Severe neonatal thrombocytopenia is a hematological emergency that can be due to increased platelet destruction(such as immune-mediated and peripheral platelet consumption) or congenital failure of platelet production. The definitive diagnosis of the underlying cause of neonatal thrombocytopenic purpurais based on both clinical and laboratory findings.Case report; We present two infants with persistent severe thrombocytopenia of distinct aetiologies: neonatal alloimmune thrombocytopenic purpura and hepatitis B virus exposure. Their clinical course, haematological profile and treatments are discussed.Conclusion: This reportreiterates the need to think laterally while considering the differential diagnoses of neonatal thrombocytopenic purpura. Moreover, ithighlightsits treatment challenges in peripheral health facilities, especially in resource-limited settings

B, Badejoko

MT, Abiodun

RO, Oluwafemi

English

AJOL - African Journals Online

ABSTRACTNEONATAL THROMBOCYTOPENIC PURPURA: REPORT OF TWO CASES AND REVIEW OF LITERATURE1  2  3 Abiodun MT, Badejoko B, Oluwafemi RO 1  Department of Child Health, University of Benin Teaching Hospital, Benin City, Nigeria.2Department of Paediatrics, Mother and Child Hospital, Ondo, Ondo State, Nigeria.3Department of Paediatrics, Mother and Child Hospital, Akure, Ondo State Nigeria.Correspondence and reprint request to: Dr. MT Abiodun;  Email: Department of Child Health, University of Benin Teaching Hospital, Benin City, Nigeria moses.abiodun@uniben.eduKeywords: Neonatal thrombocytopenic purpura, Differential diagnoses, Haematological profileIntroduction: Severe neonatal thrombocytopenia is a hematological emergency that can be due to increased platelet destruction(such as immune-mediated and peripheral platelet consumption) or congenital failure of platelet production. The definitive diagnosis of the underlying cause of neonatal thrombocytopenic purpurais based on both clinical and laboratory findings.Case report; We present two infants with persistent severe thrombocytopenia of distinct aetiologies: neonatal alloimmune thrombocytopenic purpura and hepatitis B virus exposure. Their clinical course, haematological profile and treatments are discussed.Conclusion: This reportreiterates the need to think laterally while considering the differential diagnoses of neonatal thrombocytopenic purpura. Moreover, ithighlightsits treatment challenges in peripheral health facilities, especially in resource-limited settings.CASE REPORT Page 92                                                                   Kanem Journal of Medical Sciences  2018;12(2): 92-96INTRODUCTIONSevere neonatal thrombocytopenia (less than 50,000/ul) is a hematological emergency. It is rare in apparently healthy newborns but its incidence ranges from 2.4% to 5.0% among infants admitted to 1,2the neonatal intensive care unit (NICU). Neonatal thrombocytopenia is often due to increased platelet destruction (such as immune-mediated  and peripheral platelet consumption) or congenital failure of platelet p r o d u c t i o n  i n c l u d i n g  a m e g a k a r y o c y t i c  thrombocytopenia and thrombocytopenia absent 3 - 5radius (TAR) syndrome. Also, neonatal thrombocytopenia can occur in perinatal asphyxia and pre-eclampsia, perhaps related to hypoxia and d e c r e a s e d  m a t e r n a l  p l a t e l e t  l e v e l   2,6respectively. The definitive diagnosis of neonatal thrombocytopenia  is based on both clinicaland laboratory findings.Neonatal alloimmune thrombocytopenia purpura (NATP) occurs when fetal platelets contains paternal antigen that is recognized as foreign by maternal immunity, eliciting immunoglobulin G (IgG) antiplatelet antibodies that cross placenta and 7destroy fetal platelets. This is the platelet 7equivalent of Rhesus disease of the newborn. The 7incidence of NATP is 1 in 4,000 to 5,000 live births .  Affected infants typically develop generalized petechiae and purpura in the early neonatal period, but they are otherwise healthy. Intracranial hemorrhage may be present in up to 30% of severe 7,8cases.  Laboratory confirmation is by detecting antiplatelet alloantibodies in mother's serum while DNA sequencing of parental blood identify platelet 7,9antigen genotypes.Furthermore, congenital viral infections such ascytomegalovirus and hepatitis B virus (HBV) can lead to neonatal thrombocytopenia by increased 10peripheral platelet consumption.  