6. Clotting Disorders

Question 1

What are the two sections of the clotting pathway?

Answer 1

1) Extrinsic Section

2) Intrinsic Section

Question 2

What happens in the extrinsic pathway of the clotting cascade?

Answer 2

Tissue factor (TF) is released from damaged endothelial cells of vessel walls, and it activates factor VII.

Question 3

What happens in the intrinsic pathway of the clotting cascade?

Answer 3

Pre-Kallikrein (PK) and high molecular weight Kininogen (HK) activate factors XI and XII

Question 4

What do the activated factors of the intrisic and extrinsic pathway do?

Answer 4

They activate factor Xa

Question 5

What are the activated factors of the intrinsic and extrinsic pathway?

Answer 5

Intrinsic - XI and XII

Extrinsic - VII

Question 6

What does factor Xa do in the clotting cascade once it is activated?

Answer 6

Activated Xa goes on to activate thrombin, which in turn then forms fibrin, forming the fibrin clot.

Question 7

What system is activated once a fibrin clot is produced? What effect does this have?

Answer 7

The plasmin and plasminogen system is activated, so the body begins to dissolve the clot.

Question 8

Which test measures the extrinsic pathway?

Answer 8

Prothrombin time

Question 9

Which test measures the intrinsic pathway?

Answer 9

APTT

Question 10

Which test measures the common pathway?

Answer 10

Thrombin Time (TT)

Question 11

In a simple view, what is the extrinsic pathway? ie. x → y → z

Answer 11

TF → VIIa → Xa

Question 12

In a simple view, what is the intrinsic pathway? ie. x → y → z

Answer 12

IX - XII → VIIIa → Xa

Question 13

In a simple view, what is the common pathway? ie. x → y → z

Answer 13

Xa → Thrombin

Question 14

What does a coagulation screen consist of?

Answer 14

• Prothrombin Time (PT)
• Activated Partial Thromboplastin Clotting Time (APTT)
• Fibrinogen Level (Fibrinogen)

Question 15

What are the common causes of a prolonged prothrombin time (PT)? What else prolongs it?

Answer 15

COMMON

• Warfarin - This is especially the case in elderly patients
• VII deficiency

OTHERS

• II deficiency
• V deficiency
• X deficiency

Question 16

What are the causes of a prolonged Activated Partial Thromboplastin Clotting Time (APTT)?

Answer 16

• Heparin
• VIII deficiency
• IX deficiency
• XI deficiency
• XII deficiency (but there’s no bleeding or abnormal bruising)
• Von Willebrand’s Disease

Question 17

A deficiency in which clotting factor causes an increased APTT but no bleeding or abnormal bruising?

Answer 17

Factor XII

Question 18

What conditions do you need to think of if there is a prolonged PT and APTT?

Answer 18

If both the PT and APTT are prolonged, then you need to think of abnormalities of multiple coagulation factors, which often include vitamin K deficiency, disseminated intravascular coagulation (DIC), heparin toxicity and rarely severe deficiencies of factor V and X

Question 19

What components are required in order to make a diagnosis of a bleeding disorder?

Answer 19

• Personal History of Bleeding
• Family history of Bleeding
• Supportive Laboratory Tests

Question 20

If you suspect someone has a bleeding disorder, what would you expect to find in their personal history of bleeding?

Answer 20

• Bruising in unexpected places, without an injury
• Frequent epistaxis (nosebleeds) which last longer than 30 minutes each time
• GI bleeds (consider from mouth all the way down to anus)
• Long menstrual bleeding duration
• Haematuria
• Postpartum haemorrhage (PPH) in women who were pregnant

Question 21

What is the proper name for nose bleeds?

Answer 21

Epistaxis

Question 22

What part of a patients personal bleeding history would steer you away from diagnosing a bleeding disorder?

Answer 22

If they have had a previous surgery (ie. appendicectomy) and a few teeth removed without significant bleeding

Question 23

If someone says they have a family history of bleeding, what do you need to do?

Answer 23

You need to verify the information of it. Try to get details of

• where they were tested
• who tested them
• when they were tested

This is because patients can often get details wrong, and you shouldn’t solely rely on their word.

Question 24

What are the 3 main sections that you want to test for in someone with a suspected bleeding disorder

Answer 24

1. Platelets
2. Tests of Coagulation
3. Tests of Clot Stability

Question 25

What tests for the platelets do you want to do in someone with a suspected bleeding disorder?

Answer 25

• FBCs to see the amount of platelets, and whether they are anaemic
• Microscopy to see if there are any abnormalities of the platelets
• Platelet Function Analysis (PFA), this is sensitive enough to pick up all platelet disorders, but is good enough that we use it

Question 26

What are some microscopic abnormalities of the platelets?

Answer 26

Large platelets = Bernard Soulier Syndrome

Small platelets = Wiskott Aldrich Syndrome

Neutrophil Inclusions = May Hegglin Anomaly

Platelet Inclusions = Paris Trousseau / Jacobsen’s

Question 27

What is Bernard Soulier Syndrome?

Answer 27

Large platelets

Question 28

What is Wiskott Aldrich Syndrome?

Answer 28

Small platelets

Question 29

What is May Hegglin Anomaly?

Answer 29

Neutrophil Inclusions

Question 30

What is Paris Trousseau / Jacobsen’s?

Answer 30

Platelet Inclusions

Question 31

How do you test an individuals coagulation?

Answer 31

1 blood test send for a coagulation screen. It involves testing the;

• PT
• APTT
• TT
• Fibrinogen

Question 32

What should you do if the coagulation results show either a raised PT or APTT?

Answer 32

You should perform a 50/50 mixture test.

Question 33

What can a 50/50 mixture test show?

Answer 33

If the prolonged PT or APTT corrects = a factor deficiency

If the prolonged PT or APTT fails to correct = a factor inhibitor.

Question 34

How do you test the clot stability in individuals?

Answer 34

This is normally left to the haematologists to perform as they are very specialised and only appropriate for a small number of patients.