Xanthochromia in Cerebrospinal Fluid Analysis
Xanthochromia refers specifically to the yellow discoloration of cerebrospinal fluid (CSF) after centrifugation, not at initial inspection or in all yellow fluids. 1
Understanding Xanthochromia
Xanthochromia is the yellow discoloration of CSF that occurs due to the breakdown of hemoglobin into bilirubin following a subarachnoid hemorrhage (SAH). This finding is critical in diagnostic medicine for several reasons:
- It is detected in the supernatant after CSF centrifugation, not in the initial visual inspection of unprocessed CSF 2, 1
- It develops several hours after bleeding into the subarachnoid space
- It serves as a key diagnostic marker when CT imaging is negative but SAH is still suspected
Clinical Significance
Xanthochromia analysis is primarily used in the diagnosis of SAH when initial neuroimaging is negative or equivocal:
- CT sensitivity for SAH decreases over time: 98-100% within 12 hours, 93% at 24 hours, and only 57-85% by day 6 1
- When performed correctly, CSF xanthochromia testing has excellent diagnostic properties:
- Sensitivity: 100%
- Specificity: 98.1%
- Negative predictive value: 100%
- Positive predictive value: 65.9% 3
Proper Technique for Xanthochromia Detection
For accurate detection of xanthochromia:
- CSF must be collected via lumbar puncture at least 12 hours after symptom onset (ideally after 24 hours) 1, 3
- The sample must be centrifuged to separate cellular components from the supernatant
- The supernatant is then examined for yellow discoloration
- Spectrophotometric analysis is the preferred method for detection, following guidelines such as the UK-NEQAS method 3
Pitfalls and Limitations
Several important caveats must be considered when interpreting xanthochromia:
- False positives can occur in approximately 13% of LPs 1
- Traumatic LPs with high RBC counts (>30,000 RBC/μL) can demonstrate xanthochromia immediately after collection 4
- Samples with 20,000 RBC/μL can show xanthochromia within one hour, and those with 10,000 RBC/μL within two hours 4
- Other causes of xanthochromia include:
Diagnostic Algorithm
When SAH is suspected but CT is negative:
- Perform lumbar puncture >12 hours after symptom onset (preferably >24 hours)
- Centrifuge the CSF sample immediately
- Examine the supernatant for xanthochromia (yellow discoloration)
- Confirm with spectrophotometric analysis
- Interpret results in context of clinical presentation and RBC count:
- Xanthochromia with <5,000 RBC/μL strongly suggests SAH
- Xanthochromia with >10,000 RBC/μL may be due to traumatic tap 4
In conclusion, xanthochromia is a valuable diagnostic finding when properly assessed in centrifuged CSF samples, not in the initial visual inspection or in all yellow body fluids.