Bleeding Disorders

Question 1

What can cause failure of primary haemostasis (i.e. the platelet plug)?

Answer 1

Vascular
- e.g. lack of collagen

Platelets
- Reduced number or function

Von Willebrand Factor

Question 2

What vascular abnormalities can cause failure of primary haemostasis?

Answer 2

Hereditary (weak collagen)

• Marfan’s
• Hyperflexibility Disorders

Acquired
Vasculitis
eg Henoch-Schonlein Purpura
(not actually problem with platelets, just leaky vessels)

Question 3

What can cause a reduced NUMBER of platelets?

Answer 3

Decreased production
- Bone marrow problem

Increased Destruction (caused by:)

• Disseminated Intravascular Coagulation (DIC)
• Immune Thrombocytopenic Purpura (ITP)
• Hypersplenism

Question 4

What can decrease platelet function?

Answer 4

Drugs (eg Aspirin, NSAIDs)
- this is often deliberate (antiplatelets used to prevent arterial thrombosis in at risk patients)

Renal failure
- uraemia can interfere with platelet function

Question 5

How is vWF deficiency normally inherited?

Answer 5

Autosomal dominant

Question 6

If platelets are being prematurely destroyed, production of platelets increases in the bone marrow to compensate. What would the blood film look like if this was the case?

Answer 6

Large platelets
(larger on Day 1 than Day 7)
=> more large platelets = increased production

Question 7

What are the main causes for failure of secondary haemostasis?

Answer 7

Multiple clotting factor deficiencies
- acquired (eg DIC)

Single clotting factor deficiency
- hereditary (eg Haemophilia)

Question 8

What are the potential causes for multiple clotting factor deficiencies?

Answer 8

• Liver failure (makes clotting factors)
• Vitamin K Deficiency/Warfarin therapy (Vit K antag.)
  [Factor II, VII, IX, X all rely on Vit K]
• Complex coagulopathy
• DIC

Question 9

Why may a platelet transfusion not be useful in patients who have increased destruction due to an autoimmune cause?

Answer 9

platelets will be destroyed by autoantibodies soon after they are given
- instead steroids should be used to suppress immune system and Ab

• platelet transfusion may be more useful if marrow failure

Question 10

If multiple clotting factors are affected, will PT or APTT be abnormal?

Answer 10

Both will be prolonged

Question 11

Where do we find vitamin K and how is it absorbed?

Answer 11

• Diet (green leafy veg)
  BUT can also be produced by bacteria in gut
• Absorbed in upper intestine
• Requires bile salts for absorption

Question 12

What can cause a vitamin K deficiency?

Answer 12

• Poor dietary intake
• Malabsorption
• Obstructive jaundice
• Vitamin K antagonists (warfarin)
• Haemorrhagic disease of the newborn (lack of vit K as none in breast milk, and not enough bacteria in bowel)

Question 13

WHat is disseminated intravascular coagulation?

Answer 13

• activation of clotting EVERYWHERE
• Primary and secondary haemostasis and fibrinolysis
• Microvascular thrombus formation => end organ failure
• Clotting factors used up
  => Bruising, purpura

Question 14

Using up all clotting factors has what effect on PT and APTT?

Answer 14

Prolonged (as body takes longer to clot if it cant find clotting factors)

Question 15

Which of PT and APTT is first to become abnormal in DIC?

Answer 15

PT first as Factor VII has shortest T1/2

Question 16

What can potentially cause DIC?

Answer 16

• sepsis
• obstetric emergencies
• malignancy (chronic rather than rapid DIC)
• hypovolaemic shock

Question 17

WHat types of malignancy are thought to cause DIC?

Answer 17

Adenocarcinomas

=> bowel or prostate cancers common

Question 18

HOw is DIC treated?

Answer 18

• Treat the underlying cause
• Replacement therapy
  Platelet / Plasma transfusions
  Fibrinogen replacement (especially if obstetric emergency)

Question 19

How is haemophilia inherited and which of Haemophilia A/B is more common?

Answer 19

X-linked Recessive
=> females carriers and males affected
females can be affected if inherit carrier gene and then gain another new mutation in utero

Haemophilia A 5x more common than Haemophilia B

Question 20

What symptoms are usually experienced by patients with haemophilias?

Answer 20

• bleeding from medium to large vessels
  i. e. into joints/ muscles
• Prolonged bleeding after dental extractions, surgery and invasive procedures

Question 21

Why are haemophilia patients more likely to get recurrent joint bleeds?

Answer 21

• inflammation of synovium from initial joint bleed causes neovascularisation (new fragile blood vessels form)
• these can then rupture and cause problems in the joint again

Question 22

What happens to the PT and APTT in haemophilia?

Answer 22

PT normal

APTT prolonged

Question 23

What treatment can be given to patients with haemophilia?

Answer 23

Factor VIII or IX concentrate to replace missing clotting factor

IV clotting factor VIII given every 2 days to start with (due to short T1/2)

• often treatment starts when children start weight bearing on joints as this is when the joint bleeds start (Age 1 or 2)