Drugs for Drugs for Coagulation Coagulation DisordersDisorders

Andrew N. Schmelz, PharmDAndrew N. Schmelz, PharmDPost-Doctoral Teaching FellowPost-Doctoral Teaching Fellow

Purdue UniversityPurdue UniversityOctober 8, 2008October 8, 2008

anschmel@purdue.eduanschmel@purdue.edu

ObjectivesObjectives

List important steps of hemostasis and List important steps of hemostasis and fibrinolysisfibrinolysis

Describe thromboembolic disorders that Describe thromboembolic disorders that are indications for coagulation modifiersare indications for coagulation modifiers

Identify the primary mechanism for Identify the primary mechanism for each coagulation modifying-drug each coagulation modifying-drug discusseddiscussed

Match specific coagulation-modifying Match specific coagulation-modifying drugs to lab tests with which they are drugs to lab tests with which they are appropriately monitoredappropriately monitored

Objectives (cont)Objectives (cont)

Categorize coagulation-modifying Categorize coagulation-modifying drugs based on their classification drugs based on their classification and mechanism of actionand mechanism of action

List important adverse effects for List important adverse effects for each coagulation-modifying drug each coagulation-modifying drug discusseddiscussed

Process of HemostasisProcess of Hemostasis

Hemostasis:Hemostasis: Protects the body from Protects the body from both external and internal injuryboth external and internal injury

Injury to blood vessels causes:Injury to blood vessels causes:– Vessel spasms (causing constriction)Vessel spasms (causing constriction)– Platelet adherence to injury sitePlatelet adherence to injury site– Platelets aggregate and form plugPlatelets aggregate and form plug– Insoluble fibrin strands form and Insoluble fibrin strands form and

coagulatecoagulate

Process of HemostasisProcess of Hemostasis

(Factor Xa)

Intrinsic Pathway(In response to injury)

Extrinsic Pathway(Blood enters tissue spaces)

Removal of Blood ClotsRemoval of Blood Clots

FibrinolysisFibrinolysis: Removal of clot so : Removal of clot so that tissue can resume its normal that tissue can resume its normal activityactivity

Diseases of HemostasisDiseases of Hemostasis

Thromboembolic disordersThromboembolic disorders (MI (MI and CVA)and CVA)– Stationary clot (thrombus) grows and Stationary clot (thrombus) grows and

deprives specific areas of oxygendeprives specific areas of oxygen Deep Vein ThrombosisDeep Vein Thrombosis (DVT) (DVT)

– Formation of clots in large veins (usually Formation of clots in large veins (usually legs)legs)

EmbolusEmbolus– Thrombus may break off and be carried Thrombus may break off and be carried

by bloodstream to affect other areasby bloodstream to affect other areas

Diseases of Hemostasis Diseases of Hemostasis (cont)(cont)

ThrombocytopeniaThrombocytopenia– Low number of platelets, cannot Low number of platelets, cannot

properly form clotsproperly form clots HemophiliasHemophilias

– Genetic deficiencies of clotting factorsGenetic deficiencies of clotting factors

Mechanisms of ActionMechanisms of Action

AnticoagulantsAnticoagulants– Inhibition of clotting factorsInhibition of clotting factors

AntiplateletsAntiplatelets– Inhibition of platelet functionInhibition of platelet function

ThrombolyticsThrombolytics– Lyse thrombiLyse thrombi

HemostaticsHemostatics– Inhibition of fibrinolysisInhibition of fibrinolysis

Inhibition of Clotting Inhibition of Clotting FactorsFactors

(Anticoagulants)(Anticoagulants)

HeparinHeparin

ExampleExample: Heparin (Heplock®): Heparin (Heplock®) MOAMOA: Enhances inhibitory effect of : Enhances inhibitory effect of

antithrombin III (inhibits factor Xa)antithrombin III (inhibits factor Xa)

HeparinEnoxaparin

(Factor Xa)

HeparinHeparin

ExampleExample: Heparin (Heplock®): Heparin (Heplock®) MOAMOA: Enhances inhibitory effect of : Enhances inhibitory effect of

antithrombin III (inhibits factor Xa)antithrombin III (inhibits factor Xa) RouteRoute: IV (continuous infusion), SC: IV (continuous infusion), SC MonitoringMonitoring: aPTT (25-40 s), : aPTT (25-40 s),

platelets, s/sxs of hemorrhageplatelets, s/sxs of hemorrhage Adverse EffectsAdverse Effects::

– HemorrhageHemorrhage– AnaphylaxisAnaphylaxis– Thrombocytopenia (HIT)Thrombocytopenia (HIT)

Low-Molecular-Weight Low-Molecular-Weight HeparinsHeparins

ExampleExample: Enoxaparin (Lovenox®): Enoxaparin (Lovenox®) MOAMOA: Enhances inhibitory effect of : Enhances inhibitory effect of

antithrombin III (inhibits factor Xa)antithrombin III (inhibits factor Xa) RouteRoute: SC: SC MonitoringMonitoring: Anti-factor Xa, SCr, : Anti-factor Xa, SCr,

plateletsplatelets Adverse EffectsAdverse Effects::

