Tag Archives: lab tests

A Blood Test For TBI? Part 3

The FDA announced approval of a blood test that incorporates both GFAP and UCH-L1. Approval was based on two as yet to be published studeis titled Evaluation of Biomarkers of Traumatic Brain Injury (ALERT-TBI) and Evaluation of Biomarkers of Traumatic Brain Injury Extension Study (ALERT-TBIx), and passed after less than 6 months of evaluation. Yes, more silly acronyms, I know.

The studies were designed to “evaluate the utility of the Banyan UCH-L1/GFAP Detection Assay as an aid in the evaluation of suspected traumatic brain injury (Glasgow Coma Scale score 9-15) in conjunction with other clinical information within 12 hours of injury to assist in determining the need for a CT scan of the head.”

The former study started in 2012 and involved 2011 patients! The latter had only 119 patients, starting in 2015. Now, I have no access to their data, so I can’t tell what the FDA saw.

From Banyan Biomarkers’ website:

“The CT scan is widely available to assist clinicians in the evaluation of TBI, however, CT scans do not provide a clear and objective answer and scanning may increase the risk for radiation-induced cancer. Furthermore, over 90% of patients presenting to the emergency department with mild TBI, sometimes described as “concussion”, have a negative CT scan. Despite these limitations, nearly all patients are sent for a CT, which results in increased costs to the healthcare system and unnecessary patient exposure to radiation.”

Here are the (very) few factoids that I can find:

  • CT scan results were compared to the Brain Trauma Indicator (BTI) blood test (GFAP + UCH-L1)
  • BTI predicted a positive CT scan 98% of the time
  • It predicted a negative CT scan 99.6% of the time
  • Time to process the test is currently 4 hours

Bottom line: Sounds promising, right? Based on the data summarized over the last two days, I wouldn’t be too excited about this test, but the FDA was able to look at a study that I can’t. It appears that the negative predictive value is excellent, so I can see the application.

That being said, 4 hours is way to long. We can’t have a patient sitting in the ED waiting for the results to come back to decide whether they need a head CT. And how long will it take the assay to be widely available?

The devil will be in the details. What types of intracranial lesions were detected. Are the negative predictive values the same for subarachnoid, subdural, epidural, or intraparenchymal bleeds? And finally, how expensive will it be? How does the cost for the test compare to the cost of a CT scan done in 5 minutes?

I’ll let you know more as the details emerge. But don’t look for, or plan to use, this test at your hospital any time soon. There’s more work to do!

Reference: Banyan Biomarkers (banyanbio.com)

A Blood Test For TBI? Part 2

Yesterday, I wrote about one blood biomarker, GFAP, and its possible application in detecting traumatic brain injury (TBI). Today, I’ll discuss a complementary marker called UCH-L1.

Fewer studies have been done looking at the utility of UCH-L1 in detecting TBI than of GFAP.  A review article published last month pooled existing literature to get a sense of how good this biomarker really is. It also examined the risk of bias due to the small numbers of studies involved.

Here are the factoids:

  • Only 38 abstracts were eligible, but full text was available for analysis in only 13 (meaning it was only an abstract and never passed muster for publication). The authors of the published studies were contacted for additional information, which is an interesting (and helpful) practice.
  • Of all of those, only 4 were selected for meta-analysis! This significantly limited the value of the analysis.
  • Serum UCH-L1 has a high accuracy in predicting CT findings in mild to moderate TBI, but there is a high risk of bias affecting this result
  • Plasma UCH-L1 has a moderate accuracy predicting CT findings across all GCS levels, with a low risk of bias
  • Pooling all studies, this is high accuracy in predicting CT findings in patients with TBI across all GCS levels, but there is a high risk of bias affecting the results

Bottom line: UCH-L1 show promise as a predictor of CT findings in patients with TBI. However, the research papers were few and far between, and the possibility of bias was high. What does this mean? That using this test alone is better than a coin toss, but not good enough to change our practice in ordering CT scans in head injured patients. More well-designed studies are needed tell us whether this new (and undoubtedly expensive) test is worth the trouble.

Tomorrow, I’ll discuss a blood test incorporating both UCH-L1 and GFAP that was recently approved by the FDA.

Reference: The diagnostic values of UCH-L1 in traumatic brain injury: A meta-analysis. Brain Inj 32(1):1-17, 2018.

A Blood Test For TBI? Part 1

Traumatic brain injury (TBI) is an extremely common problem encountered by trauma professionals. Diagnostic and management pathways are fairly well-defined, and rely mainly on physical examination, as well as CT imaging in select cases.

In recent years, work has been done to identify markers of brain injury in the blood. The theory is that the injured brain may release substances that can be assayed with a simple blood test. The presence of these blood markers could then influence our use of CT for diagnosis, decision to admit or send home, and possibly help identify patients likely to develop post-concussive symptoms.

Two particular biomarkers are being evaluated: UCH-L1 and GFAP. A recently published review examined the current status of GFAP in diagnosis of head injury.

