Coagulation Factors Flashcards
what is the Fibrin Forming Coagulation System?
- system for formation of a fibrin clot = 2 hemostasis
- reinforces the plt plug
what is the Fibrin Forming Coagulation System made up of?
- coag factors present in blood
- mainly produced in liver
- roman numerals; common name
Classification of Coagulation Factors by Hemostatic function
- substrate: fibrinogen is the substrate which is converted to a fibrin clot
- cofactors: stabilize or enhance the activity of enzymes
> factor V, VIII, HMWK, Tissue Factor, Protein S, Protein Z, Thrombomodulin - enzymes: inactive form in blood (zymogens or pro-ezyme)
> activated = “a”
> may be activated to serine protease or transglutanimase
transglutaminase
- active site contains cysteine instead of serine
- only factor XIIIa; creates cross-linkages between fibrin monomers to produce fibrin polymers
serine protease
- serine at active site
- start as zymogen = activated when another protease cleaves inactive enzyme at one or more sites = cascade effect
classification of coag factors based on physical properties
- contact group
- prothrombin group
- fibrinogen group
EXTRINSIC VS INTRINSIC PATHWAY
The extrinsic pathway is activated by external trauma that causes blood to escape from the vascular system (endothelial cells release TF). … The intrinsic pathway is activated by trauma inside the vascular system, and is activated by platelets, exposed endothelium, chemicals, or collagen.
contact goup
- XI, XII, PK, HMWK
- initial phase of intrinsic coagulation
- deficiencies lead to abnormal lab results BUT only def in factor XI associated with bleeding
- not consumed during clotting; present in serum
T or F. Contact Groups are present in serum
T! not consumed during clotting
Prothrombin Group
- II, VII, IX, X
- Vit. K- dependent coagulation factors
- glutamic acid nead amino end
- require vit K to add another carboxyl to gamma-carbon
= net neg charge which allows Ca 2+ to bind
= complex can bind to phospholipids on PLT membrane - only prothrombin (II) consumed in clotting => VII, IX, and X are present in serum
vitamin K antagonist
Warfarin/Coumadin
fibrinogen group
- I, V, VIII, XIII
- thrombin sensitive (interacts w thrombin)
> enhance activity of factors V, VIII
> converts fibrinogen (I) to fibrin
> activates XIII - ALL consumed; not in serum
- found in PLT alpha granules +cytoplasm
- acute phase reactants (elevated during infection)
prothrombinase complex
Xa, Va, Ca 2+, PF3
- converts prothrombin (II) to thrombin (IIa)
_____ binds to PF3 to activate X to Xa
TF:VIIa
???
common pathway
- thrombin converts fibrinogen to fibrin monomers
> cleaves off fibrinopeptides A and B to form soluble fibrin monomers - fibrin monomers join end-to-end and side-to-side and are held together by weak hydrogen bonds
- thrombin causes activation of XIII to XIIIa in presence of Ca 2+
- XIIIa catalyzes the cross-linking of fibrin with covalent bonds to form a stable fibrin clot
Intrinsic Pathway
- starts with activation of contact factors
- XII activated by contact w a negatively charged foreign surface (ex: collagen and phospholipids)
- XIIa converts prekallikrein to kallikrein
> in presence of HMWK enhances XIIa activation
> XIIa with HMWK activates XI
this complex activates factor X
tenase complex
- IXa, VIIIa, PF3, Ca 2+
prothrombinase complex
Xa, Va, PF3, Ca 2+
- continues into common pathway
- forms fibrin
promotes release of thromboxane A2
primary hemostasis
coagulation control
thrombin bound to thrombomodulin will activate protein C to suppress coagulation
fibrinolytic control
activates thrombin activatable fibrinolysis inhibitor (TAFI)
T or F. coagulation is a positive feedback mechanism
T, amplifies coagulation by activating cofactors V, VIII, and factor IX
cell based model of coagulation
- two pathways function independently in classical model but in vivo they are interdependent
- coagulation requires two cell types:
> cells that release TF
> PLTs - two phases in cell-based model
> initiation
> propagation
initiation (phase in cell based model for coagulation)
- vascular injury = TF released by damaged cells
- factor VIIa binds to TF on membrane of Tf-bearing cells
> forms extrinsic tenase complex
> activates low levels of IXa and Xa
> Xa:Va (prothrombinase complex) produces a small amt of thrombin - tiny amount of thrombin made can activate PLTs, cofactors, and procoagulants to form initial PLT plug and fibrin
propagation phase of cell based model of coagulation
- PLTs localize to site of injury (partially activated by collagen and thrombin)
- more rxns can occur on PLT surfaces (produce bulk of thrombin)
- provides surface for formation/amplification of intrinsic tenase and prothrombinase complexes
> intrinsic tenase = IXa, VIIIa, PF3, Ca 2+
> prothrombinase = Xa, Va, PF3, and Ca 2+ - much more Xa produced in this phase, which allows for more thrombin to be made*
- fibrin clot forms
