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Maternal Antiphospholipid Antibodies and Vitreous Hemorrhages in the Newborn: A Case Report
Arch Ophthalmol. 2001;119:914-916.
INTRODUCTION
Vitreous hemorrhage in the newborn, first described by Schleich1 in 1890, is a rare occurrence. The differential diagnoses include birth trauma, Terson syndrome, disseminated intravascular coagulation, galactosemia,2 and retinopathy of prematurity. Nonaccidental trauma, such as shaken baby syndrome, is a diagnosis of exclusion, which must be considered in all cases.
More recently, hereditary thrombophilic states, such as a protein C or, protein S deficiency3-4 have been identified as a cause of vitreous hemorrhage in the newborn. Antiphospholipid antibody syndrome is a well-recognized cause of hypercoagulation.5 This syndrome, in association with vitreous hemorrhage during the first week of life, has not been reported. The following case report highlights this possible association.
Report of a Case
The patient had experienced an uneventful 38-week gestation period, with a birth weight of 3175 g. The Apgar scores were 6 and 9 at 1 and 5 minutes, respectively. The infant was discharged from the hospital at 30 hours on parental request so that they could attend a wedding. Physical examination at the time of discharge was unremarkable except for a right cephalohematoma.
The 38-year-old white, gravida 1, para 1, abortio 0 mother has a past history of myocardial infarction at the age of 31 years, with the risk factors of obesity, cigarette smoking, and hypertension. She was taking aspirin daily during the first trimester, as well as metoprolol tartrate during the pregnancy. The father, aged 52 years, has 2 healthy adult offspring from a previous union.
At 60 hours of life, the infant became progressively lethargic, and the parents noted an unusual breathing pattern, as well as abnormal limb movements. Assessment at the emergency department described a poorly responsive and hypotensive female infant with periodic apnea and tonic-clonic movements of left upper and both lower limbs. The neonate was afebrile, jaundiced, and hypoglycemic, with a serum glucose level of less than 0.56 mmol/L (10 mg/dL). The patient was intubated and admitted to a level II neonatal intensive care unit. There were no rash, bruises, or abnormal skin markings other than the previously noted right cephalohematoma. The anterior fontanel was full, but not bulging. The pupils measured 3 mm and reacted sluggishly. Subconjunctival hemorrhages, as well as bilateral hyphemas were noted, but the fundus could not be visualized. Laboratory investigations revealed a normal hemoglobin level, hematocrit level, prothrombin time, and partial thromboplastin time.
The white blood cell count was 8.6x 109/L, and the platelet count was 95x 109/L. Urine analysis and urine amino acid screen results were normal. The lumbar puncture was traumatic, with clearing of fluid with collection. The laboratory report documented bloody-appearing cerebrospinal fluid (CSF) with 3500x 106/L red blood cells and 3x 106/L white blood cells. The CSF protein level was 80 mg/dL and glucose level was 2.3 mmol/L (41 mg/dL). Cultures of blood, urine, and CSF all showed no growth. Viral CSF cultures also showed no growth.
Ophthalmology consultation on the tenth day of life noted resolution of the hyphemas, but documented dense, bilateral, vitreous hemorrhages. A computed tomography scan performed on day 12 was read as showing subarachnoid and subdural hemorrhages. A renal ultrasonography performed at day 10 revealed bilateral, large, adrenal hemorrhages. A second ultrasonography performed 6 weeks later showed normal size adrenal glands, thus confirming the original impression of adrenal hemorrhage. On day 45, bilateral vitrectomy was performed for removal of the nonresolving vitreous hemorrhages. The underlying retina at the time of surgery was noted to be normal.
A consultation with pediatric ophthalmology was arranged by the county Child Protection Services at age 3 months because of the suspicious and unexplained cause of the infant's illness. Social service investigation for possible child abuse had been inconclusive.
On examination, the child would blink to the bright light of the indirect ophthalmoscope, but would not follow a face or objects presented at 33 cm. Frequent bursts of vertical nystagmus were noted, and the pupils, though equal, responded slowly to light. A fine, prepupillary membrane was noted bilaterally, but the remainder of the slitlamp examination results were normal. The retina appeared normal except for pallor of the optic nerve head temporally in each eye. The clinical impression was that of optic atrophy, as well as central visual impairment. A repeated computed tomography scan showed extensive occipital changes consistent with the later diagnosis (Figure 1).
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Figure 1. Computed tomography scan at age 3 months. Note massive bilateral occipital changes consistent with prior severe ischemia or infarction.
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The original computed tomography scan performed at age 12 days was reviewed with a pediatric neuroradiologist, who interpreted the original scan as indicative of extensive ischemia rather than subarachnoid and subdural hemorrhages (Figure 2 and Figure 3).
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Figure 2. Computed tomography scan at day 12. Encircled areas are actually vessels rather than hemorrhages. Note attenuation of detail in occipital and parietal regions indicative of probable ischemia.
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Figure 3. Computed tomography scan at day 12. Note attenuation of detail in occipital and parietal regions indicative of probable ischemia.
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Because of the maternal history of a myocardial infarction at age 31 years, and the similarity of the infant's case with cases of neonatal cerebral artery infarction associated with antiphospholipid antibodies, titers were drawn at age 6 months.
