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.”

“Lower calcium levels might simply be a marker or surrogate for another disease-modifying condition,” they suggest.

“Although the causal and mechanistic links are currently abstruse, this new study provides important insights into novel factors that may influence ICH size and the risk of expansion,” the editorial concludes. “Considering the relative lack of progress in unraveling the pathophysiology of ICH, these new findings are welcome and needed. We can easily and rapidly increase serum calcium levels if this simple intervention might reduce the risk of hematoma expansion. But I doubt it will be that simple. It almost never is when dealing with strokes.”

Dr. Walter M. van den Bergh from University Medical Center Groningen, The Netherlands told Reuters Health by email, “What is surprising is that low calcium levels almost double the risk, but the most interesting is that the relation with ICH expansion offers a window for intervention (e.g., calcium supplementation).”

“That remains to be seen after an intervention study,” he cautioned. “In massive bleeding, calcium supplementation is routine; this might be the case in ICH management if future randomized controlled trials are successful.”