Hemostasis Introduction Part I Flashcards
What is the converging factor between the 2 pathways?
factor X
Why is it called the extrinsic pathway?
requires tissue factor to function
Why is it called the intrinsic pathway?
the components are contained w/I the plasma
How is the extrinsic pathway initiated?
tissue factor binds to factor VIIa
How is the intrinsic pathway initiated?
contact factors activate factor XI
What are the contact factors?
factor XII, prekallikrein, HMWK
What is the common pathway?
events after activation of factor X (the convergence)
Extrinsic pathway steps?
tissue factor binds to factor VIIa, which activates factor X, Xa with cofactor Va activates factor II to IIa, which then converts fibrinogen to fibrin
Intrinsic pathway steps?
activation of contact factors, leading to activation of factor XI, then with cofactor VIIIa, activation of factor X, then with cofactor Va, activate factor II, converting fibrinogen to fibrin, then activate factor X
Where are the proteins of the coagulation cascade synthesized?
in the liver
What is bleeding diathesis?
bleeding tendency or predisposition
What are the exceptions to liver production of coagulation cascade proteins?
- tissue factor (surface of many cells)
2. VWF (endothelial cells and megakaryocytes)
Where is tissue factor synthesized?
on the surface of many cells
Where is VWF synthesized?
endothelial cells and megakaryocytes
Where is factor VIII produced?
the liver, spleen, lung, kidney
What does the suffix “a” indicate?
the activated form
Which factor has the shortest half life? Why is this important?
factor VII; it’s one of the first factor to deplete in disease
Almost all of the enzymes in the coagulation cascade are _____.
serine proteases
Inactive precursor proteins are called ____.
zymogens
Zymogens that become active serine proteases include ____ (7).
- factor XII (12)
- prekallikrein
- factor XI (11)
- factor IX (9)
- factor X (10)
- factor VII (7)
- factor II (2- prothrombin)
Which are the vitamin-K dependent factors? (6)
- factor II (2)
- factor VII (7)
- factor IX (9)
- factor X (10)
- anticoagulant protein C
- protein S
What to the vitamin-K dependent factors have in common?
Gla domains that bind Ca++ to cause conformational change of protein into active form
Why is factor XIII (13) unique? What does it do?
enzyme that is not a serine protease- it’s a transglutaminase; covalently links fibrin molecules together to form a stable clot
Why are cofactors important in the coagulation cascade?
they initiate and accelerate enzymatic rxns by bringing components together and orienting them correctly
Name the cofactors in the coag. cascade. (4)
- tissue factor
- factor VIII (8)
- factor V (5)
- HMWK
What protein makes the actual clot?
fibrinogen
What does VWF stand for?
von Willebrand Factor
What does VWF do?
it’s the carrier protein for factor VIII (8) in the plasma
Where is VWF produced and stored?
Weibel-Palade bodies in endothelial cells and in alpha-granules of platelets
Why does VWF bind to factor VIII (8)?
to protect it (prolong its half life)
What happens in VWF-deficient pts?
low levels of circulating factor VIII (8), leading to a bleeding disorder similar to hemophilia A
What do enzyme complexes consist of?
protease + cofactor + phospholipid surface + Ca++
