Anticoagulants/Thrombolytics Flashcards
Anticoagulants
Vitamin K antagonist (Warfarin)
Unfractionated heparin
Low molecular weight heparin
Direct oral anticoagulants
Warfarin (Coumadin)
Vitamin K antagonist Inhibits vitamin K dependent coagulation proteins (factors II, VII, IX, & X) Prevent thromboembolisms Rapid absorption 97% protein bound Hepatic metabolism & conjugation Excreted via bile & urine Teratogenic - crosses placenta
Warfarin Onset & DOA
Onset 3-4 days
DOA 2-4 days
Elim 1/2 time 24-36hr after PO admin
Warfarin Dose
1.5-20mg PO
Warfarin Lab Values
PT/INR
2-3 Afib, treat VTE/PE, high risk surgery prophylaxis, tissue heart valves
2.5-3.5 mechanical heart valve, prevent recurrent MI, VTE history w/ INR 2-3
Warfarin Reversal
Minor surgery dc 1-5 days preop & restart 1-7 days postop
Immediate surgery 24-48hr or active bleeding admin vitamin K 2.5-20mg PO or 1-5mg IV
Emergency admin FFP or 4-factor concentrate K-centra
Unfractionated Heparin
Anticoagulant
Naturally occurring polysaccharide that inhibits coagulation
Released endogenously by mast cells & basophils
Binds to antithrombin & enhances AT ability to inactivate coagulation enzymes
Unfractionated Heparin DOA
DOA 1.5-4hr
Dose-dependent elimination 1/2 life
Unfractionated Heparin Dose
VTE prophylaxis 5,000u SC Q8-12hr
VTE treatment 5,000u IV + continuous infusion goal PTT 1.5-2.5x control value
Cardio-pulmonary bypass 400u/kg IV
Vascular interventions 100-150u/kg IV
Unfractionated Heparin Lab Values
aPPT 1.5-2.5x
Activated clotting time ACT
HEPTEM
Unfractionated Heparin Reversal
Protamine 1-1.5mg per 100u Heparin
Low Molecular Weight Heparin
Anticoagulant Enoxaparin (Lovenox) Binds to antithrombin Inhibits factors Xa & IIa ↓thrombin activity Prevents fibrin clot formation
Enoxaparin Dose
Once daily
Elimination 1/2 time 24hr
Enoxaparin Advantages
↓dosing
More predictable PK response
↓effect on platelet function
Less monitoring required - no routine labs
Enoxaparin Disadvantages
More expensive
Surgery delay 12hr post-dose
Protamine only neutralizes 65%
More complete reversal w/ FFP
Direct Oral Anticoagulants (DOACs)
Direct thrombin (IIa) inhibitors Direct factor Xa inhibitors - VTE treatment (Warfarin alternative) - Prevent embolic stroke - Surgical prophylaxis
DOACs Surgical Management
Minimal bleeding risk procedures continue
Low bleeding risk dc 24hr prior
High bleeding risk dc 48hr prior
Dabigatran (Pradaxa)
DOAC
Direct thrombin (IIa) inhibitor
Rapid onset w/ peak 24hr
1° renal elimination
Elim 1/2 time 12hr unless impaired renal function
Monitoring - coagulation assay, dilute thrombin time, aPPT, or ROTEM
Dabigatran (Pradaxa) Reversal
Idarucizumab (Praxbind)
Specific antidote
Binds w/ 350x ↑affinity than thrombin
Elim 1/2 time 45min
Direct Factor Xa Inhibitors
DOACs
- Rivaroxaban (Xarelto)
- Apixaban (Eliquis)
- Edoxaban (Savaysa)
65-70% hepatic metabolism
Monitoring - coagulation assay (anti Xa), ROTEM, or PT (Rivaroxaban)
Antiplatelet
Cyclooxygenase inhibitors
P2Y12 receptor antagonists
Platelet glycoprotein IIb/IIIa antagonists
Aspirin
Antiplatelet COX inhibitor
Suppresses platelet function
Inhibits thromboxane A2 synthesis via interfering w/ COX 1 & 2 isoenzymes therefore present subsequent adenosine diphosphate release from platelets
IRREVERSIBLE
Aspirin Dose
81-325mg PO
Platelet Lifespan
8-12 days
Discontinue ASA at least 7 days prior to surgery d/t irreversible binding
New platelets required to reverse effects
Aspirin Clinical Indications
Prevent CVA (stroke)
Myocardial infarction prophylaxis
Vascular thrombosis complications
Aspirin 1° vs. 2° Prophylaxis
1° hyperlipidemia w/o established CV disease
Continue ASA prophylaxis up to/including DOS hold few days per surgeon discretion
2° Afib, previous MI, or stents
Discontinue ASA requires explicit discussion w/ physician to consider cardiac vs. bleeding risk
Cyclooxygenase Inhibitors
Aspirin NSAIDs - Ketorolac - Naprosyn - Ibuprofen
NSAIDs
Non-selective COX inhibitors
Antiplatelet temporary effects 24-48hr duration
Discontinue prior to surgery
P2Y12 Receptor Antagonists
