Transcript Drugs for Coagulation Disorders

Drugs for Coagulation
Disorders
Andrew N. Schmelz, PharmD
Post-Doctoral Teaching Fellow
Purdue University
October 8, 2008
[email protected]
Objectives
List important steps of hemostasis and
fibrinolysis
 Describe thromboembolic disorders that
are indications for coagulation modifiers
 Identify the primary mechanism for each
coagulation modifying-drug discussed
 Match specific coagulation-modifying
drugs to lab tests with which they are
appropriately monitored

Objectives (cont)
Categorize coagulation-modifying drugs
based on their classification and
mechanism of action
 List important adverse effects for each
coagulation-modifying drug discussed

Process of Hemostasis
Hemostasis: Protects the body from both
external and internal injury
 Injury to blood vessels causes:

– Vessel spasms (causing constriction)
– Platelet adherence to injury site
– Platelets aggregate and form plug
– Insoluble fibrin strands form and coagulate
Process of Hemostasis
Intrinsic Pathway
(In response to injury)
(Factor Xa)
Extrinsic Pathway
(Blood enters tissue spaces)
Removal of Blood Clots

Fibrinolysis: Removal of clot so that
tissue can resume its normal activity
Diseases of Hemostasis

Thromboembolic disorders (MI and
CVA)
– Stationary clot (thrombus) grows and deprives
specific areas of oxygen

Deep Vein Thrombosis (DVT)
– Formation of clots in large veins (usually legs)

Embolus
– Thrombus may break off and be carried by
bloodstream to affect other areas
Diseases of Hemostasis (cont)

Thrombocytopenia
– Low number of platelets, cannot properly
form clots

Hemophilias
– Genetic deficiencies of clotting factors
Mechanisms of Action

Anticoagulants
– Inhibition of clotting factors

Antiplatelets
– Inhibition of platelet function

Thrombolytics
– Lyse thrombi

Hemostatics
– Inhibition of fibrinolysis
Inhibition of Clotting
Factors
(Anticoagulants)
Heparin
Example: Heparin (Heplock®)
 MOA: Enhances inhibitory effect of
antithrombin III (inhibits factor Xa)

Heparin
Enoxaparin
(Factor Xa)
Heparin
Example: Heparin (Heplock®)
 MOA: Enhances inhibitory effect of
antithrombin III (inhibits factor Xa)
 Route: IV (continuous infusion), SC
 Monitoring: aPTT (25-40 s), platelets,
s/sxs of hemorrhage
 Adverse Effects:

– Hemorrhage
– Anaphylaxis
– Thrombocytopenia (HIT)
Low-Molecular-Weight Heparins
Example: Enoxaparin (Lovenox®)
 MOA: Enhances inhibitory effect of
antithrombin III (inhibits factor Xa)
 Route: SC
 Monitoring: Anti-factor Xa, SCr, platelets
 Adverse Effects:

– Hemorrhage
– Thrombocytopenia
– Hypersensitivity (anaphylaxis)
Vitamin K-Dependant Clotting
Factor Inhibitors
Example: Warfarin (Coumadin®)
 MOA: Inhibits enzymes responsible for
cyclic conversion of Vitamin K
 Route: PO
 Monitoring: PT/INR (12-15 / 2-3.5),
s/sxs of hemorrhage
 Adverse Effects:

– Hemorrhage
– Anemia
– Bruising
Direct Thrombin Inhibitors
Examples: Argatroban (Novastan®)
Bivalirudin (Angiomax®)
 MOA: Directly inhibit thrombin
(preventing formation of fibrin clots)

(Factor Xa)
Argatroban
Bivalirudin
Direct Thrombin Inhibitors
Examples: Argatroban (Novastan®)
Bivalirudin (Angiomax®)
 MOA: Directly inhibit thrombin
(preventing formation of fibrin clots)
 Route: IV
 Monitoring: aPTT (25-40 s)
 Adverse Effects:

– Serious internal hemorrhage
– Back pain (bivalirudin)
Nursing Considerations
Medication Safety
 Assess patients for signs of bleeding

