P2A284: Methemoglobinemia and Cerebral Venous Sinus Thrombosis in a Neonate with Dehydration

Introduction: Feeding difficulties and dehydration is a common chief complaint in neonates presenting to the emergency room. A rare but well described neonatal complication of diarrhea and dehydration with hypoxemia is acquired methemoglobinemia. Many of the signs in these patients, including severe dehydration, acute systemic illness, and sepsis, are also risk factors associated with cerebral venous sinus thrombosis (CSVT). We present a unique case of a critically ill neonate presenting with severe dehydration caused by diarrhea, resulting in methemoglobinemia and CSVT.

Case Description: A 4-week-old full term female with an unremarkable prenatal history presented with several days of diarrhea, emesis, and tactile fever. Physical exam noted a weak infant with delayed capillary refill, tachycardia, and tachypnea. Initial blood gas was pH 6.8, bicarbonate 3.8 mmHg, lactate 5, and methemoglobin 19%. Electrolyte panel was consistent with dehydration. Patient was intubated and empiric antibiotics were initiated. Initial head CT was significant for thrombosis in superior sagittal sinus. Clinically, patient had signs of coagulopathy including early clotting of the blood samples and immediate femoral thrombus extending from the central line. Initial coagulation profile and platelets were unremarkable. On hospital day 5, patient had focal seizures with repeat CT showing intraparenchymal hemorrhage in frontoparietal lobes with surrounding vasogenic edema. Due to concerns of the new hemorrhage originating from the sagittal sinus thrombosis and now extending anteriorly, heparin was started with monitoring of the levels and daily head ultrasound. To note, work up for methemoglobinemia included Hg F 85%, urine blood culture positive for Escherichia Coli, and normal cytochrome b5 reductase activity. Thrombophilia and iron deficiency was negative for work up for CSVT.

Discussion: Red blood cells (RBC) in neonates are at a higher risk of oxidation leading to methemoglobinemia. This is due to easily oxidized hemoglobin F and immature erythrocyte cytochrome b5 reductase activity. Neonates with gastroenteritis are more critically ill given increased bacterial production of nitrite leading to hemoglobin oxidation and metabolic acidosis decreasing the rate of methemoglobin reduction. The most common risk factors of CSVT in neonates are perinatal complication and dehydration. Literature on adult population have proposed dehydration causing rheological changes from increased hematocrit and RBC aggregation. We question whether our patient’s thrombosis was a consequence of both dehydration and methemoglobinemia. Basic science research indicate that methemoglobin is a potent activator of endothelial cells by stimulating IL-6 and IL-8 production, increasing coagulation.

Conclusion: Methemoglobinemia and CSVT are two extremely uncommon conditions in neonates that can present critically ill. Severe dehydration has been linked to both conditions, but to our knowledge, no case with both sequelae has been reported until now. Further research will need to explore if hypoxia secondary to methemoglobin could trigger CSVT in otherwise previously healthy neonates.