Bleeding Disorders

Question 1

Components of the normal haemostatic system?

Answer 1

Formation of the platelet plug (AKA primary haemostasis)

Formation of the fibrin clot (AKA secondary haemostasis)

FIbrinolysis - degradation of clots

Anti-coagulant defenses - switch off secondary haemostasis, e.g: PC, PS, anti-thrombin

Question 2

Issues that may occur with platelet plug formation?

Answer 2

Commonly, unwanted platelet aggregation leads to arterial thrombosis

Bleeding disorders may also occur

Question 3

Causes of a failure of platelet lug formation?

Answer 3

The following are all components of primary haemostasis:
• Vascular
• Platelets - reduced number (thrombocytopaenia) OR reduced function
• vWF

Question 4

Causes of vascular abnormalities?

Answer 4

Hereditary, e.g: Marfan’s

Acquired (more common)
• Vasculitis, e.g: Henoch-Schonlein Purpura (HSP) in children

Question 5

Causes of thrombocytopaenia?

Answer 5

Hereditary

Acquired:
• Reduced production (marrow problem)
• Increased destruction

Question 6

Causes of peripheral platelet destruction?

Answer 6

Coagulopathy, e.g: DIC

Autoimmune, e.g: Immune Thrombocytopaenic Purpura (ITP)

Hypersplenism

Question 7

Causes of platelet functional defects?

Answer 7

Hereditary

Acquired:
• Drugs, e.g: aspirin, NSAIDs (alter platelet function)
• Renal failure

Question 8

Causes of vWF deficiency?

Answer 8

Acquired (rare)

Hereditary - common, as it is autosomal dominant; it has variable severity, although it is generally mild and presents as:
• Menorrhagia (in females)
• Prolonged bleeding following a dental extraction

Question 9

What is the most common cause of primary haemostatic failure?

Answer 9

Thrombocytopaenia

It is usually acquired and causes include:
• Marrow failure
• Peripheral destruction

Question 10

Symptoms and signs of HSP?

Answer 10

Purpuric rash and potentially GI bleeding

PLTs are normal and coagulation screen normal

It is self-limiting and is a diagnosis of exclusion

Question 11

Symptoms that patients experience when there is a failure of primary haemostasis?

Answer 11

Purpura (usually visible on lower limbs due to effects of gravity)

Mucosal lesions

Fundal haemorrhages

Question 12

Causes of a failure of fibrin clot formation?

Answer 12

Multiple clotting factor deficiencies - usually acquired, e.g:
• Liver failure
• Vitamin K deficiency / warfarin therapy
• Complex coagulopathy (DIC)

Single clotting factor deficiency - usually hereditary, e.g: haemophilia

Question 13

Lab features of multiple factor deficiencies?

Answer 13

Prolonged prothrombin time (PT)

AND

Prolonged activated partial thromboplastin time (APTT)

Question 14

Synthesis of coagulation factors?

Answer 14

All coagulation factors are synthesised in hepatocytes; this is reduced in liver failure

Question 15

Function of vitamin K?

Answer 15

Carboxylates factors II, VII, IX and X, which is essential for their function

Question 16

Sources of vitamin K?

Answer 16

Diet

Intestinal bacteria

Question 17

Absorption of vitamin K?

Answer 17

Occurs in the upper intestine and, as vitamin K is fat-soluble, it requires bile salts for absorption

Question 18

Causes of vitamin K deficiency?

Answer 18

Poor dietary intake

Malabsorption

Obstructive jaundice (reduced bile salts in upper intestine)

Vitamin K antagonists, like WARFARIN

Newborns - administer IM vitamin K at birth to reduce the risk of haemorrhagic disease of the newborn

Question 19

What is DIC?

Answer 19

Excessive and inappropriate activation of the haemostatic system, inc:
• Primary haemostasis
• Secondary haemostasis
• Fibrinolysis (to degrade the clots)

This leads to thrombus formation in the microvasculature and end-organ failure

It also consumes all the clotting factors

Question 20

Symptoms and signs of DIC?

Answer 20

Symptoms of end-organ failure

Bruising, purpura and generalised bleeding (due to clotting factor consumption)

Question 21

Lab results with DIC?

Answer 21

Prolonged PT and APTT (multiple clotting factor deficiency)

AND

Increased FDPs, e.: D-dimers

Question 22

Causes of DIC?

Answer 22

Anything that causes a lot of tissue damage, as this exposes collagen, e.g:
• Sepsis
• Obstetric emergencies
• Malignancy
• Hypovolaemic shock

Question 23

Management of DIC?

Answer 23

Treat underlying cause

Replacement therapy:
• Platelet transfusions
• Plasma transfusions
• Fibrinogen replacement (cryoprecipitate)

NOTE - cryoprecipitate is where frozen plasma is thawed and factor VIII and fibrinogen are removed and given to the patient

Question 24

What is haemophilia?

Answer 24

X-linked hereditary disorder in which abnormally prolonged bleeding recurs episodically at 1 or a few sites on each occasion

It affects secondary haemostasis, with no abnormality of primary haemostasis

Patients bleeding from medium-large blood vessels

Question 25

Types of haemophilia?

Answer 25

Haemophilia A (much more common) - factor VIII deficiency Haemophilia B - factor IX deficiency

Question 26

Occurrence of haemophilia?

Answer 26

Males are affected Haemophilia A is 5x more common Families can be mildly, moderately and severely affected, depending on factor VIII/IX levels

Question 27

Symptoms and signs of haemophilia?

Answer 27

Recurrent haemarthroses (bleeding into joints) Recurrent soft tissue bleeds (into muscles); this can cause bruising in toddlers Prolonged bleeding after dental extractions, surgery and invasive procedures NOTE - as primary haemostasis is unaffected, paper cuts are fine

Question 28

Lab features of haemophilia?

Answer 28

Isolated prolonged APTT (single factor deficiency of either factor VIII or IX

Question 29

Why are the joints of children with haemophilia undamaged nowadays?

Answer 29

Can replace the deficient factor, which has been created using recombinant technology