1. health and fitness
2. disorders

Intracranial Hemorrhage after Blunt Head Trauma in Children with
Bleeding Disorders
Lois K. Lee, MD, MPH, Peter S. Dayan, MD, MSc, Michael J. Gerardi, MD, Dominic A. Borgialli, DO, MPH,
Mohamed K. Badawy, MD, James M. Callahan, MD, Kathleen A. Lillis, MD, Rachel M. Stanley, MD, Marc H. Gorelick, MD,
MSCE, Li Dong, MSc, Sally Jo Zuspan, RN, MSN, James F. Holmes, MD, MPH, and Nathan Kuppermann, MD, MPH, and the
Traumatic Brain Injury Study Group for the Pediatric Emergency Care Applied Research Network (PECARN)
Objective To determine computerized tomography (CT) use and prevalence of traumatic intracranial hemorrhage
(ICH) in children with and without congenital and acquired bleeding disorders.
Study design We compared CT use and ICH prevalence in children with and without bleeding disorders in a multicenter cohort study of 43 904 children <18 years old with blunt head trauma evaluated in 25 emergency departments.
Results A total of 230 children had bleeding disorders; all had Glasgow Coma Scale (GCS) scores of 14 to 15.
These children had higher CT rates than children without bleeding disorders and GCS scores of 14 to 15 (risk ratio,
2.29; 95% CI, 2.15 to 2.44). Of the children who underwent imaging with CT, 2 of 186 children with bleeding disorders had ICH (1.1%; 95% CI, 0.1 to 3.8) , compared with 655 of 14 969 children without bleeding disorders (4.4%;
95% CI, 4.1-4.7; rate ratio, 0.25; 95% CI, 0.06 to 0.98). Both children with bleeding disorders and ICHs had symptoms; none of the children required neurosurgery.
Conclusion In children with head trauma, CTs are obtained twice as often in children with bleeding disorders,
although ICHs occurred in only 1.1%, and these patients had symptoms. Routine CT imaging after head trauma
may not be required in children without symptoms who have congenital and acquired bleeding disorders.
(J Pediatr 2011;158:1003-8).
I
ntracranial hemorrhage (ICH) is a significant and potentially life-threatening
complication for children with congenital or acquired bleeding disorders.1-9
There is evidence that these children are at increased risk for sustaining ICH
even after minor blunt head trauma.2,6,10 Studies in children with hemophilia
have reported ICH rates of 2% to 16% after head trauma, including some children
with no signs or symptoms of trauma. The risk of ICH varies with the severity of
hemophilia, and children with severe hemophilia (factor level <1%) are at highest
risk, from spontaneous and traumatic ICH.2,10-13 Although there are few studies
on the risk of ICH after head trauma in children with von Willebrand disease, they
seem to be at less risk than children with hemophilia.2,12,14
The risk of ICH in patients with other congenital and acquired bleeding disorders is less well described.1,2,15 In patients with immune (idiopathic) thrombocytopenic purpura (ITP), ICH, including spontaneous and traumatic, is rare,
with a reported incidence of 0.1% to 1.0%.1,9,16,17 However, the prevention of
ICH has been a primary goal in the management of ITP, because ICH risk correlates with the severity of thrombocytopenia.1,4,17 The ICH risk in patients who
have taken anti-coagulants has only been reported in adults, with differing conclusions about the risk of anti-coagulation therapy.18-22
CT
ED
GCS
ICH
ITP
LOC
PECARN
RR
Computerized tomography
Emergency department
Glasgow Coma Scale
Intracranial hemorrhage
Immune (idiopathic) thrombocytopenic purpura
Loss of consciousness
Pediatric Emergency Care Applied Research Network
Rate ratio
From the Department of Pediatrics, Harvard Medical
School, Boston, MA (L.L.); Department of Pediatrics,
Columbia University College of Physicians and
Surgeons, New York, NY (P.D.); Department of
Emergency Medicine, Atlantic Health System,
Morristown Memorial Hospital, Morristown, NJ
(M.Gerardi); Department of Emergency Medicine,
University of Michigan School of Medicine and Hurley
Medical Center, Flint, MI (D.B.); Departments of
Emergency Medicine and Pediatrics, University of
Rochester School of Medicine and Dentistry, Rochester,
NY (M.B.); Departments of Emergency Medicine and
Pediatrics, SUNY-Upstate Medical University, Syracuse,
NY (J.C.); Department of Pediatrics and Emergency
Medicine, SUNY-Buffalo School of Medicine and
Biomedical Sciences, Buffalo, NY (K.L.); Department of
Emergency Medicine, University of Michigan School of
Medicine, Ann Arbor, MI (R.S.); Department of Pediatrics,
Medical College of Wisconsin, Milwaukee, WI
(M.Gorelick); Department of Pediatrics, University of
Utah and PECARN Central Data Management and
Coordinating Center, Salt Lake City, UT (L.D., S.Z.); and
Department of Emergency Medicine, University of
California, Davis School of Medicine, Davis, CA (J.H.,
N.K.)
