Idiopathic Thrombocytopenic Purpura with Intracranial Hemorrhage and Vitreous Hemorrhage Carl A. Frankel, MD*, Domenic J. Pastore, MD*
Idiopathic thrombocytopenic purpura (ITP) is a hematologic disorder of childhood encountered by most practicing pediatricians during their careers. The annual incidence is estimated to be four per 100,000 children. To date, no definite etiological agent has been identified, but as many as 65% of cases are preceeded by a viral syndrome.2 The disease is usually self-limiting, and bedrest is often the only necessary treatment. The most frequent complication of ITP include bruising, epistaxis, melena and hematuria. These resolve spontaneously even before the platelet count rebounds to normal limits. The complication of intracranial hemorrhage is uncommon. McClure3 observed only five cases of intracranial hemorrhage in his series of 413 children with ITP, and Lusher and Iyer4 were not able to identify any complications of intracranial hemorrhage in 350 cases of
*
From the
Opthalmology Department,
Milton S.
Hershey Medical
Center, Penn State University College of Medicine, Hershey, PA. Presented in part at the Poster Session of the 15th Annual Meeting of the American Association for Pediatric Opthalmology and Strabismus, Kiawah Island, South Carolina, April 16-20, 1989. Correspondence to: Carl A. Frankel, MD, Assistant Professor of Opthalmology and Pediatrics, Milton S. Hershey Medical Center, P.O. Box 850, Hershey, PA 17033.
childhood ITP. The prognosis for survival is poor when intracranial hemorrhage does occur. Of the eighteen cases of ITP complicated by intracranial hemorrhage reviewed by Woemer,~ seven of them resulted in death. Walker and Walker,6 in reviewing all the reported deaths of children with ITP in England and Wales, noted that 11 of 12 children died of intracranial hemorrhage. Intracranial hemorrhage constitutes virtually all of the 1 % mortality rate associated with ITP. Very little has been written about the ocular complications in children with ITP. In many large series, there are only few accounts of subconjunctival and intraretinal hemorrhages.2,7.8 To date, there are no reports of frank vitreous hemorrhages in children with ITP. The absence of a red reflex as determined with the direct ophthalmoscope should alert the pediatrician to the possibility of the occurrence of a vitreous hemorrhage. Interference with the normally clear visual axis, as would occur in a large, central vitreous hemorrhage, can result in deprivation amblyopia in the pediatric patient whose visual system is still immature (typically before eight years of age). The following case report depicts a child with ITP complicated by an intracranial hemorrhage who also developed a vitreous hemorrhage. The mechanism of onset and the management of the vitreous hemorrhage are discussed in light of previous reports of vitreous hemorrhages resulting from the increase in intracranial pressure of a subarachnoid hemorrhage.
725 Downloaded from cpj.sagepub.com at LAKEHEAD UNIV on April 5, 2015
Case Report On May 23, 1987, a four-year-old previously healthy white female presented to the Milton S. Hershey Medical Center with bruises and petechiae on the face, trunk, and extremities. The patient had a recent upper respiratory tract infection with nausea, vomiting and a fever of 101 °F. Neurologic evaluation was unremarkable. There was a visible red reflex bilaterally, and neither subconjunctival nor intraretinal hemorrhages were noted. Laboratory studies revealed a platelet count of 17,000 with trace hemoglobin in the urine. A bone marrow aspirate was normal except for megakaryocytosis. Two days later, the platelet count dropped to 2,000 and a diagnosis of ITP was made. The patient improved clinically without treatment and was discharged in three days with instructions of bedrest and curtailment of activity. Three weeks later, the patient was readmitted with a severe headache followed by seizure activity and a left hemiparesis. The platelet count was 7,000. A direct ophthalmoscopic exam at that time revealed the absence of a red reflex and a massive vitreous hemorrhage in the right eye. A CT scan of the head showed a right intraparenchymal and subdural hemorrhage (Fig. 1). An emergency craniotomy with evacuation of the subdural hemorrhage and splenectomy were performed. The patient was treated post-operatively with Sandoglobin® (0.4 g/kg/day) for five days, and methylprednisolone (4 mg/ kg/day) and prednisone (2 mg/kg/day) consecutively for three weeks. She was then discharged to a physical rehabilitation center with a left hemiparesis. The platelet count at the time of discharge was 237,000.
