- Email: [email protected]
Hemophilia A presenting with quadriparesis, a rare clinical presentation
Accepted Manuscript Hemophilia a presenting with quadriparesis, a rare clinical presentation Supriya Gujjar Suresh, MD, Fellow, Nuthan Kumar, MD, Deenadayalan Munirathnam, FNB, J.K. Reddy, MD PII:
S2468-1245(16)30186-3
DOI:
10.1016/j.phoj.2017.01.003
Reference:
PHOJ 28
To appear in:
Pediatric Hematology Oncology Journal
Received Date: 11 November 2016 Revised Date:
23 January 2017
Accepted Date: 24 January 2017
Please cite this article as: Suresh SG, Kumar N, Munirathnam D, Reddy JK, Hemophilia a presenting with quadriparesis, a rare clinical presentation, Pediatric Hematology Oncology Journal (2017), doi: 10.1016/j.phoj.2017.01.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title Page Type of Manuscript: Letter to Editor
RI PT
Title of Manuscript: Hemophilia A Presenting With Quadriparesis, A Rare Clinical Presentation Authors and affiliations:
Supriya Gujjar Suresh MD, Nuthan Kumar MD, Deenadayalan Munirathnam FNB, *J K Reddy MD
SC
Department of Pediatric Hematology Oncology, Kanchi Kamakoti CHILDS Trust Hospital, Chennai 600034, Tamil Nadu, India
M AN U
*Department of Pediatrics, Kanchi Kamakoti CHILDS Trust Hospital, Chennai 600034, Tamil Nadu, India Correspondence Address and Requests for reprint: Dr. Supriya Gujjar Suresh, MD Fellow,
Department of Pediatric Hematology Oncology, Kanchi Kamakoti CHILDS Trust Hospital, Chennai 600034, Tamil Nadu, India.
TE D
Email: [email protected] Mobile no: +91 98806 90806
Contributors:
EP
Funding and competing interests: No funding received. Nil conflict of interest.
AC C
Supriya Gujjar Suresh: Drafted the manuscript and reviewed literature. Nuthan Kumar MK: Collected data and helped in drafting manuscript. Deenadayalan M: Concept and designed the manuscript. JK Reddy: Edited the manuscript.
ACCEPTED MANUSCRIPT
CLINICAL PRESENTATION
SC
KEYWORDS: hemophilia, spinal epidural hematoma
RI PT
LETTER TO THE EDITOR: HEMOPHILIA A PRESENTING WITH QUADRIPARESIS, A RARE
Spontaneous Spinal Epidural Hematoma is a neurosurgical emergency and warrants early diagnosis and has been
M AN U
traditionally managed by decompression laminectomy. Predisposing factors are coagulopathy, anticoagulants, and vascular anomalies. Spinal hematomas in Hemophilia is extremely rare1. Increasingly, reports have emerged indicating favorable outcome with conservative management and we report one such case.
A previously healthy 4yr old boy was brought with the history of two days duration of neck pain and rapidly worsening weakness of all four limbs with urinary retention. There was no history of seizures and trauma. Child had
TE D
no past history of bleeding episodes. No family history of hemophilia was present. An initial CT brain and spine was normal. In view of rapidly diminishing respiratory efforts, child was intubated and referred to our hospital on bag to
EP
tube ventilation.
At admission patient was afebrile, unconscious, pupils were 2mm sluggishly reactive to light with decreased air
AC C
entry bilaterally, hypotonia of all four limbs with 0/5 power MRC, and absent plantar reflex. Bruises on the back of thigh were noticed. He was put on mechanical ventilator support and vasopressor infusion. Other system examination was unremarkable
MRI brain and spinal cord done to look for cord compression was reported to have anterior spinal epidural hematoma at C1 to D3 level indenting the cord with focal cord edema at C4 -C5 level on left side. In view of extensive spinal epidural hematoma in the absence of history of trauma, hematological workup for bleeding diathesis was done which revealed prolonged aPTT, normal PT and INR. Hemophilia was considered a possibility
ACCEPTED MANUSCRIPT
and Factor VIII assay done was 2% suggestive of Hemophilia A of moderate severity. Neurosurgery consult was sought and was advised conservative management. Recombinant factor VIII replacement was started on the same day at 50 IU/kg i.v every 8hrs for 48hrs to correct levels to the normal range. Patient became hemodynamically
RI PT
stable over the next two days and was also extubated. His sensorium improved to normal. Patient’s lower limb power improved to grade 2/5 MRC in upper limb but was still grade 0/5 in lower limb on the day of extubation.
