Summer-Pharm II--PA
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| What are the two types of Thrombi? | Arterial- mainly platelets in a white clot sits on atherosclerotic plaque and
Venous- Mainly fibrin and RBCs occurs when procoagulant stimuli overwhelm the natural protective mechs
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| What are the 3 components of Virchow's Triad? | 1) Venous stasis (i.e. bed-rest)
2) Hypercoagulable state (i.e. pregnancy)
3) Endothelial damage (i.e. HTN)
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| What do Arterial Thrombi tend to cause? | MI, limb gangrene, CVA
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| What do Venous Thrombi tend to cause? | DVT, PE, Postphlebitic syndrome
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| What are some medical mpatient groups at especially high risk for DVT? | Gen surgery, GYN surgery, Urol. surgery, neuro surgery, stroke, Hip fractures, Hip or knee athroplasty, major trauma, spinal injury, critical care pts
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| What are classes of antithrombic agents? Which is the most indicated? | Most indicated: Anticoagulants
Antiplatelet drugs
Thromboltic drugs
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| The intrinsic pathway of the clotting cascade involves_____ damage, while the extrinsic pathway involves____damage | surface, tissue
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| Prothrombin Time (PT)is defined as: | Time for blood to clot in presence of thromboplastin and CaCl
measures: factors X IX VII II (1972)
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| What does INR do? | Standizes the PT (especially between hospitals) and should not normally be >1.1-1.2
INR = [Patient's measured PT (norm: 10-13s)]
_____________________________________\
mean normal PT
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| What is an aPTT? | activated Partial Thromboplastin Time
-used to monitor heparin
-measures factors XI IX VIII VII of the intrinsic pathway and II V and X of the extrinsic
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| What effects aPTT other than heparin? | Warfarin, Thrombin inhibitors, Liver disease, or factor deficiency
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| What is D-dimer? | -a breakdown product of fibrin
-marker of:
-fibrinolysis
-active inflammation
-prothrombotic states (DVT, PE, DIC)
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| What is the normal range for D-dimer? | <0.5μg/mL or <200ng/mL
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| What are the two MC used LMWH? | Enoxaparin & Deltaparin
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| What are differences between UFH and LMWH? | ratio of Xa to IIa equal in hep; 3-4:1 in LMWH
Hep less predictable dosing (30-70% bioavailable; LMWH 80-99%)
clearence hepatic and renal in heparin, only renal in LMWH
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| What is the MOA of UFH? | Binds ATIII causing confirmational change to make ATIII 1000-100000x more potent to inhibit clotting factors IIa and Xa
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| How many 1/2 lives must go by before a drug is totally eliminated? | 5 1/2
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| When is IV heparin given? When is SQ given? | to treat a clot; to prevent a clot
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| What is the target aPTT for UFH? | 60-85s for PE, venous thrombus
50-70s for acute coronary
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| What adjustment should be made to LMWH if Cr Clearence <30? | renal adjustment to dose; usu cut in 1/2
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| What levels are used to monitor a Patient on a LMWH? | -SCr
-Anti Xa
-platelets
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| What adverse drug reactions occur in only UFH? in both UFH and LMWH? | UFH only: alopecia and osteoporosis
UFH and LMWH: Bleeding, HIT, pain at injection site
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| What agent reverses UFH and LMWH? HOW? | Protamine-binds to (-) charged sulfa groups and cleaves at random
Xa- 100% neutralized
IIa- 32-44% neutralized
(reverses up to 60% of LMWH effects)
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| What is Fondaparinux? | A pentassacharide anticoagulant medication that selectively binds Xa with reversible binding
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| What are indications for Fondaparinux? | -hepatic failure
-patient compliance (1/2 life = 17-21 hours)
-no reports of HIT
-favored in orthopedics
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| What are CI of Fondaparinux? | -up-coming surgery
-not ideal for renal failure (renal clearence)
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| Why might Fondaparinux be dangerous versus UFH/ LMWH? | Although NovoSeven may have potential at reversal, there is no recognized reversal agent
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| What agent is used as a "bridging therapy", usually after a heparin? | Warfarin
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| What are the Vitamin K-dependent factors? | 1972: X IX VII II
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| How is Vit K involved in clotting? | Reduced Vit K and a Prothrombin precursor interact to form oxidized Vit K and Prothrombin
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| Why does it take about 17 days to get patients to a steady state on Warfarin? | The 1/2 lives of the clotting factors are long (up to 100 hours)
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| What is the target INR for PE? valve replacement? Afib? | Afib and PE: 2-3, Valve replacement: 2.5-3.5
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| How is Warfarin administered? metabolized? | admin: PO
metab:CYP2C9 and CYP1A2
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| Factors that increase bleeding risk | -intensity of anticoag
-concommitant conditions
-concommitant meds
-quality of management
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| Risk factors for bleeding include? | age >75, treated HTN, ASA/ NSAIDs, Heart disease, female, severe anemia, malignancy, DDI, Risk of falling, Carrier of CYP2C9*3 gene, Hx of stroke, alcoholism or liver disease, DM, anemia
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| How should INR be adjusted if it is <5.0 (no bleeding) | lower &/or omit a dose or no change
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| How should INR be adjusted if it is 5.0-9.0 (no bleeding)? | Vit K hold Warfarin until therapeutic INR
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| How should INR be adjusted if it is >9.0? | hold Warfarin, IV Vit K with fresh plasma or prothrombin complex or recombinant factor VIIa
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| Why shouldn't Vitamin K be given liberally? | Administration of a large dose of Vit K may result in warfarin resistance for up to a week or more
