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Home , Abrasion (medical), Head injury, Intracranial hemorrhage

after Blunt Head with 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 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 mul- ticenter cohort study of 43 904 children <18 years old with blunt head trauma evaluated in 25 emergency depart- ments. Results A total of 230 children had bleeding disorders; all had Glasgow 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 disor- ders 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 symp- toms; none of the children required . 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).

ntracranial hemorrhage (ICH) is a significant and potentially life-threatening Icomplication for children with congenital or acquired bleeding disorders.1-9 There is evidence that these children are at increased risk for sustaining ICH From the Department of Pediatrics, Harvard Medical even after minor blunt head trauma.2,6,10 Studies in children with hemophilia School, Boston, MA (L.L.); Department of Pediatrics, Columbia University College of Physicians and have reported ICH rates of 2% to 16% after head trauma, including some children Surgeons, New York, NY (P.D.); Department of Emergency , Atlantic Health System, with no signs or symptoms of trauma. The risk of ICH varies with the severity of Morristown Memorial Hospital, Morristown, NJ (M.Gerardi); Department of , hemophilia, and children with severe hemophilia (factor level <1%) are at highest University of Michigan School of Medicine and Hurley 2,10-13 risk, from spontaneous and traumatic ICH. Although there are few studies Medical Center, Flint, MI (D.B.); Departments of Emergency Medicine and Pediatrics, University of on the risk of ICH after head trauma in children with , they Rochester School of Medicine and Dentistry, Rochester, 2,12,14 NY (M.B.); Departments of Emergency Medicine and seem to be at less risk than children with hemophilia. Pediatrics, SUNY-Upstate Medical University, Syracuse, The risk of ICH in patients with other congenital and acquired bleeding dis- NY (J.C.); Department of Pediatrics and Emergency 1,2,15 Medicine, SUNY-Buffalo School of Medicine and orders is less well described. In patients with immune (idiopathic) thrombo- Biomedical Sciences, Buffalo, NY (K.L.); Department of Emergency Medicine, University of Michigan School of cytopenic purpura (ITP), ICH, including spontaneous and traumatic, is rare, Medicine, Ann Arbor, MI (R.S.); Department of Pediatrics, 1,9,16,17 Medical College of Wisconsin, Milwaukee, WI with a reported incidence of 0.1% to 1.0%. However, the prevention of (M.Gorelick); Department of Pediatrics, University of ICH has been a primary goal in the management of ITP, because ICH risk cor- Utah and PECARN Central Data Management and 1,4,17 Coordinating Center, Salt Lake City, UT (L.D., S.Z.); and relates with the severity of . The ICH risk in patients who Department of Emergency Medicine, University of California, Davis School of Medicine, Davis, CA (J.H., have taken anti-coagulants has only been reported in adults, with differing con- N.K.) 18-22 clusions about the risk of anti-coagulation therapy. List of members of the 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 Bu- reau, Division of Research, Education, and Training, and CT Computerized tomography the Emergency Medical Services of Children program (R40MC02461). The Pediatric Emergency Care Applied ED Emergency department Research Network is supported by cooperative agree- GCS ments U03MC00001, U03MC00003, U03MC00006, U03MC00007, and U03MC00008 from the Emergency ICH Intracranial hemorrhage Medical Services of Children program of the Health Re- ITP Immune (idiopathic) thrombocytopenic purpura sources and Services Administration/Maternal and Child LOC Loss of consciousness Health Bureau, Division of Research. The authors declare no conflicts of interest. PECARN Pediatric Emergency Care Applied Research Network RR Rate ratio 0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2010.11.036

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The objectives of this study were to determine the fre- other 110 were excluded from this study because they did quency of computerized tomography (CT) imaging after not meet the criteria for having a congenital or acquired blunt head trauma in children with bleeding disorders com- bleeding disorder at the time of the . Patients pared with children without bleeding disorders, and the prev- with hemophilia were categorized according to type of factor alence of ICH in these children. deficiency and severity (mild, moderate, or severe). For chil- dren with thrombocytopenia, platelet counts at the time of the ED evaluation were obtained, when available from the Methods medical record. Hospital admission was at the discretion of the treating ED This was an a priori planned substudy conducted as part of physician. To determine the clinical outcomes of the patients a larger prospective cohort study to derive and validate a neu- hospitalized for their head trauma, we performed a medical roimaging decision rule for children after blunt head record review, and data were recorded on a structured case trauma.23 The study was approved by the institutional review report form. For children discharged home from the ED, boards