De novo neonatal antiphospholipid syndrome: A case report and review of the literature Oren Gordon, MD, PhD a,n , Yotam Almagor, MD a , Dvora Fridler, MD a , Asaf Mandel, MD b , Hiba Qutteineh, MD a , Asaf Yanir, MD c , Shimon Reif, MD a , Shoshana Revel Vilk, MD, MSc c a Department of Pediatric, Hadassah Hebrew-University Hospital, Ein-Kerem Campus, Jerusalem 91120, Israel b Pediatric Intensive Care Unit, Hadassah Hebrew-University Hospital, Jerusalem, Israel c Department of Pediatric Hematology/Oncology, Hadassah Hebrew-University Hospital, Jerusalem, Israel article info Keywords: Neonatal thrombosis Antiphospholipid syndrome abstract Objectives: Neonatal antiphospholipid syndrome (APS) is rare and only few cases have been reported, most of them describing trans-placental passage of penetrable maternal antibodies. The current article aims at defining the clinical and biochemical features of the de novo occurrence of neonatal APS and considerations for long-term treatment. Methods: We present a case and review the medical literature using PubMed. Results: Including the current report, there are 11 reports of de novo neonatal APS. These include 8 cases of acute ischemic stroke, 2 of venous thrombosis, and 1 of mixed arterial and venous thrombosis. All cases had an additional thrombotic risk factor, either inherited or acquired. Negative maternal history together with low clinical suspicion led to late diagnosis in most cases. In all cases aPL antibodies persisted in the serum throughout the follow-up period. No recurrence of thrombotic events was reported in patients under long-term anticoagulation with either low-molecular-weight heparin (LMWH) or aspirin. There is 1 report of recurrent thrombosis where the patient did not receive anticoagulation. In this case diagnosis was made only retrospectively after recurrence. Conclusions: We recommend that de novo APS be considered in all cases of unexplained neonatal thrombosis aiming at early diagnosis and implementation of long-term anticoagulation to prevent recurrent thrombotic events. & 2014 Elsevier Inc. All rights reserved. Introduction Thromboembolic events are uncommon in children. Within the pediatric population, however, neonates bear greater risk for thrombosis and its sequela [1–4]. This may be explained by the coalescence of unique perinatal and maternal risk factors together with acquired or inherited thrombophilic risk factors [2–5]. Determining risk for recurrence is essential for the long-term management of neonatal thrombosis [6]. Antiphospholipid syndrome (APS) is a non-inflammatory auto- immune disorder characterized by the association of thrombotic events in combination with persistent elevated titers of antiphos- pholipid (aPL) antibodies, such as lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), or anti-β2 glycoprotein-I anti- bodies (aβ2GP1), as defined in the Sapporo criteria [7–9]. APS may be primary or secondary to other autoimmune diseases, mainly systemic lupus erythematosus (SLE). Pediatric APS is rare but holds a risk of death or severe morbidity [7,10]. Thus far, only a few cases of neonatal APS have been reported, most of them describing neonatal APS arising from trans-placental passage of penetrable maternal antibodies [11–15]. While it is reasonable to assume that neonatal APS related to trans-placental passage of aPL antibodies differs in clinical course and prognosis from de novo production of aPL antibodies by the neonate itself, little is known about the later. Case report A 9-day-old male infant presented with a hard, swollen, purple left leg. He is the second child to Jewish–Georgian parents, with no maternal or family history of thrombosis or autoimmunity. Preg- nancy and delivery were uneventful; he was born at 40 weeks of gestation weighing 3730 g. Perinatal history was unremarkable aside from diagnosis of developmental dysplasia of the hip (DDH). Upon arrival to the ER he had normal temperature, but a few hours Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/semarthrit Seminars in Arthritis and Rheumatism http://dx.doi.org/10.1016/j.semarthrit.2014.04.003 0049-0172/& 2014 Elsevier Inc. All rights reserved. n Corresponding author. Tel.: þ972 26 776 465; fax: þ972 26 778 921. E-mail address: orengo@hadassah.org.il (O. Gordon). Seminars in Arthritis and Rheumatism ] (2014) ]]]–]]]