# Spontaneous Epidural Hemorrhage in Sickle Cell Disease, Are They All the Same? A Case Report and Comprehensive Review of the Literature

Authors: Biplab Saha; Aditi Saha
Journal: Case Reports in Hematology
 (2019)

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## Abstract

Trauma to the skull causing injury to the middle meningeal artery, middle meningeal vein, or dural venous sinuses is responsible for most cases of epidural hemorrhage (EDH). Spontaneous EDH is a rare entity in clinical practice. Common causes include sinusitis, coagulation abnormalities, dural metastasis, and Langerhans cell histiocytosis. Isolated nontraumatic EDH is an exceedingly rare complication of sickle cell disease (SCD). We report a case of spontaneous EDH in a patient with SCD and review the world literature regarding this rare entity. A 20-year-old African American female with sickle cell disease presented with vaso-occlusive crisis. About 24 hours after hospital admission, the patient had sudden deterioration of her mental status. An emergent CT scan of the head revealed a large right-sided frontoparietal epidural hematoma with midline shift, subfalcine, and uncal herniation. The patient underwent emergent hematoma evacuation but died 24 hours after surgery.


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## Body

## 1. Introduction

Sickle cell disease (SCD) is caused by a single amino acid substitution on the beta globin chain resulting in the propensity of the hemoglobin molecule to polymerize in deoxygenated state. The abnormal polymerization is responsible for subsequent RBC injury, hemolysis, microvascular injury, and classical acute and chronic manifestations of the disease. Neurologic manifestations secondary to SCD are common and affect about 35% of patients [1]. Although reports vary [2], existing data suggest that 54% of these patients suffer from ischemic strokes and 34% from intracranial bleeding [1]. Intracerebral, subarachnoid, intraventricular, subdural, and epidural bleeds have been reported, with subarachnoid hemorrhage being the most common, especially in young adults [1–3]. Isolated nontraumatic spontaneous epidural hematoma (EDH) is an exceedingly rare complication of SCD. Other reported etiologies of spontaneous EDH are infectious [4–6], coagulation abnormalities associated with end stage renal disease and hemodialysis [7–9], dural metastasis [10–13], and Langerhans cell histiocytosis [14–16]. We present a case of spontaneous EDH in a sickle cell patient suffering from vaso-occlusive crisis and review the world literature regarding the rare entity.


## 2. Case Presentation

A 20-year-old African American female with a history of sickle cell disease (HbSS) and multiple previous admissions for vaso-occlusive crisis (VOC) presented to the hospital with severe generalized pain throughout her body. The patient was in severe distress. Her blood pressure was 155/101 mmHg, pulse 117 beats per minute, temperature 37.6 C, respiratory rate 25 breaths per minute, and oxygen saturation 98% on room air. Physical examination revealed poor bilateral air entry on lung auscultation due to splinting and an ejection systolic murmur over the aortic area. Mild-to-moderate tenderness was present over the extremities on palpation. Neurological examination was normal. Blood work showed leukocytosis, 12,800 with 53% neutrophil, 32% lymphocyte, and 1% band, hemoglobin 7.5 gm/dL, hematocrit 22.3%, platelet 181,000/dL, reticulocyte count 13%, lactate dehydrogenase 1144 IU/L, normal blood urea nitrogen, creatinine, and serum electrolyte studies. Liver function tests were normal except a total bilirubin level of 16.2 mg/dL. Chest X-ray was normal. The patient was started on IV hydration; analgesia was achieved by IV narcotics.About 24 hours after hospital admission, the patient suddenly became unresponsive. Naloxone failed to improve her mental status. An emergent CT scan of the head revealed a large right-sided frontoparietal epidural hematoma with midline shift, subfalcine, and uncal herniation. No subgaleal or subperiosteal collection was noted. There was no noticeable bone infarction overlying the hematoma (Figure1).Figure 1
(a) Mixed density right frontoparietal epidural hematoma with midline shift. (b) Bony window showing massive expansion of the diploic bone from extramedullary hematopoiesis.
(a)
(b)Laboratory data at this time demonstrated a platelet of 45,000/dL, prothrombin time 19.7 Seconds, INR 1.7, activated partial thromboplastin time 43 seconds, and a fibrinogen level of 96 mg/dL, consistent with a diagnosis of disseminated intravascular coagulation (DIC). The patient was emergently taken to the operating room for hematoma evacuation (Figure2). Intraoperatively, no obvious bony abnormality was noted. Exchange transfusion was performed. The patient, however deteriorated, became hypotensive requiring multiple vasopressors and eventually died about 24 hour after surgical intervention from DIC.Figure 2
(a) Postoperative changes following hematoma evacuation with a small collection in the subdural space and significant improvement of midline shift (b) Punctate hemorrhage in the right temporal lobe postop.
(a)
(b)Total 31 cases. R, right; L, left; N/S, not specified; B/L, bilateral; VOC, vaso-occlusive disease; FP, frontoparietal; PT, parietotemporal; DIC, disseminated intravascular coagulation; POA, present on admission; BS, bone scan; IO, intraoperatively.


