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Prenatal recognition of central nervous system complications of alloimmune thrombocytopenia
Computerized Medical Imaging and Graphics. Vol. 16, No. 2, pp. 137-142, Printed in the U.S.A. All rights reserved.
1992 Copyright
0895-61 I l/92 $5.00 + .oO 0 1992 Peqmnon Press Ltd.
PRENATAL RECOGNITION OF CENTRAL NERVOUS SYSTEM COMPLICATIONS OF ALLOIMMUNE THROMBOCYTOPENIA
Matthew J. Kuhn*, Stewart M. Couch, David H. Binstadt, Daniel A. Rightmire, August0 Morales, Narinder N. Khanna, and Scott D. Long Department
of Radiology, Southern 800 E. Carpenter,
Illinois University, School of Medicine, Springfield, IL 62769
(Received 17 September 1991)
Abstract-The radiological findings associated with alloimmune thrombocytopenia have not been well described. We present two such cases diagnosed in utero by ultrasound and discuss the radiographic findings of intracranial hemorrhage and hydrocephalus secondary to alloimmune thrombocytopenia. An awareness of this entity and its early diagnosis and intervention may greatly reduce the morbidity and mortality associated with alloimmune thrombocytopenia. Key Words: Alloimmune thrombocytopenia,
Intrauterine, Intracranial hemorrhage, Fetal hydrocephalus
INTRODUCTION
to 14%, most often due to intracerebral hemorrhage which occurs in 15% to 20% of cases (2, 9, 12, 13). Vaginal delivery and other perinatal stresses are known to increase the risk of intracranial hemorrhage in these infants ( 13). In this report we describe two cases in which evidence of fetal intracranial hemorrhage with associated hydrocephalus secondary to alloimmune thrombocytopenia was noted during prenatal ultrasound examination. Computed tomography, serial head sonography, and, in one case, magnetic resonance imaging (MRI) were performed following Caesarean delivery. The imaging findings of intrauterine and postnatal intracranial hemorrhage secondary to alloimmune thrombocytopenia are described.
Neonatal intracranial hemorrhage is a common occurrence in premature infants, affecting approximately 40% to 60% of those delivered earlier than 32 wk gestational age and weighing less than 1500 g (1). In contrast, intracranial hemorrhage in utero is thought to be a relatively infrequent observation (2-6). Several factors may place the fetus at increased risk of intracranial hemorrhage, including maternal alterations in blood pressure (e.g., a hypertensive episode or a hypotensive period with associated anoxia), maternal seizure, placental abruption, and the presence of alloimmune thrombocytopenia (2-7). The pathophysiology of alloimmune thrombocytopenia is analogous to erythroblastosis fetalis (Rh disease). If fetal platelets of a different histocompatibility type of paternal origin appear in the maternal circulation, isoimmunization may occur often during the first pregnancy. Maternal IgG antiplatelet antibodies produced against paternally derived platelet antigens, usually Pla 1 (8), cause immune destruction of antigen-positive fetal platelets (9, 10) and thrombocytopenia. Alloimmune thrombocytopenia occurs in approximately 1 in 2,000- 10,000 fetuses. The clinical course of postnatal alloimmune thrombocytopenia is variable, ranging from benign resolution within 2-3 wk to fatal hemorrhage (11). Alloimmune thrombocytopenia has an associated mortality of up
CASE
1
A 29-yr-old woman, gravida 4, para 1, abortus 2, with an obstetrical history of one term stillbirth, underwent an antenatal ultrasound examination at 18 wk (not shown) which was normal. A repeat ultrasound examination at 30 wk (Fig. 1) revealed a large solitary intracranial hemorrhage with intraventricular extension and hydrocephalus. A repeat ultrasound was performed at 35 wk, (Fig. 2) redemonstrating intraventricular hemorrhage. A 2580 g female infant was delivered by Caesarean section at 35 wk. At birth, the baby had Apgar scores at 1 and 5 min of 5 and 7 respectively, Physical examination revealed ecchymoses and generalized petechiae. Initial laboratory studies
* To whom correspondence should be addressed. 137
138
Computerized Medical Imaging and Graphics
(a)
March-April/ 1992, Volume 16, Number 2
Fig. 3. Ultrasound at day of delivery shows right temporal lobe hemorrhage and ventriculomegaly.
showed an Hgb of 10.9 g/d1 and an Hct of 32.6%. The platelet count was 9,000/mm3. Follow-up ultrasound of the brain was performed on the day of delivery (Fig. 3), and computed tomography (CT) (Fig. 4) of the brain was performed on the next day. These studies demonstrated marked ventricular dilatation and right temporal lobe hemorrhage. MRI revealed large right temporal lobe hemorrhage
(b) Fig. 1. Two antenatal axial ultrasounds at 30 wk reveal large parenchymal hematoma with intraventricular extension and ventriculomegaly.
