Neurosurgical management in children with bleeding ...2 patients had right-sided weakness. The neurosurgical approach was tailored according to the clinical and radio - logical findings.

CLINICAL ARTICLEJ Neurosurg Pediatr 21:38–43, 2018

SpontaneouS intracranial hematoma is an unusual complication of primary and secondary coagulation diatheses in children.7,22 Management of these cases

is a challenge when the patients present with acute neu-rological deterioration. However, with prompt diagnosis and an appropriate hematological treatment plan, a good neurological outcome may be achieved. A combined ap-proach is necessary for 1) rapid access to neuroimaging for prompt radiological diagnosis, 2) correction of any coagu-lation abnormalities (including perioperative correction), and 3) immediate neurosurgical management of the hema-toma, if required.

The pediatric neurosurgical service in Dublin provides surgical care for all pediatric neurosurgical patients re-

ferred within the Irish Republic. We performed a retro-spective review of cases involving children with intracra-nial hematomas who required neurosurgical operations and examined the similarities of the cases.

MethodsWe used the available pediatric database to identify all

cases in which patients required a craniotomy for treat-ment of intracranial hematoma in the Temple Street Chil-dren’s Hospital and pediatric neurosurgical service in Beaumont Hospital during the 5-year period from 2008 to 2012. This study was a retrospective analysis of data that were collected as part of routine diagnosis and treat-

ABBREVIATIONS aPTT = activated partial thromboplastin time; GCS = Glasgow Coma Scale; GOS-E Peds = Pediatric Glasgow Outcome Scale–Extended; ICH = intrace-rebral hematoma; ITP = idiopathic thrombocytopenic purpura; rFVIIa = recombinant activated factor VII; PT = prothrombin time; SDH = subdural hematoma.SUBMITTED October 7, 2016. ACCEPTED June 1, 2017.INCLUDE WHEN CITING Published online November 10, 2017; DOI: 10.3171/2017.6.PEDS16574.

Neurosurgical management in children with bleeding diathesis: auditing neurological outcomeZaitun Zakaria, PhD, Chandrasekaran Kaliaperumal, FRCSI, FRCSEd(NeuroSurg), Darach Crimmins, FRCS, and John Caird, FRCSI(SN)

Department of Paediatric Neurosurgery, Temple Street Children’s University Hospital, Dublin, Ireland

OBJECTIVE The aim of this study was to assess the outcome of neurosurgical treatment in children with bleeding di-athesis and also to evaluate the current management plan applied in the authors’ service.METHODS The authors retrospectively analyzed all cases in which neurosurgical procedures were performed in pedi-atric patients presenting with intracranial hematoma due to an underlying bleeding tendency over a 5-year period at their institution. They evaluated the patients’ neurological symptoms from the initial referral, hematological abnormalities, sur-gical treatment, neurological outcome, and scores on the Pediatric Glasgow Outcome Scale–Extended (GOS-E Peds) obtained 1 year after the last operation.RESULTS Five patients with a bleeding diathesis who underwent surgery for intracranial hematoma were identified; the diagnosis was hemophilia A in 3 cases, idiopathic thrombocytopenic purpura in 1 case, and severe aplastic anemia in 1 case. Intracerebral hematoma (ICH) (n = 4) and acute subdural hematoma (n = 1) were confirmed on radiological inves-tigations. In 2 of the 4 patients with ICH, the diagnosis of bleeding diathesis was made for the first time on presentation. Four patients (all male) were younger than 2 years; the patient with severe aplastic anemia and spontaneous ICH was 15 years old and female. The duration of symptoms varied from 24 hours to 5 days. Neurological examination at 1 year’s follow-up showed complete recovery (GOS-E Peds score of 1) in 3 cases and mild weakness (GOS-E Peds score of 2) in 2 cases. CONCLUSIONS Neurosurgical management of patients with bleeding diathesis should be carried out in a tertiary-care setting with multidisciplinary team management, including members with expertise in neuroimaging and hematology, in addition to neurosurgery. Early diagnosis and prompt treatment of a bleeding diathesis is crucial for full neurological recovery.https://thejns.org/doi/abs/10.3171/2017.6.PEDS16574KEY WORDS bleeding diathesis; hemophilia A; idiopathic thrombocytopenic purpura; intracerebral hematoma; subdural hematoma; aplastic anemia; trauma

J Neurosurg Pediatr Volume 21 • January 201838 ©AANS 2018, except where prohibited by US copyright law

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Bleeding diathesis in neurosurgical pediatric patients

J Neurosurg Pediatr Volume 21 • January 2018 39

ment. This paper does not report on the use of experimen-tal or new protocols, and the children were diagnosed and treated according to national guidelines and agreements. Ethics board approval was therefore not required for this study.