The infant's anticardiolipin antibody titers were found to be normal, but the mother's phosphatidylserine immunoglobulin G (IgG) level, a more specific marker than anticardiolipin antibody, was markedly elevated at 121 units (normal, <30 units), the immunoglobulin M level was 31 units (normal, <30 units), and the immunoglobulin A level was 30 units (normal, <30 units). Her smooth-muscle antibody titer, as well as antinuclear antibody and anti-DNA titers were all negative. This strongly supported a diagnosis of primary antiphospholipid antibody syndrome in the mother.
The infant was also examined in consultation by a pediatric hematology specialist at age 4 months. In view of the prior normal laboratory hematologic findings and the absence of family members other than the mother having a thrombotic history, it was felt that screening for a hypercoagualable state such as protein C or protein S deficiency, antithrombin III, or factor V mutation was not necessary.
Comment
The exact cause of this infant's complications may never be ascertained, but the uneventful delivery, followed by a rapid and unexplained deterioration on day 3, corresponds well with previously described cases of maternal antiphospholipid antibody syndrome and neonatal cerebral infarction.6-8
In these cases, maternal transfer of the IgG form of antiphospholipid antibody across the placenta has been postulated to be the cause of the cerebral thrombosis. The late assessment of our child for transplacentally acquired IgG antibodies would easily explain her normal titers when tested at age 6 months.
The antiphospholipid antibody syndrome is one of the most common causes of acquired hypercoagulation. These antibodies, found in 1% to 5% of the general population, are directed against different antigens5; mainly cardiolipin, B2 glycoprotein I, phosphatidylserine, and they also react with double-stranded DNA. Although the antiphospholipid antibodies were originally identified in patients with systemic lupus, they are now well recognized to occur in the absence of an associated connective tissue disease. Such patients are considered to have primary antiphospholipid antibody syndrome, as did the mother in this case report. The clinical significance of these antibodies for producing arterial and venous thrombosis of all sizes has only been appreciated for the past decade. The mechanism of thrombosis seen with these antibodies, including why clotting is episodic, is not fully understood.
It is postulated that the antibodies may attach directly to phospholipids on the vascular endothelium, on platelet membranes, and on monocytes, causing dysfunction. Antiphospholipid antibodies are also found to be directed against a variety of phospholipid binding plasma proteins, including prothrombin, factor Xa, protein C, and protein S, thus resulting in a hypercoagulable state. The exact cause of the vitreous hemorrhage in our patient may be similar to that in patients with protein C deficiency, in which retinal vessel occlusion is a result of the hypercoagulable state.3 This leads to central retinal vein occlusion, with resulting vitreous hemorrhage. Another possible mechanism would be a massive central nervous system ischemia, leading to edema and a Terson-like syndrome.9
In summary, with our evolving understanding of the delicate balance of factors required to maintain hemostasis, the clinical-ophthalmological spectrum of antiphospholipid antibody syndrome is becoming increasingly recognized in adults.10 The possible role of these maternally transferred antibodies in the fetus, which result in unexplained prenatal and perinatal vitreous hemorrhages, must also be considered. Expanded screening of mothers and neonates who manifest idiopathic vitreous hemorrhages would now seem an important indication.
AUTHOR INFORMATION
Corresponding author: Leon-Paul Noel, MD, Department of Ophthalmology, SUNY Upstate Medical University, 1101 Erie Blvd E, Syracuse, NY 13210.
Leon-Paul Noel, MD;
Ann S. Botash, MD
Syracuse, NY
Audrey DeSilva, MD
Ithaca, NY
REFERENCES
1. Schleich T. Mittheilungen aus der Ophth. Klin Tubingen. 1890;2:44.
2. Levy HL, Brown AE, Williams SE, deJuan E. Vitreous hemorrhage as an ophthalmic complication of galactosemia. J Pediatr. 1996;129:922-925.
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3. Hattenbach LO, Beeg T, Kreuz W, Zubcov A. Ophthalmic manifestation of congenital protein C deficiency. J AAPOS. 1999;3:188-190.
4. Mintz-Hittner HA, Miyashiro MJ, Knight-Nanan DM, O'Malley RE, Marlar RA. Vitreoretinal findings similar to retinopathy of prematurity in infants with compound heterozygous protein S deficiency. Ophthalmology. 1999;106:1525-1530.
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5. Petrie M. Antiophospholipid antibody syndrome: an acquired cause of venous and arterial hypercoagulability. Mount Sinai J Med. 1997;64:376-382.
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6. Akanli LF, Trasi SS, Thuraisamy K, et al. Neonatal middle cerebral artery infarction: association with elevated maternal anticardiolipin antibodies. Am J Perinatol. 1998;15:399-402.
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7. Silver RK, MacGregor SN, Pasternak JF, Neely SE. Fetal stroke associated with elevated maternal anticardiolipin antibodies. Obstet Gynecol. 1992;80:497-499.
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8. Teyssier G, Gautheron V, Absi Z, Galambrun C, Ravni C, Lepetit JC. Anticorps anticardiolipine, ischemie cerebrale et hemorragie surrenalienne chez un nouveau-ne. Arch Pediatr. 1995;2:1086-1088.
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9. Medele RJ, Stummer W, Mueller AJ, Steiger HJ, Reulen HJ. Terson's syndrome in subarachnoid hemorrhage and severe brain injury accompanied by acutely raised intracranial pressure. J Neurosurg. 1998;88:851-854.
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10. Leo-Kottler B, Klein R, Berg PA, Zrenner E. Ocular symptoms in association with anti-phospholipid antibodies. Graefes Arch Clin Exp Ophthalmol. 1998;236:658-668.
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SECTION EDITOR: W. RICHARD GREEN, MD
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