Spontaneous Epidural Hematoma in a Child With Inherited Factor XIII Deficiency Roula A. Farah, MD, FAAP,* Jad Z. Al Danaf, BS,* Rita A. Chahinian, BS,* Nabil T. Braiteh, BS,* Naim F. Al Ojaimi, BS,* Andrea Cairo, MD,w Hussein Farhat, MD,z and Joseph R. Mantoura, MDy Summary: We report the case of a 2-year-old Lebanese male child, known to have congenital factor XIII (FXIII) deficiency, who presented to the emergency department with somnolence and projectile vomiting without any head trauma. He has been on a prophylactic dose of 10 IU/kg of FXIII concentrate every 4 weeks since birth, but he missed his last 2 doses due to shortage of supply. Imaging studies showed an epidural hematoma with a midline shift. The child was started on 20 IU/kg of FXIII replacement, and a left parietal craniotomy was performed immediately. He tolerated the surgery well with an uneventful postoperative course. Previous DNA analysis carried out for the family members detected a small deletion (c.1475-1476delGA) in exon 12 in this child and his eldest brother. This mutation has been previously reported once in another Lebanese child with FXIII deficiency who presented with spontaneous splenic rupture. To the best of our knowledge, this is the first case of acute nontraumatic spontaneous epidural hema- toma in a child with congenital FXIII deficiency. Furthermore, patients on FXIII replacement therapy have less bleeding events, thus lifelong adherence to the prophylaxis is essential to decrease the morbidities and the mortalities associated with FXIII defi- ciency, most notably intracranial hemorrhages. Key words: epidural hematoma, factor XIII, factor XIII deficiency, factor XIII mutation, spontaneous bleeding, prophylaxis (J Pediatr Hematol Oncol 2014;36:62–65) F XIII (factor 13), a tetrameric zymogen [FXIII-A (2) B (2)] composed of 2 A and 2 B subunits is converted into an active transglutaminase (FXIIIa) by thrombin and Ca 2+ in the terminal phase of the clotting cascade. 1 It plays an integral role in hemostasis by catalyzing the cross-link- ing of fibrin, platelet membrane, and matrix proteins throughout the thrombus formation, thus stabilizing the blood clot. FXIII also plays an important role in wound healing and maintenance of pregnancy. 2 FXIII deficiency is a rare bleeding disorder with an incidence of about 1 in 3 million people, 3 inherited in an autosomal recessive pattern, which can typically present with umbilical stump bleeding during the neonatal period, delayed soft tissue bruising, mucosal bleeding, and life-threatening intracranial hemo- rrhage (ICH). 4–6 There have been >70 FXIII mutations identified in the current literature in addition to single nucleotide polymorphisms that have been described, some of which have been shown to affect FXIII activity, contributing further to the heterogeneity in patient pre- sentation and severity of clinical symptoms. 7,8 In this report, we present a case of a 2-year-old Lebanese male child with a known history of FXIII defi- ciency who presented with a spontaneous epidural hema- toma after missing 2 of his prophylactic doses of human plasma FXIII concentrate. DNA analysis of the family members revealed a deletion mutation in exon 12 of subunit A of FXIII. To the best of our knowledge, this is the first case of acute nontraumatic spontaneous epidural hema- toma in a child with FXIII deficiency. PATIENT PRESENTATION A 2-year-old male child, known to have FXIII defi- ciency, presented to the emergency department with a 2-day history of somnolence, irritability, and projectile vomiting along with decreased oral intake. The parents reported no history of falls or trauma to the head or body. His family history is positive for first-degree con- sanguinity (Fig. 1). He has an older 11-year-old brother who was diagnosed with FXIII deficiency after presenting with severe postcircumcision bleeding. The 2-year-old child was born at term by C-section at an outside hospital in the periphery where there was no access to sending blood for FXIII testing. On his fifth day of life, he presented to our hospital with severe bleeding from his umbilical stump for which he was admitted to the neonatal intensive care unit and given packed red blood cells and fresh frozen plasma, and blood was sent for measuring the FXIII level in the blood. Diagnosis of FXIII deficiency was confirmed by a quantitative determination of active FXIII levels in the plasma of the patient and his family members and further measurements of the individual subunits in platelet lysate using the FXIII biotin incorporation assay 9 and FXIII-A and FXIII-B subunit enzyme-linked immunosorbent assay 10 (Table 1). Since then, the child was placed on pro- phylaxis with factor XIII human plasma concentrate replacement every 4 weeks at a dose of 10 IU/kg. At 3 months of age, he underwent uneventful circumcision and pyloric stenosis repair under FXIII replacement coverage. Since then, he had no significant episodes of bleeding. Owing to lack of access to a near and adequate health care facility at their village along with a shortage of supply of the FXIII replacement therapy, he missed 2 consecutive Received for publication September 11, 2012; accepted February 20, 2013. From the Departments of *Pediatrics; zLaboratory Medicine; yNeuro- surgery, University Medical Center-Rizk Hospital, Beirut, Lebanon; and wAngelo Bianchi Bonomi Hemophilia and Throm- bosis Center, U.O.S. Dipartimentale per la, Diagnosi e la Terapia delle Coagulopatie, Fondazione IRCCS Ca` Granda — Ospedale Maggiore, Policlinico, and Luigi Villa Foundation, Milan, Italy. The authors declare no conflict of interest. Reprints: Roula A. Farah, MD, FAAP, Department of Pediatrics, University Medical Center-Rizk Hospital, Zahar Street, Achrafieh, 1107-2030 Beirut, Lebanon (e-mail: roula.fs@dm.net.lb). Copyright r 2013 by Lippincott Williams & Wilkins ORIGINAL ARTICLE 62 | www.jpho-online.com J Pediatr Hematol Oncol  Volume 36, Number 1, January 2014