Association Between Serum Calcium Level and Extent of Bleeding in Patients With Intracerebral Hemorrhage

Abstract

IMPORTANCECalcium 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. DESIGN, SETTING, AND PARTICIPANTSProspective 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. MAIN OUTCOMES AND MEASURESTotal 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 AND RELEVANCE 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.

Prognostic Significance of Serum Calcium Level in a Sample of Egyptian Patients With Intracerebral Hemorrhage.

“…These findings were matched with the finding of Morroti et al, 14 , who conducted a cohort study of 2123 consecutive patients with ICH, 10.9% of their Patients were hypocalcemic and had a higher baseline hematoma volume than did those with normal serum Ca level. Also they observed a significant inverse correlation between serum Ca and baseline hematoma volume.…”

“…Recently, few data were published on the relation between serum Ca level and the initial hematoma volume 14 as well as outcomes after ICH [13][14][15] . However, the underlying mechanisms are poorly understood 14 .…”

Sex differences in intracerebral hemorrhage expansion and mortality

“…For the identification of Spot Sign presence, computed tomography angiography (CTA) images were obtained and reviewed as previously described(15). ICH expansion was defined as hematoma growth > 33% or > 6 mL from baseline ICH volume on the follow up CT taken at 24 h.(16,17)…”

Phenotypic characterization of haemophilia B – Understanding the underlying biology of coagulation factor IX

“…The addition of Mg 2+ to the test system significantly improved FIX activation . However, the role and balance of cationic calcium is critical, as deficiency in calcium leads to an anticoagulation effect, and for example, hypocalcaemia worsens intracranial bleeds . Intriguingly, blood collected to magnesium tubes in the absence of calcium does not coagulate .…”

“…49 However, the role and balance of cationic calcium is critical, as deficiency in calcium leads to an anticoagulation effect, and for example, hypocalcaemia worsens intracranial bleeds. 50 Intriguingly, blood collected to magnesium tubes in the absence of calcium does not coagulate. 51 Overall, the role of magnesium in routine clinical chemistry coagulation laboratories remains unknown, as Mg 2+ is chelated by citrate anticoagulant and, as opposed to that of Ca 2+ , is not substituted.…”