Toddler with hemophilia learns to walk

Factor VII Product Treats Brain Hemorrhages in Inhibitor Patients

NovoSeven demonstrated to be safe and effective
Author: Gina Shaw

Head bleeds, or cranial hemorrhages, can be a terrifying prospect for parents of children with a bleeding disorder. The cause may be an external bleed from an obvious trauma, such as when a toddler learning to walk bumps his head. Or, it may result from an internal hemorrhage, from a known trauma. It also can be spontaneous with no known cause. A head bleed can have devastating long-term consequences.

In people with hemophilia and an inhibitor, replacing the missing factor to stop a head bleed is not often possible. A new analysis of the literature indicates that recombinant activated factor VII, specifically NovoSeven®, has been demonstrated safe and effective when treating cranial hemorrhages in patients with inhibitors, whether the bleeds are external or internal. NovoSeven is called a “bypassing agent,” because it skips the natural clotting cascade pathway. Instead, it triggers the release of factor X (one of the 13 factors in the clotting process that must be activated correctly), avoiding the need for factor VIII or IX in people with inhibitors.

Charles Nakar, MD, and colleagues conducted a retrospective analysis of data collected through the Hemophilia and Thrombosis Research Society registry between January 2004 and March 2008. The study was limited by the relatively small size of the community. “It’s hard to get data on these incidents, because hemophilia is a rare disease to begin with. Then, when you limit it to patients with inhibitors who had cranial hemorrhages, you get really limited literature,” says Nakar, a pediatric hematologist at the Indiana Hemophilia & Thrombosis Center in Indianapolis.

Ultimately, 56 cases of hemorrhage among 29 patients met the criteria for inclusion in the study. Of those, 80% were external hemorrhages and 75% were the result of trauma. By combining and comparing all the data in the registry, Nakar and his team determined that NovoSeven was 100% effective in controlling extracranial bleeds and 82% effective in controlling intracranial hemorrhages, the more unpredictable and dangerous type. “There was also a very low rate of adverse events associated with intense treatment using this drug,” he says. One patient with an intracranial hemorrhage did die, despite reported control of the bleeding.

Variation in Treatment Regimens

The study, published in the July 2010 issue of Haemophilia, found a wide variability in NovoSeven treatment regimens for people with hemophilia and inhibitors who have intracranial bleeds. “Different hemophilia centers start treatment with different doses,” says Nakar. The mean initial dose found in the study, between 106 and 137 micrograms per kilogram (mcg/kg), was higher than the recommended range of 90–120 mcg/kg, but appeared to be safe, Nakar says.

“When patients with inhibitors have an intracranial bleed, it may be a life-threatening event,” Nakar says. “The sooner you treat it, the better the outcome may be. Regardless of treatment, some patients with intracranial hemorrhage will need surgery to release the pressure and clear and control the bleeding. Unfortunately, intracranial bleeds can sometimes be fatal.”

The researchers also found that for most patients with internal bleeding, treatment started in the hospital. “That’s probably because of the uncertainty of the diagnosis and the need for imaging,” Nakar says. But given the seriousness of an intracranial hemorrhage and the importance of quick treatment, he suggests taking action at home first. “If a child with hemophilia, particularly with inhibitors, is hit in the head or develops a sudden severe headache or vomiting, he should start treatment at home immediately and then get the CT scan.”