Fig. 2. Antenatal
axial ultrasound
at 35 wk is unchanged.
Fig. 4. CT at day of delivery demonstrates right temporal lobe hemorrhage with intraventricular extension and ventriculomegaly.
CNS complications of alloimmune thrombocytopenia
with intraventricular extension and hydrocephalus with additional multifocal small hemorrhages in the left occipital lobe (Fig. 5). Infusion of random donor platelets did not improve platelet counts. Infusion of platelets harvested by pheresis from the mother resulted in elevated and sustained platelet counts. The mother’s platelets were found to be Plal negative while the father’s platelets were Plal positive, with antibody in the mother’s serum reacting to paternal platelets. CASE 2
A 28-yr-old woman, gravida 2, para 1, whose first infant was thrombocytopenic at term birth, underwent
??
M. J. KUHN ef al.
139
an antenatal ultrasound examination at 35 wk, which revealed evidence of an intraventricular hemorrhage and ventriculomegaly (Fig. 6). A 3 130 g male infant was delivered by Caesarean section at 36 wk from a breech presentation. Apgar scores at 1 and 5 min were 5 and 8 respectively. Physical examination of the neonate revealed extensive ecchymoses and generalized petechiae. Laboratory studies included a hemoglobin (Hgb) of 11.7 g/d1 and a hematocrit (Hct) of 34.3%. The platelet count was 20,000/mm3. Ultrasound of the brain was performed on the day of delivery and showed a massive right frontal lobe hemorrhage and ventriculomegaly with intraventricular blood seen bilaterally (Fig. 7). CT done the next day confirmed the large right frontal and intraventricular hemorrhage (Fig. 8). Infusion of random donor platelets did not improve platelet counts. The platelet count had fallen to 32,000/mm3 by the seventh day of life, and the baby received one unit of maternal platelets which produced a platelet count of 879,000. Analysis of parental serum and platelets revealed a maternal antiplatelet antibody difficult to characterize with weak to moderate reactivity against the father’s platelets. DISCUSSION
(a)
Fig. 5. (a) MR TR 500 TE20 axial. (b) MR TR 500 TE20 saggital. (c) MR TR 2200 TE80 coronal. These images reveal multifocal hemorrhages including large right temporal lobe hemorrhage with intraventricular extension and ventriculomegaly.
Intracranial hemorrhage is a relatively common occurrence in premature and low-birth-weight infants. Intracranial hemorrhage diagnosed postnatally by ul-
(4 Fig. 5. (Continued)
Computerized Medical Imaging and Graphics
Fig. 6. Antenatal ultrasound at 35 wk shows intraventricular hemorrhage and ventriculomegaly.
trasound and CT has been well characterized ( 14- 19). Neonatal alloimmune thrombocytopenia is associated with a significant rate of infant morbidity and mortality primarily due to intracranial hemorrhage following vaginal delivery. However, it is estimated that as many as 25% of all cases of intracerebral hemorrhage observed in neonates with alloimmune thrombocytopenia may have occurred in utero (2,4). There are a limited number of case reports in the literature of intracranial hemorrhage secondary to alloimmune or isoimmune thrombocytopenia detected in utero (4, 6, 20). These cases suggest that spontaneous in utero hemorrhage can occur before the onset of labor and in the absence of any recognizable maternal stress, hypoxia, or trauma. The sonographic findings of intracranial hemorrhage vary with the location and onset of the hemorrhage. In the fetus or premature infant, the insult usually originates from the germinal matrix which is very friable and subject to hemorrhage until involution at 32-34 menstrual wk (1). Acutely, the intracranial hemorrhage appears sonographically as an echogenic area within the ventricles or within the brain parenchyma (with displacement of midline structures and ventricles) (21). Bright subependymal echoes surrounding the ventricles may be seen from associated infarction. Hydrocephalus may also be present concurrently or as a possible sequelae to intraventricular hemorrhage (22). Intracerebral hemorrhage may lead to cystic encephalomalacia. The outcome of intracranial hemorrhage in neonates is directly related to the extent of hemorrhage, with intraparenchymal hemorrhage having the worst prognosis (23). Our two cases describe the features of intracranial hemorrhage sec-
March_April/l992,
Volume 16, Number 2
Fig. 7. Ultrasound at day of delivery demonstrates massive right frontal hemorrhage with intraventricular extension and ventriculomegaly.
