Question 23.2

Examine the coagulation profile from a patient  in intensive care.



Normal Range

Prothrombin ratio (INR)


0.8 -1.2


65 sec

24 -39


240 x 109/L

150 - 400

Bleeding time

4 min

2 - 8


2.8 G/L

1.5 - 4.0


<10 mg/L

0 -10

a)  List 4 possible causes of this picture.

b)  List 4 further tests which you will perform to identify the cause of the coagulopathy  in question 23.2.

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College Answer

1)  Heparin
2)  Hemophilia A
3)  Hemophilia B
4)  Lupus anticoagulant

b)  List 4 further tests which you will perform to identify the cause of the coagulopathy  in question 23.2.

1)  Thrombin time
2)  Factor assay
3)  Anti-phospholipid antibody
4)  Reptilase test
5)  Mixing test


This is a patient with an isolated abnormality of the intrinsic pathway.

The differentials for such an isolated abnormality are discussed at great length in the chapter onabnormal coagulation studies.

In brief, the possible causes of an elevated APTT are as follows:

  • Heparin therapy
  • 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)
  • Antiphospholipid antibodies

Thus, to discriminate among all these causes, one would need to perform the following series of tests:

  • Mixing studies: excludes antophospholipid syndrome and heparin
  • Antiphospholipid antibodies
  • Factor assays

The college answer also asks for a thrombin time and a reptilase time.

In the coags pathology test chapter, these and the rest of the coagulation studies are briefly mentioned. A much better resource is, where these are discussed in greater detail.

In brief, thrombin time is a good test of the final common pathway.

It would not be affected by the absence of clotting factors (because the test itself involved dumping large amounts of thrombin into the sample). Thus, if thrombin time is completely normal and the APTT is still high, you can be confident that the fibrinogen is of normal quality, and that there is no exaggerated antithrombin-III effect (i.e. heparin is not to blame).

A reptilase time is a similar test, where instead of thrombin one uses some Botrox viper venom. This venom is not sensitive to the effects of heparin, and so the reptilase time would only ever be elevated in situations where the fibrinogen is low, or somehow abnormal, or there are abundant proteins to interfere with the process (eg. amyloidosis or paraproteinaemia).

In this case, if heparin was responsible for the raised APT, the thrombin time would be elevated, but the reptilase time would not.