A report describes a case of a 2-day-old male baby, born to a primigravida mother at 39 weeks of gestation by a forceps delivery, with a birth weight of 2.8 kg, who presented to the Emergency Department (ED) with swelling on the left thigh, poor feeding, and lethargy. No family history of bleeding disorder was reported. The baby was noted to have apnea and thus was admitted to the NICU, where he was ventilated and stabilized. 

Examination revealed bulging anterior fontanelle, anisocoria, and a 3 × 1 cm bluish swelling on the left thigh at the site of vitamin K injection. He experienced multiple episodes of seizures in the form of tonic posturing of all 4 limbs. Investigations revealed anemia, and normal leukocyte and platelet count. C-reactive protein (CRP) was elevated. The coagulation profile revealed normal prothrombin time (PT) and an isolated activated partial thromboplastin time (APTT) prolongation. A Neurosonogram on day 2 of life, revealed a subdural hemorrhage (SDH) of 8 mm in the left frontotemporal region.

He was transfused Packed red cells and fresh frozen plasma after drawing samples for clotting factors. His Factor 8 activity was FOUND TO BE < 1% and was given a diagnosis of hemophilia A. 

He was initiated Factor 8 at 125 IU twice a day, anticonvulsants, and antibiotics (Cefotaxime and Gentamicin). Computerized tomography (CT) scan on day 3 revealed an SDH of 10 mm thickness in the left frontotemporoparietal region.

On day 4 of life, he became hemodynamically stable and euglycemic but needed continued mechanical ventilation and increased oxygen. Also, a rising trend in CRP (101 mg/L on day 4) was observed despite changing the antibiotics to Meropenem and Amikacin. Conjugated hyperbilirubinemia was observed with -total bilirubin of 18.9 mg/dL and direct bilirubin of 2.58 mg/dL.

Viewing an antenatal history of maternal SARS-CoV-2 at 32 weeks of gestation, the baby was assessed for MIS-N. Anti SARS-CoV-2 IgG antibody test was reported positive (IgG − 4.36- reactive) in the baby. Maternal and neonatal reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 were found negative. Further investigations demonstrated raised inflammatory markers: Lactate dehydrogenase (LDH) -1071 U/L, ferritin-448 ng/ml, and D-dimer-973 ng/ml. Thus, the baby was given intravenous immunoglobulin (IVIG - 1 g/kg for 2 days) and methylprednisolone (1 mg/kg every 12 h for 6 days and tapered over 4 days). He showed improvement, along with a reduction in the ventilatory requirements. 

He was extubated to room air, on day 6. His CRP and other inflammatory markers also showed a decreasing trend. An echocardiogram (ECHO) revealed prominent left coronaries with aneurysmal dilatation and normal ventricular function (ejection fraction − 77%). Factor 8 was further continued targeting 100% levels and its inhibitor assay was found negative. The neurosurgery team managed his intracranial bleed conservatively.

Serial monitoring of laboratory parameters revealed an increase in CRP and other inflammatory markers on day 14, but the baby continued to improve clinically. However, on day 16 of life, he developed seizures and an MRI revealed increased bilateral SDH (maximum diameter - 2.3 cm and 0.5 cm on left and right respectively) with a midline shift to right. The features suggested total brain injury and communicating hydrocephalus. 

Progressive intracranial bleed, directed to carry out left parietal craniostomy with subdural hematoma evacuation on babys day 17 of life. Post-surgery, the seizures were managed with phenytoin and levetiracetam. 

The baby was then initiated breastfed. No focal neurological deficits were present. Gene analysis confirmed Hemophilia A with a hemizygous intron 22 inversions in the F8 gene on chromosome X (NM_000132.3). 

During the publication of this report, the baby was 2-months old and thriving on breast milk alone. Furthermore, he was on factor 8 replacement, seizure-free on levetiracetam, and under neurodevelopmental follow-up.

Arun S, Cherian TG, Philip C. Multisystem inflammatory syndrome in a neonate with severe hemophilia - a diagnostic challenge in COVID times: a case report. BMC Pediatr. 2022; 22. https://doi.org/10.1186/s12887-022-03463-3