ondary to alloimmune thrombocytopenia as recorded with in utero and postnatal ultrasound, CT, and MRI. The use of these contemporary imaging techniques has extended the scope of neurodiagnosis in utero. Ultrasound equipment is now capable of delineating fetal intracranial anatomy as early as 11 or 12 wk gestational age (5). Ultrasound usually demonstrates an echogenic intracerebral mass lesion in the acute phase. With clot lysis, echogenicity usually decreases. With CT, fresh blood, appears hyperdense. MRI, after 1 or 2 days,
Fig. 8. CT at day of delivery shows large right frontal intraventricular hemorrhage and ventriculomegaly.
and
CNS complications
of alloimmune
demonstrates increased signal intensity on both T land T2-weighted images. Tl on bleeds under 24-48 h shows diminished signal which may obscure the hemorrhage. Fresh blood produces increased signal on T2 (24). Alloimmune thrombocytopenia should be considered in the differential diagnosis of a fetus with large, solitary hemorrhage and hydrocephalus. Maternal serologic testing should be performed to detect the presence of alloantibodies against paternal platelet antigens. Percutaneous umbilical cord blood sampling can be done to type and count fetal platelets. Serious fetal hemorrhage from umbilical vessel puncture in thrombocytopenic fetuses appears to occur rarely, but has been reported (25). Those fetuses with suspected or confirmed alloimmune thrombocytopenia might benefit from maternal i.v. gamma globulin therapy or in utero platelet transfusions (26). Delivery by Caesarean section, after fetal lung maturity has been attained, should be considered to minimize birth trauma and reduce the risk of further intracranial hemorrhage. In families in which an infant has been affected with alloimmune thrombocytopenia, the rate of recurrence among subsequent infants is either 50% or 100% depending on whether the father is homozygous or heterozygous for the offending antigen (12). The degree of thrombocytopenia in subsequent infants is usually as severe as in the preceding affected sibling, or worse (2, 27). Patients with a history of platelet alloimmunization, or a previously affected infant, should be counseled about the availability of fetal blood sampling, i.v. gammaglobulin therapy, and in utero transfusion. Maternal i.v. gamma globulin therapy has been effective in up to 90% of cases (26). Close cooperation between physicians in radiology, obstetrics, fetal-maternal medicine, and pediatrics is essential for prompt diagnosis and appropriate management. REFERENCES 1. Volpe, J.L. Neonatal intraventricular hemorrhage. N. Engl. J. Med. 304:15-17; 1981. 2. Bussel, J.B. (Neonatal Immune Thrombocytopenia Study Group) Neonatal alloimmune thrombocytopenia: A prospective case accumulation study. Pediatr. Res. 23:337A, abstract; 1988. 3. Chinn, D.H.; Filly, R.A. Extensive intracranial hemorrhage in utero. J. Ultrasound Med. 2:285-287; 1983. 4. Herman, J.H.; Jumbelic, MI.; Ancona, R.J.; Kickler, T.S. In utero cerebral hemorrhage in alloimmune thrombocytopenia. Am. J. Pediatr. Hematol. Oncol. 8:3 12-3 17; 1986. 5. Kim, M.S.; Elyaderani, M.K. Sonographic diagnosis of cerebroventricular hemorrhage in utero. Radiology 142:479-480: 1982. 6. Morales, W.J.; Stroup, M. Intracranial hemorrhage in utero due to isoimmune neonatal thrombocytopenia. Obstet. Gynecol. 65: 2OS-21s; 1985. 7. Minkoff, H.; Schaffer, R.M.; Delke, I.; Grunebaum, A.N. Diagnosis of intracranial hemorrhage in utero after a maternal seizure. Obstet. Gynecol. 65:22S-243; 1985.
