Haemostasis/Clotting cascade

Question 1

Conditions where wound healing impaired that may be mistaken for a clotting disorder?

Answer 1

Ehlers Danlos
Scurvy
Cushings

Question 2

What is haemostasis?

Answer 2

The stopping of blood and forming of a clot following an injury so it can be repaired

Question 3

What is the rough order of events from injury to the clotting cascade (4)

Answer 3

Injury
Vasoconstriction
Platelet plug (vWF, platelets, tissue factor, clotting cascade activated)
Coagulation

Question 4

What cells produce platelets?

Answer 4

Megakaryocytes

Question 5

What is normal platelet count?

Answer 5

150-400 x 10^9/L

Question 6

What is the normal lifespan of platelets? Why would you stop a patients aspirin for this time before surgery?

Answer 6

7-10 days

As it inhibits platelets and therefore may inhibit healing post surgery

Question 7

What are the three A’s of platelets in forming a plug? What happens at each of them?

Answer 7

Adhesion - adhere to collagen in endothelial wall via vWF receptor
Activation - secrete ADP, thromboxane etc to bring other platelets
Aggregation - adhesion of platelets together to form a platelet plug

Question 8

What is a natural anticoagulant? What happens if you are deficient in one? Give 3 examples of these in the body

Answer 8

Stop further coagulation
Can get VTEs e.g. DVT if deficient in these
e.g. 
Protein C
Protein S
Anti-thrombin

Question 9

Where are clotting factors made? Where are anticoagulation factors made?

Answer 9

Both liver

Question 10

What do proteinC proteinS and antithrombin do?

Answer 10

They inhibit parts of the coagulation cascade pathway to prevent further coagulation

Question 11

What happens at the beginning of extrinsic vs intrinsic cascade?

Answer 11

Intrinsic - collagen exposed by injury - initiates cascade vWF binds to collagen

Extrinsic - tissue factor exposed —> initiates cascade

Question 12

What is the role of vWF (3)?

Answer 12

Stabilises factor VIII is vital
Platelet adhesion
Platelet aggregation

Question 13

What is Vit K needed for?

Answer 13

Needed for synthesis of lots of coagulation factors

Question 14

What is Ca needed for?

Answer 14

Clotting factor - needed for many things e.g. conversion of factor VII to X factor IX to X and X to prothrombin

Question 15

Which clotting blood test measures intrinsic which measures extrinsic? Which one could indicate a vit K deficiency if prolonged?

Answer 15

PT - extrinsic - this one

APTT - intrinsic

Question 16

What would you expect the result to be for PT/APTT in liver disease? Why?

Answer 16

Prolonged as clotting factors made in liver and if liver damaged sufficient clotting factors may not be made

Question 17

How does the thrombin burst occur?

Answer 17

Tissue factor exposed leads to a small amount of thrombin being formed, that then feeds back and produces a thrombin burst

Question 18

What is the role of thrombin in fibrin?

Answer 18

Thrombin cleaves fibrinogen to fibrin

Question 19

What is fibrinolysis?

Answer 19

Break down of clot

Question 20

What breaks down the clot?

Answer 20

Plasmin

Question 21

How is plasmin activated and what’s its precursor?

Answer 21

By plasminogen activator, precursor plasminogen

Question 22

What is the end product?

Answer 22

D-Dimers - fibrin degradation products

Question 23

What three things can cause a bleeding disorder?

Answer 23

Abnormality in vessel wall
Platelets
Coagulation factors

Question 24

What are some complications of clotting factor disorders?

Answer 24

Haemorrhage
Bruising - e.g. muscle
Joint pain and deformity 
Prolonged bleeding post dental extraction
Post op bleeds

Question 25

What happens with a disorder of vessel wall abnormality? Give an example of congenital vs acquired

Answer 25

Easy bruising Spontaneous bleeding from small vessels - eg. red small spots over tongue/lips/arms Congenital: HHT (Hereditary haemorrhage telangiectasia) Ehlers Danlos Acquired: Senile purpura, steroids, infections, vit C deficiency

Question 26

What are some reasons for low platelets (4)?

Answer 26

Immune destruction: Immune thrombocytopenia purpura Non Immune destruction: Microangiopathic haemolytic state e.g. DIC, cardiopulmonary bypass machine Reduced production - folate vit b12 deficiency, cancer prolif in marrow, drugs - chemo, viruses - hepatitis, HIV< EBV, CMV Pooling: Splenic pooling in splenomegaly

Question 27

Generally below what level of platelets will patients be symptomatic?

Answer 27

30

Question 28

What is DIC? What does it lead to?

Answer 28

Disseminated intravascular coagulation Many causes - always a cause Leads to microangiopathic haemolytic anaemia Pathological activation of coagulation cascade - uses up all clotting factors platelets etc

Question 29

What lab results would you see for DIC?

Answer 29

Raised PT, APTT, D dimer, INR | Lowered fibrinogen, platelets

Question 30

An increased APTT with normal PT could indicate a deficiency in which factors?

Answer 30

All intrinsic and common e.g. 12, 11, 9, 10, 8 vWF

Question 31

An increased PT with normal APTT could indicate a deficiency in which factors?

Answer 31

All extrinsic and common | e.g. 7, 3, 5, 10

Question 32

If you see low Hb and low MCV what is the most common cause?

Answer 32

Normally indicates a microcytic anaemia, most common is iron deficient anaemia

Question 33

Where are the common sites of bleeding in haemophilia compared to low platelets?

Answer 33

Haemophilia - intramuscular and joints Platelets - mucosal (nose/mouth), skin (purpura)

Question 34

Can vit B12/folate deficiency cause a platelet deficiency?

Answer 34

Yes

Question 35

If someone has low platelets with normal bone marrow and absence of other causes what are they diagnosed with?

Answer 35

Immune thrombocytopenic pupura

Question 36

What are some causes of prolonged PT that aren't directly due to coagulation factor deficiencies?

Answer 36

Vit K deficiency - malnourished Use of antibiotics - can affecting clotting time Liver disease Paracetamol overdose can affect vit K

Question 37

How do you treat DIC?

Answer 37

Not specific Treat cause Can give platelets

Question 38

Would a deficiency in protein C cause bleeding or clotting?

Answer 38

Predisposes to clotting - DVT | As it normally is a natural anticoagulant