List of members of the Traumatic Brain Injury Study
Group for the Pediatric Emergency Care Applied
Research Network (PECARN) available at www.jpeds.
com (Appendix).
Supported by a grant from the Health Resources and
Services Administration/Maternal and Child Health Bureau, Division of Research, Education, and Training, and
the Emergency Medical Services of Children program
(R40MC02461). The Pediatric Emergency Care Applied
Research Network is supported by cooperative agreements U03MC00001, U03MC00003, U03MC00006,
U03MC00007, and U03MC00008 from the Emergency
Medical Services of Children program of the Health Resources and Services Administration/Maternal and Child
Health Bureau, Division of Research. The authors declare
no conflicts of interest.
0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc.
All rights reserved. 10.1016/j.jpeds.2010.11.036
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www.jpeds.com
The objectives of this study were to determine the frequency of computerized tomography (CT) imaging after
blunt head trauma in children with bleeding disorders compared with children without bleeding disorders, and the prevalence of ICH in these children.
Methods
This was an a priori planned substudy conducted as part of
a larger prospective cohort study to derive and validate a neuroimaging decision rule for children after blunt head
trauma.23 The study was approved by the institutional review
boards at all participating institutions. Written or verbal consent for this observational study was obtained at each institution as required by their institutional review boards.
The study was conducted in 25 emergency departments
(EDs) participating in the Pediatric Emergency Care Applied
Research Network (PECARN).24,25 Children <18 years old
who were evaluated for blunt head trauma resulting from
non-trivial mechanisms within 24 hours of injury at any of
the participating EDs between June 2004 and September
2006 were eligible for the main study.23 Congenital or acquired bleeding disorder was defined as hemophilia, von Willebrand disease, congenital or acquired thrombocytopenia
(defined as platelet count <150 000/mL), a functional platelet
disorder, other bleeding disorder, or anti-coagulation therapy
(warfarin, heparin, low molecular weight heparin/enoxaparin, clopidogrel). Patients were excluded from both the
main study and this substudy when they had: (1) trivial mechanisms of injury (falls from standing height, walking, or running into stationary object) and (2) no signs or symptoms of
head injury besides a scalp laceration or abrasion. Patients
were also excluded from both studies when they sustained
penetrating trauma, when the injury occurred >24 hours before the ED evaluation, when they had a pre-existing neurological disease, known brain tumor, or history of ventricular
shunt placement, or when they had been transferred with cranial imaging from an initial treating institution to the study
facility.
A full description of the main study protocol has been published.23 In brief, the treating clinician conducted the examination and recorded the results on a structured case report
form before knowledge of any imaging studies, if performed.
Cranial CTs were obtained at the discretion of the treating
clinician. The case report form included information about
patient history (including history of bleeding disorders), injury mechanism, symptoms, and physical examination findings. When the patient had a bleeding disorder, the case
report form included check boxes for hemophilia, platelet
disorders, anticoagulation therapy, von Willebrand disease,
‘‘unknown,’’ and ‘‘other.’’ Three hundred-forty children
were indicated to have a bleeding disorder on the case report
forms. We performed a detailed secondary medical record review of these cases to determine the specific type, and when
applicable, the severity of the bleeding disorder. Of these
340 children, 230 met criteria for analysis in this study. The
1004
Vol. 158, No. 6
other 110 were excluded from this study because they did
not meet the criteria for having a congenital or acquired
bleeding disorder at the time of the head injury. Patients
with hemophilia were categorized according to type of factor
deficiency and severity (mild, moderate, or severe). For children with thrombocytopenia, platelet counts at the time of
the ED evaluation were obtained, when available from the
medical record.
Hospital admission was at the discretion of the treating ED
physician. To determine the clinical outcomes of the patients
hospitalized for their head trauma, we performed a medical
record review, and data were recorded on a structured case
report form. For children discharged home from the ED,
a follow-up telephone call was conducted by trained research
coordinators between 1 week and 3 months after the ED visit
to determine whether the patient had an unscheduled return
visit to a healthcare provider and whether any cranial imaging was performed after their initial ED visit. When a missed
traumatic brain injury was suggested at follow-up, the medical records and imaging results were obtained and reviewed,
and the patient’s outcome was recorded. When telephone
follow-up was not available, we mailed a follow-up survey
or reviewed the medical record, quality improvement reports, trauma registries, or morgue reports at the respective
sites to obtain any missing clinical information.23
The primary outcomes were rates of CT use and presence
of an ICH on CT, as reported by an attending radiologist.
ICHs included epidural hematomas, subdural hematomas,
intraventricular hemorrhages, cerebral contusions, cerebral/
cerebellar hemorrhages, subarachnoid hemorrhages, or traumatic infarctions.
Data Analysis
We tabulated basic descriptive information for children with
and without bleeding disorders for the entire study population. Because all the children with bleeding disorders presented with Glasgow Coma Scale (GCS) scores of 14 or 15,
as did 98% of the children without bleeding disorders, the remainder of the analyses was performed only for children with
GCS scores of 14 and 15. We calculated rate differences with
95% CIs of the prevalence of signs and symptoms of head
trauma in children with bleeding disorders compared with
the reference population of children without bleeding disorders. We also compared rates of CT imaging and ICH for patients with bleeding disorders versus patients without
bleeding disorders by using rate ratios (RRs) with 95% CIs.