For cases that met the inclusion criteria, data were gath-ered from the patients’ medical records, including opera-tive notes. In addition, the brain CT scans obtained at the initial presentation were reviewed to confirm the presence of intracranial hematoma. Data collected from the medical records included the clinical findings at the initial referral, surgical procedures, postoperative neurological outcome, and Pediatric Glasgow Outcome Scale–Extended (GOS-E Peds; Table 1)2 at 1 year after surgery.

ResultsA total of 5 pediatric patients met the inclusion criteria.

Surgery was required for treatment of intracerebral hema-toma (ICH) in 4 cases and subdural hematoma (SDH) in 1 case. All 5 patients were diagnosed with a bleeding diath-esis due to coagulation defects or abnormal coagulation. In 3 cases, the patients were known to have a bleeding diathesis at presentation. In the other 2 cases, the condi-tion was diagnosed as a result of a full workup during the hospitalization.

Three patients had hemophilia A (severe in 2 cases and moderate but previously undiagnosed in the other), 1 patient had idiopathic thrombocytopenic purpura (ITP), and 1 patient had severe aplastic anemia. The duration of symptoms varied from 24 hours to 5 days in patients with intracranial hematoma. All of the patients presented with neurological symptoms, such as seizure and vomiting, and 2 patients had right-sided weakness. The neurosurgical approach was tailored according to the clinical and radio-logical findings. Evidence of midline shift of > 1 cm was seen in all patients with ICH and despite the urgency for evacuation of these hematomas, optimizing the coagula-tion disorder was the priority. Of all patients, one of them only required 1 operation and the other 4 required 2–4 operations afterward. Neurological follow-up 1 year after the last operation showed complete recovery in 3 cases and mild weakness in 2. Overall, the GOS-E Peds scores were 1 (in 3 patients) and 2 (in 2 patients).

Table 2 summarizes the patients’ cases, surgical man-

TABLE 1. The Pediatric Glasgow Outcome Scale–Extended

Score Definition

1 Upper good recovery2 Lower good recovery3 Upper moderate disability4 Lower moderate disability5 Upper severe disability6 Lower severe disability7 Vegetative state8 Death

Table based on information provided in Beers et al: J Neurotrauma 29:1126–1139, 2012. TA

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Z. Zakaria et al.

J Neurosurg Pediatr Volume 21 • January 201840

agement, and outcome. Details of the 5 cases are present-ed below.

Case ReportsCase 1

This 14-month-old boy with known severe hemophilia A was admitted to the hospital with a 2-day history of headache, intermittent vomiting, irritability, and seizure. His modified pediatric Glasgow Coma Scale (GCS) score was 8, and examination showed left-sided weakness. A brain CT scan showed a right frontal intracerebral hema-toma (ICH) with mass effect (Fig. 1A). His hemoglobin level and platelet count were 6.4 g/dl and 265 × 109/L, respectively. His factor VIII level was < 1%. A bolus of 500 U of factor VIII concentrate (Advate) was adminis-tered intravenously followed by continuous infusion of 6 U/kg/hr. In addition, dexamethasone and red cell concen-trate were administered intravenously. A craniotomy was performed for evacuation of the hematoma (Fig. 1B). He developed a factor VIII inhibitor after 10 days, requiring a change of therapy to recombinant activated factor VII (rFVIIa; NovoSeven), which was continued on discharge. One month later, he presented with right-sided weakness and bilateral papilledema. A CSF hygroma causing hydro-cephalus was diagnosed on CT (Fig. 1C). The hygroma ultimately required evacuation, which was followed by ventriculoperitoneal shunt placement. Two subsequent re-vision procedures were required due to shunt malfunction. The results of neurological examination at 1 year after the initial surgery were normal (GOS-E Peds score of 1).