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141
8. Deaver, J.E.; Leppert, P.C.; Zaroulis, C.G. Neonatal alloimmune thrombocvtonenic ournura. Am. J. Perinatol. 3: 127-131: 1986. 9. Pearson, HA.; Schulman, N.R.; Marder, V.J., et al. Isoimmune neonatal thrombocytopenia purpura: Clinical and therapeutic considerations. Blood 23: 154- 177; 1964. 10. Schulman, N.R.; Marder, V.J.; Hiller, M.C., et al. Platelet and leukocyte isoantigens and their antibodies: Serologic physiologic and clinical studies. Prog. Hematol. 4:222-304; 1964. I I. Burrows, R.F.; Caco, CC.; Kelton, J.G. Neonatal alloimmune thrombocytopenia: Spontaneous in utero intracranial hemorrhage. Am. J. Hematol. 28:98- 102; 1988. 12. Schulman. N.R.: Jordan. J.R. Jr. Platelet immunolonv. In: Colman R.W.; H&h, J.; Marder, V.J.; Salzman, E.Wy[ eds. Hemostatis and thrombosis; Basic principles and clinical practice. Philadelphia: J.B. Lippincott; 1982:274-342. 13. Sitars, A.L.; Driscoll, J.M.; Wolf, J.A. Management ofisoimmune neonatal thrombocytopenia. Am. J. Obstet. Gynecol. 124:3942; 1976. 14. Babcock, D.S.; Han, B.K.; Le Quesne. G.W. B-mode gray scale ultrasound of the head in the newborn and young infant. AJR 135:457-468; 1980. hemorrhage 15. Burstein, J.; Papile, L.; Burstein, R. Intraventricular and hydrocephalus in premature newborns: A prospective study with CT. AJR 132:631-635; 1979. 16. Grant, G.G.; Schellinger, D.; Borts, F.T., et al. Real-time sonography of the neonatal and infant head. AJR 136:265-270; 1981. 17. Haber, K.; Wachter, R.D.; Christenson, PC.; Vaucher, Y.; Sahn, D.J.; Smith, J.R. Ultrasonic evaluation of intracranial pathology in infants: A new technique. Radiology 135: 173-l 78; 1980. 18. Papile, L.; Burstein, J.; Burstein, R.; Koffler, H. Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1500 grams. J. Pediatr. 921529-534; 1978. 19. Rumack, C.M.; McDonald, M.M.; O’Meara, O.P.; Sanders, B.B.; Rudikoff, J.C. CT detection and course of intracranial hemorrhage in premature infants. AJR 13 1:493-497; 1978. 20. Zalneraitis, E.L.; Young, R.S.K.; Krishnamoorthy, K.S. Intracranial hemorrhage in utero as a complication of isoimmune thrombocytopenia. J. Pediatr. 95:61 l-614; 1979. 21. Babcock, D.S.; Bokyung, K.H. Cranial ultrasonography ofinfants. Baltimore: Williams and Wilkins; 1981: 195-196. 22. Pretorius, D.; Singh, S.; Manco-Johnson, M., et al. In utero diagnosis of intracranial hemorrhage resulting in fatal hydrocephalus. J. Reprod. Med. 31:136-138; 1986. 23. Shankaran, S.; Slovist, L.; Bedard, M.P.; Poland, R.L. Sonographic classification of intracranial hemorrhage-A prognostic indicator of mortality, morbidity and short term neurologic outcome. J. Pediatr. 100:469-475; 1982. 24. Swischuk, L. Imaging of the newborn, infant and young child, 3rd edition. Baltimore: Williams and Wilkins; 1989:95 l-962. 25. Rightmire, D.A.; Ertmoed. E.E. Fetal exsanguination following umbilical cord blood sampling. Am. J. Obstet. Gynecol. 164: 339s; 1991. 26. Bussel, J.B.; McFarland, J.G.; Berkowitz, R.L. Antenatal management of fetal alloimmune and autoimmune thrombocytopenia. Transfusion Med. Rev. 4(2): 149-162: 1990. 27. Muller, J.Y.; Reznifoff-Etievant,‘M.F.; Patereau, C:, Dangu, C.; Chesnel, N. Neonatal alloimmune thrombocytopenia clinical and biological study of 84 cases. Presse Med. 14(2):83-86: 1985.
About the Author-MATTHEW J. KUHN is Chief of Neuroradiology and Associate Professor of Neurology, Neurosurgery and Neuroradiology at Southern Illinois University School of Medicine in Springfield. About the Author-STEWART M. COUCH is a fourth-year Diagnostic Radiology Resident at Southern Illinois University School of Medicine.
142
Computerized Medical Imaging and Graphics
About the Author-DAVID H. BINSTADTis Chief of Pediatric Radiology at Southern Illinois University School of Medicine.
About the Author-DANIEL A. RIGHTMIREis Associate Professor of Obstetrics and Gynecology at Southern Illinois University School of Medicine. He is board-certified in Maternal/Fetal Medicine and maintains a special interest of prenatal diagnosis and treatment of fetal disorders.
March-April/ 1992, Volume 16, Number 2 About the Author-AucuSTO MORALESis Chief of Pediatric Neurology and Assistant Professor of Pediatrics at Southern Illinois University School of Medicine. About the Author-NARINDER N. KHANNA is a Neonatologist at Southern Illinois University School of Medicine. About the Author-SCOTT D. LONGis a fourth-year medical student at Southern Illinois University School of Medicine. He plans to pursue a postgraduate position in diagnostic radiology.
