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COAGULATION CORNER: OCTOBER 2011

THE 10 MOST COMMON COAGULATION QUESTIONS PEOPLE ASK ME!

I have been lucky, I have met techs from all over the world, been privileged to lecture in so many wonderful places and learned so much from so many. Here are some of the most common questions that I am asked.

1.  How do I make sure that a sample isn’t contaminated with heparin?

Simple, perform a thrombin time.  A thrombin time is one of the most sensitive tests for heparin and will be prolonged when there is as little as 0.1U/ml of heparin. It is a really good idea to routinely perform a TT on all inpatients that have factor assays ordered on them to rule out the presence of an inhibitor.  Also, if you get a request for a heparin level on a patient and your result is <0.1 or 0.1 and the clinician insists it should be higher- perform a TT, if it is normal there is no heparin on board, or the sample was drawn too soon after administration.

2.  What does it mean if the INR is abnormal and the patient is not on warfarin?

The INR is used to monitor patients on a stable does of warfarin.  That means the patients have been on the dose for about 2 weeks.  An INR will also be abnormal when you have an elevated PT- makes sense, however, you make the diagnosis based on the PT and the follow up testing, not on the INR.  Again, the INR is used to monitor warfarin, period.

3.  What ISI should I use for my PT reagent?

Use a PT reagent with an International Sensitivity Index ( ISI )of </=1.2

Using insensitive reagents with high ISI’s will account for more variability in your results.  Remember, in the formula for the Internationalized Normalized Ratio (INR), the ISI is exponential, so the higher the ISI, the greater the error in calculating the INR.

4.  How many levels of coagulation controls should I run, and what levels?

Well, you know that you need to run 2 levels of controls both a normal and abnormal level.  Regarding routine testing, make sure the levels of your controls mimic your patient population and challenge your reagent.  If you use your reagents to screen for factor deficiencies, you might want to run just an abnormal level with the normal, but if you rely on your APTT reagent to monitor heparin levels, you might want that control to be an abnormal high level.

5.  Should I report out INR > 6.0?

So my initial answer is why? If you have an INR of >6.0 on a patient that is receiving warfarin, there needs to be some course of action – FFP, decrease in dosage, etc. Does an 10.0 tell you more than a 6.0, and what about the formula and the PT results, you have to be greater than 50 seconds, and what does that mean? 50, 69, 100 sec, we know none of them are good.  With all of that being said, the American College of Chest Physicians (ACCP) publish guidelines on  the INR, dosing, treating etc, and they want those levels about 6.0, so if your clinicians want them, go right ahead and report awa. 

6.  Should I use a Lupus sensitive or insensitive reagent?

Well now that depends on what you are looking for- just for a review.  A lupus sensitive reagent has a lower concentration of phospholipid, and will be prolonged in the presence of a lupus or lupus like inhibitor.  That is in contrast to an insensitive reagent which will have a higher level of phospholipid to mask the presence of an inhibitor.  Remember, with a lupus anticoagulant or lupus like inhibitor you are at a greater risk of clotting, than bleeding.  Many of these inhibitors are transient, and if you don’t want to investigate this phenomena, then your laboratory should use a lupus insensitive reagent.

7.  Should I perform precision testing on my assays?

Yes, Yes and Yes and on more than 1 level, at least at high, normal and low.  Don’t you want to know what your CV’s for that assay are?  At those levels, for your specific instrument/reagent combination?  How can you tell if an assay result has changed or is really the same answer and related to the CV of the assay.  Little effort, great amount of information.  I know coagulation assays are expensive, run at least 10 times, 20 is better, can use controls, but patient pools are even better, want to keep that matrix.

8.  How do you determine if a mixing study has corrected?

Okay so not my favorite question, since there are several answers.  Here is my take on this- you run your PT or APTT, you run your pooled normal plasma, and you run your 1:1 mix. Now a few things, make sure you PNP is platelet poor, make sure you have a reference range on your 1:1 normal pool- with normal subjects (run at least 20 mixes 1 part PNP: to 1 part normal donor to determine), also make sure that your PNP isn’t frozen too long, it will result in an elevated FVII, and finally make sure that you know the levels of all the factors of your PNP- if they are less than 60% they may fail to correct your 1:1 mix. So I still haven’t answered what is a correction?  Some labs use the mix that returns to the normal range, or some labs use the within 3 seconds of the PNP or some combination of the above, most important is to be consistent, set your procedures, determine what is a correction and stick with it!

9.  Should I incubate my mixing study and how long?

Second least favorite question, again if you are looking for a weak inhibitor, and if you aren’t sure if your immediate mix has really corrected, your answer may be in looking at an incubated mix.  The purpose is to really allow those weak inhibitors to inhibit, so incubating for 1 hour may help answer some of those grey areas, and 2 hours may help even more.  Did that help?

10.  Should I use an anti-Xa assay to monitor heparin instead of the APTT?

Believe it or not, I think most labs would move to this, even though I know it can be expensive.  It seems that the most resistance comes from the clinician since they prefer to use the APTT. Advantages to using this are:  you would never have to run another heparin therapeutic range!   You wouldn’t have to worry about the sensitivity of your reagents to heparin- and as you know there is no dose response relationship with heparin and the APTT- clearly cleaner answers.

So if you can, go for it!

Any questions?

Donna Castellone

About the Author

Donna Castellone,
MS, MT(ASCP)SH
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