Here are the factoids:

  • A total of 27 pertinent research papers were identified for review, and 24 of 27 demonstrated a positive association between GFAP levels and TBI
  • GFAP prediction of intracranial pathology by CT scan was good to excellent
  • GFAP appeared to be able to discriminate between mass lesions and diffuse injury
  • There was considerable variability in the average GFAP values. This means that the cutoff value that predicts significant injury is not yet clear.
  • The number of pediatric studies reviewed was low, so the results may not be generalizable to children
  • GFAP may be elevated in patients with orthopedic injuries, and this was not well controlled for in the studies reviewed. It is unclear whether GFAP can be used in patients with fractures.

Bottom line: GFAP looks promising as a marker for detecting significant TBI in some trauma patients. 

Tomorrow, I’ll take a look at the other biomarker, UCH-L1, and the following day I’ll discuss the recent FDA approval of an assay for both of these by a US company, Banyan Biomarkers.

Reference: A systematic review of the usefulness of glial fibrillary acidic protein for predicting intracranial lesions following head trauma. Frontiers in Neurology 8(652):1-16.

I have no financial interest in Banyan Biomarkers.

Another Worthless Test? Serum / Urine Myoglobin

We often rely on diagnostic testing to augment our physical examination skills. These tests may be in the form of imaging that allows us to see things that we normally cannot, or measurements of body composition using laboratory testing.

If you look at the “menu” of tests that your hospital laboratory offers, it is very extensive. You can order just about any assay imaginable on any body fluid or tissue. Diagnosis of many of the clinical diseases or disorders that we treat has come to rely on some of these assays.

Let’s take rhabdomyolysis, for example. I’ve been writing about compartment syndrome in the last few posts. One of the byproducts of a full-blown compartment syndrome is muscle breakdown. Two of the well-known substances released from injured muscle are creatine kinase (CK) and myoglobin.

Many textbooks advise the clinician to monitor levels of these substances, since myoglobin is toxic to nephrons and may lead to kidney injury. So most trauma professionals routinely write orders for serial CK, myoglobin, as well as creatinine to monitor renal function.

But most clinicians do not know their laboratory as well as they think. Your lab has the capability to perform commonly requested tests rapidly and on site. But what about assays that are rarely ordered? Does it make sense to have the reagents necessary for these uncommon tests on hand at all times? They degrade over time, and may very well expire before they are ever used, costing money to replace.

So most hospital labs send uncommon assays out to larger labs that perform the test for a large geographic area. But how does the “send out” specimen get to that lab? By courier (if local) or more commonly, by delivery service (if remote). And obviously, this takes time. And some assays are complex and may take hours or days to perform.

At my hospital lab, a serum or urine myoglobin assay is a “send out” test. And if you ask, the lab will tell you that it takes 3-4 business days to get the result. So if you send it out Wednesday, you will have the result the following Monday! Does it make any sense to get serial myoglobins? Or even a single myoglobin test? By the time you get the result, your patient will be treated and gone!

Bottom line: Think about the tests that you order very carefully. If you are ordering something out of the ordinary, check with your lab. Is it a “send out” test? How long does it take to get a result? And more importantly, how expensive is it? These tend to be pricey due to the low frequency of processing.

Then do the math. Is it worth the wait and expense? Or can you get the same information using routine, in house testing? In the case of rhabdomyolysis, serum CK levels are good markers, as is visual inspection of the urine. If it’s any darker than a light yellow, there may be myoglobin present. A quick and dirty way to confirm is some inexpensive testing: a urine specimen that is dipstick positive for blood, and with microscopic analysis shows few if any RBCs usually means myoglobin. Voila! Diagnosis now, not in 4 days.

Liver Laceration And Liver Function Tests

Over the years I’ve seen a number of trauma professionals, both surgeons and emergency physicians, order liver transaminases (SGOT, SGPT) and bilirubin in patients with liver laceration. I’ve never been clear on why, so I decided to check it out. As it turns out, this is another one of those “old habits die hard” phenomena.

Liver lacerations, by definition, are disruptions of the liver parenchyma. Liver tissue and bile ducts of various size are both injured. Is it reasonable to expect that liver function tests would be elevated? A review of the literature follows the typical pattern. Old studies with very few patients.

From personal hands-on observations, the liver tissue itself tears easily, but the ducts are a lot tougher. It is fairly common to see small, intact ducts bridging small tears in the substance of the liver. However, larger injuries can certainly disrupt major ducts, leading to major problems. But I’ve never seen obstructive problems develop from this injury.

A number of papers (very small, retrospective series) have shown that transaminases can rise with liver laceration. However, they do not rise reliably enough to be a good predictor of either having an injury, or the degree of injury. Similarly, bilirubin can be elevated, but usually not as a direct result of the injury. The most common causes are breakdown of transfused or extravasated blood, or from critical care issues like sepsis, infection, and shock.

Bottom line: Don’t bother to get liver function tests in patients with known or suspected injury. Only a CT scan can help you find and/or grade the injury. And never blame an elevated bilirubin on the injury. Start searching for other causes, because they will end up being much more clinically significant.

References:

  • Evaluation of liver function tests in screening for intra-abdominal injuries. Ann Emerg Med 20(8):838-841, 1991.
  • Markers for occult liver injury in cases of physical abuse in children. Pediatrics 89(2):274-278.
  • Combination of white blood cell count with liver enzymes in the diagnosis of blunt liver laceration. Am J Emerg Med 28(9):1024-1029, 2010.