E-ISSN 1858-8360 | ISSN 0256-4408
 

Case Report 


SUDANESE JOURNAL OF PAEDIATRICS

2020; Vol 20, Issue No. 2

CASE REPORT

Vitamin K deficiency bleeding of newborn masquerading haemophilia B

Mritunjay Kumar (1), Sidharth Kumar (1), Shivani Bajpayi (2), Rashmi Kumari (3)

(1) Department of Pediatrics and Neonatology, Apollomedics Super Speciality Hospitals, Lucknow, India

(2) Department of Neonatology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

(3) Department of Community Medicine, Dr RML Institute of Medical Sciences, Lucknow, India

Correspondence to:

Mritunjay Kumar

Department of Pediatrics and Neonatology, Apollomedics Super Speciality Hospitals, Lucknow, India.

Email: drmkumar409 [at] gmail.com

Received: 17 March 2020 | Accepted: 25 May 2020

How to cite this article:

Kumar M, Kumar S, Bajpayi S, Kumari R. Vitamin K deficiency bleeding of newborn masquerading haemophilia B. Sudan J Paediatr. 2020;20(2):176–180.

https://doi.org/10.24911/SJP.106-1584209747


ABSTRACT

The term infant is remarkably resistant to bleeding despite physiologically low levels of procoagulant proteins. However, because of their unique haemostatic systems, neonates are vulnerable to haemorrhagic disorders. The prevention of early vitamin K deficiency bleeding (VKDB) of newborn by oral or parenteral administration of vitamin K has been well established. However, rarely, a newborn can present with bleeding manifestations even after routine vitamin K prophylaxis at birth. A 2-day-old healthy male baby presented with catastrophic pulmonary haemorrhage with severely deranged coagulation profile even after receiving vitamin K prophylaxis at birth. His presentation, initial laboratory findings and course in the hospital were very much in favour of haemophilia B, but follow-up factor IX level and clinical exome sequencing did not confirm it. However, protein induced in vitamin K absence-II was found to be raised just before the discharge, and we concluded this case as a rare presentation of classical VKDB.


KEYWORDS

Newborn; Bleeding; Vitamin K deficiency bleeding (VKDB); Protein induced in vitamin K absence-II (PIVKA-II); Haemophilia.


INTRODUCTION

Healthy newborns can present with bleeding episodes during their 1st week of life due to early vitamin K deficiency bleeding (VKDB). There are multiple factors responsible for their vulnerability for vitamin K deficiency including limited placental transfer, decreased liver stores, poor gut colonization and its deficiency in breast milk. Although newborns are supposed to be protected from early VKDB after routine Vitamin K prophylaxis at birth, current evidence are not very strong in its efficacy in controlling late VKDB [1]. Commonly these babies present with bleeding from gastrointestinal (GI) tract, umbilicus and venous puncture sites [2]. It rarely presents with intracranial haemorrhage and hardly presents with pulmonary haemorrhage (PH). Here, we present a case, where a 2-day-old previously healthy male baby presented to us with massive PH, gross haematuria and upper GI bleeding. His presentation, clinical course during hospitalization and most of the laboratory findings were very much suggestive of haemophillia B till the time when levels of proteins induced in vitamin K absence -II (PIVKA-II) was found to be raised. Clinical exome sequencing couldn’t detect any pathogenic variant suggestive of haemophilla B. We finally diagnosed this case as a very rare presentation of classical VKDB.


CASE REPORT

A 2-day-old male baby was referred to us at 48 hours of life in a gasping state with profuse bleeding through the endotracheal tube (Figure 1a). At admission, the baby was severely pale and had cold extremities and feeble pulses with SpO2 <40 % on room air. After initial resuscitation, he was started on high-pressure mechanical ventilation and vasopressor support. Sepsis profile, coagulation profile and other relevant biochemical evaluations were sent. He was also started on broad-spectrum intravenous antibiotics and other supportive management. Chest X-ray (CXR) on admission showed focal ground-glass opacities and later complete ‘white-out lungs’ suggestive of massive PH (Figure 1b).

