A 58-year-old man underwent MRI total body imaging. Later that day, a chemistry profile was ordered. The total calcium was measured at 4 mg/dL (reference interval: 8.5-10.5 mg/dL) and the albumin was 4 g/dL (reference interval: 3.5-5.0 g/dL). The patient was examined and lacked any clinical evidence of hypocalcemia. One week prior to the MRI, the total calcium was normal. What is the explanation for the hypocalcemia? Answer: Certain gadolinium contrast agents falsely lower the measurement of total calcium when calcium is measured using colorimetric assays. Gadodiamide (Omniscan) and gadoversetamide (OptiMARK) have been reported to cause such "pseudohypocalcemia." [1] On the other hand, gadoteridol (ProHance) and gadopentetate dimeglumine (Magnevist) have not been reported to effect total calcium measured colorimetrically. In a recent paper from Germany, gadobutrol (Gadovist) and gadoxetate disodium (Primovist/Eovist) were reported to not affect calcium measurements. [2] If your hospital uses a gadolinium formulation that does interfere, it is recommended that calcium be measured before the procedure or more than 4 hours post-MRI when the patient's GFR is =>90 mL/min/1.73 M2 or more than 50 hours post-MRI when the GFR is reduced to ~20 mL/min/1.73 M2. [1] Emerson J, Kost G. Spurious hypocalcemia after Omniscan- or OptiMARK-enhanced magnetic resonance imaging: an algorithm for minimizing a false-positive laboratory value. Arch Pathol Lab Med. 2004 Oct;128(10):1151-6. [2] Löwe A, Breuer J, Palkowitsch P. Evaluation of the effect of two gadolinium-containing contrast-enhancing agents, gadobutrol and gadoxetate disodium, on colorimetric calcium determinations in serum and plasma. Invest Radiol. 2011 Jun;46(6):366-9. Final question: what disease can develop in patients with renal failure who receive gadolinium for scans? (answer next week).
Answer: Certain gadolinium contrast agents falsely lower the measurement of total calcium when calcium is measured using colorimetric assays. Gadodiamide (Omniscan) and gadoversetamide (OptiMARK) have been reported to cause such "pseudohypocalcemia." [1] On the other hand, gadoteridol (ProHance) and gadopentetate dimeglumine (Magnevist) have not been reported to effect total calcium measured colorimetrically. In a recent paper from Germany, gadobutrol (Gadovist) and gadoxetate disodium (Primovist/Eovist) were reported to not affect calcium measurements. [2]
If your hospital uses a gadolinium formulation that does interfere, it is recommended that calcium be measured before the procedure or more than 4 hours post-MRI when the patient's GFR is =>90 mL/min/1.73 M2 or more than 50 hours post-MRI when the GFR is reduced to ~20 mL/min/1.73 M2.
[1] Emerson J, Kost G. Spurious hypocalcemia after Omniscan- or OptiMARK-enhanced magnetic resonance imaging: an algorithm for minimizing a false-positive laboratory value. Arch Pathol Lab Med. 2004 Oct;128(10):1151-6.
[2] Löwe A, Breuer J, Palkowitsch P. Evaluation of the effect of two gadolinium-containing contrast-enhancing agents, gadobutrol and gadoxetate disodium, on colorimetric calcium determinations in serum and plasma. Invest Radiol. 2011 Jun;46(6):366-9.
Final question: what disease can develop in patients with renal failure who receive gadolinium for scans? (answer next week).
Posted by On 2/10/2012
We have 24/7 on call lab personnel for liver transplants, with one of the duties to courier samples from the OR to perfrom TEG testing in the blood bank. The OR staff is already certified to perform other non-waived testing, but the lab personnel continue to handle the TEG.
Posted by On 2/8/2012
Our institution considered TEG for years, but implementation of a very active strategic blood management program a couple of years ago made this an imperative for the institution. In the past year, new surgeons (esp. intraabdominal tx) have come on board looking for this technique to help monitor parameters as Dr. Stickle described. Collaborating with anesthesiologists in OR, our blood utilization committee, the surgeons and our department, we decided to implement ROTEM which is a slightly different analytical technique from TEG, but provides much of the same clinical information. In conjunction with recent FDA approvals of a couple of the methods, we're in the final stages of validations for instruments in the OR Lab and Core Lab. Our staff find it very interesting to use. Kind of a 'cool' concept for a clinical biochemist like me. But its use absolutely requires the buy in and support from key clinicians - especially in the anesthesiology and surgical groups. Steve Kahn, Ph.D. Loyola University Health System Maywood, IL, USA
TEGs are being aggressively marketed as a means to reduce blood product consumption. It was implemented by cardiac anesthesia at our hospital without laboratory approval. It is very difficult for laboratory POCT coordinators to oversee POCT in the ORs. I am very greatful to the CAP inspection team that visited us and investigated TEG operations in the OR. They found several major deficiencies, which brought the issue to the attention of senior hospital administration. It is being done by one anesthesiolgist and a few cardiac perfusionists on a limited basis. I'm not convinced that there is a favorable cost/benefit ratio for this test. I would like to see it recategorized as high complexity. I do not think it is appropriate for POCT by non-laboratory personnel.