Post extubation patient was started on inj Factor VIII 25 IU/kg Q12th hrly for 14 days. By day five of admission
SC
patient had upper limb power of 3/5 and lower limb power was 2/5 MRC with good bowel and bladder control.
M AN U
By the end one week he had regained normal power and was able to walk. On follow up, repeat MRI spine done two weeks later was normal.
Hemophilia has an estimated frequency of approximately one in 10,000 births. Estimations based on the WFH’s annual global surveys indicate that the number of people with hemophilia in the world is approximately 400, 0002. Hemophilia A is more common than haemophilia B, representing 80-85% of the total haemophilia population.
TE D
About 30% of individuals have no family history of haemophilia A and are likely due to new mutations.
Individuals with hemophilia are 20–50 times more likely to develop ICH than those without hemophilia, with a
EP
reported prevalence of 2·7–12% and an incidence rate of 290–748/105 patient years3, 4. De Tezanos et al analyzed 156 bleeding episodes in 106 patients from a total of 1,410 hemophiliacs and concluded that intracranial hemorrhage
AC C
happens in 7.5% of hemophiliacs whereas the incidence of Spontaneous Spinal Epidural Hematoma (SSEH) is only about 0.001% 4. Acute cord compression occurs in 40% of all SSEH 5. An early study by Kreppel et al showed its incidence as 0.1 per 100,000 people per year 6. The primary neurological status, progressive interval, spinal edema, and size of hematoma will influence the prognosis of the patient with SSEH 7. Spontaneous spinal epidural hematoma is rare in children. It is usually confined to the dorsal epidural space. Ventral spontaneous spinal epidural hematoma (SSEH) is even rarer 8.
Literature review on Spontaneous Spinal Epidural Hematoma (SSEH) by Groen et al, concluded that in the majority of cases with SSEH, the mainstay of treatment will remain surgical decompression of the neural structures and
ACCEPTED MANUSCRIPT
removal of the hematoma. The decision for conservative treatment has to be based on the severity of the neurological deficit and on the clinical course9.
In contrast to spontaneous epidural hematoma which is considered a neurosurgical emergency requiring emergency
RI PT
spinal decompression, factor VIII replacement is considered as the corner stone treatment in hemophiliacs. Initially, it should be increased to 80 to 100% of the normal value and maintained upwards of 50% for 2 weeks10.
A literature review by Keihna et al revealed 24 cases of SEH in children with hemophilia. Of these 24 cases, 11
SC
underwent laminectomy and 13 received conservative treatment. Among conservatively treated patients, 5 of whom had presented with weakness, experienced a full recovery. Of the 11 laminectomy patients, 10 presented with
M AN U
weakness and all but 3 experienced full neurological improvement. These 3 patients were notable for having previously undiagnosed hemophilia. They concluded that observation with aggressive correction of coagulopathy is a reasonable treatment choice for hemophilic patients presenting with SEH and a stable neurological examination11. Early diagnosis and immediate aggressive replacement therapy are mandatory in the management of SEH. Prompt surgical decompression to avoid any permanent neurological deficit is a safe and effective treatment option for an
TE D
SEH in selected hemophilic children12. Surgical decompression can be considered in selected hemophiliac children
AC C
EP
with rapidly progressive neurological deficits.
REFERENCES:
1.
de Tezanos Pinto M, Fernandez J, Perez Bianco P. Update of 156 Episodes of Central Nervous System Bleeding in Hemophiliacs. Pathophysiology of Haemostasis and Thrombosis. 2009;22(5):259-267.
ACCEPTED MANUSCRIPT
2.
STONEBRAKER J, BOLTON-MAGGS P, MICHAEL SOUCIE J, WALKER I, BROOKER M. A study
Antunes S, Vicari P, Cavalheiro S, Bordin J. Intracranial haemorrhage among a population of haemophilic patients in Brazil. Haemophilia. 2003;9(5):573-577.
