Anticoags Flashcards
Oral antiplatelet aggregation
Aspirin, Ticlopidine, Clopidogrel, Prasugrel, & Ticagrelor (PT cat)
IV antiplatelet aggregation
Abciximab, Eptifibatide, & Tirofiban
ate
*Aspirin MOA
Cycloxygenase (COX) inhibitor
Prevents the production of Thromboxane A2
Action is irreversible, lifespan of a platelet 10 day
*ASA prevents what, dose diseases
Recurrent Ischemic Events Stroke Myocardial infarction Symptomatic peripheral arterial disease Dosage: 81–325 mg qday
ASA precautions
drug interaction
tx for bleeding
Children (Reye’s)
Pregnancy
Asthmatics
Cardiovascular drugs
Blunts effect of ACE inhibitors, ß-blockers, & diuretics due to prostaglandin inhibition
Increased bleeding with other anticoagulants. Treatment of bleeding is platelet transfusion: have platelets circulation just don’t stick to each other so platelet count doesn’t matter
*Ticlopidine (ticlid) MOA
Thienopyridine - Blocks ADP receptor on platelet and inhibits fibrinogen binding
Ticlopidine (ticlid) use
restrictions
Used for prevention of recurrent ischemic events especially in cases of ASA intolerance
**Use is extremely restricted due to: Neutropenia, Thrombotic thrombocytopenic purpura, GI Upset, Teratogenesis
*Clopidogrel (Plavix) MOA
Thienopyridine – Irreversibly blocks ADP receptor on platelet and inhibits fibrinogen binding
*Clopidogrel (Plavix) prevention of
Used for prevention of recurrent
ischemic events:
Stroke prevention
Recent acute coronary syndrome (dual therapy better than ASA mono therapy)
Post-percutaneous coronary intervention (dual therapy better than ASA monotherapy)
which mono therapy is better ASA or Clopidogrel, but what the down side and doses of the 2
Clopidogrel monotherapy better than ASA monotherapy but cost may be prohibitive
Dosage
Loading dose of 300mg or 600mg
Daily dose of 75mg
Clopidogrel precautions
Metabolized via CYP2C19, genetic predisposition to poor metabolism along this pathway, may require increased dosing
**CYP-450 inhibitor
Dose adjustment for severe renal or
hepatic disease
Use in conjunction with other anticoagulants
Clopidogrel toxicities/bleeding
Increased risk of bleeding Serious bleeding seen most commonly in the elderly, the underweight, and pts with previous stroke or TIA Treatment of Bleeding Discontinuation of drug (at least temporarily) Platelet transfusion
*Prasugrel (effient)
New Thienopyridine
greater than clopidogrel at reducing risk of recurrent MI and in-stent thrombosis
greater risk of bleeding
works of clopidogrel non-responders
Prasugrel dose precautions
10mg qday
Precautions:
Active bleeding
Previous stroke/TIA, underweight, elderly (>75 yrs) – Consider decreasing dose to 5mg qday
*Surgery – Risk of bleeding during CV surgery was 4x greater than clopidogrel. Do not use pre-cardiac cath!
