Hemostasis and Coagulation Factors: The Cascade System Flashcards
What are clotting factors that circulate in the blood as distinct entities in an inactive form?
Zymogens
When this factor becomes activated, it’s referred to as what?
Serine protease
What binds to a particular serine protease to stabilize and increase reactivity?
Cofactors
This factor is a substrate for thrombin and polymerizes to form fibrin
Factor I/Fibrinogen
This factor is a cofactor for II → IIa and is a part of the prothrombinase complex
Factor V/Labile factor
This factor is a cofactor for X → Xa
VIII:C
This factor is a carrier protein for VIII:C and is needed for platelet adhesion to collagen
vWF
This factor is a transglutaminase which converts loose hydrogen bonds of fibrin monomers to covalent bonds
XIII/Fibrin stabilizing factor
This factor is a serine protease and a precursor to thrombin
Factor II/Prothrombin
This factor is a serine protease and activates X and IX (in vivo)
Factor VII/Stabilizing factor
This factor is a serine protease and w/ help of the cofactor VIIIa, it converts X → Xa
Factor IX/Christmas factor
This factor is a serine protease that is a part of the prothrombinase complex which converts II → IIa
Factor X/Stuart-Prower factor
This factor is a serine protease that converts IX → IXa
Factor XI/Plasma thromboplastin antecendant
This factor is a serine protease (in vivo) that is activated in the presence of HMWK and PK to activate XI → XIa
Factor XII/Hageman factor
This factor is a serine protease (in vivo) and w/ the help of cofactor HMWK it activates XII→ XIIa
Factor PK/Fletcher factor
This factor is a cofactor that participates in the (in vitro) contact activation of XI → XIa and activates the kinin system
Factor HMWK/Fitzgerald factor
Which 12 factors are synthesized in the liver?
Factors I, V, VIII:C, XIII, II, VII, IX, X, XI, XII, PK, and HMWK
Which cofactors are synthesized in the endothelial cells and megakaryocytes?
vWF
Which enzyme is generated from the coagulation pathway that is needed to convert fibrinogen to fibrin?
Thrombin
Which site provides the surface for the coagulation cascade?
PF3 (PL) (assembly molecule)
Initiation of coagulation by ____ is sufficient to initiate activation of both pathways
TF or Factor VII complex
Which pathway is being tested by prothrombin time (PT)?
Extinsic pathway
Which pathway is being tested by Activated Partial Thromboplastin Time (APTT)?
Intrinsic pathway
List the correct order of activation of factors for in vitro testing by the Prothrombin Time (PT)
- VII
- X
- V
- II
- I
List the correct order of activation of factors for in vitro testing by the Activated Partial Thromboplastin Time (APTT)
- XII (plus Fletcher and Fitzgerald )
- XI
- IX
- VIII
- X
- V
- II
- I
List the correct order of activation factors for the common pathway
X, V, II, I
What is the role of the prothrombinase complex in the common pathway?
Macromolecular complex which forms on the surface of the platelets; great amplifier of thrombin activation
- (made up of Xa, Va, PL, and calcium)
How is the unstable, soluble fibrin monomer formed in the common pathway?
- Fibrinogen is composed of three pairs of polypeptide chains (α, ß, and γ)
- Thrombin cleaves a portion of the α and ß to form fibrinopeptides A and B
- After the cleavage, the fibrinogen molecule is called a fibrin monomer
- Fibrin monomer quickly polymerizes (line up side by side) to form fibrin (unstable w/ loose hydrogen bonds)
What factor is responsible for forming the stable, insoluble fibrin clot?
Factor XIII and Ca2+ convert loose hydrogen bonds to stronger covalent (cross-linked) bonds
Four hemostatic actions of thrombin
- Converts fibrinogen to fibrin
- Activates factors XI, V, VIII, and XIII
- Induces platelet aggregation
- Binds the endothelial cell membrane protein, thrombomodulin, to activate the protein C pathway
Nomenclature of the two portions of the Factor VIII complex
vWF and VIII:C
Site of synthesis of the two portions of the Factor VIII complex
- vWF: endothelial cells and megakaryocytes
- VIII: liver
Principle biologic activity of the two portions of the Factor VIII complex
- vWF: carrier for Factor VIII
- VIII: cofactor for X → Xa
Clinical disorder due to deficiency of hte two portions of the Factor VIII complex
- vWF: von Willebrand’s Disease
- VIII: Hemophilia A
Which portion of the Factor VIII complex is responsible for normal bleeding time?
vWF
Which portion of the Factor VIII complex is responsible for normal platelet adhesion?
vWF
Which portion of the Factor VIII complex is responsible for ristocetin cofactor activity?
vWF
Which coagulation factors are present in the fibrinogen group?
- I
- V
- VIII
- XIII
Which coagulation factors are present in the prothrombin group?
- II
- VII
- IX
- X
Which coagulation factors are present in the contact group?
- XI
- XII
- PK
- HMWK
Which coagulation factors are consumed or destroyed during clotting?
I, V, VIII (VII:C/vWF), XIII, II
fibrinogen group AND II
Which coagulation factors are dependent upon vitamin K for synthesis?
II, VII, IX, X (prothrombin group)
Which coagulation factors are destroyed by plasmin?
I, V, VIII, XIII (fibrinogen group)
Which coagulation factors are heat labile?
I, V, VIII, XIII (fibrinogen group)
What is another name for coagulation/clotting factors?
Procoagulant
What are plasma GPs that serve as inhibtors to coagulation?
Anticoagulants
Describe what happens in contact activation?
Contact w/ a negatively charged surface is one means to activate the intrinsic coagulation pathway
- Examples: prosthetic valves, stents (in vivo); nonsiliconized glass, microsilica, elagic acid (in vitro)
- Contact factors, EXCEPT IX (!), do not normally have an in vivo procoagulant function