at all participating institutions. Written or verbal con- a follow-up telephone call was conducted by trained research sent for this observational study was obtained at each institu- coordinators between 1 week and 3 months after the ED visit tion as required by their institutional review boards. to determine whether the patient had an unscheduled return The study was conducted in 25 emergency departments visit to a healthcare provider and whether any cranial imag- (EDs) participating in the Pediatric Emergency Care Applied ing was performed after their initial ED visit. When a missed Research Network (PECARN).24,25 Children <18 years old traumatic brain injury was suggested at follow-up, the med- who were evaluated for blunt head trauma resulting from ical records and imaging results were obtained and reviewed, non-trivial mechanisms within 24 hours of injury at any of and the patient’s outcome was recorded. When telephone the participating EDs between June 2004 and September follow-up was not available, we mailed a follow-up survey 2006 were eligible for the main study.23 Congenital or ac- or reviewed the medical record, quality improvement re- quired bleeding disorder was defined as hemophilia, von Wil- ports, trauma registries, or morgue reports at the respective lebrand disease, congenital or acquired thrombocytopenia sites to obtain any missing clinical information.23 (defined as platelet count <150 000/mL), a functional platelet The primary outcomes were rates of CT use and presence disorder, other bleeding disorder, or anti-coagulation therapy of an ICH on CT, as reported by an attending radiologist. (warfarin, heparin, low molecular weight heparin/enoxa- ICHs included epidural , subdural hematomas, parin, clopidogrel). Patients were excluded from both the intraventricular hemorrhages, cerebral contusions, cerebral/ main study and this substudy when they had: (1) trivial mech- cerebellar hemorrhages, subarachnoid hemorrhages, or trau- anisms of injury (falls from standing height, walking, or run- matic infarctions. ning into stationary object) and (2) no signs or symptoms of head injury besides a laceration or . Patients Data Analysis were also excluded from both studies when they sustained We tabulated basic descriptive information for children with , when the injury occurred >24 hours be- and without bleeding disorders for the entire study popula- fore the ED evaluation, when they had a pre-existing neuro- tion. Because all the children with bleeding disorders pre- logical disease, known , or history of ventricular sented with Glasgow Coma Scale (GCS) scores of 14 or 15, shunt placement, or when they had been transferred with cra- as did 98% of the children without bleeding disorders, the re- nial imaging from an initial treating institution to the study mainder of the analyses was performed only for children with facility. GCS scores of 14 and 15. We calculated rate differences with A full description of the main study protocol has been pub- 95% CIs of the prevalence of of head lished.23 In brief, the treating clinician conducted the exam- trauma in children with bleeding disorders compared with ination and recorded the results on a structured case report the reference population of children without bleeding disor- form before knowledge of any imaging studies, if performed. ders. We also compared rates of CT imaging and ICH for pa- Cranial CTs were obtained at the discretion of the treating tients with bleeding disorders versus patients without clinician. The case report form included information about bleeding disorders by using rate ratios (RRs) with 95% CIs. patient history (including history of bleeding disorders), in- We performed multivariable logistic regression analyses to jury mechanism, symptoms, and physical examination find- identify factors independently associated with the use of ings. When the patient had a bleeding disorder, the case CT imaging. Children <2 years old and $2 years old were an- report form included check boxes for hemophilia, platelet alyzed separately to optimize the inclusion of the presenting disorders, anticoagulation therapy, von Willebrand disease, signs and symptoms, because some symptoms (eg, ) ‘‘unknown,’’ and ‘‘other.’’ Three hundred-forty children cannot be accurately assessed in pre-verbal patients (<2 years were indicated to have a bleeding disorder on the case report old). In these analyses, we adjusted for the diagnosis of coa- forms. We performed a detailed secondary medical record re- gulopathy and the severity of mechanism of injury and other view of these cases to determine the specific type, and when signs and symptoms suggestive of traumatic brain injury applicable, the severity of the bleeding disorder. Of these (history of loss of consciousness, headache, , acting 340 children, 230 met criteria for analysis in this study. The abnormally according to parent, altered mental status, signs 1004 Lee et al June 2011 ORIGINAL ARTICLES of fractures, and scalp hematomas).23 Altered mental Table II. status was determined a priori as a GCS score <15, agitation, Categorization of bleeding disorders (n = 230) sleepiness, slow responses, or repetitive questioning. We per- Disorder n (%) formed the data analysis with SAS software version 9.1.3 (SAS Hemophilia 129 (56.1%) Institute, Cary, North Carolina). Severe 80 (62.0%) Moderate 36 (27.9%) Mild 13 (10.1%) Results von Willebrand disease 45 (19.6%) Thrombocytopenia (platelets/mL)* 34 (14.8%) <5000 2 (5.9%) A total of 43 904 patients with non-trivial blunt head trauma 5001-20 000 2 (5.9%) were enrolled during the 28-month study period. Of these pa- 20 001-50 000 12 (35.3%) 50 001-150 000 17 (50.0%) tients, 230 had a history of congenital or acquired bleeding Unknown 1 (2.9%) disorders meeting criteria for this analysis, including 129 Anti-coagulation therapy 15 (6.5%) (56.1%) with hemophilia. The demographic and injury sever- Functional platelet disorder 6 (2.6%) ity characteristics of the children with and without bleeding Other bleeding disorder 1 (0.4%) disorders are presented in Table I. The group with bleeding *At the time of ED examination. disorders was more likely to be male and less likely to have severe mechanisms of injury than the children without hematomas, which was higher in children with bleeding bleeding disorders. Because all patients with bleeding disorders. disorders (and 98% of patients without bleeding disorders) Cranial CTs were obtained in 186 of the 230 children with presented with seemingly minor head trauma, defined with bleeding disorders (80.9%) compared with 14 969 of the 42 GCS scores of 14 or 15, the remainder of the results 412 children without bleeding disorders (35.3%), but with considers only children with GCS scores of 14 to 15. the same GCS scores of 14 to 15 (RR, 2.29; 95% CI, 2.15 to After hemophilia, Von Willebrand disease and thrombocy- 2.44). Of the children with mild mechanisms of injury, chil- topenia comprised the next largest categories of bleeding dis- dren with bleeding disorders were 3-times more likely to be orders (Table II). Of the children with thrombocytopenia, 18 examined with CT scan (66/81, 81.5%) than children without (54%) had ITP. Children with bleeding disorders presented bleeding disorders (1910/7106, 26.9%; RR, 3.03; 95% CI, 2.71 with a lower prevalence of symptoms and signs of ICH than to 3.39). Of the children with moderate or severe injury mech- did the children with GCS scores of 14 to 15, but without anisms, children with bleeding disorders had twice the CT bleeding disorders (Table III; available at www.jpeds.com). evaluation rate (114/143, 79.7%) of children without bleeding The one exception to this was the prevalence of scalp 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 symp- Table I. Patient characteristics—all Glasgow Coma toms of head injury, children <2 years old with bleeding dis- Scale scores orders had a 42-fold higher odds of having a head CT Bleeding disorder No bleeding disorder performed than patients <2 years old without bleeding disor- n = 230 n = 43 379* ders (OR, 42.52; 95% CI, 19.77 to 91.45; Table IV). In Mean age, years (SD) 6.4 (5.1) 7.1 (5.5) addition, children $2 years old with bleeding disorders had Male sex (%) 192 (83.5) 27 040 (62.3) Age <2 years (%) 65 (28.3) 10 901 (25.1) 23-fold higher odds of having a head CT performed than Severity of mechanism† (%) children $2 years old without a bleeding disorder (OR, Mild 81 (36.2) 7186 (16.7) 22.62; 95% CI, 14.75 to 34.67; Table V). The effect of GCS Moderate 131 (58.5) 29 649 (68.9) Severe 12 (5.4) 6210 (14.4) < 15 was captured in the multivariable logistic regression GCS (%) analyses as it was included in the definition of the variable #13 0 (0.0) 967 (2.2) altered mental status. Clinical characteristics of the children 14 5 (2.2) 1341 (3.1) 15 225 (97.8) 41 071 (94.7) with bleeding disorders who did not have a CT scan CT obtained (%) 186 (80.9) 15 883 (36.6) examination for their head trauma are described in Table ICH on CT (%) 2 (1.1) 993 (6.3) VI (available at www.jpeds.com). *A total of 43 904 patients were enrolled in the main head trauma study. Number with no bleed- Of the patients with GCS scores of 14 to 15 for whom a CT ing disorder and GCS 3-15 was 43 379 after the removal of 505 patients on the basis of ex- was obtained, an ICH was present in 2 of 186 children with clusion 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 bleeding disorders (1.1%; 95% CI, 0.1 to 3.8) compared with no GCS recorded; 2 had more than one exclusion) and 20 with no outcome recorded with 655 of 14 969 children without bleeding disorders (2 with GCS 3-13). †Severity of injury mechanism was defined as follows. Severe mechanisms included when the (4.4%; 95% CI, 4.1 to 4.7; RR, 0.25; 95% CI, 0.06 to 0.98). Fur- patient was ejected in a motor vehicle crash; when the patient was a passenger in a motor thermore, in the children with bleeding disorders, there were vehicle crash rollover; any passenger in the motor vehicle crash; when the patient was a pedestrian or un-helmeted bicyclist struck by automobile; fall >5 feet when $2 years no patients who initially had ED CT results that were negative old or >3 feet when <2 years old; or when the head was struck by a high-impact object (eg, golf for ICH then subsequently had positive CT results. Similarly, club). Mild injury mechanisms included falls to the ground from standing height or walking/run- ning into stationary objects associated with signs or symptoms of blunt head trauma. All other none of the children with bleeding disorders who did not un- mechanisms were considered moderate. dergo imaging in the ED had positive CT results on follow-up.

