A 52-year-old female presents with bruising and a retroperitoneal haematoma five weeks after starting warfarin for a proximal deep vein thrombosis (DVT) with a target international normalised ratio (INR) of 2.5.
Her investigations are as follows:
Parameter |
Patient Value |
Normal Adult Range |
|
Haemoglobin White Cell Count |
122 q/L* |
135 - 180 |
|
10.1 x 109/L |
4.0 - 11.0 |
||
Platelets |
298 x 109/L |
150 - 400 |
|
Prothrombin time |
29.3 sec* |
12.0 - 16.5 |
|
International normalised ratio |
2.3* |
0.9 - 1.3 |
|
Activated partial thromboplastin time |
117.0 sec* |
27.0 - 38.5 |
|
Fibrinogen |
3.9 a/L |
2.0 - 4.0 |
a) Give the likely underlying cause for this coagulation profile. (20% marks)
b) Give a test you could do to confirm this. (15% marks)
a) Factor deficiency - either VIII, IX, XI or XII
b)
Mixing study (patient plasma mixed with normal plasma 1:1 should show correction of APTT if case of factor deficiency).
Factor levels.
a)
This patient has an appropriate therapeutic INR, and an unexplains raised APTT. The college asks for the "likely underlying cause", as if there was only one possibility.
Causes of raised APTT are in fact numerous, and can be divided into factor deficiencies and factor inhibitors:
Haemophilia among women is freakishly rare, requiring both X chromosomes to be affected, which makes half of that list rather implausible. This patient has no reported history of lupus, but this whole history of a proximal DVT raises the possibility of antiphospholipid syndrome, which could result in a raised APTT with a relatively normal warfarinised PT. Nevermind that DOACs are the agent of choice to treat DVTs these days - but that does mean that one could make the conceptual leap and discuss direct thrombin inhibitor toxicity (as these might have been used to manage the DVT instead of warfarin).
b)
The ideal test would be a mixing study (to discriminate between the abovelisted differentials). However, the college did not want that- they asked for a test to "confirm the diagnosis" .
So:
Hunt, Beverley J. "Bleeding and coagulopathies in critical care." New England Journal of Medicine 370.9 (2014): 847-859.
Kamal, Arif H., Ayalew Tefferi, and Rajiv K. Pruthi. "How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults." Mayo Clinic Proceedings. Vol. 82. No. 7. Elsevier, 2007.