Lecture 18: Primary And Secondary Hemostasis

Question 1

Outline the four phases of hemostasis

Answer 1

• Process of making blood clots (Prevents hemorrhage)
  1) Vascular spam/vasoconstriction

2) Platelet plug formation = PRIMARY HEMOSTATIS
Defects =
-Glanzmann Thrombasthenia
-Von Willebrand disease
-Bernard Soulier syndrome

3) Blood coagulation cascade = SECONDARY HEMOSTASIS
- Clumping of platelets –> forms Fibrin
- Factor 8 = key

4) Clot stabilization and resorption

Question 2

Discuss vascular spasm and the role of endothelin

Answer 2

• Contraction caused by
-Local myogenic spasm
-Nervous reflexes
-Factors released from the injured
vessel wall (endothelin) 

-Cannot stop bleeding on its own

Question 3

Describe the platelet plug formation

Function, Stages, Symps of defect

Answer 3

Function:
• Greatly limits the loss of blood from the circulation by forming plugs
• Small cuts in the blood vessels are often sealed by platelet plugs

Stages:
1) Platelet adhesion to the damaged surface (Sticking platelets to subepithelium collagen)

2) Platelet activation (Recruit platelets)
3) Platelet recruitment and Platelet aggregation (Change in shape of platelet)

Defects:

• Increased bleeding time
• Defective platelet aggregation

Question 4

Explain the role of the following integrins in platelet plug formation

1. GPIB
2. GPIA
3. von Willebrand factor

Defects?

Answer 4

-Damage of epithelium, exposure of subepithelium, glycoproteins present on platelet cell membrane

1. Platelet Gp1a and Gp1b:
   - Binds to collagen –> Anchors platelet to subepithelial collagen = activation of platelet = activation of platelet –> changes shape and loses granules –> Releases ADP and thromboxane
   - (B does not do so directly)
2. Von Willebrand factor:
   - acts as a link between Glycoprotein Ib (GpIb) and the subepethilial –> Facilitating platelet adhesion to the vessel wall and platelet aggregation

Defects:

1) Gp1B = Bernard Soulier Syndrome
- -> Platelet plug cannot form

2) Von Williebrand Factor:
- Defect primary hemostasis
- Defect in secondary hemostasis (low Factor VIII, which prevents degradation)

Question 5

Describe the role of platelet-activating factors (ADP, TXA2) aka thromboxane. Discuss the utility of these factors in assessing platelet function

Answer 5

Platelet Activation Factors (ADP, TXA2):
-Release of ADP and TXA2 recruits and activates other platelets promoting aggregation

-ADP binds to platelet –> Increasing intracellular Ca2+ and decreasing intracellular cAMP = platelet change, recruits more platelets to site of injury

(W/o ADP, you have nothing)

Question 6

Describe the role of integrin GPIIb/IIIa in platelet aggregation.

Defect?

Answer 6

Platelet aggregation is mainly mediated by fibrinogen. Fibrinogen binds to GPIIB/IIIA on adjacent platelets –> Links all recruited platelets together

Defect:

• Gp11B/11A Defect = Glanzmann Thrombasthenia
• No receptor for binding Fibrinogen

Question 7

Describe the coagulation cascade, including the extrinsic, intrinsic

Tests?

Answer 7

-Overall Goal: Strengthen platelet plug by forming insoluable Fibrin threads (Conversion of fibrinogen –> Fibrin, uses thrombin)

Coagulation cascade goal:

• Form thrombin
• Proenzyme –> active form (irreversible proteolytic activation)
• 2 pathways

1) Extrinsic –> Big injury
1) Tissue injury releases Tissue Factor (III)
2) Tissue factor (III) activates Tissue Factor VIIa
3) Factor VIIa and tissue factor, in the
presence of Ca2+ and platelet
phospholipids, activate factor X
4) Xa (Active factor X)
Test: Increased PT-Prothrombin time

2) Intrinsic –> Mild injury
1) Rough endothelial surface → exposure of collagen → activation of factor XII
2) XIIa activates XI
3) XIa activates IX
4) Thrombin activates factor VIII→ VIIIa
5) IXa, VIIIa , platelet phospholipids and Ca2+ activate factor X to Xa
Test: Increased APTT

Question 8

Indicate the role of calcium in hemostasis

Answer 8

• Needed in the common cascade pathway

- Prothrombinase complex splits prothrombin to form thrombin (NEEDS Xa, Va, PL, Ca2+) to do so

Question 9

Describe the coagulation cascade:

The Common pathways.

Answer 9

Common Pathways:
Goal: activation prothrombin
–> thrombin (3c)

1) Xa combines with Va, tissue
phospholipids and Ca2+ to form
prothrombinase complex

2) Prothrombinase complex splits
prothrombin to form thrombin (NEEDS Xa, Va, PL, Ca2+)

3) Thrombin converts fibrinogen –> fibrin
(Does this by cleaving fibrinopeptides)

4) Thrombin activates factor XIII to XIIIa (Stablizes thrombus)

5) Fibrin monomers are covalently crosslinked by factor XIIIa to form
cross-linked fibrin (Hard clot)
(If linked by hydrogen bonds would be a SOFT CLOT)