They induce platelet aggregation and loss of sialic acid from [11]platelet membrane. There is a paucity of report on thrombocytopenia in HBV-exposed neonates in the CASE REPORT                 Abiodun MT                                                                            et alliterature. In a population-based cohort study in Sweden, HBV increased the risk of preterm birth 12and its associated morbidities. In addition, Salemi et alfound that adverse neurological outcome occurred more frequently in infants of HBV- [13] positive mothers. However, none of these studies reported symptomatic neonatal thrombocytopenia 12,13as a perinatal outcome.Considering the dearth of data on neonatal purpurain HBV-exposed infants and the scarcity of sophisticated diagnostic tools to aid clinicians to confirm NATP, this report highlights the clinical features, management and outcome of two Nigerianinfants with these possible underlying causes of thrombocytopenic purpura, while reviewing relevant literatures.CASE REPORTThe following infants who had generalized purpura in the early neonatal period were deliveredat the Mother and Child Hospital Ondo, by unrelated parents. Both of them had severe thrombocytopenia. Their clinical features, diagnoses and outcome are detailed below:  Case 1: A male neonate delivered at home to a 23-+0 year-old Para2 woman on May 23, 2014. Pregnancy was booked and the antenatal period was uneventful. There was no prolonged bleeding in the mother. There was no peripartum pyrexia. The infant had spontaneous regular breathing at birth. rdHowever, hepresented on the 3  day of life with complaints of fever and poor feeding of two days duration. He was well hydrated,anicteric, acyanosed and systemic examinations were normal.Generalized petechial haemorrhages and purpura were noticed on his trunk and extensor surfaces of his extremitieson the second day on admission. (Figure 1A)There was no active bleeding from the orifices.Bleeding time was prolonged. Serial complete blood count results showed persistent severe thrombocytopenia (Table 1). The diagnosis was neonatal alloimmune t h r o m b o c y t o p e n i c  p u r p u r a  ( N A T P ) a n d  probableneonatal sepsis. He was treated with intravenous cefuroxime and gentamicin as well as intravenous vitamin K 1mg/kg daily for 3 days.He ndhad exchange blood transfusions (EBTs) on the 2  thand 4  day on admission using suitable freshly donated blood.Platelet concentrate was not available.He was referred to a tertiary institution for platelet transfusionand possible anti-platelet antibody immunoassay due to persistent thrombocytopenia.However,the referral plan was not accepted by the parents due to financial constraints. Second line antibiotic was commenced as per unit protocols. Euglycemia was maintained at a glucose infusion rateof 6mg/kg/minute and he was later fed with expressed breast milk as tolerated. However,he died suddenly on the 14th day on admission due tointraventricular haemorhage; post-mortem lumbar puncture yielded a uniformly bloody cerebrospinal fluid (CSF) that did not clot. Parents counseled on relevant antenatal management o p t i o n s  o f  f e t o m a t e r n a l  a l l o i m m u n e  [8]thrombocytopenia in future pregnancies.Case 2: A male infant delivered to a primiparous woman in March 2015 via spontaneous vertex delivery.  Pregnancy was not booked.Mother did not have any febrile illness with a rash in the antenatal period. There was no prolonged rupture of membrane and no peripartum pyrexia. She was HBVsAg positive; result retrieved third day post-partum.  Baby was not asphyxiated.His birth weight was 3.6kg. He received prophylactic intramuscular vitamin K 1mg stat and was discharged home. However, the infant presented with petechial haemorrhages on the third day of life. Other physical examination findings were normal. C o m p l e t e  b l o o d  c o u n t  c o n f i r m e d  3thrombocytopenia (18x10 cells/µL). Other cell lines were normal. Bleeding time was prolonged but clotting profile was not achieved.  He was managed as a case of severe thrombocytopenia in HBV-exposed infant. The differential diagnosis was neonatal sepsis. He was treated with intravenous cefuroxime 100mg/kg/day 8hrly and IV Gentamicin 5mg/kg/day 12hrly.  