A Practical Guide to Haemostasis

Screening Tests:
Introduction & Bleeding Questionnaires

Haemostatic screening tests e.g. Prothrombin Time (PT) and the Activated Partial Thromboplastin Time (APTT) are frequently undertaken to establish whether an individual is at risk of bleeding for example in advance of surgery or an invasive procedure.  However, these tests can be misleading and can generate normal results even in individuals with significant derangements of haemostasis. The following cases illustrate this...

Case 1: The table below shows the results obtained from an individual with Type 1 Von Willebrands Disease scheduled for a total hip replacement and with a significant bleeding history. 

Test Result Reference Range
PT 13s 11-14s
APTT 32s 28-34s
Fibrinogen [Clauss] 3.9 g/L 1.9-3.7 g/L
FVIII 0.42 IU/mL 0.70-1.50 IU/mL
VWF:Ag 0.15 IU/mL 0.72-1.52 IU/mL
VWF:Act 0.16 IU/mL 0.72-1.52 IU/mL

The PT and APTT are normal and therefore as screening tests would be misleadingly reassuring. The APTT is sensitive to Factor VIII [FVIII] levels [in addition to other clotting factors] and in this individual although reduced, the reduction is too small to prolong the APTT.
This patient has Type 1 Von Willebrands Disease [vWD].

Case 2:
The table below shows the results obtained from 3-year-old boy who presented with an intra-cerebral haemorrhage. The Full Blood Count [FBC] was normal. The parents were first cousins.

Test Result Reference Range
PT 12s 11-14s
APTT 34s 28-34s
Fibrinogen [Clauss] 4.1 g/L 1.9-3.7 g/L
FXIII 0.05 IU/mL
[5 IU/dL]
0.60-1.30 IU/mL
[60-130 IU/dL]

The PT and APTT are normal and therefore as screening tests would be misleadingly reassuring. This child has moderately severe Factor XIII [FXIII] deficiency.  This would not be suggested by the screening tests and a FXIII assay must be requested.

Case 3:
The table below shows the results obtained from a 47-year-old male who gave a history of excess bleeding after circumcision and bleeding following dental surgery. His parents were first cousins and his brother died from uncontrolled haemorrhage following a road traffic accident and his sister from a 'stroke' aged 30yrs. The Full Blood Count [FBC] was normal. 

Test Result Reference Range
PT 13s 11-14s
APTT 35s 28-34s
Fibrinogen [Clauss] 2.95 g/L 1.9-3.7 g/L

The PT and APTT are normal and therefore as screening tests would be misleadingly reassuring.  The personal and family history suggests a bleeding disorder. In fact this patient has Glanzmann's Thrombasthenia - an inherited disorder of platelets that affects the GpIIb/IIIa complex. It is probable that his sister had an intra-cerebral haemorrhage and was similarly affected.

It is important to remember that laboratory screening tests are in vitro tests and may not necessarily reflect the underlying haemostatic mechanism.

The most important screening test in haemostasis is the patient’s personal bleeding history (if this can be considered a test); their use of anti-thrombotic drugs including anti-platelet agents; any over the counter [OTC] medications and whether there is any family history suggestive of an inherited bleeding disorder.  Ordering a screening test before taking a thorough history, constructing a pedigree and examining the patient is inappropriate.

Nevertheless, the tests that are commonly used as screening tests are:
         - Prothrombin Time (PT)
         - Activated Partial Thromboplastin Time (APTT)
The Fibrinogen concentration and Thrombin time are not generally considered first-line screening tests although a Fibrinogen assay is commonly performed.
It is important that the Platelet count is checked in any patient undergoing haemostatic investigations.

Structured Bleeding State Questionnaires

Mild bleeding events are commonly reported by patients both with and without inherited bleeding disorders, making it difficult for haematologists to define what constitutes a significant bleeding history.
The use of a structured bleeding state questionnaire has been validated in Type 1 VWD and in patients referred for investigation of a suspected bleeding disorder [see References] and these are invaluable in the assessment of an individual with a possible bleeding disorder. Similar schemes have been proposed for the assessment of possible bleeding disorders in children - see references.  The use of a Bleeding Assessment Tool [BAT] helps to identify individuals who require further investigation.  In a significant number of cases, patients may have an elevated bleeding score but laboratory investigations may demonstrate no abnormalities. Such individuals are frequently labelled as having an 'undiagnosed bleeding disorder.'  In this situation, screening for an underling genetic mutation can be invaluable.

These questionnaires are not designed to assess the risk of bleeding in patients about to start anticoagulants e.g. HAS-BLED score.  This is covered elsewhere on the site.

In the UK the National Institute for Health & Care Excellence (NICE) and the British Society of Haematology (BSH) have both addressed the value of screening tests in haemostasis - see references.

For additional information on Bleeding Risk Algorithms - click HERE.

For a diagnostic approach to the investigation of a patient with a mild bleeding disorder - see References - Boender et al 2016.