Management of hydrocephalus in infants with severe hemophilia A: report of 2 cases

Restricted access

The authors report on the clinical course of two infants with severe hemophilia A (HA) and concomitant progressive hydrocephalus that required management with a ventriculoperitoneal shunt. The first child, with known HA, presented with a spontaneous intracranial hemorrhage and acquired hydrocephalus. He underwent cerebrospinal fluid diversion with a temporary external ventricular drain, followed by placement of a ventriculoperitoneal shunt. The second child had hydrocephalus secondary to a Dandy-Walker malformation and was diagnosed with severe HA during preoperative evaluation. He underwent placement of a ventriculoperitoneal shunt after progression of the hydrocephalus. The authors also review the treatment of hydrocephalus in patients with HA and describe the perioperative protocols used in their two cases. Treatment of hydrocephalus in infants with HA requires unique perioperative management to avoid complications.

ABBREVIATIONS DWM = Dandy-Walker malformation; EHL = extended half-life; EVD = external ventricular drain; FVIII = factor VIII; HA = hemophilia A; ICH = intracranial hemorrhage; ICP = intracranial pressure; rFVIII = recombinant FVIII; SDH = subdural hematoma; SHL = standard half-life; VP = ventriculoperitoneal.

Article Information

Correspondence Annie I. Drapeau: Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH.

INCLUDE WHEN CITING Published online November 2, 2018; DOI: 10.3171/2018.8.PEDS18409.

Disclosures Dr. Dunn reports grants, personal fees, and nonfinancial support from Bayer, CSL Behring, Pfizer, Shire, and Hema Biologics; grants and personal fees from Bioverativ; personal fees and nonfinancial support from Medscape; grants from Alnylam and Octapharma; and personal fees and nonfinancial support from Novo Nordisk, during the conduct of the study; and other from Little Seed Inc.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Axial T2-weighted (left) and sagittal FIESTA (right) MR images obtained at presentation, showing intraventricular hemorrhage, moderate ventricular enlargement, and an incidental suprasellar cyst.

  • View in gallery

    Limited T2-weighted MR images obtained at 6 months postoperatively, showing an incidentally found Chiari malformation type 1 with cerebellar tonsillar descent to 9.8 mm below the foramen magnum.

  • View in gallery

    Preoperative sagittal T2-weighted MR image showing hypoplasia of the cerebellar hemispheres and vermis, a retrocerebellar cyst communicating with the fourth ventricle, and an enlarged posterior fossa. Also observed were hypoplasia of the brainstem and mild ventriculomegaly of the lateral and third ventricles.

  • View in gallery

    Coronal CT scans obtained preoperatively (left) and on postoperative day 1 (right). Note the bilateral subdural bleeds of 5 and 4 mm at the vertex.



Aguiar PHShu EBFreitas ABLeme RJMiura FKMarino R Jr: Causes and treatment of intracranial haemorrhage complicating shunting for paediatric hydrocephalus. Childs Nerv Syst 16:2182212000


Andersson NGAuerswald GBarnes CCarcao MDunn ALFijnvandraat K: Intracranial haemorrhage in children and adolescents with severe haemophilia A or B—the impact of prophylactic treatment. Br J Haematol 179:2983072017


Auerswald GBidlingmaier CKurnik K: Early prophylaxis/FVIII tolerization regimen that avoids immunological danger signals is still effective in minimizing FVIII inhibitor developments in previously untreated patients—long-term follow-up and continuing experience. Haemophilia 18:e18e202012


Balak NSilav GKiliç YTimur CElmaci I: Successful surgical treatment of a hemophiliac infant with nontraumatic acute subdural hematoma. Surg Neurol 68:5375402007


Bladen MMain EKhair KHubert NKoutoumanou ELiesner R: The incidence, risk and functional outcomes of intracranial haemorrhage in children with inherited bleeding disorders at one haemophilia center. Haemophilia 22:5565632016


Blanchette VSKey NSLjung LRManco-Johnson MJvan den Berg HMSrivastava A: Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost 12:193519392014


Bouras TSgouros S: Complications of endoscopic third ventriculostomy. World Neurosurg 79 (2 Suppl):22.e922.e122013


Buchbinder DSteward CGPuthenveetil GNugent DHsieh LKirov I: Successful cord blood transplantation in a patient with malignant infantile osteopetrosis and hemophilia. Pediatr Transplant 17:E20E242013


Chalmers EAAlamelu JCollins PWMathias MPayne JRichards M: Intracranial haemorrhage in children with inherited bleeding disorders in the UK 2003-2015: a national cohort study. Haemophilia 24:6416472018


Cowles TFurman PWilkins I: Prenatal diagnosis of Dandy-Walker malformation in a family displaying X-linked inheritance. Prenat Diagn 13:87911993


Ferese RZampatti SGriguoli AMFornai FGiardina EBarrano G: A new splicing mutation in the L1CAM gene responsible for X-linked hydrocephalus (HSAS). J Mol Neurosci 59:3763812016


Fewel MELevy MLMcComb JG: Surgical treatment of 95 children with 102 intracranial arachnoid cysts. Pediatr Neurosurg 25:1651731996


Flannery AMDuhaime ACTamber MSKemp J: Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 3: Endoscopic computer-assisted electromagnetic navigation and ultrasonography as technical adjuvants for shunt placement. J Neurosurg Pediatr 14 (Suppl 1):24292014