– HemorrhageHemorrhage– ThrombocytopeniaThrombocytopenia– Hypersensitivity (anaphylaxis)Hypersensitivity (anaphylaxis)

Vitamin K-Dependant Clotting Vitamin K-Dependant Clotting Factor InhibitorsFactor Inhibitors

ExampleExample: Warfarin (Coumadin®): Warfarin (Coumadin®) MOAMOA: Inhibits enzymes responsible : Inhibits enzymes responsible

for cyclic conversion of Vitamin Kfor cyclic conversion of Vitamin K RouteRoute: PO: PO MonitoringMonitoring: PT/INR (12-15 / 2-3.5), : PT/INR (12-15 / 2-3.5),

s/sxs of hemorrhage s/sxs of hemorrhage Adverse EffectsAdverse Effects::

– HemorrhageHemorrhage– AnemiaAnemia– BruisingBruising

Direct Thrombin InhibitorsDirect Thrombin Inhibitors

ExamplesExamples: : Argatroban Argatroban (Novastan®)(Novastan®) Bivalirudin (Angiomax®)Bivalirudin (Angiomax®)

MOAMOA: Directly inhibit thrombin : Directly inhibit thrombin (preventing formation of fibrin clots)(preventing formation of fibrin clots)

ArgatrobanBivalirudin

(Factor Xa)

Direct Thrombin InhibitorsDirect Thrombin Inhibitors

ExamplesExamples: : Argatroban Argatroban (Novastan®)(Novastan®) Bivalirudin (Angiomax®)Bivalirudin (Angiomax®)

MOAMOA: Directly inhibit thrombin : Directly inhibit thrombin (preventing formation of fibrin clots)(preventing formation of fibrin clots)

RouteRoute: IV: IV MonitoringMonitoring: aPTT (25-40 s): aPTT (25-40 s) Adverse EffectsAdverse Effects::

– Serious internal hemorrhageSerious internal hemorrhage– Back pain (bivalirudin)Back pain (bivalirudin)

Nursing ConsiderationsNursing Considerations

Medication SafetyMedication Safety Assess patients for signs of bleedingAssess patients for signs of bleeding

– BruisingBruising– Obvious signs of bleeding (nosebleeds, Obvious signs of bleeding (nosebleeds,

bleeding from rectum, blood in emesis)bleeding from rectum, blood in emesis)– ““Coffee Ground” or black, tarry stools / Coffee Ground” or black, tarry stools /

emesisemesis Patient educationPatient education ToxicityToxicity: warfarin – vit K : warfarin – vit K

administrationadministration heparin – protamine sulfate heparin – protamine sulfate

Patient CasePatient Case

JR is 55 YOWM recently diagnosed JR is 55 YOWM recently diagnosed with a DVT and is currently receiving with a DVT and is currently receiving enoxaparin (Lovenox).enoxaparin (Lovenox).

Before he can be d/c’ed from the Before he can be d/c’ed from the hospital, his MD wants to starts him hospital, his MD wants to starts him on chronic anticoagulation to prevent on chronic anticoagulation to prevent future DVTsfuture DVTs

Inhibition of Platelet Inhibition of Platelet FunctionFunction

(Antiplatelets)(Antiplatelets)

GP IIb/IIIa AntagonistsGP IIb/IIIa Antagonists

ExampleExample: Abciximab (ReoPro®): Abciximab (ReoPro®) MOAMOA: Inhibit GP IIb/IIIa, enzyme : Inhibit GP IIb/IIIa, enzyme

necessary for platelet aggregationnecessary for platelet aggregation

GP IIb/IIIa AntagonistsGP IIb/IIIa Antagonists

ExampleExample: Abciximab (ReoPro®): Abciximab (ReoPro®) MOAMOA: Inhibit GP IIb/IIIa, enzyme : Inhibit GP IIb/IIIa, enzyme

necessary for platelet aggregationnecessary for platelet aggregation RouteRoute: IV: IV MonitoringMonitoring: Platelets: Platelets Adverse EffectsAdverse Effects::

– HemorrhageHemorrhage– ThrombocytopeniaThrombocytopenia

Aspirin (Ecotrin®)Aspirin (Ecotrin®)

ExampleExample: Aspirin (Ecotrin®): Aspirin (Ecotrin®) MOAMOA: Irreversibly binds to COX, : Irreversibly binds to COX,

inhibiting formation of thromboxane inhibiting formation of thromboxane A2A2

Aspirin (Ecotrin®)Aspirin (Ecotrin®)

ExampleExample: Aspirin (Ecotrin®): Aspirin (Ecotrin®) MOAMOA: Irreversibly binds to COX, : Irreversibly binds to COX,

inhibiting formation of thromboxane inhibiting formation of thromboxane A2A2

RouteRoute: PO: PO MonitoringMonitoring: S/sxs hemorrhage: S/sxs hemorrhage Adverse EffectsAdverse Effects::

– Increased clotting timesIncreased clotting times– GI bleedingGI bleeding– AnaphylaxisAnaphylaxis

