Haemostasis

Question 1

What happens before, during and after haemostasis broadly and why?

Answer 1

Before- vasoconstriction to limit blood flow to site of injury
During- primary haemostasis- unstable platelet plug formed to limit blood loss and make surface for coagulation
Secondary haemostasis- stabilises platelet plug to stop blood loss
Fibrinolysis- clot is dissolved and the vessel wall is repaired to restore normal function

Question 2

Describe the mechanism of primary haemostasis

Answer 2

Following vessel wall damage, platelets bind to the vessel wall using their glycoprotein Gp1a or onto exposed collagen if VWF is present using Gp1b.
This causes thromboxane activation leading to A2 and ADP synthesis, promoting platelet activation
This causes granule release and flip-flopping of platelets- exposing Gp2b and Gp3a which bind to the vessel wall and form the platelet plug

Question 3

What three structures can be affected in primary haemostasis disorders?

Answer 3

Platelets
VWF and as a result F VIII
Vessel wall

Question 4

What are the two causes of platelet disorders and what are their causes?

Answer 4

Thrombocytopenia- caused by leukaemia or accelerated clearance (via ITP immune thrombocytopenic purpura, DIC disseminated intravascular coagulation, splenomegaly)
Impaired platelet function- hereditary eg missing glycoproteins or acquired via NSAIDS/Aspiring/Clopidogrel

Question 5

What is the cause of VWF disorders? And what are the types?

Answer 5

Von willebrand disease
Deficiency T1 & T3
Abnormal function T2

Question 6

What are the two causes of vessel wall disorders?
What do these disorders typically affect?

Answer 6

Hereditary disorders
Acquired
Collagen on vessel wall

Question 7

What is ITP?
What Is its pathophysiology?

Answer 7

Immnune thrombocytopenic purpura
Autoantibodies bind to platelets and take them to macrophages- engulfed

Question 8

How does aspirin work?
How long are its effects?
What haemostasis is it given for?

Answer 8

Inhibits synthesis of thromboxane A2 so the platelet plug cannot be formed
Typically lasts 7 days as platelets are resynthesised after this
Primary

Question 9

How does clopidogrel work?
What haemostasis is it given for?

Answer 9

Binds to ADP preventing platelet activation = no platelet plug formed
Primary haemostasis

Question 10

What are the clinical and dermatological features of primary haemostasis disorders?

Answer 10

Immediate extensive bleeding after trauma
Extensive menses
Gum bleeds
Nose bleeds
Easy bruising
Non blanching purpura
Petechiae

Question 11

What are the tests for primary haemostasis disorders?

Answer 11

Platelet count
Bleeding time

Question 12

How are primary haemostasis disorders treated?

Answer 12

Treat underlying condition eg
Replace low platelet or missing VWF
Splenectomy
Immunosuppression via prednisolone

Question 13

What is the role of the coagulation cascade?

Answer 13

Produce thrombin (factor IIa) from prothrombin (factor II) which converts fibrinogen (factor I) to fibrin (factor Ia) to stabilise platelet plug

Question 14

What are the two pathways of secondary haemostasis?
What does this convert prothrombin into?

Answer 14

Intrinsic: 12-11-9-8-10
Extrinsic: 7-10 (joins intrinsic at this point)
Factor 10a turns prothrombin into thrombin with the help of 5
Prothrombin (factor II) becomes thrombin which then makes fibrinogen into fibrin

Question 15

What are the three principles of disorders of coagulation?

Answer 15

Deficiency of coagulation factor
Dilution
Increased consumption

Question 16

What are the two types of disorder of coagulation factors and what are examples of the two?

Answer 16

Hereditary (haemophilia A/B, factor 11/12 deficiency),
Acquired (liver disease, anticoagulants)

Question 17

What are the two hallmark features of haemophilia?

Answer 17

Haemarthrosis- bleeding into joint
Muscle wasting- later on

Question 18

What injections should be avoided in haemarthrosis?

Answer 18

Intramuscular injections as muscle bleeding is hard to control

Question 19

How does dilution occur in coagulation disorders?

Answer 19

A blood transfusion is given following a haemorrhage, however this blood does not contain plasma, and therefore coagulation factors = dilution of coagulation factors

Question 20

What is Disseminated intravascular coagulation (DIC) and what is this an example of?
What can it end up causing?

Answer 20

Example of increased consumption coagulation disorder

This happens when tissue factor becomes overactive leading to rapid coagulation, which causes drainage of platelets and coagulation factors and deposition of fibrin in the vessels. This leads to organ failure

Question 21

What is consumed in DIC?
What conditions can It be associated with?
What molecule can you detect in DIC blood tests?

Answer 21

Coagulation factors and platelets
Sepsis, inflammation, major tissue damage
D-dimer- breakdown product of fibrin

Question 22

How do the clinical features of primary and secondary haemostasis defects differ?

Answer 22

Primary- superficial bleeding (due to no platelet plug) straight after injury
Secondary- deeper bleeding rather that on superficial cuts (as platelet plug can still be formed) and prolonged onset of bleeding after trauma

Question 23

What do PT and APTT measure specifically and generally?

Answer 23

PT- extrinsic pathway (factor 7)
APTT- intrinsic pathway
Both ultimately measure time to make cross linked fibrin (activation of thrombin to make fibrin)

Question 24

Describe the causes behind the following test results:
Prolonged APTT but normal PT
Prolonged PT but normal APTT
Prolonged PT and prolonged APTT
Normal PT and APTT

Answer 24

Haemophilia A/B, factor 11/12 deficiency (as these are needed before factor 10)

Factor 7 deficiency

DIC, Dilution, liver failure, anticoagulant drugs

Primary haemostasis disorder, healthy patient

Question 25

How can you replace coagulation factors?
What can they each provide?

Answer 25

Plasma- has all
Concentrates- everything but 5
Cryoprecipitate- Fibrinogen, VWF, F8

Question 26

How do pulmonary embolisms and deep vein thrombosis present?
How can DVT lead to PE?

Answer 26

PE: shortness of breath, angina, tachycardia, hypoxia, hemoptysis
DVT: painful leg, swelling, redness

Part of the clot in DVT can break off and travel to the lung causing PE

Question 27

What are the three contributory factors to thrombosis?
What name is given to these three factors?
Which of them are common in venous and arterial thrombosis?

Answer 27

Blood- venous thrombosis
Vessel wall- arterial thrombosis
Blood flow- both of them
Virchows triad

Question 28

What is the term given to a higher hereditary risk of thrombosis?
What is the major risk factor in thrombosis?

Answer 28

Thrombophilia
Increased age

Question 29

What components of blood may be decreased/affected leading to a higher risk of thrombosis? What do the first two do?

Answer 29

Protein C and S- inhibit factor 5 (C) and 8 (S)
Increased platelet formation

Question 30

What can cause blood flow alteration leading to thrombosis?

Answer 30

Decreased blood flow via long haul flights, pregnancy, surgery

Question 31

What are the anticoagulation therapies? How do they each work?

Answer 31

Heparin- enhances antithrombin by changing its active site to bind to F10a and thrombin
Warfarin- block recycling of VitK = Can’t activate factors 2,7,9,10 protein C and protein S
DOA (direct oral anticoagulants)- Rapid blocking of clotting factors