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dition who fell 3 to 5 feet. On presentation to the ED, he had Table IV. Multivariable logistic regression analysis of a GCS score of 15, complaints of a mild headache, and had factors associated with the use of computerized two episodes of emesis. Physical examination revealed a me- tomography in children younger than 2 years with dium-size temporal scalp . He had an epidural he- Glasgow Coma Scale scores of 14 or 15 matoma on CT, for which he was hospitalized for 3 nights Odds ratio for CT examination with no neurosurgical intervention. (95% CI) Variable Unadjusted Adjusted Presence of bleeding disorder 15.83 (7.55-33.23) 42.52 (19.77-91.45) Discussion Mechanism severity Mild 1.0 (reference) 1.0 (reference) Moderate/Severe 1.73 (1.52-1.96) 2.11 (1.80-2.48) In this large, prospective, multicenter study of children with History of loss of consciousness 6.04 (5.00-7.30) 6.55 (5.25-8.16) blunt head trauma, 1% of imaged patients with bleeding dis- History of vomiting 3.18 (2.85-3.55) 3.18 (2.78-3.64) orders had ICHs. This study is unique in that it included chil- Acting abnormally per 6.67 (5.91-7.53) 3.67 (3.15-4.27) parent dren with acquired and congenital bleeding disorders, who Altered mental status 9.26 (8.05-10.65) 4.85 (4.07-5.78) have varying degrees of risk for the development of traumatic Signs of basilar skull 29.34 (10.63-81.01) 28.21 (8.25-96.53) ICH on the basis of the type and severity of the bleeding dis- fracture Palpable 6.75 (5.32-8.56) 6.78 (5.07-9.08) order. Overall, patients with bleeding disorders (all with GCS Scalp hematoma scores of 14-15) were twice as likely to have a cranial CT per- None 1.0 (reference) 1.0 (reference) formed than children without bleeding disorders and with 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) GCS scores of 14 to 15. The two children with bleeding dis- orders and ICH after head trauma had other signs and symp- toms of ICH that would have warranted cranial imaging. Therefore, CT imaging may not routinely be needed in the The two patients with bleeding disorders and ICHs on CT evaluation of children with bleeding disorders after blunt scan presented with signs and symptoms of ICH. One was head trauma, particularly in those without signs and symp- a 15- year-old boy with severe factor VIII deficiency who toms suggestive of ICH. was involved in a motorcycle crash. On ED presentation, Head trauma-related ICH in patients with bleeding disor- he had a GCS score of 15, complained of a moderate head- ders has been best described in patients with hemophilia (fac- ache, and exhibited repetitive questioning. On physical ex- tor VIII and factor IX deficiency). ICH is the leading cause of amination, he had a large parietal scalp hematoma. His CT mortality from bleeding in this population, and the reported scan revealed a right parenchymal hemorrhagic prevalence of head trauma-related ICH in patients with he- contusion. He was treated with factor VIII and hospitalized mophilia ranges from 2% to 16%. Current recommendations for 2 nights because of his head injury. No neurosurgical in- for the management of head trauma in children with severe tervention was required. The second patient was a 6-year-old hemophilia are to initiate treatment with factor replacement boy receiving warfarin therapy for a congenital cardiac con- as soon as possible after the traumatic event.26,27 The signif- icant 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 Table V. Multivariable logistic regression analysis of The factor level at the time of injury and the use of factor cor- factors associated with the use of computerized rection were not evaluated in this study, because our primary tomography in children 2 years or older with Glasgow outcomes were the use of CT and presence of ICH on CT in Coma Scale scores of 14 or 15 this population and not the effect of treatment on the clinical Odds ratio for CT examination complications from the bleeding disorder. Although