*Ticagrelor (brilinta) MOA
Blocks ADP receptors from different binding site (allosteric antagonist)
- better than clopidogrel of MI and stroke
- but higher rate of non-procedure bleeding–including intracranial hemorrhage
Ticagrelor uses dose
Prevention of recurrent ischemic events after myocardial infarction
Stroke prevention
Recent acute coronary syndrome
Post-percutaneous coronary intervention
Dosage: 180mg x 1, then 90mg bid
Always given as dual therapy with ASA unless ASA is contraindicated
Ticagrelor precautions contraindications
Precautions: Hepatic dysfunction ASA use greater than 100mg/day Hold for >5 days before surgery bid dosing may have compliance considerations Contraindications: Active bleeding History of intracranial hemorrhage
*GPIIb/IIIa inhibitors MOA
Block the GPIIb/IIIa receptor preventing fibrinogen binding
*GPIIb/IIIa inhibitors uses and drug names
Acute Coronary Syndrome Percutaneous Coronary Intervention Drugs: Abciximab (ReoPro) Eptifibatide (Integrillin) Tirofiban (Agrastat)
*Abciximab uses
ACS with planned PCI – If used with heparin keep aPTT 60-85 sec PCI Most expensive agent Most prolonged effects
*Eptifibatide
ACS – IV bolus – Infusion Serum Creatinine <2.0 mg/dl 2.0 mcg/kg/min for up to 72 hours Serum Creatinine 2.0 to 4.0 mg/dl 1.0 mcg/kg/min for up to 72 hours PCI – Same as above
GPIIb/IIIa Inhibitors toxicities
Bleeding
Abciximab – reverse with platelets
Eptifibatide and Tirofiban – discontinue the drug
Interactions
Other antiplatelet and anticoagulant agents potentiate effects
Peri-op mgmt of anti platelet therapy
Temporary interruption of anti-platelet therapy should occur 7-10 days pre-op
Therapy should resume 24hrs (or next AM) post-op as long as hemostasis is achieved
Patients at high risk for cardiac events should continue ASA up and through the OR, clopidogrel should be stopped at least 5 days prior to OR
*Heparin MOA
Heterogenous mixture of polysaccharide chains
Activates Antithrombin III
Increases inhibition of Thrombin (IIa) and
Factor Xa by 1000 fold
*Heparin uses
DVT prophylaxis and treatment
Pulmonary Embolus treatment
Acute Coronary Syndrome
When warfarin started or contraindicated
Heparin doses
DVT prophylaxis: 5,000 Units SQ q8hrs
q12 hr dosing occasionally used in high-risk bleeding pts (i.e. Neurosurgery and ESRD)
Intravenous infusions
Weight-based bolus
Weight-based infusion
Adjusted based on aPTT or anti-Xa values q6hrs until stable, then qday
Heparin interactions/drawbacks
Increased risk of bleeding when used with other anticoagulant or antiplatelet agents
Drawbacks of use
Variable anticoagulant effect
Inability to inhibit clot-bound thrombin
Heparin toxicities
*Bleeding
STOP THE HEPARIN! Look for hidden heparin!
Reverse with Protamine 1mg/100 U Heparin (or just give 50mg bolus)
*Benign thrombocytopenia
*Heparin-induced thrombocytopenia (HIT)
1% @ 7days ■ 3% @ 14days
HIT non-immune mediated (type 1) and immune mediated (type 2)
1.Mild drop in platelets, usually within 4 days of start of heparin treatment, NOT progressive or associated with thrombosis
2. Follows heparin exposure (prophylactic or full)
Reduction in platelet count to < 150,000 or
a decrease of 50% from baseline (pre heparin)
Occurs 5 - 14 days after heparin exposure
Thrombocytopenia
Occurs in 2-5% (UF>LMWH)
Most common: Surgery >medical > obstetric
Typical platelet count 38,000-60,000
Typical onset (66%): Exposure 5-14 days
Delayed onset (3-5%): Exposure 2-6 weeks
Rapid onset (25-30%): hours to days, usually due to residual circulating antibodies from heparin exposure within last 100 days)
HITT venous, arterial
Thrombocytopenia with Thromboembolism (10 – 25% cases)
Venous:
(4 x more common)
DVT, PE, Venous limb gangrene, dural sinus
thrombosis
Arterial:
Cerebral infarction, limb ischemia, skin necrosis, myocardial infarctions, mesenteric ischemia, adrenal, renal, spinal artery infarctions
25 – 30% mortality, 25% amputation rate
HIT lab
ELISA: (enzyme linked immunosorbent assay)
Antigen assay measures titer of IgG antibody to heparin-PF4 complex
Easy to do and readily available
Sensitivity 90%, Specificity 80% (detects other antibodies)
C-serotonin release assay (SRA):
