Why is thrombin time (TT) normal range longer than prothrombin time (PT)?

Question

Reference range for the TT is longer than that of the PT.

Answer 1

This is a great question.

I'm going to hypothesize here because I haven't had a chance to test my theory and I'm afraid that by the time I get around to it, I may forget about this question.

The real question is, what is the variable that makes the thrombin time act differently than what you would assume? I’d wager the answer is temperature.

Protimes are performed at 37 degrees in order to simulate the in vivo environment, but also because most coagulation factors aren't active at room temp, or at least they are very slow-acting at room temp. Heating the environment speeds this process up so the test doesn't take all day.

Now, we know if you take a tube of warm normal plasma and add calcium and thrombin to it, it clots right away, right? But this is a problem because the thrombin time is a quantitative assay and we need it to be sensitive, especially for those super old-school clinicians who use it to monitor heparin instead of a more modern test like the APTT or Xa inhibition. We need to be able to tell the difference between a patient that’s gotten a bolus of heparin and a direct thrombin inhibitor. So, if you remove the heat, you slow down the conversion of fibrinogen to fibrin, and in the process you stretch the calibration curve, effectively increasing the sensitivity of the test. But this also has the effect of slowing down the conversion to where it takes 14–18 seconds rather than one or two.

If you change your test setup to have the thrombin reagent heated, my hunch is that your analyzer will give an error because the sample will have clotted by the time the analyzer reaches minimum threshold time. Or better yet, try this experiment on a fibrometer. I don’t have access to one so I can’t try it out as I’d like to.

I’d be interested in discussing this with any other experts out there, especially those that have played around in the coag lab. I may have occasion to test this out in the coming weeks; I’ll try to do it and update my answer with my results.