pathways: (one or both may be activated in response to injury) o Intrinsic – clotting factors in blood activated by damage to blood vessel o Extrinsic – clotting factors activated by damaged tissue  Clotting factor – plasma protein that causes blood clotting; inactive in blood until mobilized by injury  Coagulation – blood aggregation, clotting  Embolus (embolism) – any undissolved matter carried in a blood or lymph vessel to another location where it lodges and occludes the vessel  Fibrin – an insoluble protein that stabilizes the temporary plug formed by platelets to seal the injured vessel  Fibrinolysis – process of breaking down a formed clot  Hemophilia – uncontrollable bleeding due to genetic deficiencies of normal clotting factors  Hemostasis – series of events to slow blood flow, stop blood loss at injury site, and prevent extensive blood loss when the body begins bleeding  INR (Interational Normalized Ratio) – standardized unit developed to measure therapeutic levels of warfarin; determined by math equation and reflects pt’s PT compared w/ standardized PT value  (Activated) Partial thromboplastin time (aPTT)  Plasmin – activated plasmin lyses the blood clot about 1-2 days after bleeding stops  Platelets (thrombocytes) – fragmented cells that assist in blood clotting and clot formation  Prothrombin time (PT)  Thrombin – converts fibringogen (factor I) to fibrin, and also activated factor XIII (a fibrin-stabilizing factor); thrombin is converted from prothrombin (factor II)

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Thromboembolism – fragment of a thrombus that breaks off, travels through bloodstream and lodges in a vessel to occlude blood flow Thrombus – blood clot; arterial thrombi consist of mostly platelet aggregated held together with thin fibrin strands, and venous thrombi consist of mostly RBCs, a large amount of fibrin, and few platelets Vitamin K – fat-soluble vitamin that is continually produced in GI tract; absorption depends on amount of fat and bile o deficiency of vitamin K   normal clotting factors made   bleeding risk in pts on warfarin o infants more susceptible b/c intestinal flora inactive at birth o high levels decrease warfarin effectiveness

2. Describe the pharmacotherapeutics, pharmacokinetics, pharmacodynamics, adverse effects, Vs, and nursing management of the prototype anticoagulants, heparin and warfarin. ANTICOAGULANTS HEPARIN - parenteral  Prevents conversion of prothrombin  thrombin  Affects fibrin, prevents formation of stable clot  Low dose therapy is prophylactic  aPTT: o 1:1 is normal clotting time o No standardized number  look at effect and see if clotting time is longer o Therapeutic aPTT = 1.5-2X control (ie, control = 12 sec, then therapeutic aPTT = 18-24 sec) o If aPTT is > 2X control   risk for adverse effects (ie, bleeding) Pharmacotherapeutics  Prevent extension of blood clot for DVT and pulmonary embolisms  SHORT-TERM prophyaxis post-operatively  NOT recommended as adjunct for ischemic strokes  Continuous IV infusion needed to achieve full anticoagulation, but bolus is given initially, followed by continuous infusion  Low risk for recurrent thrombosis (ie, risk factor reversible, like surgery) – give anticoagulation therapy for 3 months

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High risk for recurrent thrombosis (ie, no apparent risk factors or persistent risk factors like cancer) – give anticoagulation therapy for 6 months to indefinitely Pharmacokinetics  istered IV or SC  Onset of action: IV – immediate; SC – 20-60 min  Half-life = 1-2 hrs (full therapeutic effect occurs at steady state, so need to know half-life to determine steady state; important for when you take aPTT)  Destroyed by gastric acid – not absorbed from GI tract Pharmacodynamics  Rapidly promotes inactivation of factor X (factor X blocks prothrombin  thrombin)  Limits formation of stable clot by affecting fibrin  Prolongs clotting time w/o affecting bleeding time  No effect on already formed blood clots Contraindications/Vs  Thrombocytopenia, bleeding disorders, active bleeding other than DIC  Allergies to beef or pork  Pre-existing prolonged bleeding time  High activity level and susceptibility to injury  Safe for pregnant women Adverse Effects  Bleeding  Heparin-induced thrombocytopenia (HIT) – life-threatening! D/C heparin, let platelet count get back to normal, and treat thrombosis with LEPIRUDIN (Refludan) and ARGATROBAN (Argatroban)  OD  GIVE ANTIDOTE = PROTAMINE SULFATE (don’t give protamine sulfate too fast b/c can cause hypotension, bradycardia, dyspnea, and anaphylaxis; only used when pt is symptomatic and bleeding out; otherwise, D/C infusion and wait for clotting time to decrease) Nursing Management