Figure 1. (a) Profuse endotracheal bleeding at the time of admission (b) Complete white out lungs on CXR suggestive of massive pulmonary hemorrhage

The baby was born at full term out of an uneventful caesarean section and was on breastfeeds till 48 hours of life when he had a heavy bout of haematemesis followed by apnoea and desaturation. A single dose of 1 mg of intramuscular vitamin K was administered immediately after birth by the attending paediatrician. There was no history of any significant antenatal maternal illness or antiepileptic medication intake. Mother was on low molecular weight heparin (LMWH) in the second trimester, but it was stopped more than a month before delivery. The baby was a product of second-degree consanguineous marriage, and the mother was on treatment for polycystic ovarian disease for the past 2 years but had conceived naturally. There was no family history of any bleeding disorder. Complete blood count (CBC) showed a haemoglobin of 10 g/dl, total leucocyte count (TLC) of 10,100/mm3, differential counts (polymorphs 37% and lymphocytes 52%) and platelet count of 150 × 109/l. C-reactive protein (CRP) was 0.92 mg/l (ref. range < 6 mg/l), and blood culture was sterile after 72 hours of incubation. Coagulation profile was severely deranged with activated partial thromboplastin time (aPTT) >140 seconds (ref. range: 21-33 seconds), prothrombin time (PT) 31.9 seconds (ref. range: 10-13 seconds) and international normalised ratio (INR) of 3.07 (ref. range: 0.8-1.2). Liver function tests (LFTs) and kidney function tests (KFTs) were unremarkable, and fibrinogen and d-dimer levels were within a normal range. Fresh frozen plasma (FFP) and packed red blood cells (PRBCs) were transfused as the baby had fresh endotracheal and gastric bleed along with frank haematuria within 24 hours of admission. The surfactant was instilled into the lungs, and it led to a reduction in ventilator pressures and a slight improvement in SpO2. Vitamin K 1.0 mg was given daily for 3 days after withdrawing sample for protein induced in vitamin K absence-II (PIVKA-II) level. The baby had a second bout of PH at 72 hours, and haemodynamic condition further deteriorated after initial improvement. It was probably due to the dislodgement of clot following chest physiotherapy for the right upper lobe collapse. Inotropes were further upgraded, and ventilator pressures needed to be increased yet again. After a discussion with the parents about the variable outcome, the second surfactant was instilled into the lungs. KFT started deteriorating (urea 84 mg/dl, creatinine 2.8 mg/dl, Na 125 mmol/l, K 7.2 mmol/l and ionised calcium 0.8 mmol/l), and the child became anuric in the next 48 hours. Urgent peritoneal dialysis (PD) was performed and continued for 72 hours. PD was stopped once dyselectrolytaemia and uraemia improved and urine output was established. After 4 FFP transfusions, factor VIII and IX levels were sent to rule out hereditary coagulation factor defects. A total of eight FFP, three cryoprecipitate, three PRBC and two platelets were transfused before bleeding could be controlled. On the 7th day of admission, coagulation profile normalised (PT 17.5 seconds, PTC 13.3 seconds, INR 1.42, aPTT 48.3 seconds, aPTC 28.0 seconds and INR 1.2). All the sepsis screens including TLC, absolute neutrophil counts and CRP were normal throughout the hospital course. All the blood cultures, urine cultures and cultures of endotracheal secretions did not show any growth. Factor VIII activity was found to be 86% (60-150), and factor IX level was found to be very low 23.7% (70-120). As factor IX level was much lower than the reference range [3] and that also after multiple FFP and cryoprecipitate transfusions, a probable diagnosis of haemophilia B was considered. At the time of discharge, PIVKA II report was made available to us, and it was found to be 52 mAU/ml (ref. range <40 mAU/ml, chemiluminescent microparticle immunoassay method). The baby was discharged on direct breastfeeds in a haemodynamically stable condition without any neurological concerns (Figure 2a) and with an unremarkable CXR (Figure 2b).

Figure 2. (a) A healthy normal looking baby at the time of discharge (b) Unremarkable CXR suggesting complete resolution of pulmonary hemorrhage

At 3-month follow-up, the baby was found to be neurologically normal with age-appropriate milestones. Magnetic resonance imaging of the brain was unremarkable, and brain stem-evoked response audiometry showed normal hearing sensitivity for both the ears. Electroencephalogram did not show any abnormal epileptic discharges, and screening for the retinopathy of prematurity was perfectly normal. Tandem mass spectroscopy, urine gas chromatography-mass spectrometry and LFT on follow-up were unremarkable. Factor assays were reviewed at 3 months to confirm the diagnosis of haemophilia B. Factor VIII level was found to be 92% (reference range 60%-150%), and factor IX level was found to be low, i.e., 33.70% (reference range 60%-150%). No factor concentrates were administered to the baby since the time of admission. Clinical exome sequencing was sent to detect mutations for haemophilia B or other coagulation defects at 3 months of life. No pathogenic or likely pathogenic variants were detected in the screened genes as per the current literature and human genome variation databases including ClinVar, 5000 Exome Global MAF and COSMIC. We finally concluded this case as a rare presentation of classical VKDB in a baby, where vitamin K prophylaxis was received at birth.