4.
Nuss R, Soucie J, Evatt B. Changes in the occurrence of and risk factors for hemophilia-associated
5.
M AN U
intracranial hemorrhage. Am J Hematol. 2001;68(1):37-42.
SC
3.
RI PT
of variations in the reported hemophilia A prevalence around the world. Haemophilia. 2010;16(1):20-32.
Holtås S, Heiling M, Lönntoft M. Spontaneous spinal epidural hematoma: findings at MR imaging and clinical correlation. Radiology. 1996;199(2):409-413.
6.
Kreppel D, Antoniadis G, Seeling W. Spinal hematoma: a literature survey with meta-analysis of 613 patients. Neurosurgical Review. 2003;26(1):1-49.
Liu Z, Jiao Q, Xu J, Wang X, Li S, You C. Spontaneous spinal epidural hematoma: analysis of 23 cases.
TE D
7.
Surgical Neurology. 2008;69(3):253-260.
Patel H, Boaz J, Phillips J, Garg B. Spontaneous spinal epidural hematoma in children. Pediatric Neurology.
EP
8.
9.
AC C
1998;19(4):302-307.
Groen R. Non-operative treatment of spontaneous spinal epidural hematomas: a review of the literature and a comparison with operative cases. Acta Neurochirurgica. 2004;146(2):103-110.
10. Hamre MHaller J. Intraspinal Hematomas in Hemophilia. Journal of Pediatric Hematology/Oncology. 1992;14(2):166-169.
ACCEPTED MANUSCRIPT
11. Kiehna E, Waldron P, Jane J. Conservative management of an acute spontaneous holocord epidural hemorrhage in a hemophiliac infant. Journal of Neurosurgery: Pediatrics. 2010;6(1):43-48.
RI PT
12. Rois P, López M, de Vergara B, de la Lama Zaragoza A, García J, Uxo J. Spinal epidural hematoma in
AC C
EP
TE D
M AN U
SC
hemophilic children: controversies in management. Childs Nerv Syst. 2009;25(8):987-991.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Fig 1: MRI Spine at diagnosis showing anterior epidural hematoma at C1 to D3 level indenting the cord with focal cord edema at C4 -C5 level on left side.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Fig 2: MRI Spine showing complete resolution of epidural hematoma 2 weeks after diagnosis
S2468-1245(16)30186-3
DOI:
10.1016/j.phoj.2017.01.003
Reference:
PHOJ 28
To appear in:
Pediatric Hematology Oncology Journal
Received Date: 11 November 2016 Revised Date:
23 January 2017
Accepted Date: 24 January 2017
Please cite this article as: Suresh SG, Kumar N, Munirathnam D, Reddy JK, Hemophilia a presenting with quadriparesis, a rare clinical presentation, Pediatric Hematology Oncology Journal (2017), doi: 10.1016/j.phoj.2017.01.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title Page Type of Manuscript: Letter to Editor
RI PT
Title of Manuscript: Hemophilia A Presenting With Quadriparesis, A Rare Clinical Presentation Authors and affiliations:
Supriya Gujjar Suresh MD, Nuthan Kumar MD, Deenadayalan Munirathnam FNB, *J K Reddy MD
SC
Department of Pediatric Hematology Oncology, Kanchi Kamakoti CHILDS Trust Hospital, Chennai 600034, Tamil Nadu, India
M AN U
*Department of Pediatrics, Kanchi Kamakoti CHILDS Trust Hospital, Chennai 600034, Tamil Nadu, India Correspondence Address and Requests for reprint: Dr. Supriya Gujjar Suresh, MD Fellow,
Department of Pediatric Hematology Oncology, Kanchi Kamakoti CHILDS Trust Hospital, Chennai 600034, Tamil Nadu, India.
TE D
Email: [email protected] Mobile no: +91 98806 90806
Contributors:
EP
Funding and competing interests: No funding received. Nil conflict of interest.
AC C
Supriya Gujjar Suresh: Drafted the manuscript and reviewed literature. Nuthan Kumar MK: Collected data and helped in drafting manuscript. Deenadayalan M: Concept and designed the manuscript. JK Reddy: Edited the manuscript.
