Anticoagulants, Antiplatelets Antifibrinolytic Flashcards
Arterial thrombosis
White clot
Mostly platelets in plug due to high blood flow
TREAT PLATELETS & ATHEROSCLEROSIS
Venous thrombosis
Red clot
Vascular stasis, especially around valves, more RBCs
Lots of fibrin forming a long tail
Can easily break loose and cause embolism
TREAT COAGULATION
Heparin
(Unfractionated heparin) Parenteral anticoagulant therapy Heparin binds to antithrombin 3 Inhibits thrombin Xa, IXa, XIa, XIIa Prolongs aPTT and thrombin time and at high doses can prolong PT
Heparin administration routes (2)
1) Continuous IV preceded by IV bolus
2) SubQ minidose for slower release
DO NOT GIVE IM OR ORAL
Heparin Use
IMMEDIATE ANTICOAGULANT
Prophylaxis of post-op thrombus
DVT and PE (large dose to inhibit established PE)
DIC
What if you need prolonged anticoagulation?
Use heparin initially and admin longer acting and longer onset warfarin or newer anticoagulants** test question
Heparin Toxicity
Bleeding from undiagnosed bleeding site!!
Treatment of Heparin Overdose
Stop heparin
Use PROTAMINE SULFATE which binds to and inactivates heparin but must be given slowly IV
Also give fresh frozen plasma to resupply the coag factors
Protamine Sulfate
Heparin antedOte that needs to be given slowly IV
NOT A WARFARIN ANTEDOTE
HIT 1
Heparin- Induced Thrombocytopenia
Transient reversible clumping of platelets >100,000
Occurs first few days
Asymptomatic and recover OK even w/o heparin withdrawal
HIT 2
Heparin- Induced Thrombocytopenia Delayed onset 5-14 dyas Severe thrombocytopenia <100,000 Immune mediated rxn, heparin Ab complex causing significant platelet aggregation Consequences of peripheral thrombus severe (stroke MI skin necrosis) Amputation needed in 25% Mortality 25% Occurs in 3% of pt
Continuous monitoring of this needs to occur when on heparin
The aPTT time to keep w/i therapeutic range
Also watch soft tissue for signs of internal bleeding
LMWH Most commonly used trade name and common name
Enoxaparin (Lovenox)
What are the advantages of using LMWH over UH?
LMWH binds to Factor Xa better and with higher selectivity
It has a longer duration (2-5x)
Simpler kinetics as it doesn’t bind to as many endo cells/proteins/platelets
CLOTTING TEST IS NOT REQUIRED (no aPTT)
No dose dependent clearance
Warfarin = Coumadin
Oral Anticoagulant
Warfarin MOA
Inhibits Vit K dependent posttranslation modification of clotting factors: thrombin, VII, IX, X, Protein C and S
Without addition of carboxyl group the clotting factors cannot bind to Ca and phospholipid surface and cannot be inactivated
The clotting factors are present but inactive?
Warfarin onset and duration and termination
All are delayed
Onset 36-72 hr bc pre-exisiting clotting factors are slowly cleared from the blood
liver and kideny metabolism
How much of warfarin is protein bound?
99%, only 1% is active which can cause lots of drug/drug interaction problems
When can you never use Warfarin?
PREGNANT PATIENTS
How is warfarin administered?
Orally
What test do you need to run on pt taking Warfarn?
INR which is an adjusted PT time, need to take often and it gets expensive
targer INR 2.0-3.0
PATIENT VARIABILITY IS HIGH
Dabigatran
Orally active, direct thrombin inhibitor
Not metabolized by hepatic enzymes
Excreted mainly in urine
Advantages of Dabigatran
Directly binds to thrombin both clothbound and circulating
Rapid onset of action
Does not require INR monitoring
Non-inferior efficacy and similar safety to warfarin
Dabigatran approved use
Prevention of thromboembolic stroke in patients with non-valvular AF
