Lecture 5 Hemostasis

Question 1

What are platelets and why are they important?

Answer 1

Platelets are fragments of megakaryocytes within the blood circulation that are used for blood clotting

Question 2

What is the half life of a platelet?

Answer 2

10 days

Question 3

What increases platelet levels in the blood?

Answer 3

Thrombopoietin

Question 4

What are the three stages of hemostasis?

Answer 4

1. Vascular phase
2. Platelet phase
3. Coagulation phase

Question 5

What happens in the vascular phase?

Answer 5

• Neurogenic and myogenic control causes vasoconstriction through local reflexes
• Vasoconstriction prolonged by
• Serotonin
• Endothelin-1
• Thromboxane A2

Question 6

What happens in the platelet phase?

Answer 6

1. von Willebrand factor binds to collagen and recruits activated platelets
2. Factors are released from platelets
3. Factors attract more platelets
4. Platelets aggregate and form plug

Question 7

What factors allow for platelet aggregation?

Answer 7

• ADP
• Platelet Activating Factor (PAF)
• Serotonin
• Thromboxane A2

Question 8

What are some physical characteristics of activated vs inactive platelets?

Answer 8

Activated
- Spiky outer surface
- adhere to each other
Inactive
- Small disklike cell fragments

Question 9

How do platelets remain inactive without injury?

Answer 9

Intact endothelium releases Prostacyclin and Nitric Oxide
- prevent platelet adhesion and are vasodilators

Question 10

What is the Coagulation Cascade?

Answer 10

Process in which inactive plasma clotting factors are cleaved and converted into active enzymes
- It is divided into an extrinsic and intrinsic pathway which lead to the common pathway

Question 11

What is the difference between the Extrinsic and Intrinsic pathway?

Answer 11

Extrinsic Pathway is active when Cellular damage occurs
Intrinsic Pathway is active upon contact activation

Question 12

What occurs in the Extrinsic Pathway?

Answer 12

1. Damage exposes Tissue Factor III
   - Blood comes in contact with factor III
2. Factor VII is activated by Factor III
3. Active Factor VII can cleave Factor X (10)
4. Active Factor VII can activate Factor IX which combines with Factor VIII (8) to cleave Factor X within the common pathway
   - Factor VIII is regulated by von Willebrand Factor
   - Active Factor X also causes positive feedback on Factor VII cleavage and activation

Question 13

What occurs in the Intrinsic Pathway?

Answer 13

1. Collagen or other activators cleave and activate Factor XII (12)
2. Active Factor XII cleaves and activates Factor XI along with calcium stimulation
3. Active Factor XI cleaves and activates Factor IX along with calcium stimulation
4. Activated Factor IX and Factor VIII can then cleave and activate Factor X within the common pathway
   - Factor VIII is regulated by von Willebrand Factor

Question 14

What occurs within the Common pathway?

Answer 14

1. Factor X is cleaved and activated via intrinsic and extrinsic pathways
2. Activated Factor X cleaves Prothrombin to Thrombin
   - Calcium, Factor V, and Phospholipids are cofactors for prothrombin
3. Thrombin cleaves Fibrinogen to Fibrin and Factor XIII to its active form
   - Thrombin also exerts positive feedback on Factor XI in the intrinsic pathway
4. Active Factor XIII binds to Fibrin along with Ca2+ which produces Cross-linked fibrin polymer which reinforces blood clot

Question 15

What are the problems with Coagulation Cascade?

Answer 15

Individuals with factor IX or factor VIII deficiency have severe bleeding even when their extrinsic and common pathways are normal

Question 16

What happens in the Cell-Based: Initiation Phase?

Answer 16

1. Tissue Factors bound to Activated Factor (VII) stimulate cleavage of Factor X and IX
2. Active Factor X cleaves prothrombin to produce Thrombin

Question 17

What happens in the Cell-Based Amplification Phase?

Answer 17

1. Thrombin Cleaves and activates Factors V, XI and VIII on surface of platelets
   - Causes shape change in activated platelets