Intro To Haemostasis

Question 1

What is haemostasis?

Answer 1

Consequence of a tightly regulated process, maintains fluid status in normal vessels, whilst permitting rapid formation of a haemostatic clot at a site of vascular injury

Question 2

What are the 3 components of haemostasis?

Answer 2

Vascular wall
Platelets
Coagulation cascade

Question 3

What are the 3 basic processes of haemostasis?

Answer 3

1. Contraction of vessel wall - decrease the pressure downstream
2. Formation of platelet plug at site
3. Formation of fibrin clot to stabilise platelet plug into a blood clot

Question 4

What happens when a vessel is injured with regards to platelets?

Answer 4

Adhesion
Activation/secretion
Aggregation

Question 5

Describe platelet adhesion

Answer 5

Happens in seconds
Damage to vessel wall, exposure underlying tissues, platelets adhere to collagen via Von Willebrand factor/receptor

Question 6

Describe platelet activation/secretion

Answer 6

Secrete granules containing ADP, thromboxane and other substances to become activated and activate other platelets.
Involved in activation of the clotting cascade.
Provide some coagulation factors by secretion from internal stores.

Question 7

Describe platelet aggregation

Answer 7

Cross linking of platelets to form a platelet plug (seconds to minutes)
Provides some stability but is friable

Question 8

What are the 3 basic tests for clotting defects?

Answer 8

All performed on platelet poor plasma (centrifuged):
Activated partial thromboplastin time (APTT)
Prothrombin time (PT)
Thrombin time (TT)

Question 9

What will APTT assess?

Answer 9

Intrinsic pathway
If prolonged, suggests a deficiency in one or more of factors VIII, IX, XI or XII

Question 10

What is a deficiency in VIII also called?

Answer 10

Haemophilia A

Question 11

What is a deficiency in IX also called?

Answer 11

Haemophilia B

Question 12

What does PT assess?

Answer 12

Extrinsic pathway
Most commonly due to a factor VII deficiency

Question 13

What are the natural anticoagulants?

Answer 13

Protein C, S and antithrombin

Question 14

Describe the mechanism of activated protein C (APC)

Answer 14

Thrombin binds to an endothelial cell receptor called thrombomodulin.
The resulting complex activates protein C
This then inactivates facts VIIIa and Va
Protein S is a cofactor for APC

Question 15

Describe the mechanism of antithrombin III

Answer 15

Plasma protein that inactivates thrombin and several other clotting factors
Activated by heparin on the surface of endothelial cells
Prevents the spread of a clot by rapidly inactivating clotting factors that are carried away from the immediate site of the clot by the flowing blood

Question 16

What is tissue factor pathway inhibitor?

Answer 16

Poses clot formation
Acts in the initiation phase of clotting
Secreted mainly by endothelial cells
Binds to tissue factor-factor VIIa complexes and inhibits the ability of these complexes to generate factor Xa

Question 17

What is thrombocytopenia?

Answer 17

Deficiency of platelets in the blood resulting in bleeding into the tissues, bruising and slow blood clotting after injury.
Platelet count of less than 100. X 10^9/L is classified as thrombocytopenia

Question 18

At what platelet count does spontaneous bleeding occur?

Answer 18

Less than 20 x 10^9/L.

Question 19

Ow does thrombocytopenia present?

Answer 19

Purpura
Petichiae
Mucosal bleeding
Epistaxis
Menorrhagia

Question 20

How can the causes of thrombocytopenia be classified as? Give an example for each

Answer 20

Decreased production of platelets e.g. due to bone marrow infiltration by malignancy
Decreased platelet survival e.g. immunologic destruction
Sequestration e.g. in hypersplenism
Dilutional e.g. due to massive blood transfusions (blood stored for >24 hrs dont contain platelets)

Question 21

What are the complication of haemophilia?

Answer 21

Muscle haematomas
Recurrent haemarthroses
Joint pain and deformity
Prolonged bleeding post dental extraction
Life threatening post-operative and post-traumatic bleeding
Intracerebral haemorrhage

Question 22

What is the difference between Haemophilia A and B?

Answer 22

No difference in presentation

However, haemophilia A is due to a lack of factor VIII. Haemophilia B is due to reduction in factor IX.

Both are X-linked recessive

Question 23

How are Haemophilia A and B treated?

Answer 23

A treated with recombinant factor VIII or DDAVP.

B treated with infusions of recombinant factor IX

Both A and B result in prolonged APTT and normal PT

Question 24

describe Von Willebrand disease

Answer 24

Relatively uncommon
Usually autosomal dominant
Reduced factor VIII amount/activity

Bleeding tendency is mild and often goes unnoticed until additional stress in most patients
Excessive bleeding from wounds e.g. dental
Menorrhagia
Prolonged bleeding time in the presence of a normal platelet count
Spontaneous bleeding from mucous membranes

Question 25

What are the complications of vessel wall abnormalities?

Answer 25

Easy bruising Spontaneous bleeding from small vessels … In the skin mainly … Can be in the mucous membranes

Question 26

What are the congenital causes of vessel wall abnormalities?

Answer 26

Hereditary haemorrhagic Telangiectasia (HHT): Autosomal dominant Dilated Microvascular swellings increase with time GI haemorrhage can lead to on deficiency anaemia Connective tissue disorders - Ehlers Danlos

Question 27

What are the acquired causes of vessel wall abnormalities?

Answer 27

Senile Purpura Steroids Infection e.g. measles, meningococcal infection Scurvy - vitamin C deficiency causing defective collagen production

Question 28

What is Disseminated Intravascular Coagulopathy (DIC)?

Answer 28

Type of microangiopathic haemolytic anaemia Pathological activation of coagulation Numerous microthrombi are formed in the circulation -> clotting factors and platelets are used up, haemolytic anaemia Failure of haemostasis -> haemorrhage

Question 29

What are the clotting test results with DIC?

Answer 29

Usually raised PT/INR Raised APTT Low fibrinogen Raised D dimers/fibrin degradation products

Question 30

How is DIC acquired?

Answer 30

There must always be a trigger e.g. Malignancy Massive tissue injury e.g. burns Infections - usually gram negative sepsis Massive haemorrhage and transfusion ABO transfusion reaction Obstetric causes

Question 31

Describe thrombophilias

Answer 31

Can be congenital or acquired Congenital - deficiency in natural anticoagulants (Protein c, s and antrithrombin) - abnormal factor V - resistance to APC Acquired causes induce antiphospholipid syndrome (due to antiphospholipid antibodies)