ACCEPTED MANUSCRIPT
CLINICAL PRESENTATION
SC
KEYWORDS: hemophilia, spinal epidural hematoma
RI PT
LETTER TO THE EDITOR: HEMOPHILIA A PRESENTING WITH QUADRIPARESIS, A RARE
Spontaneous Spinal Epidural Hematoma is a neurosurgical emergency and warrants early diagnosis and has been
M AN U
traditionally managed by decompression laminectomy. Predisposing factors are coagulopathy, anticoagulants, and vascular anomalies. Spinal hematomas in Hemophilia is extremely rare1. Increasingly, reports have emerged indicating favorable outcome with conservative management and we report one such case.
A previously healthy 4yr old boy was brought with the history of two days duration of neck pain and rapidly worsening weakness of all four limbs with urinary retention. There was no history of seizures and trauma. Child had
TE D
no past history of bleeding episodes. No family history of hemophilia was present. An initial CT brain and spine was normal. In view of rapidly diminishing respiratory efforts, child was intubated and referred to our hospital on bag to
EP
tube ventilation.
At admission patient was afebrile, unconscious, pupils were 2mm sluggishly reactive to light with decreased air
AC C
entry bilaterally, hypotonia of all four limbs with 0/5 power MRC, and absent plantar reflex. Bruises on the back of thigh were noticed. He was put on mechanical ventilator support and vasopressor infusion. Other system examination was unremarkable
MRI brain and spinal cord done to look for cord compression was reported to have anterior spinal epidural hematoma at C1 to D3 level indenting the cord with focal cord edema at C4 -C5 level on left side. In view of extensive spinal epidural hematoma in the absence of history of trauma, hematological workup for bleeding diathesis was done which revealed prolonged aPTT, normal PT and INR. Hemophilia was considered a possibility
ACCEPTED MANUSCRIPT
and Factor VIII assay done was 2% suggestive of Hemophilia A of moderate severity. Neurosurgery consult was sought and was advised conservative management. Recombinant factor VIII replacement was started on the same day at 50 IU/kg i.v every 8hrs for 48hrs to correct levels to the normal range. Patient became hemodynamically
RI PT
stable over the next two days and was also extubated. His sensorium improved to normal. Patient’s lower limb power improved to grade 2/5 MRC in upper limb but was still grade 0/5 in lower limb on the day of extubation.
Post extubation patient was started on inj Factor VIII 25 IU/kg Q12th hrly for 14 days. By day five of admission
SC
patient had upper limb power of 3/5 and lower limb power was 2/5 MRC with good bowel and bladder control.
M AN U
By the end one week he had regained normal power and was able to walk. On follow up, repeat MRI spine done two weeks later was normal.
Hemophilia has an estimated frequency of approximately one in 10,000 births. Estimations based on the WFH’s annual global surveys indicate that the number of people with hemophilia in the world is approximately 400, 0002. Hemophilia A is more common than haemophilia B, representing 80-85% of the total haemophilia population.
TE D
About 30% of individuals have no family history of haemophilia A and are likely due to new mutations.
Individuals with hemophilia are 20–50 times more likely to develop ICH than those without hemophilia, with a
EP
reported prevalence of 2·7–12% and an incidence rate of 290–748/105 patient years3, 4. De Tezanos et al analyzed 156 bleeding episodes in 106 patients from a total of 1,410 hemophiliacs and concluded that intracranial hemorrhage
AC C
happens in 7.5% of hemophiliacs whereas the incidence of Spontaneous Spinal Epidural Hematoma (SSEH) is only about 0.001% 4. Acute cord compression occurs in 40% of all SSEH 5. An early study by Kreppel et al showed its incidence as 0.1 per 100,000 people per year 6. The primary neurological status, progressive interval, spinal edema, and size of hematoma will influence the prognosis of the patient with SSEH 7. Spontaneous spinal epidural hematoma is rare in children. It is usually confined to the dorsal epidural space. Ventral spontaneous spinal epidural hematoma (SSEH) is even rarer 8.
Literature review on Spontaneous Spinal Epidural Hematoma (SSEH) by Groen et al, concluded that in the majority of cases with SSEH, the mainstay of treatment will remain surgical decompression of the neural structures and
ACCEPTED MANUSCRIPT
removal of the hematoma. The decision for conservative treatment has to be based on the severity of the neurological deficit and on the clinical course9.