Thanks Doug, I agree, this will be unfamiliar territory for the OR staff. Athough many cardiac ORs have experience with performing ABGs and ACTs at the POC, in contrast, ROTEM requires reagents to be placed in a certain order, pipetting and reconstitution of reagents. My 2 cents: This test should not be performed POC in the ORs by OR staff. They are too distracted with other duties to be laboratorians as well. How many users will be trained, how will they remain competent? From a patient care and risk perspective, I advocate for the more expensive option of laboratory performed testing and output in the OR. (This can be complicated too depending on your LIS, distance from the OR, and how the data are transmitted eg. meeting HIPPA standards). Thanks for your post. Corinne Fantz
Posted by On 2/7/2012
TEG is a moderate-complexed instrument. The QC requirements are strict and anesthesiolgists found it difficult to comply with the every 8 hours QC requirement at the OR setting. In addition, the group finds it difficult to spend adequate time to learn patient testing and interpretations. The implementation would go well if the anesthesiolgists are dedicated to the training and have enough time to practice QC/patient testing with the instrument. Some complained about the long duration to wait for the results. Laboratoians can do a better job to run TEG on patients.
Posted by On 7/26/2011
Does Maarten mean Nephrogenic Systemic Fibrosis ?
Posted by AACC\bgarman On 7/19/2011
Bill, good case illustrating effects of gadolinium. We've also seen this a few times here. Bob/Dan - nice discussion of the effects K-EDTA contamination on chemistry tests when sample is drawn in wrong (lavender-top) tube and transferred to serum tube. This happens most frequently here for samples drawn by non-laboratory staff, although we have had a phlebotomist do this on rare occasions. Tom - we have performed simulation experiments here (with yours truly as test subject) where we intentionally tried to cause EDTA carry-over by drawing blood using the wrong order of draw but we have never been able to show any measurable effect on K, ionized Ca, or other test results, leading us to conclude that the amount of carryover is negligible.
my query to all of you How much time it takes this contrast to get cleared from the system and calcium to normalize in serum? Dr T Malati, Fmr Head, Biochemistry, Nizam's Institute of Biochemistry, India
The answer to the final question: what disease can develop in patients with renal failure who receive gadolinium for scans? Nefrogenic sytemic fibrosis (NSF)
I'm with the Gadodiamide.
repeat the test first; its not clear if the original test was in duplicate or not; it may as well be due to a random, unexplainable, compound error..,
We've seen this oftern. This is an order of draw issue with a multi-sample needle. EDTA tube drawn before the serum tube, a samall amount of EDTA whole blod is "trapped" in the rubber tipped multi-sample needle and is transferred int o the serum tube. The calxium will be reduced .... but no absent AND the alk phos will be supressed. Run an alk phos and if it is very low, that's you problem.
Thanks, Bob... all great points. It's been well over a decade since that incident occurred and I don't recall what type of EDTA was used. Perhaps a mix of sodium fluoride/sodium EDTA (gray-top) or straight disodium EDTA? Not sure how they'd alter total calcium. Also, don't recall all the testing that helped resolve, but think fibrinogen was also used to ferret out the issue... when asked, the phlebotomist was forthcoming with the explanation.
Dan, my experience with EDTA with most methods is that the calcium will be undetectable, rather than measurable but low. Sodium citrate contamination can also cause a drop in calcium. Inspection of other test results often allows recognition of these contaminations. With EDTA, K is typically very high, while CK and ALK PHOS activity are undetectable. Sodium citrate gives high sodium and very high (often > 100) anion gap.
Another possibility... after phlebotomist realizes that EDTA was the inappropriate tube, pours the "purple-top" plasma into a serum tube and sends to the lab... (yes, it's happened!)
As mentioned by the previous commenter, gadolinium will cause falsely low calcium by most methods using dye binding; however, it does not affect ISE measurements, such as are used on the Beckman Lx analyzers, nor would it affect measurements of free ("ionized") calcium, so it is important to specify which instrument is used to measure calcium.
The contrast media? Gadodiamide, used for MRI contrast, is one example.
Posted by AACC\rchery On 7/8/2011
I guess this could be a lab artifact . The patient might have received gadolinium-based magnetic resonance contrast agents for enhancement of magnetic resonance imaging (MRI) (Not mentioned on the lab request). Gadolinium dyes has the property of metal chelation in dose dependent manner, also possible interference with colorimetric assay ( predominant calcium assay method). Suggestion: In these kind of situations it is suggested to check calcium levels with alternate methods ( ISE methods) before concluding the false hypocalcaemia. Further,this dye will have more impact among people suffering from kidney disorders due to reduced capability of clearing this dye. A better communication between the radiologist and concerned lab people might help to avoid this kind of situations Submitted by Seetharam Chittiprol
Malone, B: Rethinking Ionized Calcium Test Utilization. Clinical Lab Strategies, May 2009