Case 2This 3-month-old male infant presented to a local hos-

pital with petechial rash and vomiting. On admission, his platelet count was 4 × 109/L. He was diagnosed with ITP and treated with intravenous immunoglobulin. His plate-let count improved to more than 300 × 109/L. The next day, however, he developed progressive right-sided weak-ness and increasing head circumference. A brain CT scan showed a left frontoparietal ICH with mass effect (Fig. 2A). He was transferred to our institution for an emer-gency craniotomy and was given additional intravenous immunoglobulin intraoperatively. He had an uneventful recovery and 5 days prior to transfer back to his local hos-pital, a follow-up CT scan was performed, showing a satis-factory evacuation of the hematoma (Fig. 2B). The results

of neurological examination at 1 year after surgery were normal (GOS-E Peds score of 1).

Case 3This 15-year-old female with a diagnosis of severe aplas-

tic anemia presented with a 24-hour history of pyrexia and headache and a GCS score of 12. Examination revealed right hemiplegia and dysarthria. While in the CT scanner, she developed a tonic-clonic seizure with subsequent respi-ratory arrest, necessitating intubation and ventilation sup-port. The CT scan showed a large left parietal ICH with sulcal effacement (Fig. 3A and B). Her blood test results in-cluded a hemoglobin level of 7 g/dl, a platelet count of 17 × 109/L, a white cell count of 0.2 × 109/L, a neutrophil count of 0.1 × 109/L, an activated partial thromboplastin time (aPTT) of 23.4 seconds, and a fibrinogen concentration of 4.76 g/L. Hemostasis was managed with platelet transfu-sion, factor VIIa, and tranexamic acid. She also received frozen plasma and red cells. An emergency craniectomy was performed, and the hematoma was evacuated (Fig. 3C). The patient recovered well, with residual mild right-sided weakness, and was later transferred back to the refer-ring hospital. After a successful bone marrow transplant, an autologous cranioplasty was performed 5 months after the initial surgery, with uneventful recovery. Neurological examination at 1 year after presentation showed persistent mild right-sided weakness with GOS-E Peds score of 2.

Case 4This 13-month-old male infant presented with multiple

FIG. 1. Case 1. Axial CT images obtained in a 14-month-old boy with known hemophilia A. A: Initial scan showing a large right frontal ICH with intraventricular extension. B: Day 3 postoperative scan showing successful evacuation of the hematoma. C: Scan obtained 1 month after surgery showing a CSF hygroma with hydrocephalus.

FIG. 2. Case 2. Axial CT images obtained in a 3-month-old male infant with ITP. A: Preoperative scan showing a left frontoparietal ICH with > 1 cm midline shift. B: Day 1 postoperative scan showing some residual hematoma.




bruises around his upper and lower limbs, suspicious for nonaccidental injury. He had fallen from his cot 5 days earlier and since then had been vomiting and had become irritable. He required intubation due to deteriorating con-sciousness and poor respiratory effort. A CT scan of his brain showed a right frontoparietal ICH with mass effect (Fig. 4A). His hemoglobin level, platelet count, PT, and aPTT were 5.7 g/dl, 266 × 109/L, 15.8 seconds, and 68.1 seconds, respectively. Urgent factor assays revealed a hith-erto-undiagnosed hemophilia A with a factor VIII level of < 1%. Appropriate factor VIII replacement was com-menced with levels corrected to 100%. A craniotomy was performed, the hematoma was evacuated, and an external ventricular drain was placed. A CT scan (Fig. 4B) was performed prior to the patient’s transfer back to his local hospital. Three months later, he presented with a 1-week history of irritability and pyrexia. A CT scan was per-formed and showed a cystic cavity inside the surgical site (Fig. 4C), which required placement of a ventriculoperi-toneal shunt. He had developed inhibitors to factor VIII, which necessitated treatment with a rFVIIa (NovoSeven) for subsequent hemostatic management. Neurological ex-amination at 1 year after his last surgery showed normal strength in the left upper limb and strength of 4/5 in the left lower limb (GOS-E Peds score of 2).

