Understanding Xanthochromia

When faced with a potential subarachnoid haemorrhage (SAH), the tools we use to diagnose can quite literally be life-saving. Cerebrospinal fluid (CSF) analysis plays a pivotal role, especially when common diagnostic tools like Computed Tomography (CT) scans might not catch early signs.

Traditionally, xanthochromia detection relied on visual assessment – a method that suffers from inconsistency due to subjective interpretation and lacks uniformity across the industry. Today, spectrophotometry has emerged as the preferred method for its precision and reliability in detecting xanthochromia. To ensure the highest accuracy, this technique requires stringent quality control measures. Here, we discuss xanthochromia and SAH, before introducing our dedicated Xanthochromia true third-party control.

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What is Xanthochromia?

Xanthochromia, derived from the Greek word, ‘xanthos,’ meaning yellow, refers to the yellow, or sometimes pink, discolouration of CSF, primarily due to bilirubin, a by-product of haemoglobin breakdown. Why does this matter? Because it’s a tell-tale sign of bleeding within the brain, often indicating SAH when CT scans don’t. Understanding this can help us catch and treat critical conditions before they worsen. Xanthochromia may also be an indicator of intracerebral haemorrhage, brain tumours, infection, or severe systemic jaundice¹.

Subarachnoid Haemorrhage

SAH is a spontaneous intracranial bleed characterised by significant mortality and morbidity rates. Approximately 12% of patients die before receiving medical attention, 33% within 48 hours, and 50% within 30 days of an SAH. Among the survivors, half suffer from permanent disabilities, with an estimated lifetime cost more than double that of an ischemic stroke². Patients which have displayed symptoms often complain of severe headache, nausea, vomiting, photophobia and/or phonophobia³.

CT scans, particularly non-contrasted CTs of the brain or CT angiograms (CTAs), are often the first line of diagnostic tools for suspected SAH. However, up to 5% of SAH cases may not show any signs of haemorrhage on these scans within the first 24 hours, with this figure rising to 50% by the end of the first week and remaining around 30% by the second week⁴.

In contrast, xanthochromia in the CSF can be detected as early as two hours after a bleed and is observed in over 90% of patients within 12 hours of an SAH event. This detection can persist for up to three to four weeks, offering a critical diagnostic window that imaging alone might miss. The conversion from haem to bilirubin in CSF takes roughly 6 to 12 hours, suggesting that xanthochromia is most reliably identified between 6- and 12-hours post-bleed. More than 75% of patients may still present with xanthochromia at 21 days following an SAH¹.

Pathophysiology explained

A ruptured cerebral aneurysm will begin to leak blood into the CSF. This blood is gradually degraded by macrophages to yield various by-products including oxyhaemoglobin, which is subsequently converted to bilirubin in a process lasting between 6 and 12 hours¹. Crucially, this conversion to bilirubin can only occur in vivo, providing a unique marker for diagnosing subarachnoid haemorrhage when observed in the CSF¹.

The Importance of Accurate Detection

In many parts of the world, including the US, visual detection remains a common initial test for xanthochromia in CSF.

Procedure: Spinning a CSF sample in a centrifuge and comparing the supernatant against a vial of water, held against a white backdrop to detect a yellow or pink tint.
Indication: A change in colour indicates that blood has been present in the spinal fluid for at least two hours, with all patients showing signs by 12 hours post-bleed¹.

However, this method is prone to false positives due to:

Dietary influences: High intake of carotenoids (like carrots and spinach).
Medication: Use of Rifampin.
Medical conditions: Clinical jaundice or high protein levels in CSF, which can be seen in conditions like carcinomatosis and meningitis¹.

Spectrophotometry

Spectrophotometry offers a more precise alternative by measuring light absorption in materials at specific wavelengths:

It can detect the presence of bilirubin, which absorbs light at 440 to 460 nm, a definitive indicator of xanthochromia.
Advantages over visual detection: This method eliminates the interference from other pigments or proteins and can distinguish bilirubin from oxyhaemoglobin, crucial for accurate diagnosis.

Quality control is crucial in spectrophotometry to ensure the accuracy and reliability of xanthochromia tests:

Regular Maintenance: Routine checks and maintenance of the spectrophotometer are fundamental to its operation. This helps in maintaining the instrument’s precision in measuring light absorption at specific wavelengths crucial for detecting bilirubin in CSF.
Calibration: Calibrating the spectrophotometer with known standards is essential. This process adjusts the instrument to measure the absorption accurately, particularly vital given bilirubin’s narrow detection window between 440 and 460 nm.

Implementing these stringent QC measures enhances the diagnostic precision of spectrophotometry, boosting confidence in the results. Such practices ensure that patients are diagnosed accurately and receive timely, appropriate treatment, solidifying the value of advanced diagnostic techniques in medical settings.

Introducing Randox Xanthochromia Controls

Diagnosing SAH swiftly and precisely is critical due to its significant immediate and long-term impacts. To aid precise detection, our Liquid Frozen Xanthochromia Positive & Negative Controls are essential tools for laboratories conducting CSF analysis. Here’s what makes them stand out:

Dedicated Xanthochromia true third-party control with only 2 analytes for limited cross-reactivity – Bilirubin & Oxyhaemoglobin
2-day open vial stability at 2° to 8°C and a 11-week shelf life from date of manufacture when stored at -18ºC to -24ºC.
Liquid frozen control provides suitable matrix in an easy-to-use format.
Consistent, clinically significant values.
Suitable for use with UV spectrophotometers, these controls help monitor bilirubin and oxyhaemoglobin levels effectively.

The Randox Xanthochromia Controls are ideally suited for laboratories, both public and private, as well as researchers who perform CSF analysis. Their use is crucial in ensuring the precision of SAH testing, which contributes to more accurate diagnostics and ultimately leads to better patient outcomes.

Considering the crucial role of accurate xanthochromia detection in diagnosing SAH, isn’t it time to review your lab’s capabilities? Explore how Randox Xanthochromia Controls can enhance your diagnostic processes. For more details on how to get these tools in your lab, contact us at marketing@randox.com.

In the fight against conditions like SAH, every second and every test counts. Equip your lab with Randox Xanthochromia Controls to ensure that your diagnostics are as precise and reliable as possible, helping save lives and improve healthcare outcomes.