We performed multivariable logistic regression analyses to
identify factors independently associated with the use of
CT imaging. Children <2 years old and $2 years old were analyzed separately to optimize the inclusion of the presenting
signs and symptoms, because some symptoms (eg, headache)
cannot be accurately assessed in pre-verbal patients (<2 years
old). In these analyses, we adjusted for the diagnosis of coagulopathy and the severity of mechanism of injury and other
signs and symptoms suggestive of traumatic brain injury
(history of loss of consciousness, headache, vomiting, acting
abnormally according to parent, altered mental status, signs
Lee et al
ORIGINAL ARTICLES
June 2011
of skull fractures, and scalp hematomas).23 Altered mental
status was determined a priori as a GCS score <15, agitation,
sleepiness, slow responses, or repetitive questioning. We performed the data analysis with SAS software version 9.1.3 (SAS
Institute, Cary, North Carolina).
Results
A total of 43 904 patients with non-trivial blunt head trauma
were enrolled during the 28-month study period. Of these patients, 230 had a history of congenital or acquired bleeding
disorders meeting criteria for this analysis, including 129
(56.1%) with hemophilia. The demographic and injury severity characteristics of the children with and without bleeding
disorders are presented in Table I. The group with bleeding
disorders was more likely to be male and less likely to have
severe mechanisms of injury than the children without
bleeding disorders. Because all patients with bleeding
disorders (and 98% of patients without bleeding disorders)
presented with seemingly minor head trauma, defined with
GCS scores of 14 or 15, the remainder of the results
considers only children with GCS scores of 14 to 15.
After hemophilia, Von Willebrand disease and thrombocytopenia comprised the next largest categories of bleeding disorders (Table II). Of the children with thrombocytopenia, 18
(54%) had ITP. Children with bleeding disorders presented
with a lower prevalence of symptoms and signs of ICH than
did the children with GCS scores of 14 to 15, but without
bleeding disorders (Table III; available at www.jpeds.com).
The one exception to this was the prevalence of scalp
Table I. Patient characteristics—all Glasgow Coma
Scale scores
Mean age, years (SD)
Male sex (%)
Age <2 years (%)
Severity of mechanism† (%)
Mild
Moderate
Severe
GCS (%)
#13
14
15
CT obtained (%)
ICH on CT (%)
Bleeding disorder
n = 230
No bleeding disorder
n = 43 379*
6.4 (5.1)
192 (83.5)
65 (28.3)
7.1 (5.5)
27 040 (62.3)
10 901 (25.1)
81 (36.2)
131 (58.5)
12 (5.4)
7186 (16.7)
29 649 (68.9)
6210 (14.4)
0 (0.0)
5 (2.2)
225 (97.8)
186 (80.9)
2 (1.1)
967 (2.2)
1341 (3.1)
41 071 (94.7)
15 883 (36.6)
993 (6.3)
*A total of 43 904 patients were enrolled in the main head trauma study. Number with no bleeding disorder and GCS 3-15 was 43 379 after the removal of 505 patients on the basis of exclusion criteria (230 with bleeding disorders; 110 initially categorized as bleeding disorder,
but on record review did not meet criteria for this analysis; 101 with ventricular shunts; 66
with no GCS recorded; 2 had more than one exclusion) and 20 with no outcome recorded
(2 with GCS 3-13).
†Severity of injury mechanism was defined as follows. Severe mechanisms included when the
patient was ejected in a motor vehicle crash; when the patient was a passenger in a motor
vehicle crash rollover; any passenger death in the motor vehicle crash; when the patient
was a pedestrian or un-helmeted bicyclist struck by automobile; fall >5 feet when $2 years
old or >3 feet when <2 years old; or when the head was struck by a high-impact object (eg, golf
club). Mild injury mechanisms included falls to the ground from standing height or walking/running into stationary objects associated with signs or symptoms of blunt head trauma. All other
mechanisms were considered moderate.
Table II. Categorization of bleeding disorders (n = 230)
Disorder
n (%)
Hemophilia
Severe
Moderate
Mild
von Willebrand disease
Thrombocytopenia (platelets/mL)*
<5000
5001-20 000
20 001-50 000
50 001-150 000
Unknown
Anti-coagulation therapy
Functional platelet disorder
Other bleeding disorder
129 (56.1%)
80 (62.0%)
36 (27.9%)
13 (10.1%)
45 (19.6%)
34 (14.8%)
2 (5.9%)
2 (5.9%)
12 (35.3%)
17 (50.0%)
1 (2.9%)
15 (6.5%)
6 (2.6%)
1 (0.4%)
*At the time of ED examination.
hematomas, which was higher in children with bleeding
disorders.
