Platelets and haemostasis

Question 1

Megakaryocytes

Answer 1

A myeloid blood cells that produces thrombocytes (platelets).
Each cell produces 4000 platelets
Present in the bone marrow

Question 2

Thrombocytes

Answer 2

Platelets- key cell necessary for blood coagulation.
Produced by megakaryocytes.

Very scarce in the blood: less than 50x as much as RBCs
Size- around 1.5 micrometers

Question 3

Thrombocytopenia

Answer 3

State that describes a low platelet count

Question 4

Extrinsic coagulation pathway

Answer 4

This is the initiating step in the coagulation pathway.

Factor VIIa reacts with Tissue factor (factor III) to form Extrinsic Xase.

Extrinsic Xase activates factor X with Intrinsic Xase.

Question 5

Formation of fibrin

Answer 5

Fibrinogen is activated by thrombin (Factor IIa) to form fibrin.

Question 6

Intrinsic coagulation pathway

Answer 6

Thrombin (factor IIa) activates factor VIII to VIIIa.

VIIIa is a coenzyme that activates Factor IXa to form Intrinsic Xase.

Intrinsic Xase activates X to Xa. Whilst thrombin (IIa) activates V to Va.

Va is a co-factor for Xa. Va activates Xa to form thrombinase, used to form thrombin.

Question 7

Common coagulation pathway

Answer 7

1. Prothrombin (Factor II) is activated by factor Xa to thrombin (IIa).
2. Thrombin activates fibrinogen (I) to fibrin (Ia).
   Thrombin also goes to activate VIII in the intrinsic pathway (positive feedback).
3. XIIIa activates fibrin to form a fibrin clot cross link- to stop bleeding.

Question 8

Prothrombin activators

Answer 8

VIIa- 7a

IXa- 9a

Xa- 10a

Question 9

Factors activated by thrombin

Answer 9

I- Fibrin

V- co-factor, when activated, reacts with Xa to form thrombinase (activates thrombin)

VIII- co-factor, when activated, reacts with IXa to form intrinsic Xase, which activates X.

Question 10

Vitamin K

Answer 10

Vitamin required for the synthesis of factors, made in livers: II (prothrombin), VII, IX and X (2, 8, 9, 10).

X is a Ca2+ dependant protease.

Vit K is made by bacteria in large intestines or ingested from leafy greens.
Vit K is essential for gamma carboxylation of clotting enzymes

Question 11

Vitamin K deficiency

Answer 11

Causes inadequate clotting of blood.

Causes: Liver/ GI damage.
New born babies’ intestines have not yet been colonised by bacteria which can cause clotting problems due to low Vit K.

Question 12

Warfarin

Answer 12

Anticoagulant drug that antagonises Vit K.

This prevents the synthesis of clotting factors: II, VIII, IX, X.

Question 13

Protein C

Answer 13

Enzyme that inhibits coagulation. Vit K is involved in its synthesis, in the liver.

Activated by thrombin, when there is too much clotting. Activation happens on endothelial surface.

Also inactivates other co-factors. Protein C and co-factor S inactivate Va and VIIIa together.

Question 14

Plasmin

Answer 14

Enzyme that lyses clots by breaking down fibrin.

Plasminogen is its inactive form, made in the liver. This is activated by the tissue plasminogen activator (tPA)

Question 15

Antithrombin III

Answer 15

Peptide made by the liver that inhibits factors: IIa (thrombin), Xa, IXa (2a, 10a, 9a).

A deficiency of this peptide causes a thrombotic disease- increasing risk of stroke, embolisms.

Heparin increases the activity of antithrombin III by inhibiting Xa.

Question 16

Antiplatelet agents

Answer 16

Blocks platelet activation

Examples:
Aspirin
Prasugrel/ Clopidogrel

Used to treat arterial diseases

Question 17

Fibrinolytics

Answer 17

Drugs that dissolve fibrin (clots). This is used as last resort.
Used for arterial clots

Examples:
Tissue plasminogen activator
Streptokinase
Urokinase

Question 18

Anticoagulants

Answer 18

Drugs that block clotting factors: mainly used for venous clots.
Used for:
Prophylaxis for deep vein thrombosis and pulmonary embolisms.
Low BP in pulmonary circulation.

Examples:
Warfarin
Heparins
Novel-oral anticoagulants (NOACs)

Question 19

Heparin

Answer 19

Anticoagulant used mainly for venous clots.

Works by inhibiting factor Xa with antithrombin III.

Question 20

Aspirin

Answer 20

Antiplatelet drug that blocks thromboxane in platelets.

Used for MI prophylaxis.

Question 21

Prasugrel/ Clopidogrel

Answer 21

Anti-platelet drug that is used to prevent arterial clotting.

Works by inhibiting ADP receptors on platelets.

Question 22

Novel oral anticoagulants (NOACs)

Answer 22

Anticoagulants that inhibit clotting factors.

Examples:
Dabigatran
Rivaroxaban

Question 23

Dabigatran

Answer 23

NOAC that inhibits thrombin, IIa.

Question 24

Rivaroxaban

Answer 24

NOAC that inhibits factor Xa.

Question 25

Haemophilia A

Answer 25

X-linked genetic disease that is characterised by the mutation of factor VIII (8).

VIII is a co-factor that activates IXa in the the intrinsic pathway when activated.

Symptoms:
Excessive bleeding of wounds, that bleeds for days.
Affects muscles and joints.

Treatment- injecting purified factor VIII- expensive

Question 26

Haemophilia B

Answer 26

Also known as the Christmas disease.

Lack of clotting factor IX.

IX is used to activate the intrinsic Xase, which also activates X to Xa.

Individuals also have the same symptoms as those with haemophilia A.

Question 27

Inflammatory atherogenesis

Answer 27

Monocytes enter endothelium lesions and become macrophages.

Macrophage consume cholesterol esters and become foam cells.

When the foam cells burst and release their content, they attract more monocytes, cytokines and pro-inflammatory molecules.

Question 28

Atherogenesis caused by lipids

Answer 28

LDL deposits itself in lesions.

Cholesterol is oxidised to oxygen radicals.

Oxidised lipids are eaten by macrophages to form foam cells.

Foam cells die and release their content, causing more inflammation.

Question 29

Endothelium- cause of atherogenesis

Answer 29

1. Chemoattractants.
   Endothelial cells release these which attract monocytes.
2. Stimulation of coagulation.
   When endothelium is lost, this exposes collagen, stimulating coagulation. Also-releases tissue factor.
3. Release of NO
   When endothelium is lost, this prevents NO from being released. Therefore vessels cannot dilate.

Question 30

Activation of platelets in haemostasis,

Answer 30

1. Platelets are exposed to collagen when endothelium is removed.
2. Causes them to change shape and release dense granules contain ADP, serotonin, Ca2+. Serotonin causes vasoconstriction- slows blood down, allow it to clot.
3. ADP activates P2Y receptor which causes release of cations.
4. Platelets release thromboxane A2- stimulates other platelets to be activated and also stimulates aggregation of platelets.

Release of chemicals activates other platelets causing them to also change shape and release chemicals- positive feeback.
Platelets form temporary plug to seal break in endothelium.