A case of NEC and multiple thromboses in a term baby: The role of thrombophilia

Abstract

Background: Congenital thrombophilia predisposes to arterial and venous thromboses; MTHFR mutations have been associated with brain injury. The pathogenesis of NEC may involve thrombophilia. Case report: We report the case of a term female newborn (39 weeksGA), born by vaginal delivery,with unremarkable family history. Apgar score was 9 at 1′, 10 at 5′; birth weight was 3125g. Vaginal swabs were negative for Group B Streptococci, and rupture of amniochorionic membranes occurred in the delivery room. She was admitted at our NICU at 12h of life due to suspected seizures (limb hypertone, cycling movements and cyanosis) and hypoglycaemia (23mg/dl), which was corrected by i.v. glucose infusion. EEG confirmed seizures, and she was treated with phenobarbital and thenwithmidazolamand phenitoin for refractory convulsions. Head MRI showed intraventricular hemorrage with parenchimal cavities, and bilateral thrombosis of cerebral medullary veins. On day 2, she was intubated and mechanically ventilated due to oxygen-dependency and desaturations. Escherichia coli was isolated from blood, urine and bronchoalveolar lavage fluid, and she received i.v. ampicillin and gentamicin for 14 days. Chest X-ray showed opacification of the apical right lung. On day 5, abdominal distention, gastric residuals and constipation occurred. Plain radiograph of the abdomen showed small hyperlucent areas on the descending colon. She was put NPO until the recovery of symptoms (12 days), which then relapsed on day 30. Plain radiograph of the abdomen and abdominal US showed small gut distention and airfluid levels. On day 50 abdominal signs relapsed again; barium swallow and barium enema showed a segmental stenosis of the descending colon and multiple enterocolonic fistulae. She underwent a left hemicolectomy with termino-terminal colonic anastomosis; histology showed acute transmural inflammation of the colon. Heart ultrasound showed an atrial septal defect and an atrial thrombus measuring 0.7 cm2. She received urokinase and enoxaparin with partial resolution. She also presented cutaneous ulcers on the head and trunk due to skin ischemia. We suspected a congenital thrombophilia. The following tests were normal: PT, PTT, AT-III, lipoprotein A, homocistein, lupus-like anticoaugulans, anti-cardiolipin and anti-beta-2 glycoprotein antibodies, factor II G20210A and V G1691A Leidenmutations, COL4A1 genemutations. Fibrinogen levels raised up to 550mg/dl, d-dimers up to 4300ng/ml, protein C activitywas 14%, protein S 44%, and she was found to be a compound heterozygote for C677T and A1298C mutations of MTHFR and heterozygote for 4G5G PAI mutation. Discussion:MTHFRmutations have been associated with brain MRI abnormalities among newborns with asphyxia. Less is known about the 4G5G PAI mutation. We speculate that the multiple thrombophilic mutations in our patient predisposed her to this severe clinical course, and advocate a thorough thrombophilic evaluation to term newborns with NEC-like episodes. PO30