institu- (95% CI) tional guidelines for the use of CT after head trauma are Variable Unadjusted Adjusted available, we were not able to identify any published standard Presence of bleeding disorder 6.17 (4.26-8.93) 22.62 (14.75-34.67) clinical practice guidelines on the topic. In our prospective Mechanism severity Mild 1.0 (reference) 1.0 (reference) cohort, only one of 129 patients with hemophilia who under- Moderate/Severe 1.53 (1.44-1.63) 1.71 (1.56-1.88) went imaging with CT had an ICH. He was treated with fac- History of loss of consciousness 12.73 (11.85-13.68) 14.75 (13.53-16.07) tor replacement alone. Headache 3.38 (3.21-3.56) 2.54 (2.37-2.71) History of vomiting 5.14 (4.78-5.53) 5.70 (5.16-6.29) Our results for children with hemophilia differ somewhat Altered mental status 14.01 (12.83-15.31) 10.55 (9.38-11.87) from earlier studies, which have mainly been retrospective or Signs of basilar skull 20.45 (12.63-33.10) 23.70 (13.65-41.16) small. One retrospective study of children with hemophilia fracture Palpable skull fracture 4.51 (3.81-5.34) 6.79 (5.42-8.52) identified 374 ED visits for head trauma in 11 years, with 9 Scalp hematoma episodes of ICH (2.4%). Five of these patients had no re- None 1.0 (reference) 1.0 (reference) ported signs or symptoms of ICH during the time of the Frontal 0.78 (0.74-0.83) 0.91 (0.83-1.00) Non-frontal 1.29 (1.22-1.37) 1.25 (1.15-1.36) ED evaluation, which ranged from 1 to 10 hours after the head trauma event. All patients were treated with factor 1006 Lee et al June 2011 ORIGINAL ARTICLES replacement for 10 to 14 days; none of the patients died or both had physical signs and symptoms of ICH, suggesting required neurosurgical intervention.10 A slightly higher prev- that symptomatically silent ICHs in children with bleeding alence of ICH was noted in a retrospective study of children disorders are very uncommon. Children with hemophilia with hemophilia and von Willebrand disease, with ICH oc- are also at risk for a delayed presentation of ICH after head curring in 5 of 109 episodes of blunt head trauma (4.6%). trauma; however, children presenting for ED evaluation >24 All 5 patients had hemophilia and, similar to our study, pre- hours after head trauma were not included in this study, be- sented with symptoms suggestive of ICH, including abnor- cause they were eligible only when they presented within 24 mal neurological examinations.2 A prospective study from hours. However, of the children with bleeding disorders 1981 of children and adults with hemophilia reported 6 pa- who presented within 24 hours of the injury, none had de- tients with ICH out of 47 episodes of head trauma; however, layed bleeding, which we would have detected at follow-up. few details are available to determine the symptoms and signs Despite these limitations, it is unlikely that a prospective of those with ICH.11 study larger than this one will be conducted in the near fu- The incidence of ICH is low in children with thrombocy- ture, and this study provides the largest prospectively con- topenia and has primarily been described in children with ducted study on the topic. In this prospective study of ITP.1,4,9,16,17 One review of the literature from 1954 to 1998 blunt head trauma in children with congenital and acquired identified 75 published cases of ICH in children with ITP; bleeding disorders, the prevalence of ICH was very low. The however, only 9 of these children had a history of head two patients with bleeding disorders and ICH had signs and trauma.1 A recent case control study of 40 children with symptoms suggestive of ICH, which would have warranted ITP who sustained ICH reported 33% (13/40) had a preced- cranial CT evaluation. Although patients with congenital or ing history of head trauma, compared with 80 children with acquired bleeding disorders are at risk for ICH, the low rate ITP and no ICH where only one child had a history of head of ICH suggests that they may not routinely require cranial trauma (1.2 %).17 There were 34 children