The college loves coagulopathy, and the number of questions concerned with the interpretation of coagulation studies is only exceeded by the cardiology ECG questions and arterial blood gases.
The following is a list of SAQs on the theme of “What’s wrong with these coags?”
This is a fascinating topic, and one which has surprising amount of herpetology in it. A more indepth discussion of the reptilian contribution to coagulation tests is available elsewhere. Also, there is an excellent article which details a stepwise approach to the coagulopathic patient, and the manner in which the diagnosis of an isolated coagulation abnormality should be approached. An even greater depth of explanation (and more detailed references) can be found at Practical-Haemostasis.com.
A summary of the evaluation of a patient with prolonged bleeding time can be tabulated for easy digestion. This table is initially based on a similar (and better) table from a recent NEJM article, Bleeding and coagulopathies in critical care by Beverley Hunt.
|Normal PT||Raised PT|
Thus: perform platelet function studies or go straight for TEG / ROTEM
Extrinsic pathway failure
Intrinsic pathway failure
Factor deficiency or anticoagulant factor? This is answered by mixing studies.
Intrinsic and extrinsic pathway failure
These would be rare. Essentially, this list of differentials is limited to situations which for one reason or another diminish the availability of Vitamin K for clotting factor synthesis
Is it a true deficiency of vitamin K dependent factors, or are the factors present and merely inactive to to a lack of carboxylation? One can use another snake for this. Echis carinatus is a venomous viper from the Middle East, and it happens to secrete a venom which can bypass the vitamin K dependent clotting factors to activate prothrombin. In severe liver disease, there is not enough thrombin being synthesis, and the ECT will be prolonged; but during warfarin therapy the ECT should be normal, as it bypasses the defective factors.
APTT - but not PT - will increase if , or if there is an inhibition of the intrinisic pathway.
The causes include factor deficiencies:
So, is it a factor deficiency, or is it a factor inhibitor? One performs mixing studies when one tries to distinquish one from the other.
Mixing studies distinguish between factor deficiencies and factor inhibitors.
Lets say your sample of plasma is giving a high PT or aPTT - grab your suspicious plasma sample, and mix it with normal blood, 50:50. Obviously, if some sort of "factor inhibitor" is present, the normal blood will also be affected, and the resulting mixture will give abnormal aPTT and PT results. If there is a factor deficiency, the mixed sample will result in a normal PT or aPTT.
An abnormal mixing study result implies that in spite of the addition of normal plasma, the coagulopathy persists. This suggests that a factor inhibitor is present. The objective of further investigations is to figure out what is being inhibited, and how.
The three major candidates:
Thus, one may wish to go though the following steps:
Normal mixing studies (i.e. a coagulopathy totally reversed by the addition of enough normal plasma) suggest that a factor deiciency of some sort if present.
Sensibly, one would proceed from here by performing a factor assay.
THE APTT WILL NOT PICK UP FACTOR VII DEFICIENCY. Additionally, even if you have 50% less of any given factor, your PT and aPTT should remain roughly normal, so subtle deficiencies would not be identified by APTT or mixing studies. One would need to perform a formal factor assay. This means, ordering specific factor levels.
This is a situation when everything is abnormal. The PT, the APTT, the fibrinogen level - everything is disturbed.
This pan-coagulation disturbance occurs in the following scenarios:
For this sort of really basic stuff, no matter where you look you will find essentially the same information.
I used chapters from From "William Hematology" by Lichtman et al, especially chapter 115 by Monroe III
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.
DeMuro, J. P., and A. F. Hanna. "Trauma Induced Coagulopathy: Prevention and Intervention."Scand J Trauma Resusc Emerg Med 20.47 (2014): 4.
White, Julian. "Snake venoms and coagulopathy." Toxicon 45.8 (2005): 951-967.
Kashuk, Jeffry L., et al. "Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma." Annals of surgery 252.3 (2010): 434-444.
De Stefano, Valerio, Guido Finazzi, and Pier Mannuccio Mannucci. "Inherited thrombophilia: pathogenesis, clinical syndromes, and management [see comments]." Blood 87.9 (1996): 3531-3544.
Hunt, Beverley J. "Bleeding and coagulopathies in critical care." New England Journal of Medicine 370.9 (2014): 847-859.
Stein, Eytan, et al. "The coagulopathy of acute promyelocytic leukaemia revisited." Best practice & research Clinical haematology 22.1 (2009): 153-163.