Haemostasis and bleeding disorders

Question 1

What are the three normal components of haemostasis?

Answer 1

Primary haemostasis
Secondary haemostasis
Fibrinolysis

Question 2

What is primary haemostasis?

Answer 2

Formation of a platelet clot

Question 3

What is secondary haemostasis?

Answer 3

Formation of a fibrin clot

Question 4

What happens when endothelium is damaged?

Answer 4

Collagen is exposed
Von Willebrand factor is released
Platelets stick to collagen and Von Willebrand factor provides adhesion

Question 5

What is the lifespan of a platelet?

Answer 5

7-10 days

Question 6

What are the consequences of a lack of platelet plug formation?

Answer 6

Spontaneous Bruising and Purpura
Mucosal Bleeding:
- Epistaxes
- Gastrointestinal
- Conjunctival
- Menorrhagia
Intracranial haemorrhage
Retinal haemorrhages

Question 7

Do single clotting factor deficiencies tend to be inherited or acquired?

Answer 7

Inherited e.g. haemophilia

Question 8

Do multiple clotting factor deficiencies tend to be inherited or acquired?

Answer 8

Acquired e.g. disseminated intravascular coagulation

Question 9

Which clotting factors does prothrombin time assess?

Answer 9

Tissue factor, VII, II (prothrombin), V, X and fibrinogen

Question 10

Which clotting factors does activated partial thromboplastin time assess?

Answer 10

XII, XI, IX, VIII

Question 11

What is a blood vessels response to damage?

Answer 11

Vasocontstriction

Question 12

What are the causes of peripheral platelet destruction?

Answer 12

Coagulopathy: Disseminated intravascular coagulation
Autoimmune: Immune thrombocytopenic purpura (ITP)
Hypersplenism

Question 13

What acquired functional platelet defects are there?

Answer 13

Drugs (eg Aspirin, non-steroidal anti inflammatory drugs)

Renal failure

Question 14

What mode of inheritance is Von Willebrand Factor deficiency?

Answer 14

Autosomal dominant

Question 15

What are petechiae?

Answer 15

Small spots on the skin caused by bleeding - very specific to platelet disorders

Question 16

What is the most common cause of immune mediated thrombocytopenia?

Answer 16

Immune thombocytopenia purpura

Question 17

What is the acute syndrome of immune thrombocytopenia purpura?

Answer 17

Affects children between ages of 2-6
Symptomatic thrombocytopenia occurs post infection
Resolves spontaneously

Question 18

What is the chronic syndrome of immune thombocytopenia purpura?

Answer 18

Affects middle aged women usually
No preceding infection
Must be treated with steroids and splenectomy if severe

Question 19

What drugs have been indicated to precede immune thrombocytopenia?

Answer 19

Penecillin
Oral thiazides
Heparin
Transfusion

Question 20

What chronic conditions may cause immune thrombocytopenia?

Answer 20

HIV

SLE

Question 21

What is disseminated intravascular coagulation?

Answer 21

Excessive and inappropriate activation of the haemostatic system: primary, secondary and fibrinolysis

Question 22

How might DIC present?

Answer 22

Bruising, purpura and generalised bleeding

Organ failure

Question 23

What are the complications of DIC?

Answer 23

Microvascular thrombus formation causing organ death

Clotting factor consumption

Question 24

How do disorders of coagulation typically present?

Answer 24

Delayed bleeding after surgery

Deep muscle bleeding or bleeding into joints

Question 25

What is haemophilia A and haemophilia B?

Answer 25

Both are congenital deficiencies of clotting factors Haemophilia A - clotting factor 8 Haemophilia B - clotting factor 9

Question 26

What mode of inheritance does haemophilia have?

Answer 26

X-linked recessive

Question 27

Which haemophilia is more common?

Answer 27

Haemophilia A

Question 28

What is the APTT and PT like in haemophilia?

Answer 28

APTT increased | PT normal

Question 29

What is type 1 Von Willebrand disease?

Answer 29

Partial reduction in the amount of Von Willebrand factor

Question 30

What is type 2 Von Willebrand disease?

Answer 30

Reduction in the quality of the Von Willebrand factor

Question 31

What is type 3 Von Willebrand disease?

Answer 31

Total loss of Von Willebrand factor - most severe form

Question 32

What other clotting factor deficiency may also be present in Von Willebrand disease?