DISCUSSION

Conventionally, VKDB has been categorized into early (<24 hours), classical (2-7 days) and late (2-12 weeks). Routine vitamin K prophylaxis at birth has significantly reduced the incidence of VKDB in newborns. However, there are anecdotal reports of early and late VKDB in newborns, where Vitamin K was administered at birth [4]. Maternal LMWH-related risk of bleeding is usually considered low when its administration is suspended 12 hours before delivery. There is no report of neonatal bleeding associated with LMWH therapy [5]. The incidence of PH has been reported as 1-12 per 1,000 live births with a mortality as high as 50% [6]. However, PH has never been reported as a presentation of VKDB, where vitamin K prophylaxis was received at birth. Surfactant instillation has got both etiological and therapeutic implications in neonatal PH [6]. A surfactant instillation following PH in this case resulted in improvement in PaO2 and reduction in ventilator pressures. In this case, although the coagulation profile was not very much typical of haemophilia B, we suspected this because a healthy baby without any known risk factor for sepsis presented to us with severe bleeding manifestations. Although haemophilia is mostly inherited, about 30% of cases occur because of spontaneous mutations [7]. As factor VIII levels reach normal adult levels by 20 weeks of gestation, haemophilia A can be diagnosed at birth only. However, factor IX level is just 15% of adult levels at birth, and therefore, only severe haemophilia B can be diagnosed at birth. Therefore, it is recommended that factor IX levels should be reassessed at 6 months and 9 months in all the newborns where haemophilia B is suspected [8]. PT is not a very sensitive marker for vitamin K deficiency. PIVKA-II is biologically inactive carboxylated forms of vitamin K-dependent clotting factors. It has been hypothesised that prophylactic vitamin K administration at birth leads to undetectable PIVLA-II levels in newborns [9]. The levels of PIVKA-II are increased, where vitamin K deficiency is suspected, and even a small increase in its level could be the first indicator of bleeding risk in a newborn. In a recent systematic review, the effect of antenatal vitamin K was not statistically significant for neonatal bleeding reduction except for maternal plasma vitamin K, including other outcomes, e.g., neonatal plasma vitamin K, maternal-newborn PIVKA-II factor and breast milk vitamin K [10].


CONCLUSION

This report challenges the absolute efficacy of vitamin K prophylaxis in the prevention of classical vitamin K deficiency bleeds and reports massive PH as one of the presentations of classical VKDB. Further studies are required before the role of vitamin K in pregnancy could be validated for its role in the prevention of VKDB. This case further emphasizes the importance of detailed coagulation profile evaluation, including PIVKA-II level, before considering any blood product transfusion or further vitamin K administration to pinpoint the diagnosis, where an overlapping clinical presentation is encountered.


ACKNOWLEDGEMENT

The authors would like to thank Dr Shefalika Khanna, Dr Indrapal Singh and all the NICU nursing staffs of Apollomedics Super Speciality Hospital, Lucknow, for their hard work and constant support throughout the NICU stay of this precious life.


CONFLICTS OF INTEREST

The authors declare that there are no conflicts of interest.


FUNDING

None.


ETHICS

Signed informed consent for participation and publication of medical details was obtained from the parents of this child. Informed consent was also obtained from parents for photographs included in the manuscript for publication purpose. Confidentiality of patient’s data was ensured at all stages. The authors declare that ethics committee approval was not required for this case report.