1992 Copyright
0895-61 I l/92 $5.00 + .oO 0 1992 Peqmnon Press Ltd.
PRENATAL RECOGNITION OF CENTRAL NERVOUS SYSTEM COMPLICATIONS OF ALLOIMMUNE THROMBOCYTOPENIA
Matthew J. Kuhn*, Stewart M. Couch, David H. Binstadt, Daniel A. Rightmire, August0 Morales, Narinder N. Khanna, and Scott D. Long Department
of Radiology, Southern 800 E. Carpenter,
Illinois University, School of Medicine, Springfield, IL 62769
(Received 17 September 1991)
Abstract-The radiological findings associated with alloimmune thrombocytopenia have not been well described. We present two such cases diagnosed in utero by ultrasound and discuss the radiographic findings of intracranial hemorrhage and hydrocephalus secondary to alloimmune thrombocytopenia. An awareness of this entity and its early diagnosis and intervention may greatly reduce the morbidity and mortality associated with alloimmune thrombocytopenia. Key Words: Alloimmune thrombocytopenia,
Intrauterine, Intracranial hemorrhage, Fetal hydrocephalus
INTRODUCTION
to 14%, most often due to intracerebral hemorrhage which occurs in 15% to 20% of cases (2, 9, 12, 13). Vaginal delivery and other perinatal stresses are known to increase the risk of intracranial hemorrhage in these infants ( 13). In this report we describe two cases in which evidence of fetal intracranial hemorrhage with associated hydrocephalus secondary to alloimmune thrombocytopenia was noted during prenatal ultrasound examination. Computed tomography, serial head sonography, and, in one case, magnetic resonance imaging (MRI) were performed following Caesarean delivery. The imaging findings of intrauterine and postnatal intracranial hemorrhage secondary to alloimmune thrombocytopenia are described.
Neonatal intracranial hemorrhage is a common occurrence in premature infants, affecting approximately 40% to 60% of those delivered earlier than 32 wk gestational age and weighing less than 1500 g (1). In contrast, intracranial hemorrhage in utero is thought to be a relatively infrequent observation (2-6). Several factors may place the fetus at increased risk of intracranial hemorrhage, including maternal alterations in blood pressure (e.g., a hypertensive episode or a hypotensive period with associated anoxia), maternal seizure, placental abruption, and the presence of alloimmune thrombocytopenia (2-7). The pathophysiology of alloimmune thrombocytopenia is analogous to erythroblastosis fetalis (Rh disease). If fetal platelets of a different histocompatibility type of paternal origin appear in the maternal circulation, isoimmunization may occur often during the first pregnancy. Maternal IgG antiplatelet antibodies produced against paternally derived platelet antigens, usually Pla 1 (8), cause immune destruction of antigen-positive fetal platelets (9, 10) and thrombocytopenia. Alloimmune thrombocytopenia occurs in approximately 1 in 2,000- 10,000 fetuses. The clinical course of postnatal alloimmune thrombocytopenia is variable, ranging from benign resolution within 2-3 wk to fatal hemorrhage (11). Alloimmune thrombocytopenia has an associated mortality of up
CASE
1
A 29-yr-old woman, gravida 4, para 1, abortus 2, with an obstetrical history of one term stillbirth, underwent an antenatal ultrasound examination at 18 wk (not shown) which was normal. A repeat ultrasound examination at 30 wk (Fig. 1) revealed a large solitary intracranial hemorrhage with intraventricular extension and hydrocephalus. A repeat ultrasound was performed at 35 wk, (Fig. 2) redemonstrating intraventricular hemorrhage. A 2580 g female infant was delivered by Caesarean section at 35 wk. At birth, the baby had Apgar scores at 1 and 5 min of 5 and 7 respectively, Physical examination revealed ecchymoses and generalized petechiae. Initial laboratory studies
* To whom correspondence should be addressed. 137
138
Computerized Medical Imaging and Graphics
(a)
March-April/ 1992, Volume 16, Number 2
Fig. 3. Ultrasound at day of delivery shows right temporal lobe hemorrhage and ventriculomegaly.
showed an Hgb of 10.9 g/d1 and an Hct of 32.6%. The platelet count was 9,000/mm3. Follow-up ultrasound of the brain was performed on the day of delivery (Fig. 3), and computed tomography (CT) (Fig. 4) of the brain was performed on the next day. These studies demonstrated marked ventricular dilatation and right temporal lobe hemorrhage. MRI revealed large right temporal lobe hemorrhage
(b) Fig. 1. Two antenatal axial ultrasounds at 30 wk reveal large parenchymal hematoma with intraventricular extension and ventriculomegaly.