Cranial CTs were obtained in 186 of the 230 children with
bleeding disorders (80.9%) compared with 14 969 of the 42
412 children without bleeding disorders (35.3%), but with
the same GCS scores of 14 to 15 (RR, 2.29; 95% CI, 2.15 to
2.44). Of the children with mild mechanisms of injury, children with bleeding disorders were 3-times more likely to be
examined with CT scan (66/81, 81.5%) than children without
bleeding disorders (1910/7106, 26.9%; RR, 3.03; 95% CI, 2.71
to 3.39). Of the children with moderate or severe injury mechanisms, children with bleeding disorders had twice the CT
evaluation rate (114/143, 79.7%) of children without bleeding
disorders (12 895/34 993, 36.9%; RR, 2.16; 95% CI, 1.99 to
2.35).
In the multivariable logistic regression analysis, which
controlled for severity of mechanism and signs and symptoms of head injury, children <2 years old with bleeding disorders had a 42-fold higher odds of having a head CT
performed than patients <2 years old without bleeding disorders (OR, 42.52; 95% CI, 19.77 to 91.45; Table IV). In
addition, children $2 years old with bleeding disorders had
23-fold higher odds of having a head CT performed than
children $2 years old without a bleeding disorder (OR,
22.62; 95% CI, 14.75 to 34.67; Table V). The effect of GCS
< 15 was captured in the multivariable logistic regression
analyses as it was included in the definition of the variable
altered mental status. Clinical characteristics of the children
with bleeding disorders who did not have a CT scan
examination for their head trauma are described in Table
VI (available at www.jpeds.com).
Of the patients with GCS scores of 14 to 15 for whom a CT
was obtained, an ICH was present in 2 of 186 children with
bleeding disorders (1.1%; 95% CI, 0.1 to 3.8) compared
with 655 of 14 969 children without bleeding disorders
(4.4%; 95% CI, 4.1 to 4.7; RR, 0.25; 95% CI, 0.06 to 0.98). Furthermore, in the children with bleeding disorders, there were
no patients who initially had ED CT results that were negative
for ICH then subsequently had positive CT results. Similarly,
none of the children with bleeding disorders who did not undergo imaging in the ED had positive CT results on follow-up.
Intracranial Hemorrhage after Blunt Head Trauma in Children with Bleeding Disorders
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Table IV. Multivariable logistic regression analysis of
factors associated with the use of computerized
tomography in children younger than 2 years with
Glasgow Coma Scale scores of 14 or 15
Odds ratio for CT examination
(95% CI)
Variable
Unadjusted
The two patients with bleeding disorders and ICHs on CT
scan presented with signs and symptoms of ICH. One was
a 15- year-old boy with severe factor VIII deficiency who
was involved in a motorcycle crash. On ED presentation,
he had a GCS score of 15, complained of a moderate headache, and exhibited repetitive questioning. On physical examination, he had a large parietal scalp hematoma. His CT
scan revealed a right frontal lobe parenchymal hemorrhagic
contusion. He was treated with factor VIII and hospitalized
for 2 nights because of his head injury. No neurosurgical intervention was required. The second patient was a 6-year-old
boy receiving warfarin therapy for a congenital cardiac con-
Table V. Multivariable logistic regression analysis of
factors associated with the use of computerized
tomography in children 2 years or older with Glasgow
Coma Scale scores of 14 or 15
Odds ratio for CT examination
(95% CI)
Variable
Unadjusted
1006
dition who fell 3 to 5 feet. On presentation to the ED, he had
a GCS score of 15, complaints of a mild headache, and had
two episodes of emesis. Physical examination revealed a medium-size temporal scalp hematoma. He had an epidural hematoma on CT, for which he was hospitalized for 3 nights
with no neurosurgical intervention.
Adjusted
Presence of bleeding disorder
15.83 (7.55-33.23) 42.52 (19.77-91.45)
Mechanism severity
Mild
1.0 (reference)
1.0 (reference)
Moderate/Severe
1.73 (1.52-1.96)
2.11 (1.80-2.48)
History of loss of consciousness 6.04 (5.00-7.30)
6.55 (5.25-8.16)
History of vomiting
3.18 (2.85-3.55)
3.18 (2.78-3.64)
Acting abnormally per
6.67 (5.91-7.53)
3.67 (3.15-4.27)
parent
Altered mental status
9.26 (8.05-10.65)
4.85 (4.07-5.78)
Signs of basilar skull
29.34 (10.63-81.01) 28.21 (8.25-96.53)
fracture
Palpable skull fracture
6.75 (5.32-8.56)
6.78 (5.07-9.08)
Scalp hematoma
None
1.0 (reference)
1.0 (reference)
Frontal
0.90 (0.81-0.99)
1.09 (0.96-1.23)
Non-frontal
2.55 (2.28-2.85)
2.77 (2.41-3.18)
Presence of bleeding disorder
6.17 (4.26-8.93)
Mechanism severity
Mild
1.0 (reference)
Moderate/Severe
1.53 (1.44-1.63)
History of loss of consciousness 12.73 (11.85-13.68)
Headache
3.38 (3.21-3.56)
History of vomiting
5.14 (4.78-5.53)
Altered mental status
14.01 (12.83-15.31)
Signs of basilar skull
20.45 (12.63-33.10)
fracture
Palpable skull fracture
4.51 (3.81-5.34)
Scalp hematoma
None
1.0 (reference)
Frontal
0.78 (0.74-0.83)
Non-frontal
1.29 (1.22-1.37)
Vol. 158, No. 6
Adjusted
22.62 (14.75-34.67)
1.0 (reference)
1.71 (1.56-1.88)
14.75 (13.53-16.07)
2.54 (2.37-2.71)
5.70 (5.16-6.29)
10.55 (9.38-11.87)
23.70 (13.65-41.16)
6.79 (5.42-8.52)
1.0 (reference)
0.91 (0.83-1.00)
1.25 (1.15-1.36)
Discussion
In this large, prospective, multicenter study of children with
blunt head trauma, 1% of imaged patients with bleeding disorders had ICHs. This study is unique in that it included children with acquired and congenital bleeding disorders, who
have varying degrees of risk for the development of traumatic
ICH on the basis of the type and severity of the bleeding disorder. Overall, patients with bleeding disorders (all with GCS
scores of 14-15) were twice as likely to have a cranial CT performed than children without bleeding disorders and with
GCS scores of 14 to 15. The two children with bleeding disorders and ICH after head trauma had other signs and symptoms of ICH that would have warranted cranial imaging.
