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Hemostasis
the physiologic process (coagulation cascade) by which bleeding is stopped
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Thrombosis
the physiologic process by which a thrombus is formed. Indicates abnormal hemostasis
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Thrombus
- clot in a blood vessel or the heart
- *Embolism= more dangerous
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Anticoagulants
- Parenteral
- -Heparin and heparin-related drugs
- -Direct Thrombin Inhibitors
- Oral
- -Warfarin (Coumadin®)
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Heparin mech of action, admin, important issues
- Mechanism of action: inactivates thrombin and other clotting factors indirectly by increasing activity of antithrombin à decreases clot formation especially in veins
- Administration: parenteral (IV, SC) only. Too large to cross membranes
- Some important uses:Prevent postoperative venous thrombosis, Treat various embolic diseases (PE, stroke, DVT), Decrease clotting in heart-lung machines and dialysis units
- -line patency
- -during pregnancy (instead of Coumadin)
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Heparin part 2 sources, adrs, contradictions
- Sources: beef lung and pig intestine
- Important ADR’s:
- Hemorrhage (the most common complication) (platelet ct 150-400k)
- Thrombocytopenia
- Hypersensitivity reactions (from animal source)
- Contraindications:
- Active bleeding (<BP, >HR, <RBC, <HgB, ss of anemia, cold, SOB)
- Thrombocytopenia
- Certain surgeries/procedures (brain, spinal cord, eye)
- Important drug interactions: drugs that also increase risk of bleeding (NSAIDs)
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Protamine sulfate
Heparin overdose (binds to heparin to neutralize)
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aPTT
- Monitor for Heparin
- -Normal aPTT: 40 sec.
- -Goal for anticoagulation: 1.5-2 x normal (60-80 sec.) (takes longer to clot)
- -If aPTT too high, decrease dose
- -If aPTT too low, increase dose
- -Remember, to treat clots, the aPTT must be higher than normal without causing bleeding -Monitor aPTT q4-6 hrs. initially (then 1x/d)
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HIT
- heparin induced thrombocytopenia
- IGG mediated immune response to heparin
- platelet count drops by 50+%
- NEVER give heparin again
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Low Molecular Weight Heparin
- enoxaparin (Lovenox)
- -heparin preparations that are composed of smaller molecules than standard preparations.
- Differences from standard heparin:
- -Does not inactivate thrombin like heparin, but does inactivate other clotting factors
- -Is usually given SC only; rarely given IV
- -Can be administered at home because…
- -can be given on a fixed-dose schedule
- -no need to monitor aPTT
- -Less likely to cause thrombocytopenia
- -Cheaper! Because given at home
- -if creatine clearance <30 only admin 1x/d(<dose)
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Factor XA Inhibitor
- Example of heparin-like drug:
- **Fondaparinux (Arixtra®)
- -Smaller than LMWH
- -Use to prevent and treat DVT/PE
- ADR: Bleeding
- -Do not use in patients with creatinine clearance below 30ml/min or weigh less than 50 kg
- HIT not an issue
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Direct Thrombin Inhibitors
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oMechanism: inhibit thrombin directly whereas the heparin and heparin-like drugs inhibit indirectly
- oExamples:
- Bivalirudin (Angiomax®)- IV only; used with ASA to prevent clots in patients with USA undergoing coronary angioplasty
- Lepirudin (Refludan®)- IV only; used for prophylaxis and treatment for thrombosis in patients with HIT
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Warfarin (Coumadin®) mech of action, admin, main use, ADR, contradiction
- Mechanism of action: blocks the synthesis of 4 clotting factors (VII, IX, X, and prothrombin; which are vitamin K-dependent) à decreases clotting
- Administration: oral
- Main use is long-term prophylaxis for:
- -venous thrombosis and DVT
- -prosthetic heart valves
- -atrial fibrillation
- ADR: hemorrhage
- Contraindications: pregnancy
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Wafarin Tx, drug interaction
- Treatment in overdose: Vitamin K which is phytonadione (Mephyton/Aquamephyton)
- Drug interactions: MANY! Probably has the most drug interactions of any drug!