Answer 32

Factor 8

Question 33

How does Von Willebrand disease usually present?

Answer 33

Petechiae Eccymoses Mucocutaneous bleeding

Question 34

How might coagulation tests be altered in Von Willebrand disease?

Answer 34

May be normal | May have both increased APTT and PT

Question 35

How is Von Willebrand disease treated?

Answer 35

Desmopressin

Question 36

How is haemophilia managed?

Answer 36

Lifelong replacement with frozen factor concentrate

Question 37

Why is vitamin K important?

Answer 37

Required for carboxylation of factors II, VII, IX and X

Question 38

How might coagulation tests be altered in vitamin K deficiency?

Answer 38

Both PT and APTT raised

Question 39

What are the causes of vitamin K deficiency?

Answer 39

Malnutrition and malabsorption Warfarin therapy Obstructive jaundice Haemorrhagic disease of the newborn

Question 40

How is vitamin K deficiency managed?

Answer 40

Give vitamin K

Question 41

How does liver disease cause a coagulation disorder?

Answer 41

Coagulation factors are produced in the liver | Also causes platelet problems as platelets pool in enlarged spleens caused by portal hypertension

Question 42

What are the causes of DIC?

Answer 42

``` Disseminated gram negative sepsis Placental abruption Mismatched blood transfusions End stage malignancy Hypovolaemic shock ```

Question 43

How might coagulation tests be altered in liver disease?

Answer 43

Prolonged PT and APTT as all factors are affected

Question 44

How is DIC managed?

Answer 44

``` Treat the underlying cause Replacement therapy: - Platelet transfusions - Plasma transfusions - Fibrinogen replacement ```

Question 45

Why is aspirin not helpful in the prevention of venous thrombus formation?

Answer 45

Platelets are not activated - it is all the coagulation cascade

Question 46

What is thrombophilia?

Answer 46

Familial or acquired disorders of the haemostatic mechanism which are likely to predispose to thrombosis

Question 47

By what mechanism does thrombophilia predispose to clot formation?

Answer 47

Decreased anticoagulant activity

Question 48

What naturally occuring anticoagulants are there?

Answer 48

Serine protease inhibitors e.g. antithrombin III Protein C Protein S Factor V leiden

Question 49

When should screening for thrombophilia be offered?

Answer 49

Venous thrombosis

Question 50

What is factor V leiden?

Answer 50

A point mutation in factor V that may be present in up to 10% of the population This causes normal procoagulin activity but an altered response to inhibition by anticoagulant factors

Question 51

What is the pathogenesis of antiphospholipid syndrome?

Answer 51

Antibodies lead to a conformational change in β2 glycoprotein 1 (a protein with unknown function in health) which leads to activation of both primary and secondary haemostasis and vessel wall abnormalities

Question 52

How is antiphospholipid syndrome managed?

Answer 52

Aspirin Warfarin (since both arterial and venous thrombosis)

Question 53

What is the action of unfractionated heparin?

Answer 53

Stabilises bond between antithrombin 3 and fibrinogen

Question 54

What is the action of LMWH?

Answer 54

Stabilises bond between antithrombin 3 and factor Xa

Question 55

What monitoring is required for unfractionated heparin?

Answer 55

APTT

Question 56

What is a complication associated with long term use of heparin and why?

Answer 56

Osteoporosis - heparin interferes with osteoclast activity

Question 57

How can heparin be reversed?

Answer 57

Stop heparin - has short half life | Severe bleeding - protamine sulphate

Question 58

Does protamine sulphate completely reverse heparin?

Answer 58

Completely reverses unfractionated heparin | Partially reverses LMWH

Question 59

Where is vitamin K absorbed?

Answer 59

Upper intestine

Question 60

What is required for vitamin K absorption?

Answer 60

Bile salts (hence obstructive jaundice can cause vitamin K deficiency)

Question 61

Why is calcium required in haemostasis?

Answer 61

Activation of fibrin clot

Question 62

How is INR calculated?

Answer 62

(patients PT time/mean normal PT)^ISI

Question 63

How can bleeding on warfarin be reversed?

Answer 63

Give Vit K - 6 hours | Give clotting factors - immediate

Question 64

What are rivaroxiban and apixiban?

Answer 64

Direct factor Xa inhibitors

Question 65

What is dabigatran?

Answer 65

Direct thrombin inhibitor