Therefore, CT imaging may not routinely be needed in the
evaluation of children with bleeding disorders after blunt
head trauma, particularly in those without signs and symptoms suggestive of ICH.
Head trauma-related ICH in patients with bleeding disorders has been best described in patients with hemophilia (factor VIII and factor IX deficiency). ICH is the leading cause of
mortality from bleeding in this population, and the reported
prevalence of head trauma-related ICH in patients with hemophilia ranges from 2% to 16%. Current recommendations
for the management of head trauma in children with severe
hemophilia are to initiate treatment with factor replacement
as soon as possible after the traumatic event.26,27 The significant decrease in mortality rate from ICH (spontaneous and
traumatic) in patients with hemophilia has been attributed to
the wide availability of factor concentrates for replacement.10
The factor level at the time of injury and the use of factor correction were not evaluated in this study, because our primary
outcomes were the use of CT and presence of ICH on CT in
this population and not the effect of treatment on the clinical
complications from the bleeding disorder. Although institutional guidelines for the use of CT after head trauma are
available, we were not able to identify any published standard
clinical practice guidelines on the topic. In our prospective
cohort, only one of 129 patients with hemophilia who underwent imaging with CT had an ICH. He was treated with factor replacement alone.
Our results for children with hemophilia differ somewhat
from earlier studies, which have mainly been retrospective or
small. One retrospective study of children with hemophilia
identified 374 ED visits for head trauma in 11 years, with 9
episodes of ICH (2.4%). Five of these patients had no reported signs or symptoms of ICH during the time of the
ED evaluation, which ranged from 1 to 10 hours after the
head trauma event. All patients were treated with factor
Lee et al
ORIGINAL ARTICLES
June 2011
replacement for 10 to 14 days; none of the patients died or
required neurosurgical intervention.10 A slightly higher prevalence of ICH was noted in a retrospective study of children
with hemophilia and von Willebrand disease, with ICH occurring in 5 of 109 episodes of blunt head trauma (4.6%).
All 5 patients had hemophilia and, similar to our study, presented with symptoms suggestive of ICH, including abnormal neurological examinations.2 A prospective study from
1981 of children and adults with hemophilia reported 6 patients with ICH out of 47 episodes of head trauma; however,
few details are available to determine the symptoms and signs
of those with ICH.11
The incidence of ICH is low in children with thrombocytopenia and has primarily been described in children with
ITP.1,4,9,16,17 One review of the literature from 1954 to 1998
identified 75 published cases of ICH in children with ITP;
however, only 9 of these children had a history of head
trauma.1 A recent case control study of 40 children with
ITP who sustained ICH reported 33% (13/40) had a preceding history of head trauma, compared with 80 children with
ITP and no ICH where only one child had a history of head
trauma (1.2 %).17 There were 34 children in our study population with thrombocytopenia (<150 000 platelets/mL);
none of them sustained an ICH.
Only a small percentage of our study patients were receiving anti-coagulation therapy. Of the 16 patients receiving
anti-coagulation therapy in this study, only one child (receiving warfarin) sustained an ICH after a 3- to 5-foot fall and
had symptoms (headache and vomiting). Traumatic ICH
in patients receiving anti-coagulation therapy has primarily
been described in the adult literature, with conflicting conclusions about the associated risks of ICH. One prospective
case-control study of adults medicated with warfarin found
a trend toward increased mortality after head trauma.21 A
retrospective study of 144 adult patients receiving warfarin
who were defined as low-risk for ICH by symptoms (no
symptoms, dizziness, or headache), identified 10 patients
with clinically important CT findings.19 In contrast, a smaller
retrospective study of 65 patients receiving warfarin with minor head trauma without loss of consciousness found that
none had ICH on CT.18 With a growing number of children
surviving with chronic medical conditions requiring anticoagulation (eg, congenital heart disease), caution should
still be advised about the potential risk of ICH with head
trauma while more data are gathered.
