Antithrombotics Flashcards
What is the action of anticoagulants?
Prevents clot formation & extension (doesn’t help against pre-existing clots)
What is the action of fibrinolytics?
Breaks up existing clots
What is the action of antiplatelets?
Interferes with platelet activity
What are the 2 types of thrombi?
White thrombus
Red thrombus
Describe the makeup of white thrombi and where they form. Which medication class would be most effective?
- Platelet rich
- Forms in the arteries i.e. coronary artery clot
- Antiplatelets: good for s/p M.I for 2nd prevention
Describe the makeup of red thrombi and where they form. Which medication class would be most effective?
- Fibrin and RBC-rich
- Forms in the veins i.e. DVT, P.E.
- Anticoagulants
What are some common sites for DVTs? Complication? White clot or red clot?
- Iliac vein, femoral vein, popliteal vein, small saphenous vein
- Proximal leg veins more likely to become P.E
- Fibrin-rich red clot
Is a P.E. thrombus likely a white or red clot?
Red clot
Is a CVA more likely a white or red clot?
White clot
Is an acute myocardial infarction mor4e likely a white or red clot?
White clot
What is the action of thromboxane A2 (TXA2)?
- Vasoconstriction
- Platelet activation
What does vonWillebrand Factor do?
Links exposed collagen with platelets
What does fibrinogen do?
Forms platelet bridges –> occlusion
What does thrombin (Fx IIa) do?
- Generates a more stable clot
- Converts fibrinogen –> fibrin
Which factors does thrombin (Fx IIa) activate?
F8
F5
What is the final result of the coagulation cascade?
- Fibrinogen –> Fibrin
- Fibrin: seals hemostatic/ platelet plug
What are the 7 steps to platelet activation?
- Injury
- Collagen and vWF exposed
- Platelet adherence & activation
- Vasoconstrictors (i.e. TXA2) platelet recruiters (ADP), platelet activators (TXA2)
- Conformational change to IIb/IIIa receptor (on platelet surface)
- Binding of fibrinogen (crosslink platelets)
- Aggregation and platelet plug formation
What is the role of Serotonin in platelet activation?
Is serotonin a target of anti-platelet therapy?
What is the risk of SSRIs and clot formation?
- Key role in platelet aggregation, vasoconstriction
- NO
- SSRIs carry an increased bleeding risk d/t its effects on platelet aggregation
What are the 3 key/ target factors in anti-platelet therapy?
- ADP
- TXA2
- GPIIb/IIIa Receptor
What is the role of ADP?
Platelet activation
What is the role of an activated GPIIb/IIIa receptor?
When activated, binds fibrinogen
What are the 3 pathways of the coagulation cascade?
- Intrinsic pathway
- Extrinsic pathway
- Common pathway
What is the intrinsic pathway activated by?
Damaged cells
What is the extrinsic pathway activated by?
Damaged vessel walls
What is the common pathway? Which clotting factor does it start with?
- The convergence of the intrinsic/ extrinsic pathways
- Factor XA
What are the 3 key steps in the Extrinsic pathway of clotting?
- Damaged endothelium/ tissue trauma produces TISSUE FACTOR
- Tissue factor binds to FACTOR VII –> activates
- Tissue Fx/ Fx VIIA complex activates Fx X –> FACTOR XA
What are the 5 key steps in the Intrinsic pathway of clotting?
- Damaged cells produce POLY P
- Poly P activates PRE-KALLIKREIN & FACTOR XII
- Fx XIIA activates FACTOR XI
- Fx XIA activates FACTORS IX & VIII
- Factors VIIIA & IXA complex –> ACTIVATES Fx X –> FACTOR XA
What is the end product of both intrinsic/ extrinsic pathways of clotting?
Factor XA
What are the 3 key steps in the common pathway of clotting?
- Factor XA converts Prothrombin (Fx II) to Thrombin (Fx IIA)
- Thrombin converts FIBRINOGEN TO FIBRIN (ultimate goal)
- Stable fibrin clot forms
What are some co-factors in the common pathway of clotting?
Ca2+
Platelet phospholipids
Prothrombin activator
What is the role of anti-thrombin?
Can deactivate thrombin (Fx IIA) to prevent massive clotting
What does factor II do in the clotting cascade? Where does it act?
- Found in the common pathway aka Prothrombin
- Converted to thrombin (Fx IIA) by Factor XA
What does factor VII do in the clotting cascade? Where does it act?
- Binds to/activated by tissue factor to form a complex that will activate Fx XA
- End of extrinsic pathway of clotting
What does factor IX do in the clotting cascade? Where does it act?
- Activated by Fx XIA to form a complex with Fx VIII
- Complex with Fx VIIIA activates Fx XA to end the intrinsic pathway of clotting
What does Factor X do in the clotting cascade? Where does it act?
- Factor X is activated in both the intrinsic & extrinsic pathways of clotting
- Starts the common pathway of clotting by converting prothrombin (Fx II) to thrombin (Fx IIA)