The Role of the Iron Stain in Assessing Intracranial Hemorrhage

Rudy J. Castellani1, 2, *, Gruschenka Mojica1, George Perry3
1 University of Maryland School of Medicine, Baltimore, Maryland, USA
2 Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, Michigan, USA
3 College of Sciences, University of Texas, San Antonio, Texas, USA

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© Castellani et al.; Licensee Bentham Open

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the University of Maryland School of Medicine, Baltimore, Maryland 300 Portage Street, Kalamazoo, Michigan, 49007, USA; Tel: 410-328-5555; Fax: 410-328-5508; E-mail:


The timing of the breakdown of red blood cells and organization of hemorrhage has significance in the catabolism of heme and the processing of iron, but also has a practical application in terms of assigning, or attempting to assign, a time course with respect to traumatic events (e.g. contusions and hemorrhages). Attempts to date contusions, however, have generally been unsuccessful by macroscopic observation, whereas the microscopic observations provide broad data but are also anatomically imprecise as a function of time. Intracranial lesions are of particular significance with respect to the timing of organizing hemorrhage given the acute, and often life-threatening nature of the hemorrhages, and the medicolegal investigation into potential crimes. Of concern is that the Prussian Blue reaction for iron, a relatively straightforward histochemical reaction that has been in use for over 150 years, is sometimes suggested as a diagnostic test for chronicity. Therefore, this study examined the utility of the Prussian Blue iron stain in living patients with intracranial hemorrhages and well-defined symptom onset, to test whether the presence of Prussian Blue reactivity could be correlated with chronicity. It was found that out of 12 cases with intracranial hemorrhage, eight cases showed at least focal iron reactivity. The duration from symptom onset to surgery in those eight cases ranged from < 24 hours to more than 3 days. Of those cases with no iron reactivity, the duration from symptom onset to surgery ranged from < 24 hours to six days. In conclusion, the Prussian Blue reaction was unreliable as an indicator of timing in intracranial hemorrhage. The use of the Prussian blue reaction as an independent indicator of chronicity is therefore not valid and can be misleading. Caution is indicated when employing iron staining for timing purposes, as its only use is to highlight, as opposed to identify, pre-existing lesions. With respect to brain lesions, the Prussian blue reaction should not be used in place of the clinical timing of the neurologic decline, or clinical data that is otherwise more accurate and less susceptible to false positive results.

Keywords: Hemosiderin, Intracranial hemorrhage, Iron, Prussian blue.