Freshly donated blood in  Page 93                                                                   Kanem Journal of Medical Sciences  2018;12(2): 92-96CASE REPORT                      Abiodun MT                                                                          et alst rdaliquots of 20ml/kg was transfused on the 1  and 3  day on admission but there was persistent thrombocytopenia. Typical haematological profile of the infant while on admission is shown on table 1. He received HBV vaccine and immunoglobulin on ththe 5  day of life; the delay was due to parental financial constraints. He was referred for platelet transfusion in a tertiary centre after 5 days on admission. Page 94                                                                   Kanem Journal of Medical Sciences  2018;12(2): 92-96A B CFigure 1A-C: Neonatal thrombocytopenic purpura in two Nigerian infants;A:Generalized petechiae and purpura in a suspected case of neonatal alloimmune thrombocytopenic purpura; B&C: HBV-exposed infant with generalized purpura worse on the lower extremities.  Cases Complete Blood counts3WBC (x10 /µL) Hematocrit(%) 3Platelet(x10 /µL) Lymphocyte(%) Neutrophil(%)NATPDay 3 20.7 40.5 14.0 10.1 86.7,5 2.7 43.7 4.0 38.9 57.5,7 8.4 42.0 7.0 34.0 62.8HBV-exposedDay 3 16.5 36.8 18.0 24.7 72.8, 5 12.0 42.5 10.0 32.6 63.5, 7 14.5 48.0 12.0 37.9 58.0Table 1: Selected complete blood count results of the infants on admissionDISCUSSIONThe most significant manifestation of neonatal thrombocytopenia is bleeding and it can involve vital organs as seen in the first infant. Cutaneous bleeding is common in severe neonatal 7 Baer 2thrombocytopenia. et al reported that 30% of cases of severe thrombocytopenia in a large series presented in the first 3 days of life and cutaneous bleeding was more common in infants with platelet counts of <20000/µl, consistent with the findings in this report.  They found no significant correlation between platelet counts and pulmonary, 2gastrointestinal, or intraventricular bleeding.  Likewise, Stanworth et al reported that one third of neonates enrolled in their series developed thrombocytopenia of <20000/µl, but only 9% 1developed major hemorrhage. Hence, the threshold for spontaneous major bleed is variable in CASE REPORT                   Abiodun MT                                                                              et al Page 95                                                                   Kanem Journal of Medical Sciences  2018;12(2): 92-96affected neonates and may be influenced by co-morbidities. The diagnostic criteria of NATP include the presence of symptomatic thrombocytopenia as in our patient and serological evidence of maternal antiplatelet antibodies against paternally derived 7,9neonatal platelet antigens. Parental platelet antigen genotypes can be identified on DNA sequencing. These were not achieved in our patients due to the lack of relevant laboratory capacity. Infants with NATP are often otherwise well. The initial presence of non-specific symptoms in our patient could be due to co-existing sepsis following thepossibly unhygienic delivery environment. However, the persistent severe thrombocytopenia in this infant could not be attributed to sepsis alone. Although bleeding diathesis can occur in severe sepsis, the repeated isolated depletion of platelet following EBTs with freshly-donated blood was consistent with the presence of transferred platelet antibodies in the 8,9infant.  This culminated in the likely CNS bleed and his demise. The elder sibling was not affected by the condition apparently due to her non-inheritance of the offending paternal platelet 7antigen.In a recent cohort study evaluating 5000 births to women with viral hepatitis, HBV exposurewas not significantly associated with anadverse neonatal 13 outcome. This does not preclude the risk of perinatal transmission of HBV. Maternal antenatal screening for HBVsAg and prompt administration of HBV vaccine and immumogloblin in the first 24hours of life reduce the risk of neonatal HBV 14infection and chronic complications. The maternal HBV status was known post-delivery in this patient because the pregnancy was not booked. Nonetheless, the infant received hepatitis thimmunoglobulin on the 5  day of life partly due to financial constraints; ideally, it should be administered within the first 12 hours of birth in HBV-exposed infants with acceptable efficacy by th 14the 48  hour of life. Neutrophil predominance is typicalof early neonatal period. As seen in our patients, other full blood count parameters may be 11normal in neonatal purpura.The management of thrombocytopenic purpura comprises treatment of the underlying causes and p l a t e l e t  t r a n s f u s i o n s .  