Detects platelet activation
Labor intensive, Not readily available, Usually a “send-out” test
Sensitivity & Specificity 95%
Used primarily as a confirmatory test
**Do not delay treatment waiting for test results!
HIT clinical mgmt
Stop all drugs known to cause thrombocytopenia
STOP Heparin and START non-heparin anticoagulant (usually Argatroban)
Look for any history of heparin exposure
Look for unrecognized heparin sources
Heparinized flush bags
Heparin-coated catheters
Prophylactic sq heparin
*Low Molecular Weight Heparin (enoxaparin) MOA/uses
Saccharide chains ~ 5,000 daltons Binds with Antithrombin III and inhibits Factor Xa Uses: DVT prophylaxis Acute Coronary Syndrome VTE treatment
Low Molecular Weight Heparin dose
Dosage (subcutaneous injection) Depends on indication
DVT Prophylaxis
Standard: 40mg q24hrs
Hip or knee replacement: 30 mg q12hrs
DVT Treatment: 1 mg/kg q12h or 1.5 mg/kg qd
Acute Coronary Syndrome: 1mg/kg q12h
*Dosage effects not routinely monitored, can check anti-Xa levels
Low Molecular Weight Heparin precautions, tx
Precautions
Pregnant women – monitor anti-Xa levels
Obese patients – use weight-based dosing
*Not recommended in severe renal insufficiency (Cr Cl <30 ml/min). If no other alternative, reduce dose by 50%
Not for use with spine surgery patients or patients with epidural catheters
*Treatment of bleeding – Protamine provides ~60% reversal
*Fondaparinux (Arixtra) MOA, uses
Synthetic Factor Xa inhibitor Binds with Anti-thrombin III to potentiate Xa inhibition (by 300 times) No direct effect on IIa (thrombin) Uses: Acute Coronary Syndrome PE/DVT tx DVT prophylaxis
Fondapariunx dosage, contraindications, *tx
Dosage 7.5mg subcutaneous qd for prophylaxis, 10mg for VTE or wt > 100kg, duration depends on reason for use Contraindications: CrCl < 30 ml/min Spinal anesthesia or lumbar puncture Treatment of bleeding No known reversal agent FFP is ineffective in reversal Discontinue the drug and provide supportive care
*IV direct Thrombin (IIa) inhibitors MOA, uses
Do not require Antithrombin III
IV Agents include Hirudin, Lepirudin, Desirudin, Hirulog, Argatroban (reversible), Bivalirudin
Uses: HIT (Argatroban, Lepirudin)
Percutaneous coronary intervention (Bivalirudin)
IV direct Thrombin (IIa) inhibitors toxicities, Interactions, *Tx of bleeding
*Toxicities:
Bleeding
Lepirudin and Desirudin can only be used once d/t problems w/ anaphylaxis
*Interactions:
Increased bleeding with additional anticoagulants, thrombolytics, or anti platelet agents
*Treatment of bleeding:
Stop the infusion
May respond to a combination of Factor VII, FFP, and cryoprecipitate
*Warfarin MOA
Interferes with the production of Vitamin K-dependent clotting factors (II, VII, IX, & X)
Interferes with the carboxylation of natural anticoagulants Protein C and Protein S
*Warfarin uses
Prevention of thrombosis/embolism DVT Atrial fibrillation Mechanical heart valves Long-term treatment of VTE
Warfarin dosage
Start with 5-10mg/day x 2-5 days, then
**Dose based on Prothrombin time/INR
Most indications, therapeutic INR goal is 2.0–3.0
High risk patients (i.e. mechanical heart valves, previous thrombus, anti- phospholipid syndrome) goal of 2.5-3.0
**Overlap with heparin or LMWH for 1-2 days
Duration of therapy for uncomplicated DVT and PE = 3 months
Warfarin toxicities,
Toxicities:
Bleeding, Birth defects, Cutaneous necrosis
Warfarin interactions increased effect
Amiodarone
Cimetidine
Acetaminophen
Phenylbutazone
Warfarin interactions decreased effects
Sucralfate Cholestyramine Spironolactone Barbituates Vitamin K containing foods
Warfarin precautions
Concomitant anti-platelet therapy and/or NSAID use
Warfarin INR
Sub-therapeutic INR: Continue same dose, recheck in 1-2 wks: Super-therapeutic INR without bleeding, Hold next dose, recheck within 1 wk
Reversal/Treatment of bleeding: Vitamin K – either oral or IV, FFP -(1.4 to 1.5 of INR) can’t get INR below 1.5 with FFP
Periop mgmt of Warfarin Therapy
- Pts who require temporary interruption of warfarin and normalization of INR, warfarin should be held 5 days prior to OR
