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


CONCLUSIONS
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.
*Division of Neurosciences Critical Care and‡Department of Neurological Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland;§Department of Medicine, Technion Institute of Technology, Haifa, Israel;¶Department of Neurological Surgery, Emory University, Atlanta, Georgia;‖Center for Surgical Trials and Outcomes Research, Johns Hopkins University, Baltimore, Maryland.
Santosh B
SB
Murthy
Justin
J
Caplan
Andrew P
AP
Levy
Gustavo
G
Pradilla
Yogesh
Y
Moradiya
Eric B
EB
Schneider
Hadar
H
Shalom
Wendy C
WC
Ziai
Rafael J
RJ
Tamargo
Paul A
PA
Nyquist
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007177:Inappropriate ADH Syndrome / Q000097:blood / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000150:complications* / Q000235:genetics*
D015415:Biomarkers; C485359:HP protein, human; D006242:Haptoglobins