6. Clotting Disorders Flashcards
What are the two sections of the clotting pathway?
1) Extrinsic Section
2) Intrinsic Section
What happens in the extrinsic pathway of the clotting cascade?
Tissue factor (TF) is released from damaged endothelial cells of vessel walls, and it activates factor VII.
What happens in the intrinsic pathway of the clotting cascade?
Pre-Kallikrein (PK) and high molecular weight Kininogen (HK) activate factors XI and XII
What do the activated factors of the intrisic and extrinsic pathway do?
They activate factor Xa
What are the activated factors of the intrinsic and extrinsic pathway?
Intrinsic - XI and XII
Extrinsic - VII
What does factor Xa do in the clotting cascade once it is activated?
Activated Xa goes on to activate thrombin, which in turn then forms fibrin, forming the fibrin clot.
What system is activated once a fibrin clot is produced? What effect does this have?
The plasmin and plasminogen system is activated, so the body begins to dissolve the clot.
Which test measures the extrinsic pathway?
Prothrombin time
Which test measures the intrinsic pathway?
APTT
Which test measures the common pathway?
Thrombin Time (TT)
In a simple view, what is the extrinsic pathway? ie. x → y → z
TF → VIIa → Xa
In a simple view, what is the intrinsic pathway? ie. x → y → z
IX - XII → VIIIa → Xa
In a simple view, what is the common pathway? ie. x → y → z
Xa → Thrombin
What does a coagulation screen consist of?
- Prothrombin Time (PT)
- Activated Partial Thromboplastin Clotting Time (APTT)
- Fibrinogen Level (Fibrinogen)
What are the common causes of a prolonged prothrombin time (PT)? What else prolongs it?
COMMON
- Warfarin - This is especially the case in elderly patients
- VII deficiency
OTHERS
- II deficiency
- V deficiency
- X deficiency
What are the causes of a prolonged Activated Partial Thromboplastin Clotting Time (APTT)?
- Heparin
- VIII deficiency
- IX deficiency
- XI deficiency
- XII deficiency (but there’s no bleeding or abnormal bruising)
- Von Willebrand’s Disease
A deficiency in which clotting factor causes an increased APTT but no bleeding or abnormal bruising?
Factor XII
What conditions do you need to think of if there is a prolonged PT and APTT?
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
What components are required in order to make a diagnosis of a bleeding disorder?
- Personal History of Bleeding
- Family history of Bleeding
- Supportive Laboratory Tests
If you suspect someone has a bleeding disorder, what would you expect to find in their personal history of bleeding?
- 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
What is the proper name for nose bleeds?
Epistaxis
What part of a patients personal bleeding history would steer you away from diagnosing a bleeding disorder?
If they have had a previous surgery (ie. appendicectomy) and a few teeth removed without significant bleeding
If someone says they have a family history of bleeding, what do you need to do?
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.
What are the 3 main sections that you want to test for in someone with a suspected bleeding disorder
- Platelets
- Tests of Coagulation
- Tests of Clot Stability
What tests for the platelets do you want to do in someone with a suspected bleeding disorder?
- 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
What are some microscopic abnormalities of the platelets?
Large platelets = Bernard Soulier Syndrome
Small platelets = Wiskott Aldrich Syndrome
Neutrophil Inclusions = May Hegglin Anomaly
Platelet Inclusions = Paris Trousseau / Jacobsen’s
What is Bernard Soulier Syndrome?
Large platelets
What is Wiskott Aldrich Syndrome?
Small platelets
What is May Hegglin Anomaly?
Neutrophil Inclusions
What is Paris Trousseau / Jacobsen’s?
Platelet Inclusions
How do you test an individuals coagulation?
1 blood test send for a coagulation screen. It involves testing the;
- PT
- APTT
- TT
- Fibrinogen
What should you do if the coagulation results show either a raised PT or APTT?
You should perform a 50/50 mixture test.
What can a 50/50 mixture test show?
If the prolonged PT or APTT corrects = a factor deficiency
If the prolonged PT or APTT fails to correct = a factor inhibitor.
How do you test the clot stability in individuals?
This is normally left to the haematologists to perform as they are very specialised and only appropriate for a small number of patients.