N A T P  r e q u i r e s  administration of antenatal intravenous gamma-globulin(IVIG) to the mother. Delivery by cesarean 8section is recommended. Transfusion of platelet concentrate (especially washed maternal platelets) is indicated in this case but not available in our free healthcare facility and the parents could not comply with referral for tertiary care.As attempted in this patient, EBTs with freshly donated blood could behelpful, removingsome anti-platelet antibodies from the neonatal circulation. However, treatment with IVIG is necessary in some cases of NATP and 8rarely intravenous methylprednisolone.  The outcome of neonatal thrombocytopenic purpura is variable depending on the underlying cause and associated systemic complications, especially vital organ haemorrhages. A limitation of this reportis the non-availability of serology andHumanPlatelet Antigen genotyping at our centre to confirm NATP. Also, referral feedback on the HBsAg-status of 14thesecond infant at six weeks of age is desirable.In conclusion, the differential diagnoses of neonatal thrombocytopenic purpura arebeyond bacterial sepsis.Frontline clinicians should think laterally when assessing neonates with persistent severe thrombocytopenia. Prompt supportive care is pertinent to good outcome. Specialized testingcould enable definitive diagnosis.REFERENCES1.  Stanworth SJ, Clarke P, Watts T, et al. Prospective, observational study of outcomes in neonates with severe thrombocytopenia. Pediatrics 2009; 124: e826.2.   Baer VL, Lambert DK, Henry E, Christensen RD. Severe Thrombocytopenia in the NICU. Pediatrics 2009; 124: e1095.3 .  K a p l a n  C .  N e o n a t a l  a l l o i m m u n e  thrombocytopenia. Haematologica 2008;93: 805–807. 4. Bör Ö, Turhan AB, Yarar C. Congenital amegakaryocytic thrombocytopenia with severe neurological findings. Blood Coagul Fibrinol 2016; 27(8):936-939.5.   Toriello HV. Thrombocytopenia Absent Radius CASE REPORT                  Abiodun MT                                                                                et al Page 96                                                                   Kanem Journal of Medical Sciences  2018;12(2): 92-96Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al. (Eds). GeneReviews®. Seattle (WA): University of Washington, Seattle; 2016.6.    Backes CH, Markham K, Moorehead P, Cordero L, Nankervis CA, Giannone PJ. Maternal preeclampsia and neonatal outcomes. J Preg 2011; 2011:214365. 7. Scott JP, Montgomery RR.  Neonatal Thrombocytopenia. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF (Eds). Nelson Textbook of Pediatrics. 18th Edition. Philadelphia, PA: Saunders Elsevier 2007: 484.9.8.  Ghevaert C, Campbell K, Walton J, et al. Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia. Transfusion 2007; 47:901.9.  Killie MK, Husebekk A, Kaplan C, et al. Maternal human platelet antigen-1a antibody level correlates with the platelet count in the newborns: a retrospective study. Transfusion 2007; 47:55.10. Whitley RJ, Cloud G, Gruber W, et al. Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis 1997; 175:1080.11. Andrew M, Brooker LA. Hemostatic disorders in newborns. In: Avery's Diseases of the Newborn, Taeusch HW, Ballard RA (Eds), WB Saunders, Philadelphia 1998. p.1045.12. Stokkeland K, Ludvigsson JF, Hultcrantz R, Ekbom A, Höijer J, Bottai M, Stephansson O. Pregnancy outcome in more than 5000 births to women with viral hepatitis: a population-based cohort study in Sweden. Eur J Epidemiol 2017; 32(7): 617-625. 13.  Salemi JL, Whiteman VE, August EM, Chandler K, Mbah AK, Salihu HM. Maternal hepatitis B and hepatitis C infection and neonatal neurological outcomes. J Viral Hepat 2014; 21(11):e144-53 14. Breakwell L, Tevi-Benissan C, Childs L, Mihigo R, Tohme R. The status of hepatitis B control in the African region. Pan Afr Med J 2017; 27(Suppl 3):17

Neonatal thrombocytopenic purpura: report of two cases and review of literature

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Neonatal thrombocytopenic purpura: report of two cases and review of literature

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