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A Premature Neonate With Leukocytosis

Alvaro Moreira, Rayne Rouce, C. Joan Richardson and Sunil Jain CLIN PEDIATR 2012 51: 692 originally published online 27 April 2011 DOI: 10.1177/0009922811405519 The online version of this article can be found at: http://cpj.sagepub.com/content/51/7/692

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Brief Reports

A Premature Neonate With Leukocytosis

Alvaro Moreira, MD1, Rayne Rouce, MD1, C. Joan Richardson, MD1, and Sunil Jain, MD1 Case Report
A 35-week preterm female, weighing 1850 g, is born to a gravida 4, para 4, 38-year-old mother by Cesarean section for fetal intolerance to labor. The pregnancy was complicated by an abnormal triple screen; however, amniocentesis was declined. Maternal hepatitis surface antigen, human immunodeficiency virus, and rapid plasma regain, and group B streptococci were negative. Membranes were ruptured artificially at delivery with clear fluid and Apgar scores of 8 and 8 at 1 and 5 minutes, respectively. The infant was transferred to neonatal intensive care unit for further care.

Clinical Pediatrics 51(7) 692693 The Author(s) 2012 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0009922811405519 http://cpj.sagepub.com

bilirubin was 14.9 mg/dL at 19 hours of life. Physical exam findings as well as karyotyping were consistent for trisomy 21. Cardiac echocardiogram was significant for small membranous ventricular septal defect.

Hospital Course
The infant was treated for respiratory distress syndrome with several days of NCPAP and one dose of surfactant. The infant was placed on empiric antibiotics and discontinued once blood cultures were negative for 72 hours. She was started on total parenteral nutrition. Phototherapy was used for the first week of life. Repeat blood counts showed worsening leukocytosis and thrombocytosis. Pediatric hematology was consulted and recommended daily blood counts (Figure 1).

Physical Examination
On presentation to the unit, the patient was in respiratory distress; her respiratory rate was 60 to 70 breaths per minute, heart rate 155 beats per minute, temperature 97.8F, and oxygen saturation of 94% on nasal continuous positive airway pressure (NCPAP) of 5 cm of H2O and FiO2 of 30%. On physical examination, the infant had a soft, large anterior fontanelle and upward slanting palpebral fissures. The nares were patent bilaterally with nasal prongs in place; she also had a large tongue and low set ears. The lungs had appropriate air entry with equal breath sounds and visible tachypnea with intercoastal retractions. Cardiac auscultation was unremarkable for murmurs, rubs, or gallops, but thoracic examination was significant for widely spaced nipples. Abdomen was soft, nondistended with positive bowel sounds, and the liver was palpated 4 cm below the coastal margin. Musculoskeletal exam was significant for hypotonia and clinodactyly to fifth digits.

Final Diagnosis
Transient myeloproliferative disorder.

Discussion
Trisomy 21, or Down syndrome, occurs in one of every 600 to 1000 live births in the United States.1,2 In addition to having cardiac, endocrine, neurologic, and musculoskeletal involvement, children with Down syndrome are at increased risk for various hematologic disorders.3 Transient myeloproliferative disorder (TMD), also known as transient leukemia, is a hematologic abnormality that occurs in up to 10% of newborns with trisomy 21.4 Although this condition is rare, knowing how these patients present and its possible complications is significant when caring for infants with trisomy 21. TMD can have different presentations in newborns but usually includes leukocytosis with increased blast
University of Texas Medical Branch at Galveston, Galveston, TX, USA Corresponding Author: Alvaro Moreira, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77550, USA Email: agmoreir@utmb.edu
1

Pertinent Laboratory Values

The white blood cell count was 57.2 103/L, granulocyte 16%, bands 18%, lymphocyte 23%, monocyte 6%, and peripheral smear showed 33% blasts, hemoglobin 16.1 g/dL, hematocrit 49.1%, and platelets 633 103/L. Serum electrolytes, blood urea nitrogen, creatinine were all within the reference range for age. Unconjugated

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Moreira et al

693 should be aware that a complete blood count with manual differential within the first month of life is recommended. Declaration of Conflicting Interests
The authors declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.

