|Year : 2019 | Volume
| Issue : 3 | Page : 180-182
Term neonate with necrotizing enterocolitis and prothrombin mutation
Samuel Morrison Miller, Amanda Zhou, David J Worhunsky, Daniel G Solomon, Doruk E Ozgediz
Department of Pediatric Surgery, Yale School of Medicine, New Haven, CT, USA
|Date of Web Publication||6-Aug-2019|
Dr. Samuel Morrison Miller
111 Park Street, Apt 8T, New Haven, CT 06511
Source of Support: None, Conflict of Interest: None
The pathophysiology of necrotizing enterocolitis (NEC) in term neonates is unknown. A 37-week-old coagulopathic newborn with NEC was taken to the operating room for exploratory laparotomy and was found to have intermittent areas of necrosis from the cecum through the transverse colon. Right hemicolectomy was performed with end ileostomy. Genetic testing at 9 months of age revealed a prothrombin G20210A mutation. Hypercoagulation workup should be considered for term neonates found to have NEC without a clear etiology.
Keywords: Necrotizing enterocolitis, neonate, prothrombin G20210A mutation, term
|How to cite this article:|
Miller SM, Zhou A, Worhunsky DJ, Solomon DG, Ozgediz DE. Term neonate with necrotizing enterocolitis and prothrombin mutation. J Clin Neonatol 2019;8:180-2
|How to cite this URL:|
Miller SM, Zhou A, Worhunsky DJ, Solomon DG, Ozgediz DE. Term neonate with necrotizing enterocolitis and prothrombin mutation. J Clin Neonatol [serial online] 2019 [cited 2020 Aug 4];8:180-2. Available from: http://www.jcnonweb.com/text.asp?2019/8/3/180/264036
| Introduction|| |
Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies in newborns. The majority of cases occur in preterm infants, but approximately 10% of cases are seen in term infants. These term babies often have predisposing risk factors such as congenital heart disease, intrauterine growth restriction (IUGR), or perinatal hypoxia among others.,
We report a case of term NEC in a neonate with a heterozygous prothrombin G20210A mutation. To our knowledge, this is the first case of reported term NEC in a neonate with a prothrombin mutation. We report this case to suggest that genetic coagulopathies should be considered in instances of term NEC, and that genetic testing should be included in the workup for these cases.
| Case Report|| |
On day-of-life (DOL) one (DOL1), an ex-37-week-old baby boy born to a mother with Class C diabetes and bilateral kidney transplants with pregnancy complicated by IUGR and preeclampsia was observed to have bilious emesis after his first feed. The baby was delivered by emergency cesarean section for failure to descend after induction in the setting of worsening preeclampsia. Abdominal X-ray revealed pneumatosis coli [Figure 1]. His abdomen became increasingly tender, with lactate level of 4.3 mmol/L and international normalized ratio of 5.9. Prothrombin time and partial thromboplastin time were both elevated at 62.4 s and 85.7 s, respectively. Lumbar puncture revealed bloody cerebrospinal fluid. Preoperative echocardiogram exhibited a small patent foramen ovale and a small patent ductus arteriosus with good left ventricular function and without evidence of left ventricular outflow obstruction. He was determined to have grossly normal intracardiac structure and function. He was suspected to have term NEC and was taken to the operating room for exploratory laparotomy on DOL2.
Ascites was noted upon entry of the peritoneal cavity. Necrosis of the cecum with patchy areas of necrosis extending up to the right colon and along the proximal two-thirds of the transverse colon was observed. The small bowel appeared healthy, as did the left colon, sigmoid colon, and rectum. An extended right hemicolectomy with end ileostomy was performed, taking bowel from the terminal ileum to the distal transverse colon.
Postoperatively, the neonate continued to be coagulopathic and became thrombocytopenic with platelets to 27,000/μL. Between DOL2 and DOL7, he received multiple blood products, including four units of fresh frozen plasma, five pools of platelets, one unit of cryoprecipitate, and two doses of Vitamin K. The hematology service recommended thrombophilia evaluation when he was at least 6 months old, and levels of protein C, protein S, and antithrombin III had been given sufficient time to normalize. By DOL19, his coagulation parameters had normalized. He was weaned off from the ventilator on DOL7 and was discharged home on DOL24.
Surgical pathology revealed hemorrhagic necrosis of the intestine with pneumatosis coli and eosinophilic infiltration consistent with NEC [Figure 2]. Two months after the initial operation, the neonate underwent an uncomplicated ileostomy takedown and was discharged home in stable condition. At 9 months of age, the patient was found to be heterozygous for the prothrombin G20210A mutation. His most recent follow-up was at 17 months of age, and he has not experienced any other thrombotic or ischemic events. He has been eating well, has been stooling adequately, and has been gaining weight, tracking along the 15th percentile for body mass index. The hematology service has recommended no active treatment for this mutation. However, at their suggestion, he will need to be evaluated prior to future procedures to determine his potential need for anticoagulation.
|Figure 2: (a) Pneumatosis present in transverse colonic mucosa. (b) Eosinophilic infiltration of transverse colonic mucosa. (c) Necrosis of transverse colonic mucosa|
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| Discussion|| |
Prothrombin G20210A is a relatively common mutation, with a prevalence of about 2% in the general population. This point mutation causes an increase in plasma prothrombin levels and is associated with hypercoagulability, with those having heterozygous mutations being up to four times more likely to experience venous thromboembolism. Its association with arterial thromboembolism is less clear, but prior research suggests a relationship between this mutation and arterial thromboembolic events such as myocardial infarction and ischemic stroke.
Bowel ischemia due to venous thrombosis has been described in the setting of PTHR G20210., In fact, in one study, 28% of patients with ischemic colitis tested positive for coagulopathic disorders including factor V Leiden, protein S deficiency, anticardiolipin antibodies, and the prothrombin G20210A mutation. In another case, PTHR G20210A was thought to cause recurrent ischemic colitis through occlusion of the small vessels supplying the colon. These cases, however, have not been documented in neonates.
Many term neonates with NEC do not have overt ischemic events. Thus, although hypoxic risk factors such as birth asphyxia and sepsis are associated with NEC, the etiology of NEC in these term infants can be unclear. Multiple studies suggest that underlying congenital diseases, such as heart disease and endocrine dysfunction, may put term infants at risk for NEC., In addition, cystic fibrosis and neonatal infection have been associated with developing term NEC.
We suggest that in the setting of term NEC, a prothrombotic mutation should also be considered as a potential cause of the bowel ischemia that allows for the bacterial invasion of the intestinal mucosa and subsequent inflammation. This neonate was neither premature nor did he have a known anoxic event at birth, a cyanotic cardiac defect, or an exchange transfusion that may have led to intestinal ischemia. Therefore, the precipitating event of his NEC may have been a mesenteric venous thrombosis, given the increased risk of venous thromboembolism associated with both homozygous and heterozygous prothrombin mutations. Thrombotic occlusion would then result in the observed ischemic damage to the intestinal wall, compromising the intestinal mucosa, facilitating bacterial invasion, and allowing for penetration of the intestine by a necrotizing pathogen.
Clinicians caring for term neonates with NEC should evaluate the possible etiologies of bowel ischemia that are plausible in each individual scenario. In the absence of known risk factors, thrombophilias should be considered, and genetic testing for hypercoagulable disorders should be performed. The results of this testing may inform future management of these patients.
| Conclusion|| |
Term NEC is a pathology with an unknown etiology. The workup for term NEC in neonates with an unknown etiology of bowel ischemia should include genetic testing for disorders of hypercoagulability.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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