ADP Receptor BlockersADP Receptor Blockers

ExampleExample: Clopidogrel (Plavix®): Clopidogrel (Plavix®) MOAMOA: ADP-receptor blockers: ADP-receptor blockers

ADP Receptor BlockersADP Receptor Blockers

ExampleExample: Clopidogrel (Plavix®): Clopidogrel (Plavix®) MOAMOA: ADP-receptor blockers: ADP-receptor blockers RouteRoute: IV (loading dose), PO: IV (loading dose), PO MonitoringMonitoring: S/sxs hemorrhage: S/sxs hemorrhage Adverse EffectsAdverse Effects::

– Increased clotting timeIncreased clotting time– GI bleedingGI bleeding– Blood dyscrasias (TTP)Blood dyscrasias (TTP)

Agents for Intermittent Agents for Intermittent ClaudicationClaudication

ExampleExample: Cilostazole (Pletal®): Cilostazole (Pletal®) MOAMOA: PDE-3 inhibitor: PDE-3 inhibitor RouteRoute: PO: PO MonitoringMonitoring: S/sxs hemorrhage, : S/sxs hemorrhage,

heartheart Adverse EffectsAdverse Effects::

– Palpitation, tachycardia,Palpitation, tachycardia,– Nausea, vomittingNausea, vomitting

Nursing ConsiderationsNursing Considerations

Careful monitoring of patient Careful monitoring of patient condition (increased risk of bleeding)condition (increased risk of bleeding)

Combination with anticoagulants – Combination with anticoagulants – increased risk of bleedingincreased risk of bleeding

Injection / venipuncture sites will Injection / venipuncture sites will require prolonged pressure to control require prolonged pressure to control bleedingbleeding

Patient educationPatient education

Pharmacotherapy Pharmacotherapy with Thrombolyticswith Thrombolytics

ThrombolyticsThrombolytics

ExampleExample: Alteplase (Activase®, : Alteplase (Activase®, TPA)TPA)

MOAMOA: Fibrin-enhanced conversion of : Fibrin-enhanced conversion of plasminogen to plasmin plasminogen to plasmin

ThrombolyticsThrombolytics

ExampleExample: Alteplase (Activase®, TPA): Alteplase (Activase®, TPA) MOAMOA: Fibrin-enhanced conversion of : Fibrin-enhanced conversion of

plasminogen to plasmin plasminogen to plasmin RouteRoute: IV: IV MonitoringMonitoring: S/sxs hemorrhage, : S/sxs hemorrhage,

coagulation tests, H/H, platelets, coagulation tests, H/H, platelets, mental status, dysrhythmias (MI)mental status, dysrhythmias (MI)

Adverse EffectsAdverse Effects::– Serious internal bleedingSerious internal bleeding– Intracranial hemorrhageIntracranial hemorrhage

Nursing ConsiderationsNursing Considerations

Identify underlying conditions that Identify underlying conditions that exclude patient from receiving exclude patient from receiving thrombolyticsthrombolytics– Recent trauma, surgery, or biopsyRecent trauma, surgery, or biopsy– Arterial emboliArterial emboli– Recent cerebral embolismRecent cerebral embolism– HemorrhageHemorrhage– ThrombocytopeniaThrombocytopenia– Childbirth (within 10 days)Childbirth (within 10 days)

Pharmacotherapy Pharmacotherapy with Hemostaticswith Hemostatics

HemostaticsHemostatics

ExampleExample: Aprotinin (Trasylol®): Aprotinin (Trasylol®) MOAMOA: Inhibits fibrinolysis (affects : Inhibits fibrinolysis (affects

multiple mediators)multiple mediators)

HemostaticsHemostatics

ExampleExample: Aprotinin (Trasylol®): Aprotinin (Trasylol®) MOAMOA: Inhibits fibrinolysis (affects : Inhibits fibrinolysis (affects

multiple mediators)multiple mediators) RouteRoute: IV: IV MonitoringMonitoring: Clotting, peripheral : Clotting, peripheral

pulses, paresthesias, (+) pulses, paresthesias, (+) HomansHomans’ sign ’ sign

Adverse EffectsAdverse Effects::– ClottingClotting– ExtravasationExtravasation

QuestionsQuestions

SummarySummary

Hemostasis protects the body from Hemostasis protects the body from injuryinjury

Several pathologies may affect Several pathologies may affect hemostasishemostasis

Four main drug categories are used to Four main drug categories are used to treat coagulation disorderstreat coagulation disorders

Nurses play an important roleNurses play an important role– Monitoring drug efficacyMonitoring drug efficacy– Monitoring patient for adverse effectsMonitoring patient for adverse effects

Drugs for Drugs for Coagulation Coagulation DisordersDisorders

Andrew N. Schmelz, PharmDAndrew N. Schmelz, PharmDPost-Doctoral Teaching FellowPost-Doctoral Teaching Fellow

Purdue UniversityPurdue UniversityOctober 8, 2008October 8, 2008

anschmel@purdue.eduanschmel@purdue.edu