1400 1200 1000 800 600 400 200 0 1 2 3 4 5 6 7 8 9 10 11 12 Day of Life WBC Platelet Blast

70 60 50 40 Platelet x103 WBC x 103 30 Blast % 20 10 0

Funding
The authors received no financial support for the research, authorship, and/or publication of this article.

Figure 1. Hematologic findings in the patient with transient myeloproliferative disorder

References
1. Henry E, Walker D, Wiedmeier, Christensen RD. Hematological abnormalities during the first week of life among neonates with Down syndrome: data from a multihospital healthcare system. Am J Med Genet A. 2007;143: 42-50. 2. Xu G, Nagano M, Kanezaki R, et al. Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome. Blood. 2003;102:2960-2968. 3. Kruger B. Transient myeloproliferative disorder associated with trisomy 21. Neonatal Netw. 2007;26:7-19. 4. Rhoderick J, Bradshaw W. Transient myeloproliferative disorder in a newborn with Down syndrome. Adv Neonatal Care. 2008;8:208-218. 5. Roy A, Roberts I, Norton A, Vyas P. Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder (TMD) in Down syndrome: a multi-step model of myeloid leukaemogenesis. Br J Haematol. 2009;147:3-12. 6. Heald B, Hilden J, Zbuk K, et al. Severe TMD/AMKL with GATA1 mutation in a stillborn fetus with Down syndrome. Nat Clin Pract Oncol. 2007;4:433-438. 7. Hirono K, Miura M, Kanegane H. Hepatocyte growth factor in transient myeloproliferative disorder of Down syndrome. Pediatr Int. 2009;51:754-755. 8. Ahmed M, Sternberg A, Hall G, et al. Natural history of GATA1 mutations in Down syndrome. Blood. 2004;103:2480-2489. 9. Apollonsky N, Shende A, Ouansafi I, Brody J, Atlas M, Aygun B. Transient myeloproliferative disorder in neonates with and without Down syndrome: a tale of 2 syndromes. J Pediatr Hematol Oncol. 2008;30:860-864. 10. Hojo S, Tsukimori K, Kitade S, et al. Prenatal sonographic findings and hematological abnormalities in fetuses with transient abnormal myelopoiesis with Down syndrome. Prenat Diagn. 2007;27:507-511. 11. Craze JL, Harrison G, Wheatley K, Hann IM, Chessells JM. Improved outcome of acute myeloid leukaemia in Downs syndrome. Arch Dis Child. 81:32-37.

cells.5 Transient leukemia is usually considered a benign condition since it spontaneously resolves within the first 3 months of life. However, there is a 400 to 500 times greater risk for infants with TMD to go on to develop acute megakaryoblastic leukemia (AMKL) before school age.6 In addition, 20% of the time it can manifest with multi-organ involvement, including hepatosplenomegaly, hyperbilirubinemia, liver failure, pericardial effusion, ascites, pulmonary edema, and even hydrops fetalis.7 The exact pathogenesis of TMD remains a mystery, although recent studies have found a link between blast cells from patients with trisomy 21 who develop TMD and mutations in the transcription factor (GATA1), which controls erythropoiesis.6 Ahmed et al has also found that GATA1 mutations have been observed in both TMD and AMKL.8 Furthermore, samples of patients with trisomy 21 who developed AMKL do not have measurable GATA1 abnormalities once their cells have been treated and are now in remission. Research has also shown that TMD has been connected to a small number of patients who do not have trisomy 21.9 Although peripheral blood samples are most helpful in diagnosing TMD, one can only truly diagnose the disorder once time reveals normalization of blast cell count. Most patients with transient leukemia can be managed with supportive care. However, patients with elevated liver enzymes, respiratory or cardiac failure, or those with white blood cell count >100 000/mm3 have shown improvement with chemotherapeutic agents, such as cytosine arabinoside.9,10 When cytosine is given, it is usually administered for less than 1 week as infants with Down syndrome may be more susceptible to infectious agents.11 Fortunately, our patient had an improvement in her white blood cell counts by the second week of life (refer to Figure 1). In accordance with the American Academy of Pediatrics, physicians caring for newborns with Down syndrome

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