Bleeding Disorders Laboratory Approach
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Direct answer
Bleeding disorders are localised by pairing the prothrombin time (PT) and activated partial thromboplastin time (aPTT) with the platelet count and bleeding time, then confirming the defect with a mixing study. A prolonged PT points to the extrinsic pathway and factor VII, while a prolonged aPTT points to the intrinsic pathway. A normal PT and aPTT with a prolonged bleeding time suggests a platelet or von Willebrand defect.
What you must remember
- PT: tests the extrinsic and common pathways, using factor VII, and is prolonged by warfarin, liver disease and vitamin K deficiency; the INR standardises it.
- aPTT: tests the intrinsic and common pathways, covering factors VIII, IX, XI and XII, and is prolonged by heparin, haemophilia and lupus anticoagulant.
- Bleeding time: reflects platelet function but is operator-dependent, so platelet function analysers such as PFA-100 are now preferred.
- Mixing study: immediate correction indicates a factor deficiency, while failure to correct, especially after incubation, suggests an inhibitor.
- Platelet count: spontaneous bleeding is typically seen below about 20,000 per microlitre, while surgery usually needs a higher count.
- Haemophilia A and B: X-linked recessive, with factor VIII or IX assays identifying the deficient factor; an inhibitor screen is needed when correction fails.
- Von Willebrand disease: low ristocetin cofactor activity with a prolonged bleeding time, and factor VIII is often secondarily reduced.
A worked case: haemarthrosis in a child
An 8-year-old boy has recurrent knee bleeds after minor trauma, with a normal PT and platelet count, a prolonged aPTT and a normal bleeding time. A mixing study corrects immediately, and the factor VIII assay returns under 1 percent of normal, which is severe haemophilia A, an X-linked condition needing factor replacement on bleeding.
| Pattern | Likely cause | Next test |
|---|---|---|
| Prolonged PT, normal aPTT | Extrinsic pathway, factor VII | Review warfarin use, liver function and vitamin K status |
| Prolonged aPTT, corrects on mixing | Factor deficiency such as haemophilia A | Specific factor VIII or IX assay |
| Prolonged aPTT, fails to correct | Inhibitor, including lupus anticoagulant | Inhibitor screen and dilute Russell viper venom time |
| Normal PT and aPTT, prolonged bleeding time | Platelet function defect or von Willebrand disease | Platelet function analyser and von Willebrand studies |
Read the table from the top: the PT and aPTT localise the pathway, and the mixing study separates a deficiency from an inhibitor. Bleeding time is an old and insensitive test, so examiners increasingly expect the answer to say so. A normal result does not exclude a clinically significant platelet defect.
Where the examiner sets the trap
Several traps arise when a normal or prolonged result is read at face value.
- Trap: reading a prolonged aPTT as a bleeding risk. Correct: lupus anticoagulant prolongs the aPTT in the test tube but is linked with thrombosis rather than bleeding, so a dilute Russell viper venom time is the check.
- Trap: accepting a normal PT and aPTT as reassurance. Correct: platelet function defects give normal coagulation tests, so the bleeding time or platelet function analyser is needed.
- Trap: labelling a factor deficiency without checking the sample. Correct: heparin contamination of a sample prolongs the aPTT, so the sampling route is confirmed before a factor deficiency is labelled.
Frequently asked questions
What does a prolonged aPTT with a normal PT suggest?
A prolonged aPTT with a normal PT points to an intrinsic pathway defect such as haemophilia A or B, factor XI deficiency or von Willebrand disease, or to heparin effect or lupus anticoagulant. A mixing study and specific factor assays then localise the cause.
How does a mixing study distinguish a factor deficiency from an inhibitor?
When patient plasma is mixed with normal plasma, a factor deficiency corrects immediately, while an inhibitor fails to correct, especially after incubation. Failure to correct requires an inhibitor screen, and a Bethesda assay quantifies a factor VIII inhibitor.
Why is bleeding time less useful than it used to be?
Bleeding time is operator-dependent and insensitive, so platelet function analysers such as PFA-100 are preferred for screening platelet function. A normal result does not exclude a clinically significant platelet defect.
Does a prolonged aPTT always indicate a bleeding risk?
No, lupus anticoagulant prolongs the aPTT in vitro but is associated with thrombosis rather than bleeding. A prolonged aPTT without a bleeding history should be checked with a dilute Russell viper venom time before a bleeding disorder is diagnosed.