1. NEONATAL THROMBOEMBOLISM: RISK FACTORS, CLINICAL FEATURES, AND OUTCOME Nihal DEMIREL 1, Mustafa AYDIN 1, Aysegul ZENCIROGLU 1, Nurullah OKUMUS 1, Mehmet Sah IPEK 1, Nese YARALI 2 Dr. Sami Ulus Children’s Hospital, Departments of 1 Neonatology and 2 Pediatric Hematology, Ankara, Turkey Thromboembolic phenomenon is unusual during infancy and childhood compared to adults. In the pediatric age group, the neonatal period carries a relatively high risk for thrombosis particularly in the premature, ill infants. The incidence of symptomatic neonatal thromboembolism (TE) is reported to be 0.51 per 10,000 livebirths, with approximately half of the cases being venous TEs and half arterial. The objective of this study was to determine the risk factors, clinical features, and outcome of newborn infants diagnosed with TE. METHOD This study consisted of 19 patients (15 term, 4 preterm) diagnosed as neonatal TE between January 2005 and April 2008 in one NICU. Clinical data, laboratory testing for thrombophilic conditions, radiological studies, medications and outcomes were recorded. RESULTS Mean age at time of diagnosis was 12.13 ± 7.73 (range, 0-25) days. Ten patients (52.6%) were male and nine (47.4%) female. Overall, 12 venous (63.2%), 7 arterial (36.8%) TEs were noted. Catheter placement detected in 13 patients (68.4%), but only seven of them (36.8%) had had undergone to exchange transfusion for hyperbilirubinemia. In arterial thrombosis group, five patients with congenital heart disease (CHD) had been catheterized for angiographic studies and one preterm neonate with respiratory distress syndrome for blood sampling. The sites of thrombosis were portal vein (10), renal vein (1), bilateral iliac and renal arteries (1), left renal artery (1), right femoral artery (3), right iliac artery (2), and multiple veins (1). Hereditary thrombotic mutations [heterozygous MTHFR plus heterozygous factor V Leiden gene mutation (1), homozygous MTHFR gene mutation plus homozygous protein C deficiency (1), and heterozygous MTHFR plus heterozygous protrombin 20210A gene mutation (1)] were determined in three patients. In one patient anticardiolipin antibody was detected. Additional perinatal risk factors were available in 13 patients (68.4%) [CHD (5), septicemia (3), dehydration (3), meconium aspiration syndrome (1), respiratory distress syndrome (1), pneumonia (1), polycythemia (1), maternal diabetes (1), and perinatal asphyxia (1)]. While most of the patients (84.2%) recovered after anticoagulant (94.7%) or fibrinolytic therapy (27.8%); three patients (15.8%) died (familial hemophagocytic lymphohistiocytosis (FLH), purpura fulminans, and prematurity with respiratory distress syndrome). All patient except the case of FHL received anticoagulant or fibrinolytic medication. The cases of arterial thrombosis occurred after catheterization for angiographic studies received additional fibrinolytic therapy. Results were summarized in table 1. Case no Age (days) Gestational age / Gender Site of thrombosisCatheter placement Exchange transfusion Laboratory testing for TEAdditional risk factorsCoexistent diagnosisMedicationPatients outcome 117Term, FPortal veinYes NormalSepticemia, polycythemia, dehydration Down syndrome, septicemia, dehydration AnticoagulantRecovery 212Preterm, MPortal veinYes NormalNoHyperbilirubinemiaAnticoagulantRecovery 35Term, MPortal veinYes NormalNoFamilial hemophagocytic lymphohistiocytosis NoExitus 48Term, MPortal veinYes NormalGestational diabetesHyperbilirubinemiaAnticoagulantRecovery 50Term, MRenal veinNo Heterozygous MTHFR gene mutation plus heterozygous factor V Leiden mutation Meconium aspiration syndrome Meconium aspiration syndrome, renal vein thrombosis AnticoagulantRecovery 623Term, FBilateral iliac and renal arteries No Anticardiolipin antibody positivity Septicemia, dehydration Septicemia, dehydration AnticoagulantRecovery 75Preterm, FPortal veinYes NormalNoHyperbilirubinemiaAnticoagulantRecovery 86Term, MPortal veinNo NormalPerinatal asphyxia AnticoagulantRecovery 96.5Term, FPortal veinYes NormalNoHyperbilirubinemiaAnticoagulantRecovery 1019Preterm, MMultiple veinsNo Homozygous MTHFR gene mutation plus homozygous protein C deficiency NoPurpura fulminansAnticoagulantExitus 1125Term, MPortal veinNo Heterozygous MTHFR plus heterozygous protrombin 20210A gene mutation Pneumonia AnticoagulantRecovery 1214Term, FPortal veinNo NormalSepticemia, dehydration AnticoagulantRecovery 1315Term, MPortal veinYes NormalNoHyperbilirubinemiaAnticoagulantRecovery 145Preterm, FLeft renal arteryYesNoNormalRespiratory distress syndrome AnticoagulantExitus 1523Term, FRight femoral artery YesNoNo evaluatedCHDFistulization of right coroner artery to right ventricle Anticoagulant / Fibrinolytic Recovery 1624Term, FRight iliac arteryYesNoNo evaluatedCHDTetralogy of FallotAnticoagulant / Fibrinolytic Recovery 178Term, MRight femoral artery YesNoNo evaluatedCHDTransposition of great arteries Anticoagulant / Fibrinolytic Recovery 186Term, FRight femoral artery YesNoNo evaluatedCHDTransposition of great arteries Anticoagulant / Fibrinolytic Recovery 199Term, MRight iliac arteryYesNoNo evaluatedCHDTetralogy of FallotAnticoagulant / Fibrinolytic Recovery DISCUSSION Thromboembolic events in sick neonates are being increasingly recognized. The developing neonatal hemostatic system, coupled with perinatal risk factors increase the susceptibility of neonates to thromboembolic events. As seen in our cases, the most significant etiologic risk factors for thromboembolic events in neonates are placement of a central catheter and some genetic thrombophilic conditions. Additionally, the present study indicated that perinatal risk factors such as septicemia, dehydration, asphyxia, poor cardiac output, maternal diabetes, and polycythemia may increase the susceptibility of neonates to thromboembolic events. In our series, among the TEs, there was venous predominance compared to arterial Tes. In the cases of who had undergone to exchange transfusion, two had additional perinatal risk factors. It is observed that mortality was mainly associated with the underlying disease and severe hereditary thrombophilic conditions have fatal outcomes. Arterial TEs were chiefly associated with catheterization and occasionally with genetic predisposition. CONCLUSION Since TEs encounter more frequently in catheterized sick neonates, presence of a central catheter must be terminated as soon as possible especially in the patients who had perinatal risk factors; and if presence of a TE detected, testing for thrombophilic conditions must be done. Table 1: Demographic and clinical features of the neonates with thromboembolism TE: Thromboembolism; F: Female; M: Male; MTHFR: Methylenetetrahydrofolate reductase; CHD: Congenital heart disease