Coagulation Factors

Question 1

what is the Fibrin Forming Coagulation System?

Answer 1

• system for formation of a fibrin clot = 2 hemostasis

- reinforces the plt plug

Question 2

what is the Fibrin Forming Coagulation System made up of?

Answer 2

• coag factors present in blood
• mainly produced in liver
• roman numerals; common name

Question 3

Classification of Coagulation Factors by Hemostatic function

Answer 3

• 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

Question 4

transglutaminase

Answer 4

• active site contains cysteine instead of serine

- only factor XIIIa; creates cross-linkages between fibrin monomers to produce fibrin polymers

Question 5

serine protease

Answer 5

• serine at active site

- start as zymogen = activated when another protease cleaves inactive enzyme at one or more sites = cascade effect

Question 6

classification of coag factors based on physical properties

Answer 6

• contact group
• prothrombin group
• fibrinogen group

Question 7

EXTRINSIC VS INTRINSIC PATHWAY

Answer 7

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.

Question 8

contact goup

Answer 8

• 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

Question 9

T or F. Contact Groups are present in serum

Answer 9

T! not consumed during clotting

Question 10

Prothrombin Group

Answer 10

• 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

Question 11

vitamin K antagonist

Answer 11

Warfarin/Coumadin

Question 12

fibrinogen group

Answer 12

• 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)

Question 13

prothrombinase complex

Answer 13

Xa, Va, Ca 2+, PF3

- converts prothrombin (II) to thrombin (IIa)

Question 14

_____ binds to PF3 to activate X to Xa

Answer 14

TF:VIIa

???

Question 15

common pathway

Answer 15

• 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

Question 16

Intrinsic Pathway

Answer 16

• 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

Question 17

this complex activates factor X

Answer 17

tenase complex

- IXa, VIIIa, PF3, Ca 2+

Question 18

prothrombinase complex

Answer 18

Xa, Va, PF3, Ca 2+

• continues into common pathway
• forms fibrin

Question 19

promotes release of thromboxane A2

Answer 19

primary hemostasis

Question 20

coagulation control

Answer 20

thrombin bound to thrombomodulin will activate protein C to suppress coagulation

Question 21

fibrinolytic control

Answer 21

activates thrombin activatable fibrinolysis inhibitor (TAFI)

Question 22

T or F. coagulation is a positive feedback mechanism

Answer 22

T, amplifies coagulation by activating cofactors V, VIII, and factor IX

Question 23

cell based model of coagulation

Answer 23

• 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

Question 24

initiation (phase in cell based model for coagulation)

Answer 24

• 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

Question 25

propagation phase of cell based model of coagulation

Answer 25

• 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