in our study pop- CT imaging after minor blunt head trauma in the absence ulation with thrombocytopenia (<150 000 platelets/mL); of signs or symptoms of ICH. n none of them sustained an ICH. Only a small percentage of our study patients were receiv- ing anti-coagulation therapy. Of the 16 patients receiving We thank Rene Enriquez at the PECARN Data Center (University of anti-coagulation therapy in this study, only one child (receiv- Utah) for his dedicated and diligent work, the research coordinators in ing warfarin) sustained an ICH after a 3- to 5-foot fall and PECARN, without whose dedication and hard work this study would had symptoms (headache and vomiting). Traumatic ICH not have been possible, and all the clinicians around the PECARN in patients receiving anti-coagulation therapy has primarily who enrolled children in this study. been described in the adult literature, with conflicting con- Submitted for publication Aug 16, 2010; last revision received Sep 20, 2010; clusions about the associated risks of ICH. One prospective accepted Nov 15, 2010. case-control study of adults medicated with warfarin found Reprint requests: Lois K. Lee, MD, MPH, Division of Emergency Medicine, 21 a trend toward increased mortality after head trauma. A Children’s Hospital, Boston, 300 Longwood Ave, Boston, MA 02115. E-mail: retrospective study of 144 adult patients receiving warfarin [email protected] who were defined as low-risk for ICH by symptoms (no symptoms, dizziness, or headache), identified 10 patients References with clinically important CT findings.19 In contrast, a smaller retrospective study of 65 patients receiving warfarin with mi- 1. Butros LJ, Bussel JB. Intracranial hemorrhage in immune thrombocyto- penic purpura: a retrospective analysis. J Pediatr Hematol Oncol 2003; nor head trauma without loss of consciousness found that 18 25:660-4. none had ICH on CT. With a growing number of children 2. Dietrich AM, James CD, King DR, Ginn-Pease ME, Cecalupo AJ. Head surviving with chronic medical conditions requiring anti- trauma in children with congenital coagulation disorders. J Pediatr Surg coagulation (eg, congenital heart disease), caution should 1994;29:23-32. still be advised about the potential risk of ICH with head 3. Klinge J, Auberger K, Auerswald G, Brackmann HH, Mauz-Korholz C, Kreuz W, et al. Prevalence and outcome of intracranial haemorrhage trauma while more data are gathered. in haemophiliacs—a survey of the paediatric group of the German Soci- This study has some limitations. Although this was a very ety of and Haemostasis (GTH). Eur J Pediatr 1999; large prospective study of pediatric head trauma, there were 158(Suppl 3):S162-5. limited numbers of patients with congenital or acquired 4. Lilleyman JS, Paediatric Haematology Forum of the British Society for bleeding disorders in our study population, especially those Haematology. Intracranial haemorrhage in idiopathic thrombocytope- nic purpura. Arch Dis Child 1994;71:251-3. with severe hemophilia, severe thrombocytopenia, or receiv- 5. Ljung RCR. Intracranial haemorrhage in A and B. Br J Hae- ing anti-coagulation therapy. Therefore, the precision of our matol 2007;140:378-84. findings is limited. Analysis of the larger head trauma study 6. Lutschg J, Vassella F. Neurological complications in hemophilia. Acta from which this subanalysis was performed demonstrated Paediatr Scand 1981;70:235-41. that the missed eligible population was similar to the study 7. Martinowitz U, Heim M, Tadmor R, Eldor A, Rider I, Findler G, et al. Intracranial hemorrhage in patients with hemophilia. Neurosurgery population, making it unlikely that a substantial number of 23 1986;18:538-41. children with bleeding disorders were not enrolled. Al- 8. Stieltjes N, Calvez T, Demiguel V, Torchet MF, Briquel ME, though only two patients in our cohort sustained ICHs, Fressinaud E, et al. Intracranial haemorrhages in French haemophilia

