Blood Clots Flashcards
What are the three steps in the formation of a blood clot?
- Vessel constriction
- Platelet plug
- Coagulation cascade
What factors are released in the vessel constriction phase?
Prostaglandin F 2alpha and thromoxane A2
Thromboxane A2, prostaglandin F 2alpha, ADP, and serotonin are all released by ____________.
Activated platelets
What is the affect of platelet aggregation on the integrin receptor?
Allows it to bind fibrinogen -> platelets then bind to cross-linked fibrinogen to form platelet plug
Proteolytic cleavage of fibrinogen to form _________, followed by chemical cross-linking by ___________ produces a blood clot.
Fibrin; factor XIII
What cleaves the fibrinogen into fibrin?
Thrombin
What has to bind to factor VII in order to activate it?
Tissue factor (TF)
*Extrinsic pathway
Why is tissue factor only exposed to blood during tissue damage?
It is in the basement membrane
What is activated by the active TF-VIIa?
Factors IX and X
_____________ is produced by the liver and will inhibit several coagulation enzymes including thrombin.
Antithrombin
Activity increases with heparin
What factors are most inhibited by Protein C?
Factor V and factor VIII
How is protein C activated?
When it binds to thrombin
Activity increases with presence of thrombomodulin and EPCRs
______________ can reversible inhibit Factor X.
Tissue factor pathway inhibitor (TFPI)
___________ prevents clots from growing and becoming problematic.
Fibrinolysis
T/F: Plasminogen is turned to its active form, plasmin, in order to break down clots.
True
T/F: Indirect thrombin inhibitors act on antithrombin.
True
T/F: When using unfractionated heparin, it is especially important to dose correctly.
True
___________ binds to AT, and increases its activity about 1000 fold.
Heparin
What is the major adverse effect of heparin?
Bleeding
T/F: Direct thrombin inhibitors act on antithrombin.
False
______________ is a synthetic version of hirudin, a naturally occuring direct thrombin inhibitor found in leeches.
Bivalirudin
T/F: Argatroban is a direct thrombin inhibitor.
True
What is the WARF in warfarin?
Wisconsin Alumni Research Foundation
What are most oral direct thrombin inhibitors derived from?
Coumarin
Which drug (warfarin or heparin) will give an immediate effect?
Heparin
How do oral direct thrombin inhibitors (coumarins) work?
They inhibit an enzyme which will cause the body to run out of vitamin K which is needed to activate thrombin
What are the antidotes for overdoses on heparin or warfarin?
Hep - protamine sulfate
Warf - vitamin K
What are three ways that platelet aggregation is blocked pharmaceutically?
- Inhibition of thromboxane A2 synthesis (aspirin)
- Block ADP receptors (plavix)
- Block GPIIb/IIIa
How are hereditary bleeding disorders often treated?
Replacement therapy
What are some common types of medications that can cause an increased risk for bleeding when the patient is on warfarin?
Antibiotics, antifungals, antidepressants, anti-inflammatory agents, acetaminophen
