Coagulants and Anti-Coagulants Flashcards
What are physiological activators of platelets?
Thrombin ADP Epinephrine Collagen Arachidonic acid Thromboxane A2
What are platelet inhibitors?
Prostacyclin
Nitric oxide
What state does the body prefer?
Vasodilation and anticoagulant state
What produces thrombin to stimulate platelets to release arachadonic acid?
Collagen
What is arachidonic acid converted to for an inc in platelet aggregation?
Thromboxane
What is heparin?
Prevention of venous thrombosis
Treatment of deep venous thromboembolism
Early treatment of pts with unstable angina and acute MI
Normal heparin is in a ______ preparation.
Heterogeneous
What releases the heparin to bind at more sites?
Antithrombin-protease interaction
What does the half-life depend on for heparin?
Dose
What is a major complication of heparin?
Bleeding excessively
Thrombocytopenia
Osteoporosis with long time use
What is the molecule difference between low molecular weight heparin (LMWH) and regular heparin?
More homogeneous mixture
What are the characteristics of LMW heparin?
Reduced interaction with platelets
Half-life is twice and long
Bio-availability at 90%
More predictable anticoagulant response
How can heparin toxicity be minimized?
Right pt
Careful control of dose
Close monitoring of aPTT
What should be done for all pts receiving heparin?
Platelet count should be performed frequently
New thrombus
When should heparin be discontinued?
If thromboembolic disease is due to heparin
What are the contraindications for heparin?
Hypersensitivity
Active bleeding
Co-morbidies
How must heparin be administered?
IV dose parenterally
Intermitten
NEVER IM
What should be done for heparin reversal?
Administer protamine sulfate (negates anticoagulant action)
How does warfarin work?
Blocks the carboxylation of glutamate residues in prothrombin, factors VII, IX and X and proteins C and S
Results in biologically inactive molecules - no coagulation
Interferes with vit K
What does warfarin prophylax or treat?
Venous thrombosis + extension
Pulmonary embolism
Thrombic complications
What are the major adverse effects of warfarin?
Hemorrhage
Crosses the placenta and is teratogenic
What is considered the most reliable clinical test for clotting?
Prothrombin time (PT)
What is the International Normalized Ratio (INR)?
Mathematical correction of the PT ratio for differences in sensitivity of thromboplastin reagents
Should a large loading dose of warfarin be used?
Probably not
When switching from heparin to warfarin, how should it be cone?
Can be started along with heparin
Heparin should be continued for at least 4 days
What should the dosing monitoring for warfarin be like?
Start with a low dose (5 mg)
Stabilize the dose via INR and monitor
Adjust if/when necessary
Monitor INR regularly
What are the signs of warfarin OD?
Unsual bleeding
in stool or urine, excessive menstral bleeding, nose bleeds or gums, bleeding from tumor, ucler or lesions
If warfarin falls below INR 2.0 what occurs?
A diminished effect
If warfarin falls below INR 1.5 what occurs?
No efficacy
If warfarin is above INR 4 what occurs?
Safety is compromised
What are the warfarin analogs?
Dicumarol (incomplete absorb, GI issues)
Phenindione (Renal and hepatic effects)
What should be for warafin reversal?
Discontinue drug
Administer vit K
May need plasma, prothrombin complex or VIIa
What are the new oral anticoagulants?
Dabigatran
Rivaroxaban
Apixaban
What is the mechanism of action for dabigatran
Factor Iia Inhibitor
Prodrug - converted by nonspecific esterases in plasma and liver
Reversibly and competitively binds to active site free and clot-bound thrombin (factor IIa)
What are the indications for dabigatran?
Prevention of stroke and systemic embolism in pts with atrial fibrillation
Primary prevention of venous thromboembolism
What are the side effects to dabigatran?
Excessive bleeding
Severe dyspepsia
What is the mechanism of action for rivaroxaban?
Factor Xa inhibitor
Binds to active site of factor Xa and affects free and platelet bound factor Xa
What are the indications for rivaroxaban?
Primary prevention of venous thromboembolism
Prevention of stroke and systemic embolism in pts with AF
What are the side effects of rivaroxaban?
Mild hepatic impairment Bleeding Musculoskeletal pain Pruitus Blisters Upper ab pain Syncope
What is apixaban?
Oral direct inhibitor of factor Xa
Selective and reversible inhibitor of free and clot-bound factor Xa as well as prothrombinase activity
What are the indications for apixaban?
Prevent stroke and systemic embolism in AF
Primary prevention of venous thromboembolism
What is Ecarin Clotting Time?
Meizothrombin generation test used to measure thrombin inhibitors
Added to plasma an time to clot formation is measured
How does aspirin work?
Blocks prostoglandin synth by inhibiting cycooxygenase
Thromboxane A2 formation is inhibited
When do hemostatic levels return to normal after using aspirin?
36 hours
What is the most common side effect of aspirin?
GI irriation
How do fibrinolytics create a lytic state?
By breaking down hemostatic thrombi and thromboemboli
Streptokinase
Protein synthesized by streptococci
Combines with proactivator plasminogen
Urokinase
Human enzyme synthesized by kidney
Converts plasminogen to active plasmin
Ticlodipine
Metab by liver
Renal impairment inc plasma conc
Prevention of recurrence of thrombic stroke
What are the adverse events of ticlodipine?
GI issues
Leukopenia
Thrombic thrombocytopenia purpura
Side effects limited when dose below 500 mg/d