This study has some limitations. Although this was a very
large prospective study of pediatric head trauma, there were
limited numbers of patients with congenital or acquired
bleeding disorders in our study population, especially those
with severe hemophilia, severe thrombocytopenia, or receiving anti-coagulation therapy. Therefore, the precision of our
findings is limited. Analysis of the larger head trauma study
from which this subanalysis was performed demonstrated
that the missed eligible population was similar to the study
population, making it unlikely that a substantial number of
children with bleeding disorders were not enrolled.23 Although only two patients in our cohort sustained ICHs,
both had physical signs and symptoms of ICH, suggesting
that symptomatically silent ICHs in children with bleeding
disorders are very uncommon. Children with hemophilia
are also at risk for a delayed presentation of ICH after head
trauma; however, children presenting for ED evaluation >24
hours after head trauma were not included in this study, because they were eligible only when they presented within 24
hours. However, of the children with bleeding disorders
who presented within 24 hours of the injury, none had delayed bleeding, which we would have detected at follow-up.
Despite these limitations, it is unlikely that a prospective
study larger than this one will be conducted in the near future, and this study provides the largest prospectively conducted study on the topic. In this prospective study of
blunt head trauma in children with congenital and acquired
bleeding disorders, the prevalence of ICH was very low. The
two patients with bleeding disorders and ICH had signs and
symptoms suggestive of ICH, which would have warranted
cranial CT evaluation. Although patients with congenital or
acquired bleeding disorders are at risk for ICH, the low rate
of ICH suggests that they may not routinely require cranial
CT imaging after minor blunt head trauma in the absence
of signs or symptoms of ICH. n
We thank Rene Enriquez at the PECARN Data Center (University of
Utah) for his dedicated and diligent work, the research coordinators in
PECARN, without whose dedication and hard work this study would
not have been possible, and all the clinicians around the PECARN
who enrolled children in this study.
Submitted for publication Aug 16, 2010; last revision received Sep 20, 2010;
accepted Nov 15, 2010.
Reprint requests: Lois K. Lee, MD, MPH, Division of Emergency Medicine,
Children’s Hospital, Boston, 300 Longwood Ave, Boston, MA 02115. E-mail:
[email protected]
References
1. Butros LJ, Bussel JB. Intracranial hemorrhage in immune thrombocytopenic purpura: a retrospective analysis. J Pediatr Hematol Oncol 2003;
25:660-4.
2. Dietrich AM, James CD, King DR, Ginn-Pease ME, Cecalupo AJ. Head
trauma in children with congenital coagulation disorders. J Pediatr Surg
1994;29:23-32.
3. Klinge J, Auberger K, Auerswald G, Brackmann HH, Mauz-Korholz C,
Kreuz W, et al. Prevalence and outcome of intracranial haemorrhage
in haemophiliacs—a survey of the paediatric group of the German Society of Thrombosis and Haemostasis (GTH). Eur J Pediatr 1999;
158(Suppl 3):S162-5.
4. Lilleyman JS, Paediatric Haematology Forum of the British Society for
Haematology. Intracranial haemorrhage in idiopathic thrombocytopenic purpura. Arch Dis Child 1994;71:251-3.
5. Ljung RCR. Intracranial haemorrhage in haemophilia A and B. Br J Haematol 2007;140:378-84.
6. Lutschg J, Vassella F. Neurological complications in hemophilia. Acta
Paediatr Scand 1981;70:235-41.
7. Martinowitz U, Heim M, Tadmor R, Eldor A, Rider I, Findler G, et al.
Intracranial hemorrhage in patients with hemophilia. Neurosurgery
1986;18:538-41.
8. Stieltjes N, Calvez T, Demiguel V, Torchet MF, Briquel ME,
Fressinaud E, et al. Intracranial haemorrhages in French haemophilia
Intracranial Hemorrhage after Blunt Head Trauma in Children with Bleeding Disorders
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9.
10.
11.
12.
13.
14.
15.
16.
17.
www.jpeds.com
patients (1991-2001): clinical presentation, management and prognosis
factors for death. Haemophilia 2005;11:452-8.
Woerner SJ, Abildgaard CF, French BN. Intracranial hemorrhage in children with idiopathic thrombocytopenic purpura. Pediatrics 1981;67:
453-60.
Witmer CM, Raffini L, Manno CS. Utility of computed tomography of
the head following head trauma in boys with haemophilia. Haemophilia
2007;13:560-6.
Andes WA, Wulff K, Smith WB. Head trauma in hemophilia. Arch Intern Med 1981;144:1981-3.
Hennes H, Losek JD, Sty JR, Gill JC. Computerized tomography
in hemophiliacs with head trauma. Pediatr Emerg Care 1987;3:
147-9.
Nelson MD, Maeder MA, Usner D, Mitchell WG, Fenstermacher MJ,
Wilson DA, et al. Prevalence and incidence of intracranial haemorrhage in a population of children with haemophilia. Haemophilia
1999;5:306-12.
