Introduction to Hemostasis Part I Flashcards
What is primary hemostasis?
What the platelets are doing in hemostasis. (clot formation)
What is secondary hemostasis?
What the clotting factors are doing in hemostasis. (clot stabilization)
What is the key component of the extrinsic pathway and why?
Tissue Factor. it is released and leads to fibrin accumulating and forming a more stable plug than the one found in primary hemostasis
people with hemophilia have a normal what?
PT
What are contact factors?
Prekallikrein, factor VII, HMWK
What are the basic steps in primary hemostasis?
breach in endothelium exposes collagen. vWF (von willebrand factor) binds collagen. Platelets have special receptor for vWF and bind there. Platelets stick to vWF and are activated. Activated platelets release coagulation stuff (ADP and TXA2). They also begin to express receptor for fibrinogen. Fibrinogen helps platelets aggregate.
Which factors are Vitamin K dependent?
II, VII, IX, X,
Which factors are proteases?
VII, XII, XI, IX, VIII, X, II, XIII Prekallikrein. Everything except V and fibrin
Which factors are soluble cofactors?
Tissue Factor, VIII, V, HMWK
Which factor has shortest half life?
VII
What kind of protease is factor XIII?
transglutaminase. All other proteases are serine proteases.
serine protease cleave at _______ (target) and thus activate enzymes. Thus these enzymes are ______.
arginine residues.
zymogens
Vitamin K is required for post translational modification of which factors?
2, 7, 9, 10, C and S.
Hemorrhagic disease of the newborn is due to _______ deficiency.
Vit. K
warfarin is a competitive inhibitor for what?
Vit. K
Almost all blood factors are made in the ______ except which ones?
liver.
Tissue Factor
Factor VIII (made in many places)
vWF (made in megakaryocytes and endothelial cells)
what is the basic 2 step process of coagulation?
- prothrombin + thromboplastin + calcium =thrombin
- Fibrinogen + Thrombin = fibrin
What are the modern phases of coagulation?
- Initiation
- Amplification
- Propagation
Amplification phase takes place on __________
surface of platelets which have adhered to the exposed subendothelium and been activated.
A phospholipid surface is provided by the ________
platelet surface
What is the extrinsic tenase and what does it activate?
Factor VIIa, Tissue factor.
It activates factor X, IX, and more VII
What is prothrombinase?
Factor Va, Factor Xa which activates factor II (changes prothrombin to thrombin)
What is special about activated factor X in the initiation phase?
it can generate small amounts of thrombin without the prothrombinase complex
Describe the initiation phase.
Factor VIIa and tissue factor (extrinsic tenase) activate factors IX, X and VII. Factor Xa then goes on to generate a little active factor II (thrombin) which gets the whole process rolling.
Describe the Amplification phase
activated factor II from initiation phase goes and activates factor V, factor VIII (cofactor for intrinsic tenase), and factor XI which will go on to activate factor IX (also important for the intrinsic tenase).
What is the intrinsic tenase?
factor VIIIa, factor IXa which activates factor X.
The instrinsic tenase activates much more factor X than the extrinsic tenase.
Describe the propagation phase.
formation of the intrinsic tenase allows for activation of factor X. Factor X binds to prothrombinase and activates factor II. Factor IIa clips peptides off of fibrinogen to form fibrin which then can aggregate (noncovalently) with other fibrin molecules and create network. Thrombin also activates Factor XIII which forms covalent bonds between the D domains of fibrin molecules
How do fibrin molecules aggregate?
non-covalently at first, matching up D domain on the ends of the molecule with the E domains in the middle of another fibrin molecule.
Factor IIa is the central figure in the clotting cascade. What are all the things it activates?
Fibrinogen-->Fibrin Factor V and VIII Factor XIII Factor XI It is a potent platelet activator Plays a role in anticoagulation and fibrinolysis.