How long after a subarachnoid hemorrhage (SAH) can xanthochromia be reliably excluded by lumbar puncture (LP)?

From the Guidelines

Xanthochromia can be reliably excluded by lumbar puncture (LP) after 12 hours following a subarachnoid hemorrhage (SAH). This is based on the most recent and highest quality study available, which reported a sensitivity of 100% and specificity of 95.2% for xanthochromia evaluation by spectrophotometric analysis of CSF obtained by LP after a negative or nondiagnostic head CT 1. Performing an LP earlier than 12 hours after symptom onset may yield a false-negative result, as the red blood cells from the hemorrhage have not had sufficient time to lyse and release bilirubin, which causes the yellowish discoloration known as xanthochromia.

Key Considerations

• The American College of Emergency Physicians provided an LOE C recommendation for CTA or LP as the next diagnostic study if noncontrast head CT is inconclusive in a patient with a high suspicion for SAH 1.
• CTA does not directly evaluate for SAH, only cerebrovascular pathology, and its sensitivity is ≈97.2%, with lower sensitivity for ruptured aneurysms < 3 mm 1.
• For optimal diagnostic accuracy, the LP should be performed between 12 hours and 2 weeks after symptom onset, with the highest sensitivity in the 12-hour to 7-day window.
• After approximately 2-3 weeks, the xanthochromia typically resolves as the breakdown products are cleared from the CSF.

Clinical Implications

• The presence of xanthochromia is a more specific indicator of SAH than red blood cells alone, as the latter can result from a traumatic tap during the LP procedure itself.
• Given the severe morbidity and potential mortality associated with a missed aSAH, it is crucial to maintain a high level of awareness and concern for this diagnosis and pursue appropriate workup, when necessary 1.
• Effective management of aSAH and its possible associated complications requires prompt identification and initial management, and physicians should prioritize the diagnosis of aSAH when clinically suspected 1.

From the Research

Xanthochromia and Subarachnoid Hemorrhage

• Xanthochromia, the yellow discoloration of cerebrospinal fluid (CSF) caused by hemoglobin catabolism, is classically thought to arise within several hours after subarachnoid hemorrhage (SAH) 2.
• The presence of xanthochromic supernatant is often used to distinguish the elevated red blood cell (RBC) count observed in the CSF of SAH from the elevated RBC count observed after traumatic LP 2.
• Studies have shown that xanthochromia may be observed within two hours after traumatic LP and sooner in samples with greater than 10,000 RBC/μL 2.
• CSF-xanthochromia testing using the revised UK-NEQAS method is fit-for-purpose for the use as a second line test to exclude SAH in patients with negative CT-brain, including delayed presentation more than 24 hours after headache onset 3.
• Xanthochromia can be reliably excluded by lumbar puncture (LP) 12 hours or more after symptom onset, as the sensitivity and specificity of CSF-xanthochromia testing were 100% and 98.1%, respectively, in patients who underwent LP more than 12 hours after symptom onset 3, 4, 5.

Timing of Lumbar Puncture

• The American College of Emergency Physicians recommends that patients presenting with acute non-traumatic headache concerning for subarachnoid hemorrhage (SAH) undergo lumbar puncture (LP) when non-contrast head computed tomography (CT) is negative 6.
• Some authorities recommend delaying lumbar puncture by 12 hours following onset of symptoms to ensure sufficient time has elapsed for xanthochromia to develop 4.
• However, nearly all hospital clinical laboratories in the United States use visual inspection to evaluate for xanthochromia, rather than spectrophotometry, which may affect the timing of lumbar puncture 4.

Clinical Implications

• Xanthochromia is still an important diagnostic tool in the diagnosis of SAH, and a normal CT scan and the absence of xanthochromia do exclude a ruptured aneurysm, provided xanthochromia is investigated by spectrophotometry and lumbar puncture is carried out between 12 hours and 2 weeks after the ictus 5.
• The absence of xanthochromia in the CSF does not exclude a ruptured intracranial aneurysm if the lumbar puncture is performed too early after symptom onset 3, 5.