Haptoglobin 2-2 Genotype Is Associated With Cerebral Salt Wasting Syndrome in Aneurysmal Subarachnoid Hemorrhage

Neurosurgery. 2016 Jan;78(1):71-6. doi: 10.1227/NEU.0000000000001000.


Background: Haptoglobin (Hp) genotype has been shown to be a predictor of clinical outcomes in subarachnoid hemorrhage. Cerebral salt wasting (CSW) has been suggested to precede the development of symptomatic vasospasm.

Objective: To determine if Hp genotype was associated with CSW and subsequent vasospasm after aneurysmal subarachnoid hemorrhage.

Methods: Hp genotypic determination was done for patients admitted with a diagnosis of subarachnoid hemorrhage. Outcome measures included CSW, delayed cerebral infarction, and Glasgow Outcome Score of 4 to 5 at 30 days. Criteria for CSW included hyponatremia <135 mEq/L, and urine output >4 L in 12 hours with urine sodium >40 mEq/L.

Results: A total of 133 patients were included in the study. The 3 Hp subgroups did not differ in terms of baseline characteristics. CSW occurred in 1 patient (3.4%) with Hp 1-1, 8 (14.0%) patients with Hp 2-1, and 15 (31.9%) patients with Hp 2-2 (P = .004). In the multivariate regression model, Hp 2-2 was associated with CSW (odds ratio [OR]: 4.94; CI: 1.78-17.43; P = .01), but Hp 2-1 was not (OR: 2.92; CI: 0.56-4.95; P = .15) compared with Hp 1-1. There were no associations between Hp genotypes and functional outcome or delayed cerebral infarction. CSW was associated with delayed cerebral infarction (OR: 7.46; 95% CI: 2.54-21.9; P < .001).

Conclusion: Hp 2-2 genotype was an independent predictor of CSW after subarachnoid hemorrhage. Because CSW is strongly associated with delayed cerebral infarction, the use of Hp genotype testing requires more investigation, and larger prospective confirmation is warranted. Additionally, a more objective definition of CSW needs to be delineated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Female
  • Genetic Association Studies
  • Genotype*
  • Haptoglobins / genetics*
  • Haptoglobins / metabolism
  • Humans
  • Inappropriate ADH Syndrome / blood
  • Inappropriate ADH Syndrome / etiology*
  • Inappropriate ADH Syndrome / genetics*
  • Male
  • Middle Aged
  • Prospective Studies
  • Subarachnoid Hemorrhage / blood
  • Subarachnoid Hemorrhage / complications*
  • Subarachnoid Hemorrhage / genetics*


  • Biomarkers
  • HP protein, human
  • Haptoglobins