NEW YORK (Reuters Health) – The extent of bleeding in patients with intracerebral hemorrhage (ICH) is greater with low serum calcium levels, according to a retrospective analysis.

“Calcium is a key cofactor of the coagulation cascade, and hypocalcemia may lead to increased bleeding through a subtle coagulopathy,” Dr. Andrea Morotti from Massachusetts General Hospital, Boston, told Reuters Health by email.

Some have suggested that a lower serum calcium level is associated with higher hematoma volume in patients with ICH, but this has not been studied systematically.

Dr. Morotti and colleagues explored the association between serum calcium and ICH volume, as well as the risk of hematoma expansion, and investigated whether the association is mediated by impaired coagulation or hypertension.

Their retrospective analysis of an ongoing prospective study included 2103 patients with spontaneous ICH.  Median baseline hematoma volume was 37 mL in patients with hypocalcemia vs 16 mL in patients with normal calcium levels (P<0.001), according to the September 6th JAMA Neurology online report. Thirty-day mortality was significantly higher in hypocalcemic patients than among normocalcemic patients (59.8% vs 44.2%). The ionized calcium level on admission was inversely correlated with the international normalized ratio and the activated partial thromboplastin time, but not with the blood pressure on admission.

Multivariable regression analysis confirmed a significant inverse relationship between serum calcium level and baseline hematoma volume that was stronger for cases not associated with oral anticoagulant treatment.

In a subset of patients with follow-up CT scans, higher serum calcium level on admission was associated with a significantly reduced risk of ICH expansion.

“ICH is still the deadliest type of stroke, with lack of an acute treatment proven to improve outcome,” Dr. Morotti said. “Hypocalcemia is common in ICH and independently associated with the risk of hematoma growth. This may offer a therapeutic opportunity for prevention of hematoma enlargement in clinical trials.”

“Further large prospective studies are needed to confirm our findings and investigate whether serum calcium could be a therapeutic target for ICH clinical trials,” the researchers note.

“Mild to moderate hypocalcemia causing spontaneous ICH or ICH expansion would be a challenge to explain etiologically,” write Dr. Mark J. Alberts and Dr. Ravi Sarode from The University of Texas Southwestern Medical Center, Dallas, Texas in an editorial. “Based on these factors, there are no compelling data to suggest that mild degrees of hypocalcemia (such as those observed in the study by Morotti and colleagues) affect ICH volume or expansion via a coagulopathy.”