Progression of traumatic intracerebral hemorrhage: a prospective observational study.

ABSTRACT Preliminary evidence has shown that intracerebral hemorrhages, either spontaneous (sICH) or traumatic (tICH) often expand over time. An association between hemorrhage expansion and clinical outcomes has been described for sICH. The intent of this prospective, observational study was to characterize the temporal profile of hemorrhage progression, as measured by serial computed tomography (CT) scanning, with the aim of better understanding the natural course of hemorrhage progression in tICH. There was also a desire to document the baseline adverse event (AE) profile in this patient group. An important motive for performing this study was to set the stage for subsequent studies that will examine the role of a new systemic hemostatic agent in tICH. Subjects were enrolled if they had tICH lesions of at least 2 mL on a baseline CT scan obtained within 6 h of a head injury. CT scans were repeated at 24 and 72 h. Clinical outcomes and pre-defined AEs were documented. The data showed that 51% of the subjects demonstrated an increase in tICH volume, and that most of the increase occurred early. In addition, larger hematomas exhibited the greatest expansion. Thromboembolic complications were identified in 13% of subjects. This study demonstrates that tICH expansion between the baseline and 24-h CT scans occurred in approximately half of the subjects. The earlier after injury that the initial CT scan is obtained, the greater is the likelihood that the hematoma will expand on subsequent scans. The time frame during which hemorrhagic expansion occurs provides an opportunity for early intervention to limit a process with adverse prognostic implications.

Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial.

OBJECTIVE: Intracerebral hemorrhages, whether spontaneous or traumatic (tICH), often expand, and an association has been described between hemorrhage expansion and worse clinical outcomes. Recombinant factor VIIa (rFVIIa) is a hemostatic agent that has been shown to limit hemorrhage expansion and which, therefore, could potentially reduce morbidity and mortality in tICH. This first prospective, randomized, placebo-controlled, dose-escalation study evaluated the safety and preliminary effectiveness of rFVIIa to limit tICH progression. METHODS: Patients were enrolled if they had tICH lesions of at least 2 ml on a baseline computed tomographic scan obtained within 6 hours of injury. rFVIIa or placebo was administered within 2.5 hours of the baseline computed tomographic scan but no later than 7 hours after injury. Computed tomographic scans were repeated at 24 and 72 hours. Five escalating dose tiers were evaluated (40, 80, 120, 160, and 200 microg/kg rFVIIa). Clinical evaluations and adverse events were recorded until Day 15. RESULTS: No significant differences were detected in mortality rate or number and type of adverse events among treatment groups. Asymptomatic deep vein thrombosis, detected on routinely performed ultrasound at Day 3, was observed more frequently in the combined rFVIIa treatment group (placebo, 3%; rFVIIa, 8%; not significant). A nonsignificant trend for rFVIIa dose-response to limit tICH volume increase was observed (placebo, 21.0 ml; rFVIIa, 10.1 ml). CONCLUSION: In this first prospective study of rFVIIa in tICH, there appeared to be less hematoma progression in rFVIIa-treated patients (80-200 microg/kg) compared with that seen in placebo treated patients. The potential significance of this biological effect on clinical outcomes and the significance of the somewhat higher incidence of ultrasound-detected deep vein thromboses in the rFVIIa-treated group need to be examined in a larger prospective randomized clinical trial.