Prothrombin time test is used for the monitoring of warfarin but not heparin. Why is this used for warfarin monitoring and why is it not used for heparin monitoring?


Thats because the mechanism of action is different between warfarin and heparin. Warfarin inhibits the formation of prothrombin (also known as factor II) by inhibiting the metabolization of vitamin K (for extensive details have a look at the Wikipedia article about Warfarin).

Heparin inhibits the blood coagulation by binding to antithrombin III which functions as a inactivator of active clotting factors as factors V, IX, X, XI and XII. It also binds calcium which is important for the blood coagulation. For more details see the Wikipedia under Heparin.

Therefore Heparin interferes with the formation of Thrombin and the test does not work. A nice image of the coagulation cascade can be found here, which also shows the points where Heparin interferes. The test can be done with Batroxobin, see here.

  • $\begingroup$ So, heparin stops the formation of thrombin and warfarin stops the formation of prothromibin. But i still don't get it that why is PT test not used for heparin monitoring? $\endgroup$
    – Rafique
    Jan 4 '14 at 20:57
  • $\begingroup$ Because you can measure how much thrombin activity is left when the synthesis is inhibited (for warfarin), but when it can't be activated (for Heparin), you will not measure anything. You don't knock-down coagulation completely with Wafarin. The last link in the answer above explains the test. $\endgroup$
    – Chris
    Jan 4 '14 at 21:07

The answer and reasoning by Chris are incorrect. Heparin DOES effect both the PT time and APTT time because it affects factors in the final common pathway. Heparin activates antithrombin 3 which inactivates activated factor x (factor xa) and thrombin (AKA activated factor ii). These factors are involved in the final common pathway: activated factor x converting prothrombin to thrombin which converts fibrinogen to fibrin. Both the APTT and PT rely on the final common pathway which follows on from either the intrinsic pathway (in APTT) or extrinsic (in PT).

HOWEVER, heparin does have a much greater effect on APTT and so this is why this is used. Indeed at therapeutic concentrations PT is within normal range due to a minimal increase. However, in a heparin overdose PT will become significantly high.

I am not sure of the reason for heparins greater effect on APTT but it may be something to do with heparins mechanism of action - in addition to inactivating factor xa and thrombin, antithrombin 3 (which heparin activates) inactivates other factors (xia and ixa apparently) which are part of the intrinsic pathway (which is measured in APTT) but not the extrinsic pathway (measured in PT). I think the fact it affects multiple factors in the APTT test causes a synergistic affect so affects it more compared to the PT where it only affects two factors (xa and thrombin) so there isn't the synergistic effect.

I thought of this explanation using an explanation I found of why low molecular weight heparin (LMWH) does not have as much of an effect on APTT as unfractionated heparin (UFH). LMWH's, unlike UFHs, activation of antithrombin 3 only really causes inactivation of factor xa so the synergistic affect of effecting multiple clotting factors involved in APTT does not happen (like it does with unfractionated heparin). However, for whatever reason in real patients LMWH is as effective at anticoagulation as UFH.

Source of last paragraph : https://fritsmafactor.com/post/low-dose-heparin-and-ptt


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