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| What is HIT? | -type I and type II
- an immune-mediated adverse reaction to UFH or LMWH
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| How is HIT diagnosed? | -antiP4/ heparin Antibodies
-90% have thrombocytopenia
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| Why is HIT still an issue in the absence of thrombocytopenia? | Pts will still have endothelial damage that will predispose them to clots
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| How is thrombocytopenia defined? | Platelets <150,000/mm3 or reduced by 50% from baseline
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| How long are the antibodies present? How long does it take for platelet recovery? | 85-100 days for Antibody circulation
4-14 days for platelet recovery
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| What is rapid-onset HIT? | HIT that occurs d/t a second exposure to heparin/ LMWH within 100 days
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| Why do the thromboembolic complications of HIT contribute to high morb/mortality? | Without appropriate treatment ~1/2 patients will develop a new thrombosis
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| The risk of HIT left untreated, even when platelet counts return to normal is: | Thrombosis
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| The clinical presentation of HIT includes: | -DVT/PE
-CVA MI
-skin lesions at injection sites
-Warfarin-induced venous limb gangrene
-acute limb ischemia
-acute systemic reactions following IV bolus
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| Diagnostic Tests for HIT include: Why are 100% specific methods not always used? | SRA (C-Serotonin-release assay)
-100% specific--time consuming
HIPAA (Heparin-induced platelet activation assay)-100% specific--Time consuming
ELIZA (enzyme-linked immunosorbancy assay)
-80% effective--faster results
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| What non-pharmacological patient care should be implimented? | -Update allergy profile
-Stop all Heparin products
-Stop all platelet infusions (as they amplify the building of clot complexes)
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| What Direct Thrombin Inhibitors are FDA approved? Which is not, but may be used in treatment? | FDA approved: Argatroban and Lepirudin
Non-FDA: Bivalrudin
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| What pentasaccharide may be used in treatment of HIT? What is it indicated for? CI? | Fondaparinux- approved for tx/prophylaxis of thromboembolism (DVT, PE)
-often used in orthopedic surgery
-Heparin allergy
CI-Afib and valve replacement--d/t lack of supportive data
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| What are requirements for the prescription of Warfarin? | -not a monotherapy (or initial therapy)
- platelets must recover (to baseline)
-aPTT therapeutic (must have 2 therapeutic readings)
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| What are indications for Agatroban? CI? | -prophilaxis/ tx thrombosis in patients with HIT
CI: hepatic failure
-undergoing PCI (percutaneous coronary intervention/ cath)
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| What are indications for Lepirudin? | -in pts w/ HIT and associated thromboembolic disease to prevent further complications
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| What are indications for Bivilrudin? | Patients at risk of or w/ HIT or HITTS or undergoing PCI (cath)
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| Agatroban: what is it? MOA Onset | Agatroban:
what is it? synthetic thrombin inhibitor
MOA: Reversible binding to thrombin catalytic site
Onset: 1-3 hrs
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| Argatroban: Metabolism & Elimination 1/2 life aPTT indication | Metabolism/ Elimination: CYP450 3A4 metab/ Hepatobiliary elimination
1/2 life-24-50 min
aPTT indication- aPTT q 2 hrs, 60-85s, have two therapeutic readings
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| Argatroban: Advantages | -No interaction with Heparin-dependent Ab
-Short 1/2 life
-Easily monitored
-No dosage adjustment in renal failure
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| Argatroban: Disadvantages | -Falsely prolongs INR (scares docs)
-needs dosage adjustment in hepatic failure
-lack of data for SQ administration (only IV)
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| Lepirudin: What is it? MOA Onset | Lepirudin:
What is it? A polypeptide direct thrombin inhibitor
MOA: Irreversibly binding to catalytic sites of fibrin and thrombin
Onset: 3-4 hrs
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| Lepirudin: 1/2 life elimination aPTT indications | Lepirudin:
1/2 life: 40-120 min
elimination:renal
aPTT indications-aPTT q 4hrs
-titrate 20%
-2 therapeutic readings
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| Lepirudin: Advantages | -no interactions with Heparin-dependent Ab
-Short 1/2 life
-Easily monitored
-no dosage adjustment in hepatic failure
-may be administered SQ
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| Lepirudin: Disadvantages | -Antihirudin Ab form in patients treated for >5 days (increase anticoagulants)
-renally cleared
-expensive
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| Bivalrudin: Approved for MOA Clearence 1/2 life | Bivalrudin:
Approved for: treatment of HIT patients undergoing PCI
MOA: bivalent direct thrombin inhibitor
-reversible inhibition
-proteolytically cleaved by thrombin
Clearence: independent of organ function
1/2 life: 25 minutes
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| Summary of FDA approval: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of FDA approval:
Fondaparinux-no
Lepirudin-yes
Argatroban-yes
Bivilrudin-no
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| Summary of direct antithrombin inhibition: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of direct antithrombin inhibition
Fondaparinux-no
Lepirudin-yes
Argatroban-yes
Bivilrudin-yes
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| Summary of route of elimination: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of route of elimination
Fondaparinux-renal
Lepirudin-renal
Argatroban-hepatic
Bivilrudin-enzyme cleavage
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| Summary of 1/2 life: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of 1/2 life
Fondaparinux-17-21 hr
Lepirudin-1.3 hr
Argatroban-39-51 min
Bivilrudin-10-24 min
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| Summary of Antidote Available: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of Antidote Available:
all = no
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| Summary of Monitoring: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of Monitoring:
Fondaparinux-anti-Xa
Lepirudin-aPTT/ ECT
Argatroban-aPTT/ ACT
Bivilrudin-aPTT/ ACT
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| Summary of {regnancy Category: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of Pregnancy category:
all B
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