– Bruising
– Obvious signs of bleeding (nosebleeds,
bleeding from rectum, blood in emesis)
– “Coffee Ground” or black, tarry stools /
emesis
Patient education
 Toxicity: warfarin – vit K administration
heparin – protamine sulfate

Patient Case
JR is 55 YOWM recently diagnosed with a
DVT and is currently receiving enoxaparin
(Lovenox).
 Before he can be d/c’ed from the hospital,
his MD wants to starts him on chronic
anticoagulation to prevent future DVTs

Inhibition of Platelet
Function
(Antiplatelets)
GP IIb/IIIa Antagonists
Example: Abciximab (ReoPro®)
 MOA: Inhibit GP IIb/IIIa, enzyme
necessary for platelet aggregation

GP IIb/IIIa Antagonists
Example: Abciximab (ReoPro®)
 MOA: Inhibit GP IIb/IIIa, enzyme
necessary for platelet aggregation
 Route: IV
 Monitoring: Platelets
 Adverse Effects:

– Hemorrhage
– Thrombocytopenia
Aspirin (Ecotrin®)
Example: Aspirin (Ecotrin®)
 MOA: Irreversibly binds to COX, inhibiting
formation of thromboxane A2

Aspirin (Ecotrin®)
Example: Aspirin (Ecotrin®)
 MOA: Irreversibly binds to COX, inhibiting
formation of thromboxane A2
 Route: PO
 Monitoring: S/sxs hemorrhage
 Adverse Effects:

– Increased clotting times
– GI bleeding
– Anaphylaxis
ADP Receptor Blockers
Example: Clopidogrel (Plavix®)
 MOA: ADP-receptor blockers

ADP Receptor Blockers
Example: Clopidogrel (Plavix®)
 MOA: ADP-receptor blockers
 Route: IV (loading dose), PO
 Monitoring: S/sxs hemorrhage
 Adverse Effects:

– Increased clotting time
– GI bleeding
– Blood dyscrasias (TTP)
Agents for Intermittent Claudication
Example: Cilostazole (Pletal®)
 MOA: PDE-3 inhibitor
 Route: PO
 Monitoring: S/sxs hemorrhage, heart
 Adverse Effects:

– Palpitation, tachycardia,
– Nausea, vomitting
Nursing Considerations
Careful monitoring of patient condition
(increased risk of bleeding)
 Combination with anticoagulants –
increased risk of bleeding
 Injection / venipuncture sites will require
prolonged pressure to control bleeding
 Patient education

Pharmacotherapy with
Thrombolytics
Thrombolytics
Example: Alteplase (Activase®, TPA)
 MOA: Fibrin-enhanced conversion of
plasminogen to plasmin

Thrombolytics
Example: Alteplase (Activase®, TPA)
 MOA: Fibrin-enhanced conversion of
plasminogen to plasmin
 Route: IV
 Monitoring: S/sxs hemorrhage,
coagulation tests, H/H, platelets, mental
status, dysrhythmias (MI)
 Adverse Effects:

– Serious internal bleeding
– Intracranial hemorrhage
Nursing Considerations

Identify underlying conditions that exclude
patient from receiving thrombolytics
– Recent trauma, surgery, or biopsy
– Arterial emboli
– Recent cerebral embolism
– Hemorrhage
– Thrombocytopenia
– Childbirth (within 10 days)
Pharmacotherapy with
Hemostatics
Hemostatics
Example: Aprotinin (Trasylol®)
 MOA: Inhibits fibrinolysis (affects multiple
mediators)

Hemostatics
Example: Aprotinin (Trasylol®)
 MOA: Inhibits fibrinolysis (affects multiple
mediators)
 Route: IV
 Monitoring: Clotting, peripheral pulses,
paresthesias, (+) Homans’ sign
 Adverse Effects:

– Clotting
– Extravasation
Questions
Summary
Hemostasis protects the body from injury
 Several pathologies may affect hemostasis
 Four main drug categories are used to
treat coagulation disorders
 Nurses play an important role

– Monitoring drug efficacy
– Monitoring patient for adverse effects
Drugs for Coagulation
Disorders
Andrew N. Schmelz, PharmD
Post-Doctoral Teaching Fellow
Purdue University
October 8, 2008
[email protected]