BL Hemostasis Pt I

Question 1

Hemostasis

Answer 1

The ability of the body to stop bleeding from a damaged blood vessel, AND to be able to repair the defect in the vessel wall to resume normal blood flow.

Question 2

which coagulation factors are serine proteases

Answer 2

(7) Serine Proteases:
	• Prekallikrein
	• Factor XII
	• Factor XI
	• Factor IX
	• Factor X
	• Factor VII
	• Factor II (prothrombin)

(These are the guys that get directly made from the previous step - minus Prekallikrein, VII and XII since they come first)

others: plasmin, protein C, t-PA, u-PA

Question 3

which coagulation factors are cofactors?

Answer 3

• Tissue factor
  
  • Factor VIII
  • Factor V
  • HMWK - high molecular weight kininogen

Question 4

alternate name for:
Factor I
Factor II
Factor III

Answer 4

Factor I - fibrinogen
Factor II - prothrombin
Factor III - tissue factor, thromboplastin

Question 5

Which pathway (intrinsic or extrinsic) is considered the contact pathway? Why?

Answer 5

Intrinsic = contact

XII can be activated when it comes in contact with (-) charged surfaces

Question 6

Which pathway (intrinsic or extrinsic) is considered the most important for activating the coag cascade?

Answer 6

Extrinsic
(via VII and TF from tissue damage)

(intrinsic is more important for propagation)

Question 7

Extrinsic tenase (Xase)

Answer 7

Tissue factor + Factor VIIa on a phospholipid surface →
binds and activates Factor IX OR Factor X

-this is the extrinsic step right before X

Question 8

Intrinsic tenase (Xase)

Answer 8

Factor IXa + Factor VIIIa combine with phospholipid and calcium → bind and activate Factor X

• this is the intrinsic step right before X

Question 9

Prothrombinase complex:

Answer 9

• Activated factor X (Xa) + Factor Va on phospholipid surface and calcium → bind and activate Prothrombin (Factor II) to Thrombin (Factor IIa).

• this is the step right after X

Question 10

role of vitamin K in coagulation

Answer 10

Glutamic acid must be modified to γ-carboxy glutamic acid, which is a component in II, VII, IX, X

Reduced Vit K is a cofactor that helps makes Glutamic acid ready to be modified (precursor ready)

Question 11

The factors that are vitamin K dependent are:

Answer 11

• Factor II
  
  • Factor VII
  • Factor IX
  • Factor X
  • Anticoagulant protein C
  • Protein S

Question 12

Describe how fibrinogen is converted to fibrin by thrombin, leading to formation of an insoluble fibrin network, and how factor XIII functions in stabilizing the forming clot.

Answer 12

1. Fibrinogen is made up of 3 pairs of polypeptide chains
   - Each pp chain has 3 globules (D-E-D)
2. With activation, thrombin cleaves off two small peptides (Fibrinopeptide A and B)
3. Fibrinopeptide A leads to exposure of a site on the E domain that aligns with the complementary site in the D domain from another fibrinogen molecule - these form overlapping fibrils.
4. Fibrinopeptide B allows fibrils to aggregate
5. Factor XIIIa then covalently cross-links adjacent D domains to stabilize and strengthen the clot

Question 13

two main functions of von Willebrand factor in coagulation.

Answer 13

1. critical roles in platelet adhesion and aggregation
   2 Acts as the carrier protein for factor VIII in the plasma
   • By binding, it significantly prolongs the half-life of factor VIII from 2 hrs to 12 hours

Question 14

Prothrombin time (PT) utilizes what pathways?

Answer 14

Extrinsic pathway bc it requires thromboplastin (aka Factor III, TF)

Question 15

Activated partial thromboplastin time (PT) utilizes what pathways?

Answer 15

Intrinsic pathway

intrinsic because all of the factors needed for a normal result are contained within the plasma itself, and is activated by an anionic substrate.

Question 16

Almost all blood factors are made in the ______ except ___ ____ and ____

Answer 16

Liver

TF, Factor VIII, vWF

-Note: VIII is made in the liver, spleen AND lungs, not just liver

Question 17

Does PT or APTT distinguish normal and hemophilic plasma?

Answer 17

APTT

• PT cannot identify pts w/ classical hemophilia

Question 18

Steps of Extrinsic pathway

Answer 18

1. Tissue damage leads to exposure of plasma to TF
2. TF binds factor VIIa in the presence of calcium → Extrinsic tenase complex
3. Extrinsic tenase complex binds factor X → production of factor Xa
4. Extrinsic tenase also converts IX → IXa
5. Factor Xa binds factor Va and form the prothrombinase complex → thrombin

Question 19

What factors do thrombin (factor IIa) activate? What phase does this take place?

Answer 19

XIa
VIIIa
Va
XIII
protein C
TAFI

occurs in amplification phase (on surface of platelets)

Question 20

What phase does the intrinsic tenase complex go to work and activate more factor X on platelet surface?

Answer 20

Propagation phase

(prothrombinase complex also initiates prothrombin-> thrombin to provide burst necessary for clot formation in this phase)

Question 21

What phase does the prothrombinase complex appear to work?

Answer 21

Amplification and propagation

Question 22

what enzyme is considered the central enzyme in blood coagulation?
Why

Answer 22

Thrombin

• Cleaves fibrinogen to fibrin (fibrin production)
• Cleaves and activates profactors so that they can form the prothrombinase and intrinsic tenase complexes
○ V → Va
○ VIII → VIIIa
• Activates XI → XIa, which generates more IXa for the intrinsic tenase complex.
• Net amplification of coagulation response and “thrombin burst” to form the clot
• Once the clot has started to form, thrombin is essential for activating Factor XIII to stabilize the clot

Also activates protein C and TAFI (thrombomodulin)