L13 - Disorders of Blood Coagulation

Question 1

Why do clots form?

Answer 1

To keep blood in

To keep pathogens out

Question 2

How does clotting occur?

Answer 2

platelets and fibrinogen circulate in the blood.
when here is a damage or rupture to the endothelial wall of blood vessel, primary and secondary haemostasis occur.
Injury causes collagen to come into contact with the blood, which triggers compenents of blood to be activated.

Question 3

What is primary haemostasis?

Answer 3

platelet adhesion, aggregation, activation

Question 4

What is secondary haemostasis?

Answer 4

activation of fibrin formation through the clotting cascade

Question 5

Describe the process of primary haemostasis?

Answer 5

Endothelial cells that line blood vessels store von willebrand factor, and it is released in small amounts continously. If collagen becomes exposed to blood, von willebrand will bind to the collagen. Platelets express the receptors for both von willebrand and collagen, they become activated when binded to them.
Activated platelets are needed to express functional fibrinogen receptors to help aggregation.

Question 6

Describe what happens in secondary haemostasis?

Answer 6

When damage occurs to blood vessel, a protein called tissue factor (expressed by sub endothelial cells) is exposed.
Tissue factor activates factor 7a, which activates factor 10a. This causes an initial trickle of thrombin
Thrombin activates receptors on platelets, amplifying platelet aggregation, and initiating release of stored von willebrand factor from endothelial cells.
It also releases thromboxanes, ADP. It causes platelets to bind to fibrinogen and convert it to fibrin (its active form)

Question 7

How is thrombin amplified further?

Answer 7

thrombin activates 2 cofactors: factor 8a and 5a. They form calcium ion dependant complexes with factor 9a (the tenase complex) and 10a (prothrombinase complex) on platelets surface. They in turn increase the production of thrombin

Question 8

What is Fibrinolysis?

Answer 8

the breaking up of fibrin into smaller fragments

can also be called thrombolysis

Question 9

How does Fibrinolysis occur?

Answer 9

Plasminogen is activated to plasmin via the tissue plasminogen activator (t-PA).
Plasmin then degrades the fibrin mesh into fragments (called fibrin degradation products) which can be cleared.

Question 10

What is Anti-thrombin and and what is its function?

Answer 10

it is a serpin - serine protease inhibitor
it is a natural anticoagulant.
When bound to heparan the effects are enhanced.

Question 11

Describe how protein C and S work as natural anticoagulants?

Answer 11

Protein C is activated by thrombin binding to thrombomodulin on endothelial cells.#
Protein S is an APC cofactor which helps binding on cell surfaces.
They degrade cofactors 5a and 8a

Question 12

What is Haemophilia?

Answer 12

Failure to clot leading to haemorrhage

Question 13

What is Thrombophilia?

Answer 13

excessive clotting leading to thrombosis.

Question 14

What is Disseminated Intravascular Coagulation?

Answer 14

Whole body clots.

Question 15

Describe Haemophilia A as a bleeding disorder, and where it can it occur?

Answer 15

80% of cases
mutated factor 8a
clotting dosen’t occur normally as there isn’t sufficient amount of thrombin

bleeding into joints, gross swelling from acute haemarthroses

Question 16

Describe Haemophilia B as a bleeding disorder, and where can it occur?

Answer 16

20% of cases
mutated factor 9a
clotting dosen’t occur normally as thrombin isn’t activated. Increased bleeding

bleeding into joints, gross swelling from acute haemarthroses

Question 17

Describe von willebrand disease as a bleeding disorder and give example of where it can occur?

Answer 17

Inherited defect/deficiency in vWF.
Without this, platelets can’t go through the process of adhesion, activation and aggregation. As a result there is an increased risk of bleeding.

Affects mucous membranes. Can occur in gums/mouth.

mostly mild but bleeding can vary in severity

Question 18

Describe factor 5 Leiden mutation as an excessive coagulation disorder?

Answer 18

mutation of factor 5 leads to a resistance of the Protein C inhibition pathway. Causes resistance to APC, and as a result Factor 5a isn’t inactivated
Increases the risk of Deep Vein Thrombosis.

Question 19

Describe Anti-thrombin deficiency as an excessive coagulation disorder?

Answer 19

Deficiency or mutations within anti-thrombin, then all inhibition pathways are diminished. Nothing to stop clotting.
Increases risk of DVT

Question 20

Describe Protein C/S deficiency as an excessive coagulation disorder?

Answer 20

Deficiency or mutation in proteins C or S, don’t allow inhibition pathways to work. Nothing to stop clotting
Increases risk of DVT

Question 21

What factors do development of deep vein thrombosis depend on? Include Virchow’s Triad

Answer 21

Hypercoagulability = alterations to the constituents of blood

Stasis = changes to the normal blood flow

Vessel wall injury = damage to the endothelial layer

Question 22

What are some signs or symptoms that are associated with Deep Vein Thrombosis?

Answer 22

• pain and tenderness of veins
• limb swelling
• superficial venous tension
• increased skin temperature
• skin discoloration

Question 23

What happens during Disseminated Intravascular coagulation?

Answer 23

Too much ongoing coagulation, that there is a depletion of clotting factors and platelets before the liver can make more. This leads to bleeding.
Can occur in infection and sepsis, where the body injures its own tissue and organs

Question 24

What are anti-coagulants and give examples?

Answer 24

They prevent thrombosis/ coagulation from happening.

warfarin (injected), heparin (injected)
Direct oral anticoagulants (oral tablets) that act on specific factors in clotting cascade

Question 25

What are thrombolytics/fibrinolytics and give examples?

Answer 25

They degrade the clot back into fibrinogen and platelets

plasminogen activators like tPA or streptokinase

Question 26

What investigations would be done before treatment to a patient with Venous Thrombo-embolism?

Answer 26

• clotting screen
• full blood count
• renal screen
• liver function tests

Question 27

What treatment would be given to a patient with Deep Vein thrombosis?

Answer 27

Anti-coagulate

• heparin or warfarin
• DOACs like rivaroxaban or dabigatran

Question 28

What treatment would be given to a patient with a Pulmonary Embolism?

Answer 28

Thrombolytics

• alteplase
• streptokinase
• maybe followed by an anticoagulant

Question 29

What complications can arise from administering anti-coagulants?

Answer 29

bleeding
small haemorrhages
bruising
intracerebral bleeds