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patients (1991-2001): clinical presentation, management and prognosis 18. Garra G, Nashed AH, Capobianco L. Minor head trauma in anticoagu- factors for death. Haemophilia 2005;11:452-8. lated patients. Acad Emerg Med 1999;6:121-4. 9. Woerner SJ, Abildgaard CF, French BN. Intracranial hemorrhage in chil- 19. Li J, Brown J, Levine M. Mild head injury, , and risk of in- dren with idiopathic thrombocytopenic purpura. Pediatrics 1981;67: tracranial injury. Lancet 2001;357:771-2. 453-60. 20. Mina AA, Knipfer JF, Park DY, Bair HA, Howells GA, Bendick PJ. Intra- 10. Witmer CM, Raffini L, Manno CS. Utility of computed tomography of cranial complications of preinjury anticoagulation in trauma patients the head following head trauma in boys with haemophilia. Haemophilia with head injury. J Trauma 2002;53:668-72. 2007;13:560-6. 21. Mina AA, Bair HA, Howells GA, Bendick PJ. Complications of preinjury 11. Andes WA, Wulff K, Smith WB. Head trauma in hemophilia. Arch In- warfarin use in the trauma patient. J Trauma 2003;54:842-7. tern Med 1981;144:1981-3. 22. Cohen DB, Rinker C, Wilberger JE. Traumatic brain injury in anticoagu- 12. Hennes H, Losek JD, Sty JR, Gill JC. Computerized tomography lated patients. J Trauma 2006;60:553-7. in hemophiliacs with head trauma. Pediatr Emerg Care 1987;3: 23. Kuppermann N, Holmes JF, Dayan PS, Hoyle JD, Atabaki SM, 147-9. Holubkov R, et al. Identification of children at very low risk of 13. Nelson MD, Maeder MA, Usner D, Mitchell WG, Fenstermacher MJ, clinically-important brain after head trauma: a prospective co- Wilson DA, et al. Prevalence and incidence of intracranial haemor- hort study. Lancet 2009;374:1160-70. rhage in a population of children with haemophilia. Haemophilia 24. The Pediatric Emergency Care Applied Research Network. The Pediatric 1999;5:306-12. Emergency Care Applied Research Network (PECARN): rationale, de- 14. Mizoi K, Onuma T, Mori K. Intracranial hemorrhage secondary to von velopment, and first steps. Acad Emerg Med 2003;10:661-8. Willebrand’s disease and trauma. Surg Neurol 1984;22:495-8. 25. Dayan P, Chamberlain J, Dean JM, Maio RF, Kuppermann N. The Pedi- 15. Kyrnetskiy EE, Kun LE, Boop FA, Sanford RA, Khan RB. Types, causes, atric Emergency Care Applied Research Network: progress and update. and outcome of intracranial hemorrhage in children with cancer. J Neu- Clin Pediatr Emerg Med 2006;7:128-35. rosurg 2005;102:31-5. 26. Witmer CM, Manno CS, Butler RB, Raffini LJ. The clinical management 16. Iyori H, Bessho F, Ookawa H, Konishi S, Shirahata A, Miyazaki S, et al. of hemophilia and head trauma: a survey of current clinical practice Intracranial hemorrhage in children with immune thrombocytopenic among pediatric hematology/oncology physicians. Pediatr Blood Cancer purpura. Ann Hematol 2000;79:691-5. 2009;53:406-10. 17. Psaila B, Petrovic A, Page LK, Menell J, Schonholz M, Bussel JB. Intra- 27. Hoots WK, Shapiro AD. Treatment of hemophilia. In: Fleisher GR, Marx cranial hemorrhage (ICH) in children with immune thrombocytopenia JA, Walls RM, editors. UpToDate. www.uptodate.com. Accessed January (ITP): study of 40 cases. Blood 2009;114:4777-83. 11, 2010.

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Appendix Louis Children’s Hospital (K. Quayle, D. Jaffe); Women and Children’s Hospital of Buffalo (K. Lillis). We acknowledge the efforts of these individuals participat- Participating centers and site investigators of the Trau- ing in PECARN at the time this study was initiated: PECARN matic Brain Injury Study Group for the Pediatric Emer- Steering Committee: N. Kuppermann, Chair; E. Alpern, J. gency Care Applied Research Network (PECARN) are Chamberlain, J. M. Dean, M. Gerardi, J. Goepp, M. Gorelick, listed in alphabetical order: Atlantic Health System/Morris- J. Hoyle, D. Jaffe, C. Johns, N. Levick, P. Mahajan, R. Maio, town Memorial Hospital (M. Gerardi); Bellevue Hospital K. Melville, S. Miller (deceased), D. Monroe, R. Ruddy, R. Center (M. Tunik, J. Tsung); Calvert Memorial Hospital Stanley, D. Treloar, M. Tunik, A. Walker. MCHB/EMSC