Mizoi K, Onuma T, Mori K. Intracranial hemorrhage secondary to von
Willebrand’s disease and trauma. Surg Neurol 1984;22:495-8.
Kyrnetskiy EE, Kun LE, Boop FA, Sanford RA, Khan RB. Types, causes,
and outcome of intracranial hemorrhage in children with cancer. J Neurosurg 2005;102:31-5.
Iyori H, Bessho F, Ookawa H, Konishi S, Shirahata A, Miyazaki S, et al.
Intracranial hemorrhage in children with immune thrombocytopenic
purpura. Ann Hematol 2000;79:691-5.
Psaila B, Petrovic A, Page LK, Menell J, Schonholz M, Bussel JB. Intracranial hemorrhage (ICH) in children with immune thrombocytopenia
(ITP): study of 40 cases. Blood 2009;114:4777-83.
1008
Vol. 158, No. 6
18. Garra G, Nashed AH, Capobianco L. Minor head trauma in anticoagulated patients. Acad Emerg Med 1999;6:121-4.
19. Li J, Brown J, Levine M. Mild head injury, anticoagulants, and risk of intracranial injury. Lancet 2001;357:771-2.
20. Mina AA, Knipfer JF, Park DY, Bair HA, Howells GA, Bendick PJ. Intracranial complications of preinjury anticoagulation in trauma patients
with head injury. J Trauma 2002;53:668-72.
21. Mina AA, Bair HA, Howells GA, Bendick PJ. Complications of preinjury
warfarin use in the trauma patient. J Trauma 2003;54:842-7.
22. Cohen DB, Rinker C, Wilberger JE. Traumatic brain injury in anticoagulated patients. J Trauma 2006;60:553-7.
23. Kuppermann N, Holmes JF, Dayan PS, Hoyle JD, Atabaki SM,
Holubkov R, et al. Identification of children at very low risk of
clinically-important brain injuries after head trauma: a prospective cohort study. Lancet 2009;374:1160-70.
24. The Pediatric Emergency Care Applied Research Network. The Pediatric
Emergency Care Applied Research Network (PECARN): rationale, development, and first steps. Acad Emerg Med 2003;10:661-8.
25. Dayan P, Chamberlain J, Dean JM, Maio RF, Kuppermann N. The Pediatric Emergency Care Applied Research Network: progress and update.
Clin Pediatr Emerg Med 2006;7:128-35.
26. Witmer CM, Manno CS, Butler RB, Raffini LJ. The clinical management
of hemophilia and head trauma: a survey of current clinical practice
among pediatric hematology/oncology physicians. Pediatr Blood Cancer
2009;53:406-10.
27. Hoots WK, Shapiro AD. Treatment of hemophilia. In: Fleisher GR, Marx
JA, Walls RM, editors. UpToDate. www.uptodate.com. Accessed January
11, 2010.
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ORIGINAL ARTICLES
June 2011
Appendix
Participating centers and site investigators of the Traumatic Brain Injury Study Group for the Pediatric Emergency Care Applied Research Network (PECARN) are
listed in alphabetical order: Atlantic Health System/Morristown Memorial Hospital (M. Gerardi); Bellevue Hospital
Center (M. Tunik, J. Tsung); Calvert Memorial Hospital
(K. Melville); Children’s Hospital Boston (L. Lee); Children’s Hospital of Michigan (P. Mahajan); Children’s Hospital of New York–Presbyterian (P. Dayan); Children’s
Hospital of Philadelphia (F. Nadel); Children’s Memorial
Hospital (E. Powell); Children’s National Medical Center
(S. Atabaki, K. Brown); Cincinnati Children’s Hospital
Medical Center (T. Glass); DeVos Children’s Hospital (J.
Hoyle); Harlem Hospital Center (A. Cooper); Holy Cross
Hospital (E. Jacobs); Howard County Medical Center (D.
Monroe); Hurley Medical Center (D. Borgialli); Medical
College of Wisconsin/Children’s Hospital of Wisconsin
(M. Gorelick, S. Bandyopadhyay); St Barnabas Health
Care System (M. Bachman, N. Schamban); SUNY–Upstate
Medical Center (J. Callahan); University of California Davis
Medical Center (N. Kuppermann, J. Holmes); University
of Maryland (R. Lichenstein); University of Michigan
(R. Stanley); University of Rochester (M. Badawy, L.
Babcock-Cimpello); University of Utah/Primary Children’s
Medical Center (J. Schunk); Washington University/St.
Louis Children’s Hospital (K. Quayle, D. Jaffe); Women
and Children’s Hospital of Buffalo (K. Lillis).
We acknowledge the efforts of these individuals participating in PECARN at the time this study was initiated: PECARN
Steering Committee: N. Kuppermann, Chair; E. Alpern, J.
Chamberlain, J. M. Dean, M. Gerardi, J. Goepp, M. Gorelick,
J. Hoyle, D. Jaffe, C. Johns, N. Levick, P. Mahajan, R. Maio,
K. Melville, S. Miller (deceased), D. Monroe, R. Ruddy, R.
Stanley, D. Treloar, M. Tunik, A. Walker. MCHB/EMSC liaisons: D. Kavanaugh, H. Park; Central Data Management and
Coordinating Center (CDMCC): M. Dean, R. Holubkov, S.