The patient returned to the Milton S. Hershey Medical Center 24 hours later because of nausea, vomiting and poor visual acuity. The absence of the red reflex in the right eye persisted (Fig. 2), and the child was referred to the pediatric ophthalmology service. On exam, the vitreous blood in the right eye had become dried and coagulated obscuring all retinal details. The left eye showed a normal optic nerve with a small intraretinal hemorrhage in the region of the fovea centralis. The visual acuity was finger counting in the right eye and 20/40 in the left eye.
FIG.2. (Frankel & Pastore) &dquo;Red reflex&dquo; photo of the right eye demonstrating the absence of the red reflex due to a dense vitreous hemorrhage.
The
patient was followed in the pediatric ophthalmol-
ogy clinic at two month intervals with the vitreous hemorrhage beginning to resolve four months following craniotomy. By the tenth post-operative month, the vitreous hemorrhage continued to resolve, but the best visual acuity in the right eye could only be obtained at 20/200 in spite of a clear visual axis (Fig. 3). Occlusion therapy (patching) of the left eye was initiated and the vision in the right eye improved to 20/40 two months later and progressed to 20/30 by one year post-hemorrhage. The child had subsequently manifested a right esotropia which was corrected by extraocular muscle surgery. The remainder of the vitreous hemorrhage continued to clear and the child had a corrected visual acuity of 20/20 in both eyes at the time of this report.
Discussion To the best of
our
previously reported FIG. 1. (Frankel & Pastore) Axial CT scan of the brain intraparenchymal and subdural hemorrhage.
showing
an
a
there have not been of the onset and management of
knowledge,
cases
spontaneous vitreous hemorrhage in children with ITP
even
when
complicated by
726
Downloaded from cpj.sagepub.com at LAKEHEAD UNIV on April 5, 2015
intracranial
hemorrhage.
resulting visual acuities in the 20/20 to 20/60 range. 10,15.16 Although we observed steady vitreous clearing in our patient, the visual acuity was significantly impaired due to deprivation amblyopia. The clinical improvement of the vitreous
FIG. 3. (Frankel & Pastore) Fundus photo showing resolving hemorrhage with a clear visual axis.
vitreous
the closest analogy is the development of a hemorrhage after a subarachnoid hemorrhage (Terson’s syndrome). 9, 10,11 Castren’2 proposed that a subarachnoid hemorrhage causes a sudden increase in in-
Perhaps
vitreous
tracranial pressure which promotes the rupture of retinal venules and subsequent leakage of blood into the vitreous. Although it is difficult to estimate exactly when the blood invaded the vitreous in our patient, the timing and mechanism proposed by Castren12 is consistent with the early loss of the red reflex upon funduscopic examination at the time of presentation of the intracranial hemorrhage. Thrombocytopenia is not a well established cause of vitreous hemorrhage. Domic&dquo; noted subconjunctival, preretinal, and intraretinal hemorrhages in two cases of severe thrombocytopenia, but he did not identify any vitreous hemorrhages. In the series of patients of Rubenstein et al.1 with either anemia or thrombocytopenia or both, they found that patients with thrombocytopenia alone did not have any ocular hemorrhages. The close relationship in time between the occurrence of the intracranial hemorrhage and the vitreous hemorrhage in our patient is more consistent with a mechanism of increased intracranial pressure as the etiology of the vitreous hemorrhage rather than thrombocytopenia. Most vitreous hemorrhages are expected to clear spontaneously. The periphery of the vitreous clears first leaving a central opacity which eventually clears with time. In cases of vitreous hemorrhages associated with subarachnoid hemorrhages, the vitreous blood was noted to have substantially cleared in 10 to 24 months with
hemorrhage in this case was not associated with improving visual acuity. In addition, it was observed that the improvement in the amblyopia occurred only after occlusion therapy (patching) of the fellow eye. In children of the so-called amblyopic years (less than eight years of age) management should include periodic ophthalmologic examination in order to diagnose and treat deprivation amblyopia as the clinical appearance of the vitreous hemorrhage improves. Although nonintervention is usually advocated for vitreous hemorrhage, vitrectomy (removal of the vitreous humor of the posterior chamber of the eye) has been performed in cases where the vitreous hemorrhages were the result of a subarachnoid hemorrhage. Van Rens et al.&dquo; reported complete recovery of vision in three out of four eyes of two adult patients with bilateral vitreous hemorrhages secondary to subarachnoid hemorrhage. Vitrectomy hastened the clearing of the vitreous in one eye of a fourmonth-old child with bilateral vitreous hemorrhages following a subarachnoid hemorrhage, but the visual acuity was not reported. 18 In general, vitrectomy is usually not performed before 18 months of age following a vitreous hemorrhage or until there has been no progress in the rate of resolution of vitreous blood for at least six months. In the pediatric age group, early vitrectomy may be considered if there is a significant risk of developing deprivation amblyopia that may not be correctable with occlusion therapy (patching).