Case 5This 7-month-old male infant with known severe hemo-

philia A sustained a minor head injury after falling onto a mat and hitting the back of his head. At presentation, he

had 2 episodes of vomiting and had pyrexia, right-sided weakness, and a deteriorating level of consciousness. His hemoglobin level and platelet count were 7.6 g/dl and 332 × 109/L, respectively. His factor VIII level was < 1%, and appropriate factor VIII replacement was commenced. A CT scan of his brain showed a left acute subdural hemato-ma (SDH) (Fig. 5A) and during transfer to our hospital he had 2 prolonged right-sided seizures, requiring intubation and ventilation. A left-sided craniotomy was performed and the hematoma was evacuated without any problems. The postoperative CT scan showed satisfactory evacua-tion of the hematoma (Fig. 5B). Neurological examination at 1 year after surgery showed normal neurological recov-ery (GOS-E Peds score of 1).

DiscussionIntracranial hematoma can occur in up to 12% of

children and young adults with bleeding disorders.15,17 In approximately 10% of older infants with hemophilia A, intracranial hematoma presents without a history of trau-ma.9 In our case series, trauma did not correlate with the severity of bleeding.

Previously reported cases have identified children with bleeding diathesis who had a craniotomy and later devel-oped progressive hydrocephalus.3,13 Even though there is no strong evidence to suggest a relationship between bleeding diathesis and CSF alteration, in general, any hemorrhage into ventricles can alter CSF absorption caus-ing associated issues, including posthemorrhagic hydro-cephalus.21

FIG. 3. Case 3. Axial CT images obtained in a 15-year-old girl with severe aplastic anemia. A and B: Preoperative scans showing an acute left frontoparietal ICH with midline shift. C: Scan obtained after evacuation of ICH showing residual hematoma and some bulging of the brain parenchyma into the craniectomy defect.

FIG. 4. Case 4. Axial CT images obtained in a 13-month-old boy who presented with multiple bruises on his upper and lower limbs, suspicious for nonaccidental injury. A: Preoperative scan showing right frontoparietal ICH with intraventricular extension and midline shift. B: Postoperative CT scan confirming a successful evacuation of hematoma. C: Scan obtained 3 months after the initial surgery showing a cystic cavity inside the surgical site.


Z. Zakaria et al.

J Neurosurg Pediatr Volume 21 • January 201842

A number of points can be made based on this series of cases.1) Spontaneous ICH can be mistaken for nonaccidental

injury. Anderst et al.1 stressed the importance of evalu-ation of bleeding disorders in children with suspected nonaccidental injury, as well as complete history and a thorough physical examination. Overdiagnosis or un-derdiagnosis will have devastating effects, not only for the child, but also for the entire family.11 Bruising in a young infant could be the first presentation of a bleed-ing disorder, such as in Case 4, and hence, the nature and location of bruising can be a guide for clinical di-agnosis.1,8 All children presenting with ICH may need an urgent coagulation profile sent prior to craniotomy. Close collaboration with a pediatric hematologist is vi-tal to aid with current evaluation since they commonly encountered children with multiple bruises that turned out to have coagulation disorder, and also to guide with suitable laboratory investigation for these children at risk.9

2) Bleeding diathesis can be present with normal PT/aPTT. Even though spontaneous bleeding is more common in severe hemophilia,10 mild deficiencies in factor VIII or factor IX (mild hemophilia), which do not cause abnor-malities in the aPTT, may still result in significant in-tracranial hematoma, particularly after mild trauma.1,4 Our Case 4 is an example of this phenomenon. The pa-tient had previously undiagnosed moderate hemophilia A and presented with ICH despite a normal coagulation profile.

3) Prompt treatment of a clotting abnormality is essen-tial at the time of surgery. Surgery in the setting of a persistent clotting abnormality is unsafe and entails a high risk of mortality. Prophylactic factor replace-ment should therefore be started immediately when a bleeding diathesis is suspected and must be given to all patients with hemophilia prior to cranial surgery and intraoperatively to prevent further hemorrhage.16,18,23 The hematologist will direct that the appropriate blood samples be taken prior to the administration of frozen plasma, as transfusion of plasma may interfere with diagnostic tests. Early contact with a pediatrician and/or pediatric intensivist prior to patient transfer is also recommended to optimize perioperative medical man-agement.

