Clotting Cascade + DSA Flashcards
What is coagulation?
form fibrin clots at the site of BV injury to prevent blood loss
How do we only cause the formation of fibrin strands at the site of injury?
Fibrinogen,
the inactive form, circulates in our blood; not fibrin.
How does our body know to convert fibrinogen?
Thrombin stimulates the conversion
Are we still able to form clots If we are deficient in factor 12?
Yes.
Our extrinsic pathway will make cleave factor 10–> factor 10a
Draw out the coagulation cascade
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What is tissue factor?
Tissue factor (factor 3) is released when endothelial cells are damaged at the site of injury. This activates the intrinsic pathway
_____, from the extrinsic pathway will trigger the common pathway via factor 10
Factor 7a
What is the extrinsic pathway
The spark that activates 10 and 2, which wil lthen activate the intrinsic pathway.
How does thrombin help to activate the intrinsic pathway?
it upregulates factors
5, 7, 8, 11 and 13
(all odd multiples except 8)
Hemophilia A–> Factor ___ deficiency
Hemophilia B–>Factor __ deficiency
Hemophilia C–> Factor ___ deficiency
Hemophilia A–> Factor 8 deficiency
Hemophilia B–> Factor 9 deficiency
Hemophilia C–> Factor 11 deficiency
3 building blocks for a clot
endothelium,
platelet,
coagulation (fibrin formation)
What is primary hemostasis?
Formation of a platelet plug at the site of injury. The activated platelets undergo a conformational change and expose their phospholipid membrane, becomning sticky.
-Vasoconstriction occurs to reduce blood flow.
Secondary hemostasis
Adding fibrin to the platelet plug via coagulation, making it stronger and forming a clot
Antithrombin
released by thrombin to inhibit coagulation once an effective clot is form.
Fibrinolysis
breakdown and remove the clot to restore flow
Vitamin K-dependent factors
factor 2, 7, 9 and 10
What are Vit K dependent factors important?
Vitamin K dependent factors require the binding of Ca2+ for them to function.
Vitamin K will introduce these binding sites via y-carboxylation of glutaminc acid residues.
Vitamin K deficiency would cause what?
Impaired coagulation d/t decreased fx of these factors.
Thus, they would be bleeding a lot
Vitamin K deficiienceies are due to what?
liver dz,
malabsorption,
antibiotic,
breast-fed newbrowns,
infants whose moms are on anticonvulsant therapy during pregnancy.
Roles of thrombin (3 broad roles)
- Converts itself from prothrombin to thrombin, forming more (+ feedback)
- Activates factors 5 and 8.
- Converts fibrinogen–> fibrin
- Activates factor 13, forming fibrin polymers
- Activates platelets
- Exhibits paracrine activity which influences hemostasis- causes endothelial cells to release NO, prostacylcins, and tissue plasminogen activator, which are anticoagulants as well as ADP and vWF (von williebrand factors)
Intrinsic and extrinsic pathways occur at the same time or different times?.
simultaneously
Two basic tests to monitor coagulation
prothrombin time (PT)
activated partial thromboplastin time (aPTT).
Prothrombin time tests what?
- tests the extrinsic pathway by measuring the clotting time from 7a–> fibrin clot and measures the procoagulant factors
*
PT average time
12-13 seconds
What does coumadin (warfarin) do and what test can we run to check coagulation factors?
Coumadin (warfarin) inhibits vitamin K dependent epoxide reductase= inhibit synthesis of vitamin K dependent coagulation factors (2, 7, 9 and 10, Protein S and C).
The will bleed excessively because they are not forming these clot factors.
Check using the PT test (prothrombin test)
What do you do to people who OD on coumadin?
Give Vitamin K
Person with vit K deficiency will have deficiencies in what factors?
2, 7, 9 and 10, Protein S and C
aPTT
tests the intrinsic pathway: Clotting time from factor 12–> fibrin clot
What is the average time for 30-50 seconds?
aPTT.
What can aPTT detect?
- Hemophilia (8, 9 and 10)
- Heperin therapy–> heparin is an anticugulant that inhibits factors 9 and 10a, and thus 2a.
What does warfarin do?
Decreases the amount of vitamin K-dependent expoxide reductase, which reduces vitamin K after it has been oxidized.
Thus, it decreases the amount of usable vitamin K
Which factors have the shortest and longest half-lives?
Shortest- factor 7
Longest- Factor 2 and 10
What activates the extrinsic pathway?
External trauma, causing blood to escape the vascular system quickly
What activates the intrinisic pathway?
Trauma inside the vascular system, platelets, exposed endothelium, chemicals or collagen.
Thus, it is slower than extrinsic
What is the key difference between primary and secondary hemostasis?
Primary makes a weak platelet plug and secondary makes it stronger by adding fibrin mesh onto it.
Warfarin is a racemic mixture. Which is more active?
S warfarin
_______ is a medication used to prevent harmful blot clots.
Warfarin (coumadin)
What do Protein C and S do?
They are anti-coagulants, inactivating factor 5a and 8a
Protein C/S defiency will cause
Increased risk of venous thrombosis.
What are thrombolytics?
Thrombolytics convert plasminogen–> plasmin, which cleaves thrombin and fibrin clots.
It can be used to treat strokes
What is heparin?
Anticoagulant, which prevents the formation of blood clots, but does not actively lyse them.
What does aspirin do?
Irreversibly inhibits cyclooxygenase, which prevents platets aggregation and prevents formation of clots.
Is heparin a thrombolytic?
No.
Thrombolytics will convert plasminogen–> plasmin, which cleaves thrombin and fibrin clots.
Heparin does not actively lyse clots; it prevents their formation by inactivating 2a and 7a.