The Impact of Multi-System Trauma in Patients with Sickle Cell Disease

The impact of multi-system traumatic injury in patients with Sickle Cell Disease (SCD) is grossly understudied; only three published case studies have described such a relationship between sickle cell and multi-system trauma. These reports do not address prospective health outcomes following injury, despite strong biological plausibility to support adverse effects in trauma patients with sickle cell trait. It is likely, therefore, that trauma may increase acute complications such as vaso-occlusive events (VOC) and thus pain crises in SCD. We examined whether exposure to a traumatic injury is associated with an increase in frequency and duration of VOC.

A retrospective chart review of 356 adult patients from 2000-2022 with SCD was performed, using data from electronic health record abstraction. A total of 96 patients were identified with a prior traumatic event (TE), defined as a sudden onset of physical injuries of any severity requiring an Emergency Department (ED) visit. Patients with missing data one-year pre- and post-TE, isolated injuries, or periods of incarceration were excluded. The 62 qualifying patients were then sorted into three primary comparison groups: (A) those with severe injuries (receiving triage by Trauma Team Activation (TTA) and admission), (B) moderate injuries (receiving triage by TTA but no admission), and (C) minor injuries (receiving neither triage by TTA nor admission). To further stratify by triage status alone, groups A and B were combined to compare against those with minor injuries (triage vs no-triage). TE hospital length of stay (LOS) and 30-day mortality were noted for all groups.

To determine sickle cell-related outcomes, we recorded the time from TE discharge to first VOC event, as well as the number of VOC requiring an ED visit one-year pre- and post-TE. LOS for the VOC event immediately pre-TE was compared to the first VOC post-TE. We tested statistically significant changes in the frequency of ED visits, hospitalizations, and LOS for TE admission, stratifying pre-post estimates by severity of trauma. Favorable prospective health outcomes were defined as no significant difference in mortality, number of ED visits, hospitalizations, and VOC LOS pre- and post-TE.

Our analysis determined that the earliest time to first VOC event post-TE was noted in patients with mild injuries at 826.3 hours, followed by patients with moderate injuries at 2349.2 hours, and patients with severe injuries at 3252.6 hours. This trend may imply that unresolved injuries from a lack of triage by TTA and disease management may contribute to early onset VOC. Two-sample t-tests report that the patient cohort with mild injuries observed a 28% increase in pain crises frequency post-injury (p=0.04), followed by patients with severe injury at 20% (p=0.24), and moderate injuries at 8% (p=0.16). These results may suggest that the cohorts of SCD patients with the most favorable prospective health outcomes were those who were ultimately admitted post-injury. Similarly, duration of first VOC post-injury increased for patients with severe injuries by 472% (p=0.78), followed by patients with moderate injuries by 202% (p=0.16), suggesting that high injury severity may contribute to longer VOC LOS. No statistical difference in 30-day mortality was noted between all cohorts. Our analysis was limited by small cohort sample sizes, retrospective documentation of SCD and trauma outcomes, and lack of precedence.

Our findings are the first to provide preliminary evidence for an association between exposure to multi-system traumatic injury and poor SCD outcomes. This was especially true for patients classified as having mild traumatic injuries and thus not requiring triage by TTA or admission. In this subset, lack of further interventions following an injury may result in unforeseen physiologic stressors contributing to occurrence of VOC and prolonged hospital admissions. Only one patient of 356 record reviews had an Emergency Severity Index Triage (ESI) documented, despite NIH SCD Expert Panel's recommendation that all SCD patients be designated an ESI of 2. In SCD patients, further management of traumatic injuries, regardless of severity, may help to minimize future VOC events and other adverse outcomes. Further research is required to identify post-TE triage protocols, predict acute triggers for pain events, and target appropriate medical interventions for SCD patients suffering traumatic injuries.

Decastro:Bayer: Research Funding; Global Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ironwood Pharmaceuticals: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.