REFERENCES

  1. Sankar MJ, Chandrasekran A, Kumar P, Thukral A, Agrawal R, Paul VK. Vitamin K prophylaxis for prevention of vitamin K deficiency bleeding: a systematic review. J Perinatol. 2016;36:29–34. https://doi.org/10.1038/jp.2016.30
  2. Shah F, Khan MA, Khan J, Munir A, Karim R. Hemorrhagic disease of the newborn: clinical presentation and response to treatment with vitamin K. Gomal J Med Sci. 2013;11:101–4.
  3. Appel IM, Grimminck B, Geerts J, Stigter R, Cnossen MH, Beishuizen A. Age dependency of coagulation parameters during and puberty. J Thromb Haemost. 2012;10:2254–63. https://doi.org/10.1111/j.1538-7836.2012.04905.x
  4. Demir N, Peker E, Demiroren K, Kaba S, Tuncer O. Massive gastrointestinal bleeding due to vitamin K deficiency in a newborn. East J Med. 2015;20:238–40.
  5. Sirico A, Saccone G, Giuseppe M, Grandone E, Sarno L, Berghella V, et al. Low molecular weight heparin use during pregnancy and risk of postpartum hemorrhage: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2017;32:1893–1900. https://doi.org/10.1080/14767058.2017.1419179
  6. Zahr RA, Asfaq A, Marron-Corwin M. Neonatal pulmonary hemorrhage. NeoReviews. 2012;13(5):e302–6. https://doi.org/10.1542/neo.13-5-e302
  7. Dituri F, Buonocore G, Pietravalle A, Naddeo F, Cortesi M, Pasqualetti P, et al. PIVKA-II plasma levels as marker of subclinical vitamin K deficiency in term infants. J Matern Fetal Neonatal Med. 2012;25(9):1660–3. https://doi.org/10.3109/14767058.2012.657273
  8. Nuss R, Manco-Johnson M. Bleeding disorders in the neonate. NeoReviews. 2000;1(10):e196–200. https://doi.org/10.1542/neo.1-10-e196
  9. Dyson H. Neonatal haemophilia—a guide to recognition and management. Infant. 2006;2(4):156–9.
  10. Shahrook S, Ota E, Hanada N, Sawada K, Mori R. Vit K supplementation during pregnancy for improving outcomes: a systematic review and meta-analysis. Sci Rep. 2018;8:11459. https://doi.org/10.1038/s41598-018-29616-y


How to Cite this Article
Pubmed Style

Kumar M, Kumar S, Bajpayi S, Kumari R. Vitamin K deficiency bleeding of newborn masquerading haemophilia B. Sudan J Paed. 2020; 20(2): 176-180. doi:10.24911/SJP.106-1584209747


Web Style

Kumar M, Kumar S, Bajpayi S, Kumari R. Vitamin K deficiency bleeding of newborn masquerading haemophilia B. http://www.sudanjp.com/?mno=92551 [Access: October 28, 2020]. doi:10.24911/SJP.106-1584209747


AMA (American Medical Association) Style

Kumar M, Kumar S, Bajpayi S, Kumari R. Vitamin K deficiency bleeding of newborn masquerading haemophilia B. Sudan J Paed. 2020; 20(2): 176-180. doi:10.24911/SJP.106-1584209747



Vancouver/ICMJE Style

Kumar M, Kumar S, Bajpayi S, Kumari R. Vitamin K deficiency bleeding of newborn masquerading haemophilia B. Sudan J Paed. (2020), [cited October 28, 2020]; 20(2): 176-180. doi:10.24911/SJP.106-1584209747



Harvard Style

Kumar, M., Kumar, . S., Bajpayi, . S. & Kumari, . R. (2020) Vitamin K deficiency bleeding of newborn masquerading haemophilia B. Sudan J Paed, 20 (2), 176-180. doi:10.24911/SJP.106-1584209747



Turabian Style

Kumar, Mritunjay, Sidharth Kumar, Shivani Bajpayi, and Rashmi Kumari. 2020. Vitamin K deficiency bleeding of newborn masquerading haemophilia B. Sudanese Journal of Paediatrics, 20 (2), 176-180. doi:10.24911/SJP.106-1584209747



Chicago Style

Kumar, Mritunjay, Sidharth Kumar, Shivani Bajpayi, and Rashmi Kumari. "Vitamin K deficiency bleeding of newborn masquerading haemophilia B." Sudanese Journal of Paediatrics 20 (2020), 176-180. doi:10.24911/SJP.106-1584209747



MLA (The Modern Language Association) Style

Kumar, Mritunjay, Sidharth Kumar, Shivani Bajpayi, and Rashmi Kumari. "Vitamin K deficiency bleeding of newborn masquerading haemophilia B." Sudanese Journal of Paediatrics 20.2 (2020), 176-180. Print. doi:10.24911/SJP.106-1584209747



APA (American Psychological Association) Style

Kumar, M., Kumar, . S., Bajpayi, . S. & Kumari, . R. (2020) Vitamin K deficiency bleeding of newborn masquerading haemophilia B. Sudanese Journal of Paediatrics, 20 (2), 176-180. doi:10.24911/SJP.106-1584209747





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