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Effect of High HCT on D-dimer Results

From Heather DeVries, Indiana University Medical Center.

I’m seeking some advice on how to handle D-dimers in patients with elevated hematocrits. I saw a post on this subject in Fritsma Factor back in 2013. CLSI H59-A says to follow H21-A5 in general, which of course says to correct the anticoagulant volume. IL’s package insert for D-dimers also says to follow H21-A5. So, I revised the D-dimer procedure for our system to include adjusted tubes. Now I am being asked by one of our sites if that is really necessary. My mind goes to a possible dilutional effect, which is what the post from 2013 mentions as well. But I didn’t see any follow up and am curious to know which direction the conversation took.

Hi, Heather, and thank you for your question. As I wrote in 2013, I suggest that the H21-A5 position requiring a reduction in anticoagulant volume for patients whose HCT exceeds 55% is meant to normalize the anticoagulant/plasma ratio which would otherwise affect clot-based assay results. It may be that we are using this as a “data-free” default position for non-clot-based assays such as the D-dimer. In the 2013 post I took the position that there would likely be no dilutional or ratio effect on the D-dimer, and I still hold this position. Logic dictates that if we had to do this for D-dimer, we would have to do it for many immunoassay or chemical assay analytes performed on plasma. However, I’ve not found any references to give authority to my statement. I will contact a few of our Fritsma Factor consultants to ask for additional discussion on this topic, and I hope to resolve the issue.

Comments subsequent to Dr. Lippi’s comment below:

From consultant Bob Gosselin: Hello all, I would be cautious on a global D-dimer recommendation about whether or not a there is a dilutional effect due to polycythemia. Theoretically there could be a modest dilutional effect. Even if one takes the max end of 10%, that would still be reasonable accuracy limit, which is usually +/- 15%. My caution would be for D-dimer use in VTE exclusion, especially if age-adjusted. That small dilutional effect may cause a D-dimer positive result (close to cutoff threshold) to a negative result (secondary to potential dilutional effect). In other circumstances, any potential dilutional effect would not be clinically relevant. But that’s theoretical…and in coagulation, theories (untested claims) have often enough been proven not to be true.

Response from Dr. Lippi to Mr. Gosselin and our participants: Well, no, I do not agree. Actually, a low or high hematocrit value reflects exactly the in vivo station (blood loss or polycythemia) and thereby we shall provide a value that is aligned to patient’s status. Correcting the value would mean to generate a results that no longer reflects the in vivo blood concentration. Would be the same for troponin, PSA or whatever other molecule we are measuring in mass and not in activity. There is no single lab that would correct a troponin value for hematocrit.
Prof. Giuseppe Lippi
Professor of Clinical Biochemistry
Director of Laboratory Service
University of Verona

Bob Gosselin’s reply: Agree GL, but adding ex-vivo citrate, saline, water, buffer, etc to a blood sample is not the same as in-vivo…apples and oranges. To further support this potential issue is to look at reference intervals for tests that uses both plasma or serum samples, plasma samples have a slightly lower RI.

Comments (2)
Sep 27, 2019 11:35am

Thank you to you both for
Thank you to you both for responding. This is very helpful information. I’ll be revising back to the previous D-dimer policy and remove the adjusted citrate.

Sep 27, 2019 11:14am

According to my experience,
From Dr. Giuseppe Lippi, According to my experience, which goes far beyond hemostasis since I am basically a clinical chemist, no correction for citrate dilution (and thereby for low or high hematocrit) must be performed for whatever type of immunoassay, thus including D-dimer, either performed with turbidimetric or chemiluminescent immunoassays.

This would make simply no sense, since the sodium citrate/calcium balance impairment only affects clotting assays and has no impact on other methods. You may want to get further insights from here:

Davide Demonte, Mairi Pucci, Gian Luca Salvagno, Giuseppe Lippi
Can citrate plasma be used in exceptional circumstances for some clinical chemistry and immunochemistry tests?
Diagnosis Published Online: 2019-05-04 | DOI:$002fdx.ahead-of-print$002fdx-2019-0027$002fdx-2019-0027.xml

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