DRUGS AFFECTING COAGULATION OBJECTIVES

DRUGS AFFECTING COAGULATION OBJECTIVES

1. Define the following terms:

Anticoagulant substances that keep blood from clotting; prevent blood blots from forming or extending; dont 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) Intrinsic clotting factors in blood activated by damage to blood vessel 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 pts 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) 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

deficiency of vitamin K ( ( normal clotting factors made ( ( bleeding risk in pts on warfarin infants more susceptible b/c intestinal flora inactive at birth high levels decrease warfarin effectiveness2. Describe the pharmacotherapeutics, pharmacokinetics, pharmacodynamics, adverse effects, CPVs, 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:

1:1 is normal clotting time

No standardized number ( look at effect and see if clotting time is longer

Therapeutic aPTT = 1.5-2X control (ie, control = 12 sec, then therapeutic aPTT = 18-24 sec)

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

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

Administered 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 tractPharmacodynamics

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/CPVs

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 (dont 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

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

Dont 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

Dont administer other drugs in heparin line!

Give protamine sulfate if active bleeding occursWARFARIN (Coumadin) oral PT measured against a control, reading will vary

Thrombus/embolusMechanical Heart Valve

PT (sec)1.4-1.6X control1.5-1.7X control

INR2-32.5-3.5

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 = 1.5-1.7X 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 beingsPharmacodynamics

Competitively blocks vitamin K, prevents activation of prothrombin and other factors (doesnt 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/CPVs

Active bleeding, open wounds, GI tract ulcerations, bleeding disorders (hemophilia, thrombocytopenia) Patients undergoing surgery where hemorrhage is possible (spinal, eye, GI, cranial, arterial bypass grafting) usually D/C 7 days before surgery

Vitamin K deficiency (increases bleeding/hemorrhage risk and decreases synthesis of normal clotting factors) caused by:

poor dietary intake

obstructed bile duct 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 syndromeNursing Management

DONT 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

OD ( GIVE ANTIDOTE = VITAMIN K3. 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.

HEPARINWARFARIN

Onset of actionIV: immediate

SC: 20-60 sec24 hrs

Lab Tests-aPTT (1.5-2X control aPTT)-hematocrit

-platelet count-blood draws for PT and INRTx/Prophylaxis of thrombus or embolus:

PT: 1.4-1.6X control timeINR: 2-3

Prophylaxis for mech. heart valves:

PT: 1.5-1.7X control time

INR: 2.5-3.5

AntidotesProtamine sulfateVitamin K

5. State the expected aPTT, PT, and/or INR for selected conditions related to thrombus and embolus formation.

WARFARINThrombus/embolusMechanical Heart Valve

PT (sec)1.4-1.6X control1.5-1.7X control

INR2-32.5-3.5

6. Compare and contrast the pharmacotherapeutics, pharmacokinetics, pharmacodynamics, adverse effects, CPVs, and nursing management of the anticoagulant enoxaparin, with the prototype anticoagulants heparin and warfarin.

ANTICOAGULANT

ENOXAPARIN (Lovenox) Low MW heparin

Limited effect on thrombin

Less interaction w/ platelets

Very predictable dose response

Dont need to constantly monitor aPTTPharmacotherapeutics Reduce death, MI, and emergency revascularization in pts w/ Q-wave MI Longer half-life, only administer SC 1X/day ( good for long-term therapy

A good F/U for initial heparin therapy

Pharmacokinetics

Most absorbed after SC

Widely distributedPharmacodynamics

Affects activated factor X (decreases aPTT)

Affects clotting factor C and antithrombin

Limited effects on thrombinAdverse Effects

Bleeding, but less than heparinCPVs (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 womenNursing Management

Teach patients how to self-administer Take drug on time 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 handrails7. Describe the pharmacotherapeutics, pharmacodynamics, adverse effects, CPVs, and nursing management of aspirin when used for antiplatelet effects.8. Compare and contrast the pharmacotherapeutics, pharmacodynamics, adverse effects, CPVs, 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 plateletAdverse Effects

Bleeding GI ulceration and bleeding

Hemorrhagic stroke

neutropenia

Contraindications/CPVs

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)

asthmaNursing 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/aggregationPharmacodynamics

Irreversibly modifies platelet ADP receptor ( inhibits binding of ADP to platelet receptor ( inhibits platelet aggregation ( prolongs bleeding timeAdverse Effects

Bleeding

GI distress: abdominal pain, indigestion, diarrhea, nausea (but not ulcers or GI bleeding like w/ aspirin) neutropenia

Contraindications/CPVs

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, CPVs, and nursing management of thrombolytics (prototype: alteplase recombinant).10. Describe the pharmacotherapeutics, pharmacodynamics, adverse effects, CPVs, 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)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/CPVs

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:

signs of bleeding

VS changes (fever, arrhythmias, hypotension)

blood work abnormalities

respiratory problems (bronchospasm)

Lab values: hematocrit, Hgb level, platelet count, PT, aPTT Reconstitute in sterile water Dont 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 clotsIndications 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

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

CPVsNursing Management IV pump

NO invasive procedures

Monitor for:

signs of bleeding

VS changes (fever, arrhythmias, hypotension)

blood work abnormalities

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 EffectPrevent/Minimize/Tx

ANTICOAGULANTS

HeparinWarfarin

Heparin-induced thrombocytopenia (HIT)Fetal warfarin syndrome

D/C heparin, wait for platelet count to get back to normal, treat any thrombosis. Administer lepirudin (Refludan) and argatroban (Argatroban)Dont give to pregnant women

ANTI-PLATELETS

Aspirin

ClopidogrelSalicylate PoisoningNeutropenia or bleeding?No antidote (gastric emptying, give activated charcoal, life support)

THROMBOLYTICS

Alteplase RecombinantStreptokinaseBleeding

Severe bleedingDont 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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