4) The treatment for hemophilia may be complicated by

antibodies to factor VIII. Exposure to a high dose of factor VIII, which is necessary for treatment of an in-tracranial hematoma in children with hemophilia A, increases the likelihood of development of factor VIII antibodies. The prevalence of factor VIII inhibitors in patients with severe hemophilia A and B is estimated at 10%–30% and 1%–3%, respectively.20 The manage-ment of these patients is a major clinical challenge due to the lack of reliable treatment as well as high cost.10 Treatment requires alternatives to factor VIII, and rFVIIa has been used successfully in these cases (as in 2 of the 5 patients in our case series). However, owing to its short half-life, rFVIIa must be administered every 2 hours during the first 24-hour period of treatment. Afterward, the dosage interval can be increased to 3, 4, or 6 hours depending on the type and extent of the surgical procedure or bleeding.

5) In children with bleeding diathesis requiring neuro-surgical intervention, good outcome is possible with prompt diagnosis and correction of hemostatic abnor-malities. The main objective of neurosurgical treatment in pediatric populations is to prevent secondary brain damage once ICH occurs, and this should be consid-ered only when the patient has life-threatening CNS bleeding.5,6,12 We also noted that the initial GCS score is useful in categorizing the cases in which immedi-ate treatment is required, but it was not a predictor of outcome in this small case series. Early surgery is in-dicated for symptomatic patients with CT evidence of hematoma and midline shift and should be no differ-ent from surgery for intracranial hematoma in patients without hemophilia.23 The death rate from intracranial hemorrhage has been estimated at up to 20%, with the majority of patients suffering sequelae.14 Indeed, infants younger than 2 years represent 30% of all hemophilic patients with intracranial hemorrhage (3 of 5 patients in our series). In patients with ITP, intracranial hem-orrhage risk correlates with the severity of thrombo-cytopenia.19 There are no specific guidelines regarding the balance of conservative versus surgical approaches, but we would be more inclined toward conservative management unless there was evidence of clinical or radiological deterioration. In our series, 3 patients had excellent recovery and 2 had mild deficits.

ConclusionsWe presented 5 cases involving patients with bleed-

ing diatheses who required neurosurgical treatment over a 5-year period. The clinical presentation of such pa-tients may vary and evaluation for other possible causes of bleeding may be required. A thorough clinical history and examination, together with early collaboration with a hematologist and pediatrician, is warranted for accurate diagnosis and optimized treatment. We recommend that these patients should be managed in centralized institu-tions where neuroimaging, a hematology team with good laboratory support, and a neurosurgical service are rap-idly accessible. Optimizing coagulation perioperatively is important in optimizing the chance of full neurological recovery in these cases.

FIG. 5. Case 5. Axial CT images obtained in a 7-month-old male infant with known severe hemophilia A. A: Preoperative CT showing an acute SDH with a thickness of 1.8 cm. B: Postoperative CT showing satisfac-tory evacuation of the hematoma.




AcknowledgmentsWe would like to thank our patients’ families. We gratefully

acknowledge Dr. Philip Murphy and the Beaumont Hospital hema-tology team for helping us with data collection.

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15. Mishra P, Naithani R, Dolai T, Bhargava R, Mahapatra M, Dixit A, et al: Intracranial haemorrhage in patients with con-genital haemostatic defects. Haemophilia 14:952–955, 2008

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DisclosuresThe authors report no conflict of interest concerning the materi-als or methods used in this study or the findings specified in this paper.

Author ContributionsConception and design: Zakaria. Acquisition of data: Zakaria. Analysis and interpretation of data: Zakaria, Kaliaperumal, Caird. Drafting the article: Zakaria. Critically revising the article: Kalia-perumal, Crimmins, Caird. Reviewed submitted version of manu-script: all authors. Approved the final version of the manuscript on behalf of all authors: Zakaria. Administrative/technical/mate-rial support: Zakaria. Study supervision: Crimmins.

CorrespondenceZaitun Zakaria, Department of Paediatric Neurosurgery, The Children’s University Hospital, Temple St., Dublin 1, Ireland. email: [email protected].


Neurosurgical management in children with bleeding ...2 patients had right-sided weakness. The neurosurgical approach was tailored according to the clinical and radio - logical findings.

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