Fig. 2. Antenatal
axial ultrasound
at 35 wk is unchanged.
Fig. 4. CT at day of delivery demonstrates right temporal lobe hemorrhage with intraventricular extension and ventriculomegaly.
CNS complications of alloimmune thrombocytopenia
with intraventricular extension and hydrocephalus with additional multifocal small hemorrhages in the left occipital lobe (Fig. 5). Infusion of random donor platelets did not improve platelet counts. Infusion of platelets harvested by pheresis from the mother resulted in elevated and sustained platelet counts. The mother’s platelets were found to be Plal negative while the father’s platelets were Plal positive, with antibody in the mother’s serum reacting to paternal platelets. CASE 2
A 28-yr-old woman, gravida 2, para 1, whose first infant was thrombocytopenic at term birth, underwent
??
M. J. KUHN ef al.
139
an antenatal ultrasound examination at 35 wk, which revealed evidence of an intraventricular hemorrhage and ventriculomegaly (Fig. 6). A 3 130 g male infant was delivered by Caesarean section at 36 wk from a breech presentation. Apgar scores at 1 and 5 min were 5 and 8 respectively. Physical examination of the neonate revealed extensive ecchymoses and generalized petechiae. Laboratory studies included a hemoglobin (Hgb) of 11.7 g/d1 and a hematocrit (Hct) of 34.3%. The platelet count was 20,000/mm3. Ultrasound of the brain was performed on the day of delivery and showed a massive right frontal lobe hemorrhage and ventriculomegaly with intraventricular blood seen bilaterally (Fig. 7). CT done the next day confirmed the large right frontal and intraventricular hemorrhage (Fig. 8). Infusion of random donor platelets did not improve platelet counts. The platelet count had fallen to 32,000/mm3 by the seventh day of life, and the baby received one unit of maternal platelets which produced a platelet count of 879,000. Analysis of parental serum and platelets revealed a maternal antiplatelet antibody difficult to characterize with weak to moderate reactivity against the father’s platelets. DISCUSSION
(a)
Fig. 5. (a) MR TR 500 TE20 axial. (b) MR TR 500 TE20 saggital. (c) MR TR 2200 TE80 coronal. These images reveal multifocal hemorrhages including large right temporal lobe hemorrhage with intraventricular extension and ventriculomegaly.
Intracranial hemorrhage is a relatively common occurrence in premature and low-birth-weight infants. Intracranial hemorrhage diagnosed postnatally by ul-
(4 Fig. 5. (Continued)
Computerized Medical Imaging and Graphics
Fig. 6. Antenatal ultrasound at 35 wk shows intraventricular hemorrhage and ventriculomegaly.
trasound and CT has been well characterized ( 14- 19). Neonatal alloimmune thrombocytopenia is associated with a significant rate of infant morbidity and mortality primarily due to intracranial hemorrhage following vaginal delivery. However, it is estimated that as many as 25% of all cases of intracerebral hemorrhage observed in neonates with alloimmune thrombocytopenia may have occurred in utero (2,4). There are a limited number of case reports in the literature of intracranial hemorrhage secondary to alloimmune or isoimmune thrombocytopenia detected in utero (4, 6, 20). These cases suggest that spontaneous in utero hemorrhage can occur before the onset of labor and in the absence of any recognizable maternal stress, hypoxia, or trauma. The sonographic findings of intracranial hemorrhage vary with the location and onset of the hemorrhage. In the fetus or premature infant, the insult usually originates from the germinal matrix which is very friable and subject to hemorrhage until involution at 32-34 menstrual wk (1). Acutely, the intracranial hemorrhage appears sonographically as an echogenic area within the ventricles or within the brain parenchyma (with displacement of midline structures and ventricles) (21). Bright subependymal echoes surrounding the ventricles may be seen from associated infarction. Hydrocephalus may also be present concurrently or as a possible sequelae to intraventricular hemorrhage (22). Intracerebral hemorrhage may lead to cystic encephalomalacia. The outcome of intracranial hemorrhage in neonates is directly related to the extent of hemorrhage, with intraparenchymal hemorrhage having the worst prognosis (23). Our two cases describe the features of intracranial hemorrhage sec-
March_April/l992,
Volume 16, Number 2
Fig. 7. Ultrasound at day of delivery demonstrates massive right frontal hemorrhage with intraventricular extension and ventriculomegaly.