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Monitor aPTT to confirm therapeutic lengthening of clotting time, ie, 1.5-2X control aPTT (ie, if aPTT control time = 30 sec, therapeutic level = 45-60 sec) Measure aPTT 6-8 hrs (ie, 4-5 half-lives) AFTER infusion to ensure steady state reached Check aPTT each time dose is changed Notify MD/NP if aPTT too low/high Don’t disrupt infusion; Insert new lines asap b/c will lose therapeutic effect Monitor for signs of bleeding – gums, nose, stool, vagina, urine, IV sites Check aPTT, hematocrit, platelet count before starting therapy Use IV pump Don’t ister other drugs in heparin line! Give protamine sulfate if active bleeding occurs

WARFARIN (Coumadin) – oral  PT measured against a control, reading will vary Thrombus/embolus Mechanical Heart Valve PT (sec) 1.4-1.6X control 1.5-1.7X control INR 2-3 2.5-3.5 Pharmacotherapeutics  Given after heparin therapy to finish tx for DVP or PE (thrombus/embolism – PT = 1.4-1.6X control, or INR = 2-3)  Prophylaxis for LONG-TERM risk of thrombus formation (mitral vale replacement, hypercoagubility) – PT = 1.51.7X control, or INR = 2.5-3.5  Prophylaxis for pts w/ Atrial fibrillation (at high risk for cardioembolic stroke) Pharmacokinetics  Binds to albumin in plasma  Peak action occurs in 1-9 hrs  Therapeutic (anticoag) effects occur in 24 hrs  Steady state/max effect occurs 3-4 days after dosing beings

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Pharmacodynamics  Competitively blocks vitamin K, prevents activation of prothrombin and other factors (doesn’t affect already activated factors – need 3-4 days to achieve steady state and max effect)  Metabolized through P-450 pathway (if pt metabolizes poorly, > therapeutic effect of warfarin)  Low pre-op Hgb   response to warfarin Contraindications/Vs  Active bleeding, open wounds, GI tract ulcerations, bleeding disorders (hemophilia, thrombocytopenia)  Patients undergoing surgery where hemorrhage is possible (spinal, eye, GI, cranial, arterial by grafting) – usually D/C 7 days before surgery  Vitamin K deficiency (increases bleeding/hemorrhage risk and decreases synthesis of normal clotting factors) caused by: o poor dietary intake o obstructed bile duct o long-term antibiotic therapy which affects normal GI flora (decreased vitamin K synthesis)  Newborns – deficient in vitamin K b/c intestinal flora inactive at birth  **NOT for Pregnant women   fetal warfarin syndrome defects  Older adults – more sensitive to effects of warfarin  Diet high in vitamin K – decreases effectiveness of warfarin  Interacts w/ a lot of drugs Adverse Effects  Bleeding  Hemorrhage  Nausea, vomiting, diarrhea, abdominal cramps  Fetal warfarin syndrome Nursing Management  DON’T drastically increase dietary vitamin K intake   therapeutic effect  NO ASPIRIN or ACETAMINOPHEN & NO EXTRA  Give initial loading dose to reach therapeutic range faster; follow with maintenance dose  Give dose at 6:00 PM to allow for early morning blood draws for PT or INR

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OD  GIVE ANTIDOTE = VITAMIN K

3. Apply the principles of drug therapy for coagulation problems to their effects on the clotting cascade.

4. Explain and differentiate the onset of action, lab tests, and antidotes associated with these two prototype drugs. HEPARIN WARFARIN Onset of action IV: immediate 24 hrs SC: 20-60 sec Lab Tests -aPTT (1.5-2X control aPTT) -blood draws for PT and INR -hematocrit -platelet count Tx/Prophylaxis of thrombus or embolus: PT: 1.4-1.6X control time INR: 2-3 Prophylaxis for mech. heart valves: PT: 1.5-1.7X control time INR: 2.5-3.5 Antidotes Protamine sulfate Vitamin K 5. State the expected aPTT, PT, and/or INR for selected conditions related to thrombus and embolus formation. WARFARIN Thrombus/embolus Mechanical Heart Valve PT (sec) 1.4-1.6X control 1.5-1.7X control INR 2-3 2.5-3.5 6. Compare and contrast the pharmacotherapeutics, pharmacokinetics, pharmacodynamics, adverse effects, Vs, and nursing management of the anticoagulant enoxaparin, with the prototype anticoagulants heparin and warfarin. ANTICOAGULANT