- -Drugs that also cause increased bleeding/ or decreased clotting (Heparin, ASA)
- (heparin used in conjunction until INR=2-3)
- -Drugs that increase effects of warfarin (sulfonamide antibiotics)
- -Drugs that decrease effects of warfarin- Example: anti-seizure drugs; rifampin, phenytoin, phenobarbitol, carbamazapine, dilantin
- -Food-Green leafy veg
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INR
- Monitoring for Warfarin
- Lab test: INR (international normalized ratio)
- INR is based on the prothrombin time (PT) and a correction factor.
- -Normal prothrombin time (PT): 12 sec
- -Anticoagulation goal (INR) for most patients: 2-3
- *If INR too high, decrease dose
- *If INR too low, increase dose
- -Monitoring must be very frequent initially (daily) à monthly.
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Differences Between Heparin and Warfarin:
- -Heparin must be given parenterally, warfarin is oral.
- -Different mechanisms of action
- -Heparin acts quickly, effects are brief. Warfarin acts more slowly, effects are prolonged. (3 d before full effects)
- -Monitored differently (aPTT vs. INR)
- -Antidotes for overdose are different
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Antiplatelet Drugs Three Main Groups
- Aspirin (will cover more with pain module)
- Adenosine Diphosphate Receptor Antagonists
- *Clopidogrel (Plavix®)
- *Ticlopidine (Ticlid®)*
- Glycoprotein IIb/IIIa Receptor Antagonists
- *Abciximab (ReoPro®)
- *Eptifibatide (Integrilin®)*
- *Tirofiban (Aggrastat®)*
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Aspirin (Bayer/Ecotrin)
- Anti-platelets
- -Inhibits platelet aggregation irreversibly
- **Duration for the life of the platelets (7d)
- -Used for prevention and treatment of MI, strokes, USA and occlusion of stents
- ADR: bleeding, dyspepsia
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Clopidogrel (Plavix®)
- Mechanism of action: causes irreversible blockade of ADP receptors on platelets à prevents ADP-stimulated platelet aggregation
- Use: reduce risk of MI, stroke, cardiovascular death in those with CHD
- Effectiveness: slightly better than aspirin
- Cost: MUCH more than aspirin
- ADR’s: generally well-tolerated, similar to aspirin such as dyspepsia
- -May also cause TTP
- Administration: PO
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Abciximab (ReoPro®)
- Mechanism of action: causes reversible blockade of GP IIb/IIIa receptors on platelets à inhibits final step of platelet aggregation à decreases clotting
- Effectiveness: member of most effective antiplatelet class available; AKA “super aspirins”.
- Short-term uses:
- -Acute coronary syndrome (unstable angina and evolving MI)
- -Reduce reocclusion after angioplasty
- **drug of choice for st segment elevation
- Administration: IV
- ADR’s: hemorrhage
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Thrombolytic Drugs Mech of action, Main use, Admin
- "Clot Buster" breaks down new & existing clots (dangerous)
- Mechanism of action
: causes formation of plasmin, an enzyme that digests fibrin in clots that have already formed - Main uses:
- -Acute MI
- **best if begun ASAP within 4-6 hrs of symptom onset
- -DVT
- -Massive PE
- Administration: IV
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Thrombolytics ADR, Absolute contradictions, Therapeutic uses w/ extreme caution, drug example
- Main ADR:
- -Hemorrhage
- Absolute contraindications:
- -Active bleeding
- -Brain tumors
- -Intracranial bleeding
- -Suspected aortic dissection
- Therapeutic uses with extreme caution:
- -Ischemic stroke- must rule out intracranial hemorrhage with CT. (“tPA” has been approved for this use)
- ***Alteplase (Activase®)- “tPA”
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