ondary to alloimmune thrombocytopenia as recorded with in utero and postnatal ultrasound, CT, and MRI. The use of these contemporary imaging techniques has extended the scope of neurodiagnosis in utero. Ultrasound equipment is now capable of delineating fetal intracranial anatomy as early as 11 or 12 wk gestational age (5). Ultrasound usually demonstrates an echogenic intracerebral mass lesion in the acute phase. With clot lysis, echogenicity usually decreases. With CT, fresh blood, appears hyperdense. MRI, after 1 or 2 days,
Fig. 8. CT at day of delivery shows large right frontal intraventricular hemorrhage and ventriculomegaly.
and
CNS complications
of alloimmune
demonstrates increased signal intensity on both T land T2-weighted images. Tl on bleeds under 24-48 h shows diminished signal which may obscure the hemorrhage. Fresh blood produces increased signal on T2 (24). Alloimmune thrombocytopenia should be considered in the differential diagnosis of a fetus with large, solitary hemorrhage and hydrocephalus. Maternal serologic testing should be performed to detect the presence of alloantibodies against paternal platelet antigens. Percutaneous umbilical cord blood sampling can be done to type and count fetal platelets. Serious fetal hemorrhage from umbilical vessel puncture in thrombocytopenic fetuses appears to occur rarely, but has been reported (25). Those fetuses with suspected or confirmed alloimmune thrombocytopenia might benefit from maternal i.v. gamma globulin therapy or in utero platelet transfusions (26). Delivery by Caesarean section, after fetal lung maturity has been attained, should be considered to minimize birth trauma and reduce the risk of further intracranial hemorrhage. In families in which an infant has been affected with alloimmune thrombocytopenia, the rate of recurrence among subsequent infants is either 50% or 100% depending on whether the father is homozygous or heterozygous for the offending antigen (12). The degree of thrombocytopenia in subsequent infants is usually as severe as in the preceding affected sibling, or worse (2, 27). Patients with a history of platelet alloimmunization, or a previously affected infant, should be counseled about the availability of fetal blood sampling, i.v. gammaglobulin therapy, and in utero transfusion. Maternal i.v. gamma globulin therapy has been effective in up to 90% of cases (26). Close cooperation between physicians in radiology, obstetrics, fetal-maternal medicine, and pediatrics is essential for prompt diagnosis and appropriate management. REFERENCES 1. Volpe, J.L. Neonatal intraventricular hemorrhage. N. Engl. J. Med. 304:15-17; 1981. 2. Bussel, J.B. (Neonatal Immune Thrombocytopenia Study Group) Neonatal alloimmune thrombocytopenia: A prospective case accumulation study. Pediatr. Res. 23:337A, abstract; 1988. 3. Chinn, D.H.; Filly, R.A. Extensive intracranial hemorrhage in utero. J. Ultrasound Med. 2:285-287; 1983. 4. Herman, J.H.; Jumbelic, MI.; Ancona, R.J.; Kickler, T.S. In utero cerebral hemorrhage in alloimmune thrombocytopenia. Am. J. Pediatr. Hematol. Oncol. 8:3 12-3 17; 1986. 5. Kim, M.S.; Elyaderani, M.K. Sonographic diagnosis of cerebroventricular hemorrhage in utero. Radiology 142:479-480: 1982. 6. Morales, W.J.; Stroup, M. Intracranial hemorrhage in utero due to isoimmune neonatal thrombocytopenia. Obstet. Gynecol. 65: 2OS-21s; 1985. 7. Minkoff, H.; Schaffer, R.M.; Delke, I.; Grunebaum, A.N. Diagnosis of intracranial hemorrhage in utero after a maternal seizure. Obstet. Gynecol. 65:22S-243; 1985.
thrombocytopenia
M. J. KUHN et al.
??