## 3. Discussion

We have described a patient with SCD suffering from spontaneous EDH is the setting of VOC. Including the present case, we have identified 31 cases described in the literature, which are shown individually in Table1. Since first reported about 3 decades ago, the reporting incidence has increased precipitously in the last decade possibly due to increased awareness, radiologic advancement, and more opportunities for publication rather than actual increase in incidence (Figure 3).Table 1
Case report
Year
Age (years)
Sex
Haplotype
Presentation
Identification of EDH after hospitalization
Location of EDH
Subgaleal hemorrhage
Subperiosteal collection
Skull infarction
DIC present
Outcome
Current case
2019
19
Female
HbSS
VOC
24 hours
R FP
No
No
No (CT/IO)
Yes
Died
Komarla et al. [17]
2018
18
Female
Unspecified
VOC
24 hours
R parietal
No
No
Yes (MRI)
N/S
Survived
17
Male
Unspecified
Headache
POA
Bifrontal
Yes
Yes
Yes (MRI)
N/S
Survived
Banerjee et al. [18]
2018
Teenage
Male
HbSS
VOC
6 hours
L frontal
No
No
No (MRI)
Yes
Died
Moyen et al. [19]
2018
13
Male
HbSS
Seizure
Imaging not performed till day 8
R FP
No
N/S
No (MRI)
No
Died
Mishra et al. [20]
2017
18
Male
HbSS
VOC
120 hours
R parietal
Yes
No
Yes (IO)
No
Survived
Gajjar and Gupta [21]
2015
20
Male
Unspecified
Headache
POA
L PT
No
No
No (CT)
No
Survived
Hettige et al. [22]
2015
7
Female
HbSS
Coma
POA
B/L parietal
No
No
No (CT/IO)
Yes
Died
Yogarajah at al. [23]
2015
19
Male
HbSC
VOC
24 hours
R PT
No
No
No (CT/IO)
No
Survived
N’dri Oka et al. [24]
2015
19
Male
HbSC
Headache
POA
Occipital
Yes
No
No (CT)
No
Survived
Ilhan et al. [25]
2014
15
Male
HbSS
Headache
POA
Right frontal
Yes
No
Yes (MRI)
No
Survived
Serarslan et al. [26]
2014
19
Female
HbSS
Headache
POA
L FP
No
No
No (CT/IO)
No
Survived
Page et al. [27]
2014
20
Male
HbSS
VOC
48 hours
L frontal
Yes
No
Yes (MRI)
No
Survived
7
Female
HbSS
Coma
POA
R temporal
No
Yes (MRI)
No
Survived
Babatola et al. [28]
2012
18
Male
HbSS
Headache
POA
R Frontal
No
No
No (CT/IO)
No
Survived
Bolke and Scherer [29]
2012
19
Male
Unspecified
VOC
72 hours
L frontal
No
No
No (CT/IO)
No
Died
Patra et al. [30]
2012
13
Male
Unspecified
Headache
POA
B/L parietal
No
No
No (CT)
No
Survived
Arends et al. [31]
2011
19
Male
HbSC
Headache
POA
R parietal
No
No
Yes (MRI)
No
Survived
Sangle et al. [32]
2011
15
Male
Unspecified
Headache
12 hours
Bifrontal
No
No
No (MRI)
No
Died
Azhar [33]
2010
12
Male
HbSD
VOC
24 hours
L frontal
No
No
N/S (CT)
N/S
Survived
Dahdaleh et al. [34]
2009
18
Male
Unspecified
VOC
12 hours
B/L FP
Yes
No
No (CT/IO)
No
Survived
Kotb et al. [35]
2006
10
Male
Unspecified
Headache
N/S
Bifrontal
Yes
No
Yes (MRI)
N/S
Survived
Kalala Okito et al. [36]
2004
2
Male
HbSS
Coma
POA
R FT
No
No
N/S (IO)
N/S
Died
12
Male
HbSS
VOC
N/S
L parietal
No
No
Yes (X-ray)
No
Survived
Ganesh et al. [37]
2001
11
Male
HbSS
Proptosis
POA
Bifrontal
Yes
No
Yes (BS)
N/S
Survived
Naran and Fontana [38]
2001
16
Male
Unspecified
Headache
? POA
R Frontal
No
No
Yes (MRI/BS)
No
Survived
Cabon et al. [39]
1997
14
Female
HbSS
Unknown
Unknown
Bifrontal
Unknown
Unknown
Yes
Unknown
Unknown
Resar et al. [40]
1996
14
Male
HbSS
VOC
48 hours
Left parietal and B/L frontal
Yes
Yes
Yes (MRI/BS)
No
Survived
Tony et al. [41]
1995
35
Male
Sickle- thalassemia
Proptosis
POA
Left frontal
No
No
Yes (BS)
No
Survived
Karacostas et al. [42]
1991
19
Male
HbSS
VOC
48 hours
Left frontal
No
No
No (CT)
No
Survived
Mallouh et al. [43]
1987
13
Male
HbSS
Eye swelling
POA
Bifrontal
No
No
Yes
N/S
SurvivedFigure 3
Reported cases of EDH in patients with SCD in the literature.Most reported cases comprised males 25/31 (80%). The age ranged from 2–35 years (median 16.5) and 7–19 years (median 16), respectively, for males and females. 26/31 (84%) had SCD (17 patients with reported homozygosity and 9 known cases without specified haplotype). Other cases included 3 patients with HbSC disease, 1 with HbSD, and sickle thalassemia each.Headache was present on admission in 37% (11/30), whereas symptoms consistent with VOC, primarily pain crisis, were the initial complaint in 40% (12/30). Other presenting symptoms were eye swelling, proptosis, seizure, and coma. In patients who presented with a headache, EDH was present on admission in 82% of the time. Patients who presented with VOC, progressed to have EDH within 6–120 hours, with a median of 24 hours after hospital admission.Unilateral EDH was more common 20/31 (65%). Subgaleal hemorrhage was concurrently present in 9/30 (30%) of patients and associated with bone infarction in (7/9) 78% of cases. 