You review a 40 year old male with chest pain and shortness of breath. He had been admitted with a deep vein thrombosis in his right leg. His coagulation profile is shown below.
INR |
1 |
(0.9 TO 1.2) |
APTT |
61 seconds |
(24 to 39 sec) |
PT |
11.5 seconds |
(10.5 to 13.5 sec) |
A. List 5 causes of the abnormality in the coagulation profile
B. List 5 tests that could differentiate the cause of this abnormality
College Answer
A. List 5 causes of the abnormality in the coagulation profile
Heparin
Lupus inhibitor
Haemophilia A & B
Factor xii deficiency
Factor xi deficiency
Von Willebrands disease
Artefactual (incorrect amount of blood in the tube.)
B. List 5 tests that could differentiate the cause of this abnormality
Repeat test
Heparinase assay or antibodies
Mixing test
Thrombin time and reptilase time
Factor assay
Anti-cardiolipin antibody
Discussion
This is another "What is the cause of an isolated APTT elevation" question.
The abnormal coagulation studies page deals with this in greater detail.
The approach to a patient wth abnormal coags can be summarised in the form of a table:
Normal PT | Raised PT | |
Normal APTT |
|
Extrinsic pathway failure
|
Raised APTT |
Intrinsic pathway failureFactor deficiency or anticoagulant factor? This is answered by mixing studies.
|
Intrinsic and extrinsic pathway failure
|
In brief, the raised APPT could be caused by either an anticoagulant factor, or by a deficiency of the factors involved in the intrinsic or final common pathway.
Thus, it could be any of the following:
- Anticoagulant factor:
- Antiphospholipid antibodies
- Heparin therapy
- Heparin-like anticoaguants (malignancy)
- Low fibrinogen
- Functionally abnormal fibrinogen
- Paraproteinaemia
- Excessive fibrin degradation products
- Factor deficiency
- von Willebrand's disease (de facto Factor 8 deficiency)
- Factor 8 deficiency (Haemophilia A)
- Factor 9 deficiency (Haemophilia B)
- Factor 11 deficiency (Haemophilia C, 8% of Ashkenazi Jews)
- Factor 12 deficiency (which is freakishly rare, and usually totally asymptomatic)
The tests one would wish to perform?
- Mixing studies
- Thrombin time
- Reptilase time
- Heparinase assay: detects the influence of heparin
- Fibrinogen level
- Individual factor assays
In their answer, the college also intelligently suggest that you repeat the APTT, as it could all be an artifact of sampling.
References
Hunt, Beverley J. "Bleeding and coagulopathies in critical care." New England Journal of Medicine 370.9 (2014): 847-859.