Thrombosis

Question 1

Heamostasis and thrombosis involve three components, which are

Answer 1

Endothelium
Platelets
Coagulation Cascade

Question 2

Discuss the sequence of events in haemostasis

Answer 2

1. Vasoconstriction: mediated by neurogenic mechanisms and endothelin
2. Primary Haemostasis: exposure of subendothelial ECM causes platelet adherence and activation, release of secretory granules and platelet aggregation
3. Secondary Haemostasis: exposure of tissue factor III which combines with factor VII to form thrombin. Thrombin converts fibrinogen to fibrin and a permanent platelet plug is formed. Counter-regulatory mechanisms are also at play.

Question 3

Endothelial cells usually exhibit procoagulant activities under normal conditions.

True or false

Answer 3

False.
Antiplatelet, anticoagulant, fibrinolytic properties.

Procoagulant activities follow injury or activation

Question 4

Mention the factors that may activate endothelial cells

Answer 4

1. Trauma
2. Infectious agents
3. Hemodynamic forces
4. Plasma mediators
5. Cytokines

Question 5

The balance between anti-thrombotic and prothrombotic activities of the endothelium determines whether propagation or dissolution will occur.

True or false.

Answer 5

True

Question 6

Mention the antithrombotic properties of the endothelium

Answer 6

A. Antiplatelet Effect
•Intact endothelium
•Prostacyclin PGI2 and nitric oxide
•Adenosine diphosphatase

B. Anticoagulant Effect
•Thrombomodulin
•Tissue factor pathway inhibitor-inhibitors factors VIIa and Xa
•Protein S-cofactor of protein C and TFPI

C. Fibrinolytic Effect
•Tissue-type plasminogen activator

Question 7

Mention the prothrombotic properties of the endothelium

Answer 7

A. Platelet Effect
•Endothelial Injury-Von Willebrand factor vWF
•Procoagulant effect- Tissue factor
•Antifibrinolytic effects- Inhibitors of plasminogen activator

Question 8

Genetic disorders of vWF-Von Willebrand disease or it’s receptor- Bernard Soulier syndrome don’t result in bleeding disorders.

True or false. Why?

Answer 8

False.
Platelet adhesion to sub endothelial ECM is mediated by vWF which acts as a bridge between platelet surface receptors and exposed collagen

Question 9

The secretion that occurs after adhesion of platelets contains?

Answer 9

Calcium-required in the coagulation cascade

ADP-activator of platelet aggregation alongside TxA2

Negatively charged phospholipids-bind calcium and complexes containing coagulation factors

Question 10

Platelet activation by ADP triggers a conformational change in the platelet GpIIa-IIIb receptors

True or false.
What function does it subserve?

Answer 10

False
GpIIb-IIIa receptors receptors.
They induce binding to fibrinogen that promote platelet aggregation.

Question 11

Inherited deficiency of GpIIb-IIIa results in?

Answer 11

Glanzmann thrombasthenia

Question 12

The endothelial damage represents the ___ stage of hemostatic process

Answer 12

1st

Question 13

The Coagulation cascade represents the 2nd arm of the hemostatic process

True or false

Answer 13

False

3rd arm

Question 14

What is the most important coagulation factor?

Answer 14

Thrombin, it converts fibrinogen to fibrin

Question 15

The extrinsic pathway is the most physiologically relevant pathway for coagulation due to vascular damage

True or false

Answer 15

True

Question 16

The clinical assays used to assess the function of the coagulation pathways are?

Answer 16

1. Prothrombin time PT which assess the functions of proteins in the EXTRINSIC pathway
2. Partial thromboplastin time PTT which assess the functions of proteins in the INTRINSIC pathway

Question 17

Mention the endogenous anticoagulants that control clotting

Answer 17

1. Antithrombins- antithrombin III inhibits the activities of thrombin and serine proteases-factors IXa, Xa, XIa, and XIIa
2. Proteins C and S(Vit K-dependent) proteins that inactivate factors Va and VIIIa
3. TFPI inactivates factor VIIa complexes

Question 18

The three abnormalities that lead to thrombus formation are?

Answer 18

Virchows triad:

1. Endothelial Injury
2. Stasis/Turbulent flow
3. Hypercoagulability of blood

Question 19

Give settings that could lead to thrombus formation due to endothelial damage

Answer 19

1. Endocardial injury/Myocardial infraction
2. Ulcerated atherosclerotic plaques
3. Vascular injury-inflammatory or traumatic
4. Hypertension
5. Turbulent blood flow
6. Bacterial endotoxins
7. Radiation injury
8. Metabolic abnormalities/Hypercholesterolemia/Homocysteinemia
9. Cigarettes smoke toxins

Question 20

How does stasis/turbulence contribute to thrombosis?

Answer 20

1. Promotes endothelial activation
2. Brings platelets in contact with endothelium
3. Prevents washout/dilution of clotting factors

Question 21

Give settings that could lead to thrombus formation due to stasis/turbulence

Answer 21

1. Ulcerated atherosclerotic plaques
2. Aneurysms
3. Myocardial infarctions
4. Hyperviscosity e.g Polycythemia Vera
5. Sickle cell anemia

Question 22

Hypercoagulability is any alteration of the coagulation pathways that predisposes to thrombosis.

True or false

Answer 22

True

Question 23

The most common primary/genetic hypercoagulable states are?

Answer 23

Common:

1. Factor V mutation/Leiden
2. Prothrombin mutation
3. 5,10-methylenetetrahydrofolate reductase
4. Increased factors VIII, IX, X, fibrinogen

Rare:

1. Antithrombin III deficiency
2. Protein C deficiency
3. Protein S deficiency
4. Smoking

Very Rare:

1. Fibrinolysis defect
2. Homocystinuria

Question 24

The most common secondary/acquired hypercoagulable states are?

Answer 24

High risk:

1. Immobilization
2. Myocardial infraction
3. Atrial fibrillation
4. Tissue injury
5. Cancer
6. Prosthetic cardiac valves

Lower risk:

1. Cardiomyopathy
2. Nephrotic syndrome
3. Hyperestrogenic states
4. Oral contraceptive use
5. Sickle cell anaemia

Question 25

What is the morphological difference between an arterial thrombi and a venous thrombi?

Answer 25

Arterial thrombi grow retrograde from the point of attachment and venous thrombi extend in the direction of the flow

Question 26

What are the differences between an antemortem and a postmortem clot?

Answer 26

Antemortem clots: Dry, Granular masses, Well attached to the walls of the vessels Lines of Zahn are observed microscopically due to alternating RBC and platelet deposits Postmortem clots: Jelly like Easily detachable masses They have a reddish and yellowish(plasma) portion

Question 27

Where do mural thrombi occur in the body?

Answer 27

Heart chambers | Aortic lumen

Question 28

Arterial thrombi are frequently occlusive while venous thrombi, phlebothrombi, is invariably occlusive. True or false. Why?

Answer 28

True. | Blood moves slower in the veins and tends to contain more enmeshed red cells

Question 29

Thrombi on the heart valves are known as?

Answer 29

Vegetation

Question 30

Discuss the fate of the thrombus

Answer 30

1. Propagation 2. Embolization 3. Dissolution 4. Organization and recanalization