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8. Deaver, J.E.; Leppert, P.C.; Zaroulis, C.G. Neonatal alloimmune thrombocvtonenic ournura. Am. J. Perinatol. 3: 127-131: 1986. 9. Pearson, HA.; Schulman, N.R.; Marder, V.J., et al. Isoimmune neonatal thrombocytopenia purpura: Clinical and therapeutic considerations. Blood 23: 154- 177; 1964. 10. Schulman, N.R.; Marder, V.J.; Hiller, M.C., et al. Platelet and leukocyte isoantigens and their antibodies: Serologic physiologic and clinical studies. Prog. Hematol. 4:222-304; 1964. I I. Burrows, R.F.; Caco, CC.; Kelton, J.G. Neonatal alloimmune thrombocytopenia: Spontaneous in utero intracranial hemorrhage. Am. J. Hematol. 28:98- 102; 1988. 12. Schulman. N.R.: Jordan. J.R. Jr. Platelet immunolonv. In: Colman R.W.; H&h, J.; Marder, V.J.; Salzman, E.Wy[ eds. Hemostatis and thrombosis; Basic principles and clinical practice. Philadelphia: J.B. Lippincott; 1982:274-342. 13. Sitars, A.L.; Driscoll, J.M.; Wolf, J.A. Management ofisoimmune neonatal thrombocytopenia. Am. J. Obstet. Gynecol. 124:3942; 1976. 14. Babcock, D.S.; Han, B.K.; Le Quesne. G.W. B-mode gray scale ultrasound of the head in the newborn and young infant. AJR 135:457-468; 1980. hemorrhage 15. Burstein, J.; Papile, L.; Burstein, R. Intraventricular and hydrocephalus in premature newborns: A prospective study with CT. AJR 132:631-635; 1979. 16. Grant, G.G.; Schellinger, D.; Borts, F.T., et al. Real-time sonography of the neonatal and infant head. AJR 136:265-270; 1981. 17. Haber, K.; Wachter, R.D.; Christenson, PC.; Vaucher, Y.; Sahn, D.J.; Smith, J.R. Ultrasonic evaluation of intracranial pathology in infants: A new technique. Radiology 135: 173-l 78; 1980. 18. Papile, L.; Burstein, J.; Burstein, R.; Koffler, H. Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1500 grams. J. Pediatr. 921529-534; 1978. 19. Rumack, C.M.; McDonald, M.M.; O’Meara, O.P.; Sanders, B.B.; Rudikoff, J.C. CT detection and course of intracranial hemorrhage in premature infants. AJR 13 1:493-497; 1978. 20. Zalneraitis, E.L.; Young, R.S.K.; Krishnamoorthy, K.S. Intracranial hemorrhage in utero as a complication of isoimmune thrombocytopenia. J. Pediatr. 95:61 l-614; 1979. 21. Babcock, D.S.; Bokyung, K.H. Cranial ultrasonography ofinfants. Baltimore: Williams and Wilkins; 1981: 195-196. 22. Pretorius, D.; Singh, S.; Manco-Johnson, M., et al. In utero diagnosis of intracranial hemorrhage resulting in fatal hydrocephalus. J. Reprod. Med. 31:136-138; 1986. 23. Shankaran, S.; Slovist, L.; Bedard, M.P.; Poland, R.L. Sonographic classification of intracranial hemorrhage-A prognostic indicator of mortality, morbidity and short term neurologic outcome. J. Pediatr. 100:469-475; 1982. 24. Swischuk, L. Imaging of the newborn, infant and young child, 3rd edition. Baltimore: Williams and Wilkins; 1989:95 l-962. 25. Rightmire, D.A.; Ertmoed. E.E. Fetal exsanguination following umbilical cord blood sampling. Am. J. Obstet. Gynecol. 164: 339s; 1991. 26. Bussel, J.B.; McFarland, J.G.; Berkowitz, R.L. Antenatal management of fetal alloimmune and autoimmune thrombocytopenia. Transfusion Med. Rev. 4(2): 149-162: 1990. 27. Muller, J.Y.; Reznifoff-Etievant,‘M.F.; Patereau, C:, Dangu, C.; Chesnel, N. Neonatal alloimmune thrombocytopenia clinical and biological study of 84 cases. Presse Med. 14(2):83-86: 1985.
About the Author-MATTHEW J. KUHN is Chief of Neuroradiology and Associate Professor of Neurology, Neurosurgery and Neuroradiology at Southern Illinois University School of Medicine in Springfield. About the Author-STEWART M. COUCH is a fourth-year Diagnostic Radiology Resident at Southern Illinois University School of Medicine.
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About the Author-DAVID H. BINSTADTis Chief of Pediatric Radiology at Southern Illinois University School of Medicine.
About the Author-DANIEL A. RIGHTMIREis Associate Professor of Obstetrics and Gynecology at Southern Illinois University School of Medicine. He is board-certified in Maternal/Fetal Medicine and maintains a special interest of prenatal diagnosis and treatment of fetal disorders.
March-April/ 1992, Volume 16, Number 2 About the Author-AucuSTO MORALESis Chief of Pediatric Neurology and Assistant Professor of Pediatrics at Southern Illinois University School of Medicine. About the Author-NARINDER N. KHANNA is a Neonatologist at Southern Illinois University School of Medicine. About the Author-SCOTT D. LONGis a fourth-year medical student at Southern Illinois University School of Medicine. He plans to pursue a postgraduate position in diagnostic radiology.