Clopidogrel (Plavix) Ticagrelor (Brilinta) Inhibit platelet activation & aggregation via irreversibly binding its active metabolite to P2Y12 class adenosine disphosphate receptors on platelets
Clopidogrel (Plavix)
P2Y12 receptor antagonist
Pro-drug requires CYP450 metabolism to produce active metabolite
Irreversible effects
Platelet function studies are unreliable
Ticagrelor (Brilinta)
P2Y12 receptor antagonist
Does not require hepatic activation
P2Y12 Receptor Antagonists
Clinical Indications
Prevent 2° MI or CVA Coronary artery stent Acute coronary syndrome Peripheral artery disease Bare-metal stents 2-6wk Drug-eluding stents 6mos
P2Y12 Receptor Antagonists
Reversal
Discontinue 7 days prior to elective surgery
Emergent surgery = platelet transfusion to reverse
Platelet Glycoprotein IIb/IIIa Antagonists
Antiplatelet
- Abciximab (ReoPro)
- Tirofiban (Aggrastat)
- Eptifibatide (Integrilin)
Platelet Glycoprotein IIb/IIIa Antagonists
MOA
Act at corresponding fibrinogen receptor (important to platelet aggregation)
Blocks fibrinogen → prevents final common pathway in platelet aggregation
Platelet Glycoprotein IIb/IIIa Antagonists
PK/PD
Renal excretion
Elim 1/2 life 2.5hr
Abciximab 1/2 life 12hr w/ clinical effects lasting 48hr
Platelet Glycoprotein IIb/IIIa Antagonists
Clinical Indications
Acute coronary syndrome
Angioplasty failures
Stent thrombosis
Platelet Glycoprotein IIb/IIIa Antagonists
Considerations
- Monitor effects w/ ACTs
- Maintain ACT b/w 200-400sec
- Reversible w/ drug clearance
- Thrombocytopenia <100,000 develops then discontinue
- Reversed w/ platelet transfusion
Garlic
Herbal anticoagulant
Inhibits platelet aggregation
Discontinue 7 days
Ginkgo
Herbal anticoagulant
Inhibits platelet activating factor
Discontinue 36hr
Ginseng
Herbal anticoagulant Inhibits platelet aggregation ↓blood glucose Check PT/PTT & glucose Discontinue 24hr (preferably 7 days)
Black Cohosh
Herbal anticoagulant
Used to treat menopausal symptoms
Contains anti-inflammatory compounds including salicylic acid
Fish Oil
Herbal anticoagulant Prevent/treat atherosclerotic CV disease ↓triglycerides 800-1500mg/day Dose-dependent bleeding risk >3g/day
Feverfew
Herbal anticoagulant
Prevent migraines & inhibits platelet aggregation
Additive effects w/ other antiplatelet drugs & Warfarin
Thrombolytics
Converts plasminogen to active form → plasmin
Plasmin breaks down fibrin
More effective to dissolve newly formed platelet-rich clots w/ weaker fibrinogen bonds
Treatment window = 6hr
Urokinase
Alteplase (t-PA)
Streptokinase
Thrombolytic Contraindications
Trauma
Severe HTN
Active bleeding
Pregnancy
Adverse Effects:
- Hemorrhage or bleeding
- Re-thrombosis
Alteplase (t-PA)
Fibrin specific thrombolytic drug synthesized by endothelial cells
Elim 1/2 life 5min
Short DOA
IV bolus then infusion OR direct into embolism
Limited use w/in 1st 3-6hr ischemic stroke
Streptokinase
Thrombolytic
Protein produced by β hemolytic streptococci
NOT an enzyme
Non-covalently binds to plasminogen & converts → plasminogen-activator complex that acts on other plasminogen molecules to generate plasmin
Elim 1/2 life 20min
Bacterial product → stimulate antibody production & subsequent allergic reactions
Least expensive thrombolytic
Intrinsic Coagulation Cascade
Amplifies & propagates hemostasis
2° hemostasis
Key = thrombin (factor II)
XII → XI → IX → VIII → common pathway
Extrinsic Coagulation Cascade
Plasma mediated Hemostasis INITIATION 1° hemostasis Key = tissue factor (III) III → VII → common pathway
Common Pathway
Results in soluble fibrin clot
X → factor X activates prothrombin II → thrombin IIa → thrombin activates fibrinogen I → fibrin Ia → CLOT FORMATION
Normal Platelet Count
150,000-300,000mm^3
INR
0.9-1.2
PT
12-14 seconds
Thrombin Time
<30 seconds
Activated Clotting Time (ACT)
80-150 seconds
Fibrinogen
> 150mg/dL
aPPT
25-35 seconds
Hemophilia A
Factor VIII deficiency
Hemophilia B
Factor IX deficiency
Vitamin K Dependent Factors
II, VII, IX, & X
Blood Coagulation Mechanism
- Vasoconstriction
- Platelet plug formation
- Blood clot formation
- Dissolution