References 1.
Lilleyman JS. Idiopathic thrombocytopenic purpura-where do we
2.
Hoyle C, Darbyshire P, Eden OB. Idiopathic thrombocytopenia in childhood-Edinburgh experience 1962-82. Scott Med J
stand? Arch Dis Child 1984;59:701-3.
1986:31:174-9. 3. McClure PD. Idiopathic thrombocytopenic purpura in children: diagnosis and management. Pediatr 1975;55:68-73. 4. Lusher JM, lyer R. Idiopathic thrombocytopenic purpura in children. Semin Thromb Hemostas 1977;3:175-99. 5. Woerner SJ, Abildgaard CF, French BN. Intracranial hemorrhage in children with idiopathic thrombocytopenic purpura. Pediatr
1981;67:453-60. 6. Walker JH, Walker W. Idiopathic thrombocytopenia, initial illness and long term follow-up. Arch Dis Child 1961;36:649-57. 7. Cohn J. Thrombocytopenia in childhood: an evaluation of 433 patients. Scand J Haematol 1976;16:226-40. 8. Simons SM, Main CA, Yaish HM, et al. Idiopathic thrombocytopenic purpura in children. J Pediatr 1975;87:16-22. 9. Terson A. De l’hemorrhagie dans le corps vitre au cours de l’hemorragie cerebrale. Clin Ophthalmol 1900;6:309.
727 Downloaded from cpj.sagepub.com at LAKEHEAD UNIV on April 5, 2015
10. Vanderlinden RG, Chisholm LD. Vitreous hemorrhage and sudden increased intracranial pressure. J Neurosurg 1974:41:167-76. 11. Kahn SG, Frenkel M. Intravitreal hemorrhage associated with rapid increase in intracranial pressure (Terson’s syndrome). Am J Ophthalmol 80:37-43. 12. Castren JA. Pathogenesis and treatment of Terson syndrome. Acta
Ophthalmol 1963;41:430-4. hemorrhages in thrombocytopenia. Am J Opt Physiol 1988;65:212-4. Rubenstein RA, Yanoff M, Albert D. Thrombocytopenia, anemia and retinal hemorrhages. Am J Ophthalmol 1968;65:435-9. Riddoch G, Goulden C. On the relationship between subarachnoid and intraocular hemorrhage. Brit J Ophthalmol 1925;9:209-33.
13. Dornic DI. Ocular 14.
15.
16. Paton L. VII Diseases of the nervous system. 1. Ocular symptoms in subarachnoid hemorrhage. Trans Ophthal Soc UK 1924;110-
26. 17. Van Rens GH, Bos PJM, Van Dalen JTW. Vitrectomy in two cases of bilateral Terson syndrome. Doc Ophthalmol 1983;56:155-9. 18. Shaw HE, Landers MB. Vitreous hemorrhage after intracranial
hemorrhage.
Am J
Ophthalmol 1975;80:207-13.