liai- (K. Melville); Children’s Hospital Boston (L. Lee); Chil- sons: D. Kavanaugh, H. Park; Central Data Management and dren’s Hospital of Michigan (P. Mahajan); Children’s Hos- Coordinating Center (CDMCC): M. Dean, R. Holubkov, S. pital of New York–Presbyterian (P. Dayan); Children’s Knight, A. Donaldson; Data Analysis and Management Sub- Hospital of Philadelphia (F. Nadel); Children’s Memorial committee (DAMS): J. Chamberlain, Chair; M. Brown, H. Hospital (E. Powell); Children’s National Medical Center Corneli, J. Goepp, R. Holubkov, P. Mahajan, K. Melville, E. (S. Atabaki, K. Brown); Cincinnati Children’s Hospital Stremski, M. Tunik; Grants and Publications Subcommittee Medical Center (T. Glass); DeVos Children’s Hospital (J. (GAPS): M. Gorelick, Chair; E. Alpern, J. M. Dean, G. Foltin, Hoyle); Harlem Hospital Center (A. Cooper); Holy Cross J. Joseph, S. Miller*, F. Moler, R. Stanley, S. Teach; Protocol Hospital (E. Jacobs); Howard County Medical Center (D. Concept Review and Development Subcommittee Monroe); Hurley Medical Center (D. Borgialli); Medical (PCRADS): D. Jaffe, Chair; K. Brown, A. Cooper, J. M. College of Wisconsin/Children’s Hospital of Wisconsin Dean, C. Johns, R. Maio, N. C. Mann, D. Monroe, K. (M. Gorelick, S. Bandyopadhyay); St Barnabas Health Shaw, D. Teitelbaum, D. Treloar; Quality Assurance Sub- Care System (M. Bachman, N. Schamban); SUNY–Upstate committee (QAS): R. Stanley, Chair; D. Alexander, J. Brown, Medical Center (J. Callahan); University of California Davis M. Gerardi, M. Gregor, R. Holubkov, K. Lillis, B. Nordberg, Medical Center (N. Kuppermann, J. Holmes); University R. Ruddy, M. Shults, A. Walker; Safety and Regulatory Affairs of Maryland (R. Lichenstein); University of Michigan Subcommittee (SRAS): N. Levick, Chair; J. Brennan, J. (R. Stanley); University of Rochester (M. Badawy, L. Brown, J. M. Dean, J. Hoyle, R. Maio, R. Ruddy, W. Schalick, Babcock-Cimpello); University of Utah/Primary Children’s T. Singh, J. Wright. Medical Center (J. Schunk); Washington University/St.

Table III. Presenting findings in children with Glasgow Coma Scale scores of 14 and 15 Bleeding disorder No bleeding disorder (n = 230) (n = 42 412) Rate difference* Symptoms n/n (%) n/n (%) (95% CI) History of loss of consciousness 11/229 (4.8) 6286/40 693 (15.4) 10.6 (13.4 to 7.9) Headache† 57/157 (36.3) 12 700/28 518 (44.5) 8.2 (15.8 to 0.7) History of vomiting 8/226 (3.5) 5557/42 112 (13.2) 9.7 (12.1 to 7.2) Acting abnormally according to parent 24/225 (10.7) 6197/39 406 (15.7) 5.1 (9.1 to 1.0) Altered mental status 9/228 (3.9) 5487/42 096 (13.0) 9.1 (11.6 to 6.5) Signs of 0/229 (0.0) 287/41 991 (0.7) 0.7 (0.8 to 0.6) Palpable skull fracture (or unclear exam) 4/230 (1.7) 1044/42 311 (2.5) 0.7 (2.4 to 1.0) Scalp hematoma Frontal 59/228 (25.9) 8753/41 919 (20.9) 5.0 (0.7 to 10.7) Non-frontal 55/228 (24.1) 7761/41 919 (18.5) 5.6 (0.04 to 11.2) 2/228 (0.9) 494/41 692 (1.2) 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 with no CT (n = 44) Mild injury mechanism Moderate/severe injury mechanism n (%) n (%) n (%) Bleeding disorder Hemophilia 17 (38.6) 7 (41.2) 10 (58.8) Mild 5 (29.4) 1 (14.3) 4 (40.0) Moderate/severe 12 (70.6) 6 (85.7) 6 (60.0) von Willebrand disease 11 (25.0) 2 (18.2) 9 (81.8) Thrombocytopenia 10 (22.7) 5 (50.0) 5 (50.0) <20 000 plts/mL 1 (10.0) 1 (20.0) 0 (0.0) $20 000 plts/mL 8 (80.0) 4 (80.0) 4 (80.0) Unknown 1 (10.0) 0 (0.0) 1 (20.0) Anti-coagulation therapy 5 (11.4) 0 (0.0) 5 (100.0) Other 1 (2.3) 1 (100.0) 0 (0.0) Severity of injury mechanism Mild 15 (34.1) Moderate 27 (61.4) Severe 2 (4.5) History of loss of consciousness 0 (0.0) Headache* 6 (17.6) History of vomiting 0 (0.0) Acting abnormally per parent 0 (0.0) GCS 14 0 (0.0) 15 44 (100) Altered mental status 0 (0.0) Signs of basilar skull fracture 0 (0.0) Palpable skull fracture† 1 (2.3) Scalp hematoma Frontalz 9 (20.5) Temporal/parietalx 3 (6.8) Occipital{ 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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