Abstract
To the Editor:
The recent case report Disease, Accident, and Trauma: A Case Report on Sudden Death in Wiskott-Aldrich Syndrome (WAS), by Manral et al (1), is an issue of great interest to me. Their cautious findings in a 10-month-old male with genetically verified WAS are also a valuable endorsement of how innate bleeding diathesis can presently or be complexed by the proving results, which would have otherwise triggered alarm over a possible trauma. I would like to add more thoughts in the hope of perfecting the forensic investigation in such situations, refer to likely unexamined mechanisms in this very case, and seek progress to minimize the uncertainty in the diagnosis.
THE SITUATION IN WAS, HEMORRHAGE, AND SUDDEN DEATH
WAS can be characterized by thrombocytopenia (which is often combined with micro-platelets), eczema, immunodeficiency, and bleeding—mucosal, gastrointestinal, as well as intracranial. As has also been reported, bleeding (instead of infection) is a common killer in a subset of patients, up to 20% to 25% in certain groups (2). Like less common but also a severe manifestation, intracranial hemorrhage (ICH) (such as subarachnoid hemorrhage (SAH)) is still perceived as a severe manifestation (3). Accordingly, the discovery of the SAH in WAS is not supposed to be shocking. The mechanisms of the genesis of such hemorrhages (particularly, diffuse SAH) among WAS infants and how they may be triggered by small injuries, or how to tell the difference between postmortem and traumatic injury or abusive head trauma, have received less attention.
VITAL ANALYSIS OF THE CASE AND UNRESEARCHED ALTERNATIVE PROCESS
According to Manral et al (1), the paper has more than one petechia, a hematoma of the subscalp, and diffuse SAH over the right temporo-parietal region, and no alleged falls or significant trauma have been observed. They come up with a conclusion that death is natural since hemorrhage happens incidentally in the setting of WAS.
Nonetheless, there are several questions that deserve more attention in this case and in other cases of reporting:
Microvascular frailty and spontaneous SAH: WAS is not only the cause of thrombocytopenia but also platelet defects, platelet-based thrombendarterectosis, immune-mediated platelet endovascular reactivity, and perhaps vessel wall defects (3). Was there spontaneous rupture of tiny vessels (under the subjected minimal stress), that is, a transient increase of intracranial pressure? This would be expounded by deeper histology. Vomiting and intracranial pressure: These vomiting episodes before unconsciousness would imply temporary situations in which venous pressures rise, which may be prone to bursting the weak cerebral vessels. These hemorrhages are reported following conductive Valsalva-type bothers in infants (4). Subscalp hematoma-marker/cause: Was this accidental or a precipitated later bleed? The histological process of aging, along with comparison with findings inside, may help identify sentinel trauma and sporadic bleeding. Histological age determination: It would be conducive to an acute hemorrhage, which lacks organization, whereas hemosiderin beams or tissue response would be indicative of recurrent bleeding (5). The lack of background information regarding hospitalization creates a blank in determining baseline coagulation state. Compound causation: A prejudice disease may be the underlying cause of hemorrhage and a trifle cause, which is the proximate cause (6). It is thus necessary to put down in writing documents on minor antecedent events.
RESEARCH IMPLICATIONS ON FORENSIC PRACTICE AND CASE REPORTING
Based on this case and my considerations, I would propose several best practices:
Routine histopathologic examination of cerebral and meningeal vessels, meeting the stains in chronic hemorrhage. Postmortem (computed tomography, magnetic resonance imaging with susceptibility sequences) to due to differentializing between SAH and subdural bleeding and minor fractures (7). Autopsy and platelet coagulation profiling by molecular autopsy and platelet. The organized description of minor antecedent events, including coughing or vomiting. Inclusion of clinical records, in particular, recent transfusions and labs.
ORIGINAL HYPOTHESIS: INTRACRANIAL THRESHOLD OF VOMITING-INDUCED INTRACRANIAL HEMORRHAGE IN WAS
It is my hypothesis that, even in the absence of direct trauma, infants constituted with the most severe forms of WAS can exhibit a smaller threshold to cause intracranial bleeding as a result of vomiting-induced rises in venous pressure. Such a threshold may be based on the number of platelets, platelet activity, vessel wall vulnerability, and the past bleeding history. Provided they are right, forensic studies are supposed to habitually investigate about vomiting or other instigators, like stress to a fatal SAH in WAS.
CONCLUSION
The case presented by Manral et al is a precious contribution to the literature body regarding the issue of WAS and sudden death during infancy. It brings to the forefront how dysfunctions of forensic warrants of trauma may come to pass in connection with natural hemorrhage in extreme hematologic complications. Future case reports must contain character histology, imaging, coagulation condition, and light antecedent incidents. Further on, the theory about a vomiting-induced threshold of a hemorrhage in WAS is the direction that should be studied systematically to improve clinical care and the police issue of forensic responsibility of the vomiting process.
Footnotes
ACKNOWLEDGMNTS
The authors would like to recognize the support of the following institutions: (1) Don Mariano Marcos Memorial State University, Bacnotan, La Union, Philippines, (2) London School of Hygiene and Tropical Medicine, London, United Kingdom, (3) Far Eastern University, Manila, Philippines, (4) University of Makati, Makati City, Philippines, and (5) De La Salle University, Manila, Philippines.
ETHICAL APPROVAL
There were no human or animal subjects. Ethical approval is not applicable in this letter.
STATEMENT OF HUMAN AND ANIMAL RIGHTS
Not applicable.
STATEMENT OF INFORMED CONSENT
Not applicable.
AUTHOR CONTRIBUTIONS
Emarson L. Sison and Jomar L. Aban—conceptualization, manuscript draft, formal analysis, and investigation. JLA—supervision, resources, software, writing, and review and editing. DEP—supervision, resources, and software.
FINANCIAL DISCLOSURE
The authors received no financial support for the research, authorship, and/or publication of this article.
DISCLOSURES & DECLARATION OF CONFLICTING INTERESTS
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
DATA AVAILABILITY STATEMENT
Not applicable.