- Warfarin should be resumed 12-24 hours post-op as long as hemostasis has been achieved
- For high-risk patients bridging with heparin up until 4-6hrs of surgery is recommended
*Dabigatran (pradaxa) MOA, uses, dosage
Direct Thrombin Inhibitor (IIa)
Uses: Prevention of stroke in non-valvular atrial fibrillation (2010) and treatment of DVT/PE (2014)
Dosage: 110mg bid vs 150mg bid
Lower dosing suggested if high-risk for bleeding, elderly, or mod/severe renal impairment
Dabigatran
superior to 150mg bid of warfarin for stroke and systemic embolism, no significant difference in major bleeding
*110mg bid just as good as warfarin for preventing with a 20% relative risk reduction for major bleeding
Dabigatran advantages
No routine monitoring required, predictable pharmacokinetics
Less influence by diet and drug interactions
Rapid time to peak action (1 hr)
Short half-life (12-14 hrs) in pts with normal renal function
Dabigatran disadvantages
High cost and bid dosing which may impact compliance
No antidote yet
– Idarucizumab, an antibody, is currently under investigation. May be a potentially effective and rapid antidote
No assay for monitoring of anticoagulant effect
No long term data – Several reports of post- marketing serious or fatal bleeding events that requires investigation
*Rivaroxaban (Xarelto) MOA uses dose
Direct Factor Xa inhibitor
Uses: Stroke and systemic embolism prevention in
non-valvular atrial fibrillation
Prevention of DVT after hip or knee replacement surgery
Treatment of PE/DVT
Dosage: 20mg qday
Rivaroxaban *
just as good as warfarin for prevention
overall risk of bleeding same by decreased risk of intracranial and fatal bleeding compared to warfarin
RIvaroxaban advantages
No routine monitoring required, predictable pharmacokinetics
Less influence by diet and drug interactions
Once daily dosing may improve compliance
Rapid time to peak action (2.5-4 hrs)
Short half-life (7-11 hrs)
Rivaroxaban disadvantages
High cost which may impact compliance
No antidote: Andexanet, a Factor Xa decoy currently under
investigation, may assist in reversal of the effects
No assay for monitoring of anticoagulant effect
No long term data
*Apixaban (Eliquis) MOA uses dose
Direct Factor Xa inhibitor
Uses: Stroke and systemic embolism prevention in non-valvular atrial fibrillation, prevention of DVT in hip and knee replacement surgery, and treatment of DVT/PE
Dosage: 5mg bid
*Apixaban
clear benefit over ASA for pt who are not candidates for warfarin
superior to warfarin in prevention and has significant decreased in bleeding risk
Apixaban advantages
No routine monitoring required, predictable pharmacokinetics
Less influence by diet and drug interactions
Rapid time to peak action (3 hrs)
Short half-life (12 hrs)
Apixaban disadvantages
High cost and bid dosing which may impact compliance
Reversed only with prothrombin complex concentrate
No assay for monitoring of anticoagulant effect
No long term data
*Fibrinolytic what they do and drug names
Plasminogen activators convert plasminogen to plasmin Plasmin causes fibrinolysis *Agents: Streptokinase Urokinase Tissue-type Plasminogen Activator (t-PA) Recombinant t-PA (Alteplase, Reteplase) Tenecteplase (TNK-ase)
*Fibrinolytic use
Acute ST-elevation myocardial infarction Acute ischemic stroke (within 6 hours of onset of symptoms) - tPA Urokinase Central venous catheter de-clotting Pulmonary embolism
Fibrinolytics dose, toxicities
Recombinant tPA: 10 Units over 2 min; Repeat in 30 min
TNKase: 30 – 50 mg single bolus over 5 seconds (wt-
based)
Toxicities
Bleeding - Evaluate absolute versus relative contraindications for the administration of fibrinolytics
Firbinolytics absolute contraindications
Previous hemorrhagic stroke
Ischemic stroke within 3 months
Known intracranial neoplasm
Active internal bleeding (excluding menses)
Suspected aortic dissection
Significant closed head or facial trauma within 3 months
Fibrinolytics relative contraindications
Recent trauma within 2-4 weeks (including
traumatic CPR)
Major surgery < 3 weeks
Recent (2-4 weeks) internal bleeding or active PUD
Pregnancy
For streptokinase - allergy or prior exposure (5 days to 2 years)
