Association Between Serum Calcium Level and Extent of Bleeding in Patients With Intracerebral Hemorrhage.
OBJECTIVE
Calcium is a key cofactor of the coagulation cascade and may play a role in the pathophysiology of intracerebral hemorrhage (ICH).


OBJECTIVE
To investigate whether a low serum calcium level is associated with an increase in the extent of bleeding in patients with ICH as measured by baseline hematoma volume and risk of hematoma expansion.


METHODS
Prospective cohort study of 2103 consecutive patients with primary ICH ascertained during the period between 1994 and 2015 at an academic medical center. The statistical analysis was performed in January 2016.


METHODS
Total calcium level was measured on admission, and hypocalcemia was defined as a serum calcium level of less than 8.4 mg/dL. Baseline and follow-up hematoma volumes, detected by noncontrast computed tomography, were measured using a computer-assisted semiautomatic analysis. Hematoma expansion was defined as an increase of more than 30% or 6 mL from baseline ICH volume. Associations between serum calcium level and baseline hematoma volume and between serum calcium level and ICH expansion were investigated in multivariable linear and logistic regression models, respectively.


RESULTS
A total of 2123 patients with primary ICH were screened, and 2103 patients met the inclusion criteria (mean [SD] age, 72.7 [12.5] years; 54.3% male patients), of whom 229 (10.9%) had hypocalcemia on admission. Hypocalcemic patients had a higher median baseline hematoma volume than did normocalcemic patients (37 mL [IQR, 15-72 mL] vs 16 mL [IQR, 6-44 mL]; P < .001). Low calcium levels were independently associated with higher baseline ICH volume (β = -0.13, SE = .03, P < .001). A total of 1393 patients underwent follow-up noncontrast computed tomography and were included in the ICH expansion analysis. In this subgroup, a higher serum calcium level was associated with reduced risk of ICH expansion (odds ratio, 0.55 [95% CI, 0.35-0.86]; P = .01), after adjusting for other confounders.


CONCLUSIONS
Hypocalcemia correlates with the extent of bleeding in patients with ICH. A low calcium level may be associated with a subtle coagulopathy predisposing to increased bleeding and might therefore be a promising therapeutic target for acute ICH treatment trials.
Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy2Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston3J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
Andrea
A
Morotti
J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
Andreas
A
Charidimou
Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston3J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
Chia-Ling
CL
Phuah
J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
Michael J
MJ
Jessel
J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
Kristin
K
Schwab
J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
Alison M
AM
Ayres
Neuroradiology Service, Department of Radiology, Massachusetts General Hospital, Boston.
Javier M
JM
Romero
J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
Anand
A
Viswanathan
J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
M Edip
ME
Gurol
J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
Steven M
SM
Greenberg
Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston3J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
Christopher D
CD
Anderson
Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston3J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston.
Jonathan
J
Rosand
Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston3J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston5Department of Emergency Medicine, Massachusetts General Hospital, Boston.
Joshua N
JN
Goldstein
D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000097:blood*; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged
D002118:Calcium