728
Downloaded from cpj.sagepub.com at LAKEHEAD UNIV on April 5, 2015
Idiopathic thrombocytopenic purpura (ITP) is a hematologic disorder of childhood encountered by most practicing pediatricians during their careers. The annual incidence is estimated to be four per 100,000 children. To date, no definite etiological agent has been identified, but as many as 65% of cases are preceeded by a viral syndrome.2 The disease is usually self-limiting, and bedrest is often the only necessary treatment. The most frequent complication of ITP include bruising, epistaxis, melena and hematuria. These resolve spontaneously even before the platelet count rebounds to normal limits. The complication of intracranial hemorrhage is uncommon. McClure3 observed only five cases of intracranial hemorrhage in his series of 413 children with ITP, and Lusher and Iyer4 were not able to identify any complications of intracranial hemorrhage in 350 cases of
*
From the
Opthalmology Department,
Milton S.
Hershey Medical
Center, Penn State University College of Medicine, Hershey, PA. Presented in part at the Poster Session of the 15th Annual Meeting of the American Association for Pediatric Opthalmology and Strabismus, Kiawah Island, South Carolina, April 16-20, 1989. Correspondence to: Carl A. Frankel, MD, Assistant Professor of Opthalmology and Pediatrics, Milton S. Hershey Medical Center, P.O. Box 850, Hershey, PA 17033.
childhood ITP. The prognosis for survival is poor when intracranial hemorrhage does occur. Of the eighteen cases of ITP complicated by intracranial hemorrhage reviewed by Woemer,~ seven of them resulted in death. Walker and Walker,6 in reviewing all the reported deaths of children with ITP in England and Wales, noted that 11 of 12 children died of intracranial hemorrhage. Intracranial hemorrhage constitutes virtually all of the 1 % mortality rate associated with ITP. Very little has been written about the ocular complications in children with ITP. In many large series, there are only few accounts of subconjunctival and intraretinal hemorrhages.2,7.8 To date, there are no reports of frank vitreous hemorrhages in children with ITP. The absence of a red reflex as determined with the direct ophthalmoscope should alert the pediatrician to the possibility of the occurrence of a vitreous hemorrhage. Interference with the normally clear visual axis, as would occur in a large, central vitreous hemorrhage, can result in deprivation amblyopia in the pediatric patient whose visual system is still immature (typically before eight years of age). The following case report depicts a child with ITP complicated by an intracranial hemorrhage who also developed a vitreous hemorrhage. The mechanism of onset and the management of the vitreous hemorrhage are discussed in light of previous reports of vitreous hemorrhages resulting from the increase in intracranial pressure of a subarachnoid hemorrhage.
725 Downloaded from cpj.sagepub.com at LAKEHEAD UNIV on April 5, 2015
Case Report On May 23, 1987, a four-year-old previously healthy white female presented to the Milton S. Hershey Medical Center with bruises and petechiae on the face, trunk, and extremities. The patient had a recent upper respiratory tract infection with nausea, vomiting and a fever of 101 °F. Neurologic evaluation was unremarkable. There was a visible red reflex bilaterally, and neither subconjunctival nor intraretinal hemorrhages were noted. Laboratory studies revealed a platelet count of 17,000 with trace hemoglobin in the urine. A bone marrow aspirate was normal except for megakaryocytosis. Two days later, the platelet count dropped to 2,000 and a diagnosis of ITP was made. The patient improved clinically without treatment and was discharged in three days with instructions of bedrest and curtailment of activity. Three weeks later, the patient was readmitted with a severe headache followed by seizure activity and a left hemiparesis. The platelet count was 7,000. A direct ophthalmoscopic exam at that time revealed the absence of a red reflex and a massive vitreous hemorrhage in the right eye. A CT scan of the head showed a right intraparenchymal and subdural hemorrhage (Fig. 1). An emergency craniotomy with evacuation of the subdural hemorrhage and splenectomy were performed. The patient was treated post-operatively with Sandoglobin® (0.4 g/kg/day) for five days, and methylprednisolone (4 mg/ kg/day) and prednisone (2 mg/kg/day) consecutively for three weeks. She was then discharged to a physical rehabilitation center with a left hemiparesis. The platelet count at the time of discharge was 237,000.