48% of patients (15/31) with EDH showed evidence of overlying bony infarction. The overall mortality among the reported cases was 23% (7/30). Interestingly, patients with evidence of overlying bone infarction had a survival of 100% and patients with DIC had a mortality of 100%.The most common cause of EDH is trauma causing injury to the middle meningeal artery, middle meningeal vein, the diploic vein, or the dural venous sinuses [44]. Spontaneous nontraumatic EDH is a rare manifestation of SCD and variant sickle cell syndromes. The pathophysiology of this rare occurrence is not completely understood.Most reported cases in the literature are males. Whether any gender specific etiology is responsible for this discrepancy is not known. Low steady-state hemoglobin and high leukocyte count are known risk factors for hemorrhagic stroke in patients with SCD [1]. Whether this is also true for EDH is not clear. In the landmark study by Ohene-Frempong et al., hemorrhagic strokes were more prevalent in the adult SCD patients in the age range of 20–30 years [1]. However, EDH appears to be more prevalent in the adolescent age group.Three pathophysiologic explanations have been proposed over the years for the causation of this rare entity: (1) Vaso-occlusion of the haematopoietically active calvarial diploic bone resulting in bone infarction and subsequent leaking of blood and proteinaceous material in the subperiosteal, epidural, or subgaleal space [38–41, 43, 45]. (2) Acute rapid expansion of hematopoiesis with resultant microfracture of already thinned inner cortex and extravasation of blood and hematopoietic tissue [24, 28, 36]. (3) Sludging of sickle cells in the diploic veins hampering venous drainage and oozing of blood due to vascular injury and elevated back pressure. A combination of different mechanisms could also be responsible. Presence of coagulopathy or platelet dysfunction worsens hematoma expansion and portends a dire clinical outcome.Patients admitted with VOC developed EDH, did so with a median of 24 hours, suggesting early deterioration is expected in this patient population. Patients who suffered from concurrent bony infarction or subgaleal hemorrhage had a survival rate of 100%. This may indicate that vaso-occlusive etiology of the EDH carries better prognosis. This would also explain presence of EDH with contralateral subgaleal hemorrhage as skull bone infarction could be diffused [40]. The identification of bone infarction can be challenging. MRI appears to be the most sensitive tool. CT scan has low yield especially in the acute phase of the disease [18]. Infarcted bone can appear normal intraoperatively although thinning of the inner cortex is frequently seen. In 3 out of 7 patients who succumbed to their disease, an MRI ruled out any bony infarction. In the other 4 cases, no bone damage was noted by CT scan or on intraoperative inspection. We propose that patients without any obvious bony disruption and infarction, most likely suffer from microfracture of the inner table and extrusion of blood and hematopoietic cells in the epidural space due to rapid expansion of hematopoiesis. Presence of coagulopathy as in DIC makes the bleeding significantly worse. Patients who suffered from spontaneous EDH and suffered from DIC had a 100% mortality.


## 4. Conclusion

The understanding regarding this clinical entity is rapidly evolving in the era of advanced technology and improved awareness among healthcare providers. We believe this review will shed more light on the clinical as well as the pathophysiological aspect of the disease process and help in rapid identification of patients at risk of deterioration and formulate management plan accordingly.



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