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ENOXAPARIN (Lovenox)  Low MW heparin  Limited effect on thrombin  Less interaction w/ platelets  Very predictable dose response  Don’t need to constantly monitor aPTT Pharmacotherapeutics  Reduce death, MI, and emergency revascularization in pts w/ Q-wave MI  Longer half-life, only ister SC 1X/day  good for long-term therapy  A good F/U for initial heparin therapy Pharmacokinetics  Most absorbed after SC  Widely distributed Pharmacodynamics  Affects activated factor X (decreases aPTT)  Affects clotting factor C and antithrombin  Limited effects on thrombin Adverse Effects  Bleeding, but less than heparin Vs (same as heparin)  Thrombocytopenia, bleeding disorders, active bleeding other than DIC  Allergies to beef or pork  Pre-existing prolonged bleeding time  High activity level and susceptibility to injury  Safe for pregnant women Nursing Management  Teach patients how to self-ister  Take drug on time

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Follow regular dosage schedule Get follow-up blood analyses done as recommended Safety – clear pathways, remove loose scatter rugs, wear nonskid footwear, obtain adequate lighting, use handrails

7. Describe the pharmacotherapeutics, pharmacodynamics, adverse effects, Vs, and nursing management of aspirin when used for antiplatelet effects. 8. Compare and contrast the pharmacotherapeutics, pharmacodynamics, adverse effects, Vs, and nursing management of clopidogrel and aspirin. ANTIPLATELETS ASPIRIN  Anti-inflammatory effects (peripheral inhibition of prostaglandin synthesis; other mediators of inflammation)  Anti-thrombotic effects (inhibits prostaglandin responsible for platelet aggregation) Pharmacotherapeutics  Prevents MI & stroke (Give w/i 24-48 hrs of onset)  Adjunct in revascularization procedures  Decrease incidence of coronary heart disease in those w/ increased risk (ie, men > 40 y/o, postmenopausal women, HTN, DM, smoking, hyperlipidemia, obesity, family hx)  Prophylaxis against thromboembolic complications in CV disease (MI and TIA = transient ischemic attack)  Atrial fibrillation to prevent stroke (noncardioembolic) Pharmacodynamics  Irreversibly inhibits platelet COX and synthesis of thromboxane A (vasoconstrictor that facilitates platelet aggregation) for the life of the platelet Adverse Effects  Bleeding  GI ulceration and bleeding  Hemorrhagic stroke  neutropenia Contraindications/Vs

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Peptic ulcer disease, bleeding disorders, pts on anticoagulant therapy Gout Renal/liver impairment or disease Children < 16 y/o w/ varicella or flu-like illness  Reye syndrome (swelling in brain,  intracranial pressure, seizures) Pregnant and lactating women (pregnancy category D) asthma

Nursing Management  NEVER give to pregnant women in 3rd trimester b/c high risk of maternal hemorrhage and adverse fetal effects  NEVER give to children < 16 y/o w/ flu-like symptoms (Reye syndrome)  Caution for pts > 60 y/o  Ask about OTCs, smoking, alcohol  Give with milk or food to relieve GI distress  Get CBC, platelet count, liver/renal function tests for pts on long-term therapy CLOPIDOGREL (Plavix) Pharmacotherapeutics  Prevent atherosclerotic events in patients who have had/are at risk for MI, stroke, vascular death, peripheral artery disease (PAD)  Manage acute coronary syndrome (post-MI w/ elevated QT)  Prevent thrombosis post coronary stent  Reduce platelet adhersion/aggregation Pharmacodynamics  Irreversibly modifies platelet ADP receptor  inhibits binding of ADP to platelet receptor  inhibits platelet aggregation  prolongs bleeding time Adverse Effects  Bleeding  GI distress: abdominal pain, indigestion, diarrhea, nausea (but not ulcers or GI bleeding like w/ aspirin)