The patient returned to the Milton S. Hershey Medical Center 24 hours later because of nausea, vomiting and poor visual acuity. The absence of the red reflex in the right eye persisted (Fig. 2), and the child was referred to the pediatric ophthalmology service. On exam, the vitreous blood in the right eye had become dried and coagulated obscuring all retinal details. The left eye showed a normal optic nerve with a small intraretinal hemorrhage in the region of the fovea centralis. The visual acuity was finger counting in the right eye and 20/40 in the left eye.
FIG.2. (Frankel & Pastore) &dquo;Red reflex&dquo; photo of the right eye demonstrating the absence of the red reflex due to a dense vitreous hemorrhage.
The
patient was followed in the pediatric ophthalmol-
ogy clinic at two month intervals with the vitreous hemorrhage beginning to resolve four months following craniotomy. By the tenth post-operative month, the vitreous hemorrhage continued to resolve, but the best visual acuity in the right eye could only be obtained at 20/200 in spite of a clear visual axis (Fig. 3). Occlusion therapy (patching) of the left eye was initiated and the vision in the right eye improved to 20/40 two months later and progressed to 20/30 by one year post-hemorrhage. The child had subsequently manifested a right esotropia which was corrected by extraocular muscle surgery. The remainder of the vitreous hemorrhage continued to clear and the child had a corrected visual acuity of 20/20 in both eyes at the time of this report.
Discussion To the best of
our
previously reported FIG. 1. (Frankel & Pastore) Axial CT scan of the brain intraparenchymal and subdural hemorrhage.
showing
an
a
there have not been of the onset and management of
knowledge,
cases
spontaneous vitreous hemorrhage in children with ITP
even
when
complicated by
726
Downloaded from cpj.sagepub.com at LAKEHEAD UNIV on April 5, 2015
intracranial
hemorrhage.
resulting visual acuities in the 20/20 to 20/60 range. 10,15.16 Although we observed steady vitreous clearing in our patient, the visual acuity was significantly impaired due to deprivation amblyopia. The clinical improvement of the vitreous
FIG. 3. (Frankel & Pastore) Fundus photo showing resolving hemorrhage with a clear visual axis.
vitreous
the closest analogy is the development of a hemorrhage after a subarachnoid hemorrhage (Terson’s syndrome). 9, 10,11 Castren’2 proposed that a subarachnoid hemorrhage causes a sudden increase in in-
Perhaps
vitreous
tracranial pressure which promotes the rupture of retinal venules and subsequent leakage of blood into the vitreous. Although it is difficult to estimate exactly when the blood invaded the vitreous in our patient, the timing and mechanism proposed by Castren12 is consistent with the early loss of the red reflex upon funduscopic examination at the time of presentation of the intracranial hemorrhage. Thrombocytopenia is not a well established cause of vitreous hemorrhage. Domic&dquo; noted subconjunctival, preretinal, and intraretinal hemorrhages in two cases of severe thrombocytopenia, but he did not identify any vitreous hemorrhages. In the series of patients of Rubenstein et al.1 with either anemia or thrombocytopenia or both, they found that patients with thrombocytopenia alone did not have any ocular hemorrhages. The close relationship in time between the occurrence of the intracranial hemorrhage and the vitreous hemorrhage in our patient is more consistent with a mechanism of increased intracranial pressure as the etiology of the vitreous hemorrhage rather than thrombocytopenia. Most vitreous hemorrhages are expected to clear spontaneously. The periphery of the vitreous clears first leaving a central opacity which eventually clears with time. In cases of vitreous hemorrhages associated with subarachnoid hemorrhages, the vitreous blood was noted to have substantially cleared in 10 to 24 months with
hemorrhage in this case was not associated with improving visual acuity. In addition, it was observed that the improvement in the amblyopia occurred only after occlusion therapy (patching) of the fellow eye. In children of the so-called amblyopic years (less than eight years of age) management should include periodic ophthalmologic examination in order to diagnose and treat deprivation amblyopia as the clinical appearance of the vitreous hemorrhage improves. Although nonintervention is usually advocated for vitreous hemorrhage, vitrectomy (removal of the vitreous humor of the posterior chamber of the eye) has been performed in cases where the vitreous hemorrhages were the result of a subarachnoid hemorrhage. Van Rens et al.&dquo; reported complete recovery of vision in three out of four eyes of two adult patients with bilateral vitreous hemorrhages secondary to subarachnoid hemorrhage. Vitrectomy hastened the clearing of the vitreous in one eye of a fourmonth-old child with bilateral vitreous hemorrhages following a subarachnoid hemorrhage, but the visual acuity was not reported. 18 In general, vitrectomy is usually not performed before 18 months of age following a vitreous hemorrhage or until there has been no progress in the rate of resolution of vitreous blood for at least six months. In the pediatric age group, early vitrectomy may be considered if there is a significant risk of developing deprivation amblyopia that may not be correctable with occlusion therapy (patching).