Gouw SCvan den Berg HMFischer KAuerswald GCarcao MChalmers E: Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study. Blood 121:404640552013


Hoppe-Hirsch ESainte Rose CRenier DHirsch JF: Pericerebral collections after shunting. Childs Nerv Syst 3:971021987


Jouet MRosenthal AArmstrong GMacFarlane JStevenson RPaterson J: X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nat Genet 7:4024071994


Kanemura YOkamoto NSakamoto HShofuda TKamiguchi HYamasaki M: Molecular mechanisms and neuroimaging criteria for severe L1 syndrome with X-linked hydrocephalus. J Neurosurg 105 (5 Suppl):4034122006


Kulkarni RPresley RJLusher JMShapiro ADGill JCManco-Johnson M: Complications of haemophilia in babies (first two years of life): a report from the Centers for Disease Control and Prevention Universal Data Collection System. Haemophilia 23:2072142017


Ljung RLindgren ACPetrini PTengborn L: Normal vaginal delivery is to be recommended for haemophilia carrier gravidae. Acta Paediatr 83:6096111994


Mahlangu JNRagni MGupta NRangarajan SKlamroth ROldenburg J: Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) for perioperative haemostatic management in severe haemophilia A. Thromb Haemost 116:182016


Matsuda MHanda JAsato RHanda HYasunaga K: Surgical treatment of intracranial hematoma and hydrocephalus in an infant with hemophilia A. Surg Neurol 7:1992031977


Mbekeani JNAhmed M: An incidental large arachnoid cyst associated with compensated hydrocephalus in a patient with hemophilia A. Int J Pediatr and Adol Med 2:1661672015


McCarthy JWCoble LL: Intracranial hemorrhage and subsequent communicating hydrocephalus in a neonate with classical hemophilia. Pediatrics 51:1221241973


Merkler AECh’ang JParker WEMurthy SBKamel H: The rate of complications after ventriculoperitoneal shunt surgery. World Neurosurg 98:6546582017


Mohanty ABiswas ASatish SPraharaj SSSastry KV: Treatment options for Dandy-Walker malformation. J Neurosurg 105 (5 Suppl):3483562006


Nelson MD JrMaeder MAUsner DMitchell WGFenstermacher MJWilson DA: Prevalence and incidence of intracranial haemorrhage in a population of children with haemophilia. The Hemophilia Growth and Development Study. Haemophilia 5:3063121999


Osenbach RKMenezes AH: Diagnosis and management of the Dandy-Walker malformation: 30 years of experience. Pediatr Neurosurg 18:1791891992


Philip NChabrol BLossi AMCardoso CGuerrini RDobyns WB: Mutations in the oligophrenin-1 gene (OPHN1) cause X linked congenital cerebellar hypoplasia. J Med Genet 40:4414462003


Sadek SABin-Nakhi HAAl-Naqeeb NKumar R: Intracranial hemorrhage in a newborn with hemophilia. Ann Saudi Med 20:4334352000


Sasaki-Adams DElbabaa SKJewells VCarter LCampbell JWRitter AM: The Dandy-Walker variant: a case series of 24 pediatric patients and evaluation of associated anomalies, incidence of hydrocephalus, and developmental outcomes. J Neurosurg Pediatr 2:1941992008


Srivastava ABrewer AKMauser-Bunschoten EPKey NSKitchen SLlinas A: Guidelines for the management of hemophilia. Haemophilia 19:e1e472013


Stieltjes NCalvez TDemiguel VTorchet MFBriquel MEFressinaud E: Intracranial haemorrhages in French haemophilia patients (1991–2001): clinical presentation, management and prognosis factors for death. Haemophilia 11:4524582005


Vos YJde Walle HEBos KKStegeman JATen Berge AMBruining M: Genotype-phenotype correlations in L1 syndrome: a guide for genetic counselling and mutation analysis. J Med Genet 47:1691752010


Warf BCCampbell JWRiddle E: Initial experience with combined endoscopic third ventriculostomy and choroid plexus cauterization for post-hemorrhagic hydrocephalus of prematurity: the importance of prepontine cistern status and the predictive value of FIESTA MRI imaging. Childs Nerv Syst 27:106310712011


Warf BCDewan MMugamba J: Management of Dandy-Walker complex-associated infant hydrocephalus by combined endoscopic third ventriculostomy and choroid plexus cauterization. J Neurosurg Pediatr 8:3773832011


Weller SGärtner J: Genetic and clinical aspects of X-linked hydrocephalus (L1 disease): Mutations in the L1CAM gene. Hum Mutat 18:1122001


Zakaria ZKaliaperumal CCrimmins DCaird J: Neurosurgical management in children with bleeding diathesis: auditing neurological outcome. J Neurosurg Pediatr 21:38432018


Zanni GBertini ES: X-linked disorders with cerebellar dysgenesis. Orphanet J Rare Dis 6:242011


Zanon EIorio ARocino AArtoni ASantoro RTagliaferri A: Intracranial haemorrhage in the Italian population of haemophilia patients with and without inhibitors. Haemophilia 18:39452012




All Time Past Year Past 30 Days
Abstract Views 58 58 58
Full Text Views 17 17 17
PDF Downloads 22 22 22
EPUB Downloads 0 0 0


Google Scholar