In contrast to spontaneous epidural hematoma which is considered a neurosurgical emergency requiring emergency
RI PT
spinal decompression, factor VIII replacement is considered as the corner stone treatment in hemophiliacs. Initially, it should be increased to 80 to 100% of the normal value and maintained upwards of 50% for 2 weeks10.
A literature review by Keihna et al revealed 24 cases of SEH in children with hemophilia. Of these 24 cases, 11
SC
underwent laminectomy and 13 received conservative treatment. Among conservatively treated patients, 5 of whom had presented with weakness, experienced a full recovery. Of the 11 laminectomy patients, 10 presented with
M AN U
weakness and all but 3 experienced full neurological improvement. These 3 patients were notable for having previously undiagnosed hemophilia. They concluded that observation with aggressive correction of coagulopathy is a reasonable treatment choice for hemophilic patients presenting with SEH and a stable neurological examination11. Early diagnosis and immediate aggressive replacement therapy are mandatory in the management of SEH. Prompt surgical decompression to avoid any permanent neurological deficit is a safe and effective treatment option for an
TE D
SEH in selected hemophilic children12. Surgical decompression can be considered in selected hemophiliac children
AC C
EP
with rapidly progressive neurological deficits.
REFERENCES:
1.
de Tezanos Pinto M, Fernandez J, Perez Bianco P. Update of 156 Episodes of Central Nervous System Bleeding in Hemophiliacs. Pathophysiology of Haemostasis and Thrombosis. 2009;22(5):259-267.
ACCEPTED MANUSCRIPT
2.
STONEBRAKER J, BOLTON-MAGGS P, MICHAEL SOUCIE J, WALKER I, BROOKER M. A study
Antunes S, Vicari P, Cavalheiro S, Bordin J. Intracranial haemorrhage among a population of haemophilic patients in Brazil. Haemophilia. 2003;9(5):573-577.
4.
Nuss R, Soucie J, Evatt B. Changes in the occurrence of and risk factors for hemophilia-associated
5.
M AN U
intracranial hemorrhage. Am J Hematol. 2001;68(1):37-42.
SC
3.
RI PT
of variations in the reported hemophilia A prevalence around the world. Haemophilia. 2010;16(1):20-32.
Holtås S, Heiling M, Lönntoft M. Spontaneous spinal epidural hematoma: findings at MR imaging and clinical correlation. Radiology. 1996;199(2):409-413.
6.
Kreppel D, Antoniadis G, Seeling W. Spinal hematoma: a literature survey with meta-analysis of 613 patients. Neurosurgical Review. 2003;26(1):1-49.
Liu Z, Jiao Q, Xu J, Wang X, Li S, You C. Spontaneous spinal epidural hematoma: analysis of 23 cases.
TE D
7.
Surgical Neurology. 2008;69(3):253-260.
Patel H, Boaz J, Phillips J, Garg B. Spontaneous spinal epidural hematoma in children. Pediatric Neurology.
EP
8.
9.
AC C
1998;19(4):302-307.
Groen R. Non-operative treatment of spontaneous spinal epidural hematomas: a review of the literature and a comparison with operative cases. Acta Neurochirurgica. 2004;146(2):103-110.
10. Hamre MHaller J. Intraspinal Hematomas in Hemophilia. Journal of Pediatric Hematology/Oncology. 1992;14(2):166-169.
ACCEPTED MANUSCRIPT
11. Kiehna E, Waldron P, Jane J. Conservative management of an acute spontaneous holocord epidural hemorrhage in a hemophiliac infant. Journal of Neurosurgery: Pediatrics. 2010;6(1):43-48.
RI PT
12. Rois P, López M, de Vergara B, de la Lama Zaragoza A, García J, Uxo J. Spinal epidural hematoma in
AC C
EP
TE D
M AN U
SC
hemophilic children: controversies in management. Childs Nerv Syst. 2009;25(8):987-991.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Fig 1: MRI Spine at diagnosis showing anterior epidural hematoma at C1 to D3 level indenting the cord with focal cord edema at C4 -C5 level on left side.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Fig 2: MRI Spine showing complete resolution of epidural hematoma 2 weeks after diagnosis