References 1.
Lilleyman JS. Idiopathic thrombocytopenic purpura-where do we
2.
Hoyle C, Darbyshire P, Eden OB. Idiopathic thrombocytopenia in childhood-Edinburgh experience 1962-82. Scott Med J
stand? Arch Dis Child 1984;59:701-3.
1986:31:174-9. 3. McClure PD. Idiopathic thrombocytopenic purpura in children: diagnosis and management. Pediatr 1975;55:68-73. 4. Lusher JM, lyer R. Idiopathic thrombocytopenic purpura in children. Semin Thromb Hemostas 1977;3:175-99. 5. Woerner SJ, Abildgaard CF, French BN. Intracranial hemorrhage in children with idiopathic thrombocytopenic purpura. Pediatr
1981;67:453-60. 6. Walker JH, Walker W. Idiopathic thrombocytopenia, initial illness and long term follow-up. Arch Dis Child 1961;36:649-57. 7. Cohn J. Thrombocytopenia in childhood: an evaluation of 433 patients. Scand J Haematol 1976;16:226-40. 8. Simons SM, Main CA, Yaish HM, et al. Idiopathic thrombocytopenic purpura in children. J Pediatr 1975;87:16-22. 9. Terson A. De l’hemorrhagie dans le corps vitre au cours de l’hemorragie cerebrale. Clin Ophthalmol 1900;6:309.
727 Downloaded from cpj.sagepub.com at LAKEHEAD UNIV on April 5, 2015
10. Vanderlinden RG, Chisholm LD. Vitreous hemorrhage and sudden increased intracranial pressure. J Neurosurg 1974:41:167-76. 11. Kahn SG, Frenkel M. Intravitreal hemorrhage associated with rapid increase in intracranial pressure (Terson’s syndrome). Am J Ophthalmol 80:37-43. 12. Castren JA. Pathogenesis and treatment of Terson syndrome. Acta
Ophthalmol 1963;41:430-4. hemorrhages in thrombocytopenia. Am J Opt Physiol 1988;65:212-4. Rubenstein RA, Yanoff M, Albert D. Thrombocytopenia, anemia and retinal hemorrhages. Am J Ophthalmol 1968;65:435-9. Riddoch G, Goulden C. On the relationship between subarachnoid and intraocular hemorrhage. Brit J Ophthalmol 1925;9:209-33.
13. Dornic DI. Ocular 14.
15.
16. Paton L. VII Diseases of the nervous system. 1. Ocular symptoms in subarachnoid hemorrhage. Trans Ophthal Soc UK 1924;110-
26. 17. Van Rens GH, Bos PJM, Van Dalen JTW. Vitrectomy in two cases of bilateral Terson syndrome. Doc Ophthalmol 1983;56:155-9. 18. Shaw HE, Landers MB. Vitreous hemorrhage after intracranial
hemorrhage.
Am J
Ophthalmol 1975;80:207-13.
728
Downloaded from cpj.sagepub.com at LAKEHEAD UNIV on April 5, 2015
