White (platelet-rich) thrombi form in arteries under what type of pressure?
What are 2 pathologic conditions of coronoary arteries associated w/ white thrombi?
- Unstable angina
Red (fibrin-rich) thrombi form in vessels under what type of pressure and in which location?
Low-pressure veins and in the heart
Anticoagulants are primarily used to prevent clots form forming where?
Which specific type of thrombi?
- Venous system and heart
- Red (fibrin) thrombi
Antiplatelet drugs are primarily used to preven clots from forming in which vessels?
What specific type of thrombi?
- White thrombi
What are the 3 classes and drugs in each of parenteral anticoagulants which act as indirect thrombin and factor Xa (FXa) inhibitors?
- Unfractionated (HMW) heparin = Heparin sodium
- LMW heparins = Enoxaparin, Tinzaparin, and Dalteparin
- Synthetic pentasaccharide = Fondaparinux
Which 3 drugs belong to the direct thrombin inhibitor class and are used as parenteral anticoagulants?
The indirect thrombin and factor Xa (FXa) inhibitors bind to what in the plasma?
Serine protease inhibitor antithrombin III
Unfractionated (HMW) heparin inhibits the activity of?
Thrombin and factor Xa
LMW heparins inhibit what?
Factor Xa w/ little effect on thrombin
Which 2 drugs in the parenteral direct thrombin inhibitor class are bivalent and bind at both the active site and substrate recognition site of thrombin?
Which parenteral class of heparin has increased bioavailability from the SC injection site and allows for less frequent injections and more predictable dosing?
LMW Heparin (-aparin's)
Heparins are used during surgery or in hospitalized patients to reduce the risk of what?
Reduces risk of emboli
Heparin is administered to patients with what disorders?
- Atrial arrhythmias
Why must heparins be given via IV or SC routes?
What are 2 AE's associated with Heparin?
- Heparin-induced thrombocytopenia (HIT)
What are heparin locks used for?
Prevents clots from forming in catheters
What 2 lab studies are used to monitor patients on Heparin?
- Activated partial thromboplastin time (aPTT)
- Anti-Xa assay
Heprain-induced thrombocytopenia (HIT) is due to what underlying mechanism?
Immunogenicitiy of the complex of heparin with platelet factor 4 (PF4)
What 2 things should you be looking for in a patient on Heparin?
Treatment for hepain-induced thrombocytopenia?
Discontinue heparin and administer DTI
What are 4 contraindications for using Heparin?
- Severe HTN
- Active TB
- Ulcers of GI tract
- Patients w/ recent surgeries
What is used clinically for reversal (antidote) of heparin action?
The synthetic pentasaccharide, Fondaparinux, used as an anticoagulant binds to and inhibits what?
Acts as antithrombin III catalyst --> indirectly inhibit factor Xa (NO effect on thrombin)
In what 3 ways does the anticoagulant, Fondaparinux, differ from heparins?
- Does not inhibit thrombin acitivity
- Rarely induces HIT (thrombocytopenia)
- Action is not reversed by Protamine sulfate
What are 3 clinical indications for the use of Fondaparinux?
- Prevention of DVT's
- Tx of acute DVT (in conjunction w/ Warfarin)
- Tx of pulmonary embolism
Which parenteral direct thrombin inhibitor binds only at the thrombin active site?
Which parenteral direct thrombin inhibitor is an irreversible inhibitor of thrombin?
Which parenteral direct thrombin inhibitor is a reversible inhibitor of thombin and also inhibits platelet aggregation?
*Think Bi = 2 mechanisms!
Which parenteral direct thrombin inhibitor is short acting and used IV?