Spinal epidural hematoma in a child with hemophilia A with high titer inhibitors and follow-up with prophylactic emicizumab: case report and literature review

Abstract

Hemorrhage in the central nervous system is the most severe and debilitating manifestation affecting patients with hemophilia A. The spinal epidural space is the most unusual and clinically challenging site of central nervous system hemorrhage in hemophilia A. These patients often show insidious neurological signs and symptoms that delay diagnosis and treatment. We share our experience treating a 4-year-old male patient with severe hemophilia A and high titer inhibitors with a spontaneous spinal epidural hematoma. The patient presented initially with intense headache and neck pain. After blood tests and imaging studies, bypassing agent therapy with recombinant-activated factor VII was used until discharge; this was later replaced with emicizumab. After 18 months, the patient is without neurological sequelae and has not experienced subsequent bleeding episodes. We review the available literature and discuss the relevance of emicizumab compared with standard therapies in the context of spontaneous spinal epidural hematoma.

Spontaneous spinal epidural hematoma in a pediatric hemophiliac

“…In a review of the literature, 28 of 38 pediatric patients with SSEH were successfully managed conservatively, while only 10 cases warranted surgery [ Table 1 ]. [ 1 - 3 , 5 , 7 , 9 - 18 , 24 - 29 , 32 , 33 , 35 - 40 ] Notably, there was just one death (i.e., expiration due to a postoperative complication) and just one other patient who requiring additional surgery to address a recurrent spinal epidural hematoma [ Table 2 ].…”

“…In a review of the literature, 28 of 38 pediatric patients with SSEH were successfully managed conservatively, while only 10 cases warranted surgery [Table 1]. [1][2][3]5,7,[9][10][11][12][13][14][15][16][17][18][24][25][26][27][28][29]32,33,[35][36][37][38][39][40] Notably, there was just one death (i.e., expiration due to a postoperative complication) and just one other patient who requiring additional surgery to address a recurrent spinal epidural hematoma [Table 2]. Jones and Knighton [17] 1956 1 12 y M A Yes C6-T2 Yes No Persistence of paraplegia 2.…”

The good, the bad and the ugly of pain in haemophilia: Recent evidence on the epidemiology, molecular mechanisms and knowledge gaps preventing optimal treatment

“…A recent report of a diagnosis of lateral chest wall haematoma in a patient with congenital haemophilia B presenting with severe back pain in the absence of any trauma suggests that a high degree of attention should be maintained in PWH, as bleeding can also occur in atypical locations 22 . The importance of a timely and careful evaluation of pain in PWH is also supported by the successfully treated case of spinal epidural haematoma in a paediatric patient with severe haemophilia A, who presented a sudden onset of intense headache followed by severe neck pain without any previous history of trauma 24 …”

“…22 The importance of a timely and careful evaluation of pain in PWH is also supported by the successfully treated case of spinal epidural haematoma in a paediatric patient with severe haemophilia A, who presented a sudden onset of intense headache followed by severe neck pain without any previous history of trauma. 24 Back and joint pain in PWH is not necessarily due to arthropathy, and an accurate differential diagnosis is required, particularly in patients with concomitant diseases and treatments. 25 HCPs should consider a wide range of aetiologies for severe pain in PWH, with an approach that includes an extensive pain and medication history.…”

From a bispecific monoclonal antibody to gene therapy: A new era in the treatment of hemophilia A

“…There is little information on the effectiveness of emicizumab administered to children, but factors that can contribute to the decrease in the efficacy of the treatment are knownt: immunologic naivety, lower production of vitamin K dependent proteins, and higher clearance of emicizumab 28 . But emicizumab administered prophylactically for 18 months protected a child with severe hemophilia A and high titer inhibitors from bleeding, after treating him with recombinant-activated factor VII for a spontaneously occurring spinal epidural hematoma 29 .…”