Intracranial Bleeding in Adults with Sickle Cell Disease: Unveiling the Hidden Dangers
Authors: Vojjala Nikhil , Kyasa Sai Brigisha , Sharma Aditi , Kotla Nikhil Kumar , Prabhu Rishab Rajendra , Singh Vijendra 
Published: December 2024

Introduction:

Sickle cell disease (SCD) is an inherited hemoglobinopathy resulting in abnormal polymerization of the beta-globin chain. Although it is known for defects in hemostasis and thrombotic complications, site-specific bleeding complications have been described. Intracranial bleeding (ICB) is a very rare fatal bleeding diathesis in these patients that usually occurs because of abnormal neo-vascularization and friable vessels. Though it is a dreaded complication, not much is known about its prevalence and outcomes in this subset of patients.

Aims and Methods:

We conducted a retrospective cohort study using the Nationwide Inpatient sample database from 2016 to 2020 to identify hospitalizations with Sickle cell disease, using the ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) codes D57 and D57.1. Descriptive analysis was performed to report patient demographics, hospital characteristics, various comorbid conditions, and complications. The prevalence of ICB was derived using a secondary diagnosis using ICD-10 CM codes I60, I61.9, and I62.9. The all-cause mortality rate was calculated, and the odds of each factor contributing towards mortality were derived. The analysis produced national estimates after applying weights, utilizing the methodology provided by the Healthcare Cost and Utilization Project.

Results:

Out of 468,070 adult SCD admissions between 2016 and 2020 in the United States, 825 had intracranial bleeding (nontraumatic intraparenchymal and/or subarachnoid bleeding). Of these, 410 (49.7%) were males, and 380 (46.0%) were aged over 45 years. The mean age was slightly higher in the SCD-ICB group compared to the non-ICB group (44.6 years vs. 34.3 years). Furthermore, the majority were admitted to a teaching hospital (86.7%), all of which were in urban areas with at least 1 million residents. Although 13.3% had sequelae from a prior stroke, only 29.8% of patients had an Elixhauser comorbidity index of ≥ 3. The incidence of various comorbid conditions such as hypertension, dyslipidemia, prior stroke of any form, hypothyroidism, carotid artery atherosclerosis, aortic atherosclerotic disease, and peripheral arterial disease was significantly higher in the SCD-ICB category compared to the non-ICB category, while the incidence of cancer was lower in the ICB category (12.1% vs. 46.9%, p &lt; 0.001). Notably, atherosclerotic cardiovascular disease was seen in 100% of SCD admissions with ICB compared to 8.9% in non-ICB (p &lt; 0.001). Regarding complications, sepsis occurred in 19.3% of the admissions with SCD-ICB, vasopressor requirement was seen in 7.8%, and about 43.6% required mechanical ventilation. On multivariable logistic regression, the incidence of acute chest syndrome and non-ICB bleeding tendencies was not different between the two groups. The mean length of stay for the ICB group was 14.9 days, and 210 deaths occurred during the index hospitalization, resulting in a 25.4% inpatient mortality rate, which was much higher than 0.6% in SCD-non-ICB patients (p &lt; 0.001). This translated to higher odds of death on adjusted analysis with an adjusted odds ratio of 16.34; 95% CI 9.22-28.97 (p &lt; 0.001), a longer mean length of stay by 8.4 days (p &lt; 0.001), and a statistically significant higher mean total hospitalization charge of $194,585.

Conclusion:

In conclusion, this study highlights the significant burden and severe outcomes of intracranial bleeding in adult SCD patients, including higher mortality, longer hospital stays, and increased healthcare costs. The high prevalence of bleeding diathesis and conventional risk factors underscores the need for effective atherosclerotic cardiovascular disease risk factor control to prevent these catastrophic events.