Knight, A. Donaldson; Data Analysis and Management Subcommittee (DAMS): J. Chamberlain, Chair; M. Brown, H.
Corneli, J. Goepp, R. Holubkov, P. Mahajan, K. Melville, E.
Stremski, M. Tunik; Grants and Publications Subcommittee
(GAPS): M. Gorelick, Chair; E. Alpern, J. M. Dean, G. Foltin,
J. Joseph, S. Miller*, F. Moler, R. Stanley, S. Teach; Protocol
Concept Review and Development Subcommittee
(PCRADS): D. Jaffe, Chair; K. Brown, A. Cooper, J. M.
Dean, C. Johns, R. Maio, N. C. Mann, D. Monroe, K.
Shaw, D. Teitelbaum, D. Treloar; Quality Assurance Subcommittee (QAS): R. Stanley, Chair; D. Alexander, J. Brown,
M. Gerardi, M. Gregor, R. Holubkov, K. Lillis, B. Nordberg,
R. Ruddy, M. Shults, A. Walker; Safety and Regulatory Affairs
Subcommittee (SRAS): N. Levick, Chair; J. Brennan, J.
Brown, J. M. Dean, J. Hoyle, R. Maio, R. Ruddy, W. Schalick,
T. Singh, J. Wright.
Table III. Presenting findings in children with Glasgow Coma Scale scores of 14 and 15
Symptoms
History of loss of consciousness
Headache†
History of vomiting
Acting abnormally according to parent
Altered mental status
Signs of basilar skull fracture
Palpable skull fracture (or unclear exam)
Scalp hematoma
Frontal
Non-frontal
Seizure
Bleeding disorder
(n = 230)
n/n (%)
No bleeding disorder
(n = 42 412)
n/n (%)
Rate difference*
(95% CI)
11/229 (4.8)
57/157 (36.3)
8/226 (3.5)
24/225 (10.7)
9/228 (3.9)
0/229 (0.0)
4/230 (1.7)
6286/40 693 (15.4)
12 700/28 518 (44.5)
5557/42 112 (13.2)
6197/39 406 (15.7)
5487/42 096 (13.0)
287/41 991 (0.7)
1044/42 311 (2.5)
10.6 (13.4 to 7.9)
8.2 (15.8 to 0.7)
9.7 (12.1 to 7.2)
5.1 (9.1 to 1.0)
9.1 (11.6 to 6.5)
0.7 (0.8 to 0.6)
0.7 (2.4 to 1.0)
59/228 (25.9)
55/228 (24.1)
2/228 (0.9)
8753/41 919 (20.9)
7761/41 919 (18.5)
494/41 692 (1.2)
5.0 (0.7 to 10.7)
5.6 (0.04 to 11.2)
0.3 (1.5 to 0.9)
*Rate difference calculated from bleeding disorder and no bleeding disorder cohorts with GCS scores of 14 to 15, because all 230 bleeding disorder subjects had GCS scores of 14 to 15.
†Only recorded for children $2 years old.
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Table VI. Characteristics of patients with bleeding disorders who were not examined with computerized tomography
Bleeding disorder
Hemophilia
Mild
Moderate/severe
von Willebrand disease
Thrombocytopenia
<20 000 plts/mL
$20 000 plts/mL
Unknown
Anti-coagulation therapy
Other
Severity of injury mechanism
Mild
Moderate
Severe
History of loss of consciousness
Headache*
History of vomiting
Acting abnormally per parent
GCS
14
15
Altered mental status
Signs of basilar skull fracture
Palpable skull fracture†
Scalp hematoma
Frontalz
Temporal/parietalx
Occipital{
Bleeding disorder
with no CT (n = 44)
n (%)
Mild injury mechanism
n (%)
Moderate/severe injury mechanism
n (%)
17 (38.6)
5 (29.4)
12 (70.6)
11 (25.0)
10 (22.7)
1 (10.0)
8 (80.0)
1 (10.0)
5 (11.4)
1 (2.3)
7 (41.2)
1 (14.3)
6 (85.7)
2 (18.2)
5 (50.0)
1 (20.0)
4 (80.0)
0 (0.0)
0 (0.0)
1 (100.0)
10 (58.8)
4 (40.0)
6 (60.0)
9 (81.8)
5 (50.0)
0 (0.0)
4 (80.0)
1 (20.0)
5 (100.0)
0 (0.0)
15 (34.1)
27 (61.4)
2 (4.5)
0 (0.0)
6 (17.6)
0 (0.0)
0 (0.0)
0 (0.0)
44 (100)
0 (0.0)
0 (0.0)
1 (2.3)
9 (20.5)
3 (6.8)
5 (11.4)
*Ten children had missing data (6 were <2 years old).
†This child had hemophilia.
zSix children had hemophilia.
xOne child had hemophilia.
{Two children had hemophilia.
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