Haematology (clotting)

Question 1

What does an activated partial thromboplastin time (APTT) 50:50 test check for?

Answer 1

Tests for the cause of increased prothrombin/activated prothrombin time.

1. Mix the subject blood plasma with normal blood plasma.
2. The normal blood is a source of factors.

3.If APTT (or PT) are corrected by this:
There is a factor deficiency in the subject blood

4. If there is no change In APTT/PT:
   There are factor inhibitors present in the subject blood

(e.g. heparin, antiphospholipid antibodies or coagulation factor specific inhibitors)

Question 2

Which pathway of the coagulation system does Prothrombin time (PT) look at?

Answer 2

The extrinsic pathway (Tissue; extrinsic to the blood).
Faster clotting time than APTT: 10-12 seconds.
(Since a cut needs faster clotting than an internal clot).

MOA: Excess tissue factor is added to plasma sample.

This is made up of two features:

Tissue factor (exposed by damage to epithelium)
Factor 7

MOA: TF activates factor 7

• > Activates factor 10 of the common pathway
• > Activates prothrombin: fibrin is produced

Question 3

Which pathway of the coagulation system does activated partial thromboplastin time (APTT) look at?

Answer 3

The intrinsic pathway (within the blood).
Slower clotting time than PT: 20-30 seconds
(Since a cut needs faster clotting than an internal clot)

MOA: Intrinsic pathway is triggered by silica, so only the intrinsic pathway is activated.

This is made up of three factors:

Factor 9
Factor 12
Factor 8

MOA: Factor 9 activates factor 12

• > Activates factor 8
• > Activates factor 10 of the common pathway
• > Activates prothrombin: fibrin is produced

Question 4

Which factors/drugs can prolong prothrombin time?

Extrinsic pathway

Answer 4

Warfarin

Factors:
7
2
5 
10

Question 5

Which factors/drugs can prolong activated partial thromboplastin time but leave PT time normal?

(Intrinsic pathway)

Answer 5

Heparin

Unless it causes heparin toxicity: then it will also prolong PT.

Factors:
12
8
9
11
Von willebrand factor

Question 6

What does the thrombin time (TT) test?

Answer 6

TT tests the common pathway (but not factor 10 and factor 5): Thrombin on until fibrin formation.

MOA: An excess of thrombin (Factor 2) is added to a sample and the resultant speed of clot formation is measured. (Extrinsic and intrinsic pathways are bypassed entirely, clot is entirely dependent on fibrinogen level ONLY)

Long TT = fibrinogen deficiency or dysfunctional fibrinogen

Question 7

What can give a prolonged PT and APTT but leave the TT normal?

Answer 7

Heparin toxicity (normal heparin dose will only prolong APTT)

Factor 10 deficiency

Factor 5 deficiency

Vitamin K deficiency - liver disease or malabsorption (causes all deficiency of factors 2, 7, 9, 10)

(Vitamin K is the cofactors necessary for carboxylating a glutamic acid residue and activating prothrombin to thrombin)

Question 8

What can cause increased PT, increased APTT and increased TT?

Answer 8

Disseminated intravascular coagulation (DIC)

Explanation: The TT is the most important since it means low fibrinogen, if we have low fibrinogen then the PT and APTT will be long, since ALL of the tests can’t be faster without enough fibrinogen.

Question 9

Which tests can be run for a suspected bleeding disorder?

(Think: what components do you need for a clot? Are there enough of them? Are they functioning?

Answer 9

1. FBC - platelet number
2. Microscopy - platelet shape
3. Platelet function assay - platelet function
4. Prothrombin time - Extrinsic; TF and Factor 7
5. Activated partial thrombin time - Intrinsic; Factors 9, 12 and 8
6. Thrombin time - Fibrinogen presence/ dysfunction
7. Factor 8 and VwF assay - bound together

Question 10

Which clinical prediction model is used for quantifying VTE risk?

Answer 10

The wells score.

Predicts likelihood and risk of DVT or PE, each condition has its own set of criteria.

Does not apply to pregnant women, they were not included in the studies used to create the scoring system.

Question 11

What are the scoring signs/risk factors that contribute to a wells score for DVT?

Answer 11

Active cancer

Recent immobilisation

Localised calf tenderness

Entire leg swollen or Calf swelling >3cm

Unilateral pitting oedema (painless DVT)

Previous DVT

Collateral superficial veins

Question 12

What are the scoring signs/risk factors that contribute to a wells score for PE?

Answer 12

HR is >100

More than 3 days recent immobilisation

Previous DVT or PE (remember, DVT is a source of PE but PE isn’t a source of DVT)

Haemoptysis

Malignancy

Question 13

What is the diagnostic pathway for DVT and PE?

Answer 13

Clinical signs suggest DVT/PE:

1. Calculate Wells score - decides next action
2. If High probability: Imaging
   DVT: USS Doppler of lower limb
   PE: CT pulmonary angiogram (CTPA)
3. If low probability: D-dimer test
4. If D-dimer is negative: no VTE
5. If D-dimer is positive: Imaging
   DVT:-USS Doppler of lower limb
   PE:- CT pulmonary angiogram of lungs

Question 14

What is a D-Dimer test?

Answer 14

A test for D-fragments of fibrin protein, these are fibrin degradation products, and confirm clot presence.

You cannot have D-fragments without a clot present, so it is a very sensitive test.

Has low specificity but high sensitivity: risk of false negatives but no risk of false positives.

Infection is likely to cause a false positive since there will be clotting as a part of normal immune function.

Question 15

What is the diagnostic pathway for Von willebrands disease?

Answer 15

1. Positive bleeding history

2. Initial haemotology tests:
FBC
APTT
PT
TT or Fibrinogen level

3. APTT is normal or prolonged (Intrinsic pathway, bound to factor 8) but corrects on APTT 50:50 (since VWF have been replaced)
4. VWF assays

Question 16

What is the diagnostic pathway for haemophilia?

Answer 16

1. Positive bleeding history and often a positive family history of haemophilia

2. Initial haemotology tests:
FBC (rule out thrombocytopenia)
APTT
PT
TT or Fibrinogen level

3. APTT is prolonged (Intrinsic pathway, factors 8 and 9) and corrects on APTT 50:50 (since the factors 8 and 9 have been replaced)
4. VWF assays to exclude VWF disease
5. Factor 8 and 9 assays confirm the diagnosis

Question 17

If both APTT and PT are prolonged, which factors could be the cause?

Answer 17

Factor 5 (stabilises active factor 10)

Factor 10

Prothrombin (factor 2)

Question 18

What is the most likely cause of prolonged PT with normal APTT in a person who is not on warfarin?

Answer 18

Factor 7 deficiency