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Coagulation Corner

Wednesday, July 5, 2017

Guidelines: Do We Need Them? Should We Use Them? Are They Helpful?

Written By Donna Castellone, MS, MT (ASCP) SH | LinkedIn

Coagulation laboratories are always looking for help. Coagulation testing has lots of challenges- different reagents with different sensitivities, different types of deficient plasma, different methodologies, standard curves, calibrators- you can mix and match or stick to what is matched to your analyzer. Add in different technologists running assays and adding their own touch and interpretation, it amazing any results get reported with confidence!

What are laboratories looking for? They want robust assays, that are reproducible which accurately evaluate a patient's hemostatic profile. Will they bleed, will they thrombose, are they properly anticoagulated- is the therapy working? How do labs do this? How do we ensure that we are providing quality results?

If you Google current available guidelines in coagulation you get over 13 million hits- everything from recommendations for hemophilia, laboratory practices, evaluating DIC, how to administer products - just to mention a few. But what do we need? What can help us the most, what are laboratories looking for?

After working on several guidelines, one of the most important things I have learned is that statements should be evidence based. There are many things that are "historical" in coagulation but really need to be backed by data. Another benefit of guidelines would be using a grading system, which like in the ACCP guidelines, directives are graded as to their level of importance. There is a big difference in a statement that says a laboratory should versus a laboratory must.

It is also important that the right people are sitting around the table writing the guidelines. Who are the key players that can contribute the most relevant information. Should there be clinicians, nurses, pharmacists in addition to laboratory personnel? What if there a conflict of interest regarding a subject, it may influence input into the document. Should manufacturers have input? Who should sit on this committees? Each person will contribute based on their perspective and experience. Depending on the scope of the document, it has been suggested that even patients could add beneficial information to help in establishing guidelines. However, conflict of interest should be minimized.

What happens if I decide to publish a guideline based on just experience? No peer evaluated documents, no supporting literature review? What about the quality of those recommendations? Well, I have a lot of laboratory experience, but many of the things that I can tell you are part science and part voodoo! They still have merit- but for sure would be considered low quality guidelines. Certain practices will fit different parts of the world. I can tell you for sure my baseline fibrinogen levels are higher in NYC than is Indianapolis- acute phase reactants? Or just crazy stressed NYers! Don't think I can give that a grade.

What about the kids that are having their adenoids and tonsils out, and have a prolonged PT and or aPTT with totally normal factors, or inhibitors? Is this due to chronic infections, or antibiotics or elevated CRP, or just a non-specific inhibitor that we can't identify- not sure how to grade that evidence- but those results are there.

How about platelet aggregations that looks like hyperactive platelets, resulting in fast slopes despite working with adjusted platelet counts of 200,000. Many times despite adjusting with platelet poor plasma, PPP samples have something (lipids?) that can interfere with those platelets. Try spinning that PPP for 30 minutes before adjusting the platelet count - lipids can interfere with the aggregation and give you these drastic slopes.

More? What about performing inhibitor assays? At present we do not heat inactivate plasma- but we do not run inhibitor assays on patients with factor levels > 25% - why, I am not sure where that level came from, but that is what we use... really we need to validate heat inactivation- but for the last I don't know how many years, that is the cut off level that we used. I don't know where it came from- but it has become standard practice in three of the laboratories I have worked in!

How about mixing studies? Now that is voodoo- you have the immediate mix, I can live with that- but what is a correction? Normal range, 2 seconds from PNP? 20% from PNP? If I ask 10 people I can get 10 different answers- what about the incubated mix? How long do I incubate- 1 hour, 2 hours- do I incubate together, separate- then again what do I compare against? Who does the interpretation? Gives me a headache, some labs no longer use this test, they just go on to factor assays and then if no issues to inhibitor testing. Very confusing.

Even things like reagent testing, how far do you go? Factors, Heparin, DOAC's, LMWH, stability for routine testing? Do I check all factors on old versus new, or if the aPTT and PT are okay, do I accept that? Do I do representative assays? I can tell you right now, we test everything- I think the better you know and understand how your reagent performs, the better prepared you are in understanding how your reagent performs for many coagulation tests. There are some guidelines on this, but also lots of experienced based opinion, not sure how that would be graded.

What about standard curves in coagulation? 3 points is the minimum and mandated by CAP, but what is the difference in results if you use more points? Or multiple curves? Most of the limitations laboratories use come from the analyzers and their lower limit of detection. Laboratories, in particular hemophilia centers need to be able to distinguish between levels of <1, 1 and 5% and above. This is a big variable, as treatment will different based on these results and most guidelines give minimal requirements, so that laboratories can be compliant based on analyzers functionality. I think the more points that you have on a curve the less variability- but then of course you add deficient plasma, dilutions, buffers and methodology into the mix and you aren't sure if those recommendations are one size fits all.

Guidelines should help to point laboratories in the right direction and help them to enhance the accuracy and robustness of their assays, and to have the test predict outcomes- do they need treatment? Will they bleed? Will having this test improve patient outcomes, will the patient be better off? Laboratories are not only looking for the "how" to best perform the test, but also the why, what and when in testing.



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