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 neutropenia Contraindications/Vs  peptic ulcers or intracranial hemorrhage  platelet function  liver function  CV status  Neuron status  Children < 18 y/o, pregnancy and lactation Nursing Management  Take with food to relieve GI distress  Check WBCs if signs of infection  D/C 7 days before surgery to prevent excessive bleeding  Apply pressure on wounds until bleeding stops  Avoid behaviors that may lead to injury  Make home environment more “fall proof” 9. Describe the pharmacotherapeutics, pharmacokinetics, pharmacodynamics, adverse effects, Vs, and nursing management of thrombolytics (prototype: alteplase recombinant). 10. Describe the pharmacotherapeutics, pharmacodynamics, adverse effects, Vs, and nursing management of streptokinase. THROMBOLYTICS ALTEPLASE RECOMBINANT  Drug of choice for CVA  Fewer systemic effects  Tissue plasminogen activator (tPA)  Converts plasminogen to plasmin when fibrin is present; attaches directly to fibrin in clot (ie, must have fibrin to work)

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Pharmacotherapeutics  Acute evolving MI from acute coronary artery thrombus (initiate at onset of symptoms)  Acute ischemic stroke (ONLY drug to treat this; must initiate w/i 3 hrs of onset of stroke and after IC bleeding has been ruled out by CT scan)  Massive pulmonary embolism Pharmacokinetics  IV for immediate effect  Rapid clearance – 80% cleared w/i 10 min after infusion has completed Pharmacodynamics  Binds to fibrin in a clot and converts trapped plasminogen to plasmin  fibrinolysis (break down of clot) Adverse Effects  Bleeding (but less than streptokinase) Contraindications/Vs  Active internal bleeding, evidence of IC bleeding on pre-tx evaluation, suspicion of subarachnoid hemorrhage  Recent (w/i last 2 months) stroke  IC surgery or sever head trauma  Intraspinal surgery or trauma  IC neoplasm  Seizure at onset of stroke  Arteriovenous malformation or aneurysm  Severe uncontrolled HTN (systolic BP  180 or diastolic BP  110)  Co-Anticoagulant therapy (heparin), Co-antiplatelet therapy (aspirin)  Current pregnancy or delivery of child w/i last 10 days  Older adults – more susceptible to IC bleeding Nursing Management  IV pump  NO invasive procedures  Monitor for:

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o signs of bleeding o VS changes (fever, arrhythmias, hypotension) o blood work abnormalities o respiratory problems (bronchospasm) Lab values: hematocrit, Hgb level, platelet count, PT, aPTT Reconstitute in sterile water Don’t shake or agitate too much Infuse over 90 min (recommended) or over 3-hrs, or accelerated Cardiac monitor during and after tx (when MI) Check RR, dyspnea, pulse ox, ABGs (when pulmonary embolism) Check BP closely (when acute ischemic stroke)

STREPTOKINASE  BREAKS DOWN formed blood clots Indications  Treat acute evolving MI  Treat acute evolving thrombotic CVA  pulmonary embolism  acute, extensive DVT  arterial thrombosis  opens occluded arteriovenous catheters (w/ lower doses) How it works:  activates plasminogen and acts w/ plasminogen to convert plasminogen to plasmin (dissolves fibrin, fibrinogen, and other clot-forming proteins)  fibrin NOT needed for plasminogen activation

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Adverse Effects  severe bleeding  GIVE ANTIDOTE = AMINOCAPROIC ACID  life-threatening bleeding (b/c it changes fibrin throughout body)  blood transfusion  allergic reactions: fever, chills (in 30% of pts)  hypotension Vs Nursing Management  IV pump  NO invasive procedures  Monitor for: o signs of bleeding o VS changes (fever, arrhythmias, hypotension) o blood work abnormalities o respiratory problems (bronchospasm) 11. List the life-threatening adverse effects of each of the anti-coagulants, anti-platelet agents, and thrombolytics. 12. List measures to prevent, minimize, and treat these life-threatening effects. Life-threatening Adverse Effect ANTICOAGULANTS Heparin Warfarin ANTI-PLATELETS Aspirin

Heparin-induced thrombocytopenia (HIT) Fetal warfarin syndrome Salicylate Poisoning

Prevent/Minimize/Tx D/C heparin, wait for platelet count to get back to normal, treat any thrombosis. ister lepirudin (Refludan) and argatroban (Argatroban) Don’t give to pregnant women No antidote (gastric emptying, give activated charcoal, life )

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Clopidogrel THROMBOLYTICS Alteplase Recombinant Streptokinase

Neutropenia or bleeding? Bleeding Severe bleeding

Don’t give to pregnant women or to women that have delivered w/i past 10 days. Caution w/ older adults b/c more likely to have IC bleeding. blood transfusion

13. Prepare teaching plans for patients receiving specific anti-coagulant therapy at home. 14. Apply nursing management principles to case studies of patients receiving home coagulation therapy.

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