A Preterm Infant With Intrauterine Skin Necrosis

To the Editor: Newborns have a physiological tendency to hypercoagulation. When hereditary thrombophilic risk factors contribute to that physiological status, the development of the thromboembolic events in these patients becomes easier.1,2 We present a case of a preterm female infant with intrauterine growth retardation, and heterozygous prothrombin G20210A and homozygous methylenetetrahydrofolate reductase C677T mutations, who was born at 32 weeks of gestation with extensive skin necrosis. The patient was referred to our hospital because of multiple bruises on the skin at birth. Her mother suffered from placental abruption and vaginal bleeding during pregnancy; however, there was no thrombosis in family history. She had the body weight, height, and head circumference below 10 percentile. Physical examination revealed skin necroses located on the lateral surface of the right thigh (4 6 cm), lateral surface of the left lower extremity (1 1 cm), right inguinal region 1 1cm), left antecubital area (1 1cm), and left lower quadrant of the abdomen (4 6 cm) (Fig. 1). On laboratory examination carried out on first day of life, hemoglobin of 22 g/dL, platelet count of 165,000/ mm, and white blood cell count of 21,500/mm were detected. Blood urea nitrogen, creatinine, and liver function tests were within normal limits. Coagulation studies were as follows: prothrombin time 17 seconds (N: 10.6–16.2 s), activated partial thromboplastin time over 2 minutes (N: 27.5 to 79.4 s), international normalized ratio 2.5 (N: 0.53 to 1.62), D-dimer 8.6mg/L (N: 0.1 to 0.5mg/L), protein C 34 % (N: 35%±0.09%), protein S 13 % (N: 36%±12%), and antithrombin-III 35 % (N: 70% to 120%). Plasma homocysteine level was 36.6 mmol/L (N: 4.14 to 15 mmol/L) and methionine level was 3.38 mmol/L (N: 3.7 to 10.3 mmol/L). After vitamin K administration, activated partial thromboplastin time and international normalized ratio values returned to normal ranges. Genetic studies revealed homozygous MTHFR C677T and heterozygous prothrombin G20210A mutations in the patient; heterozygous MTHFR C677T, heterozygous PM G20210A, and heterozygous factor V Leiden mutations in her mother and heterozygous MTHFR C677T mutation in her father. The patient required mechanical ventilation because of respiratory distress syndrome. She was started on subcutaneous low-molecular weight heparin (150U/kg twice a day) and other medications including folic acid (1mg/d), acetylsalicylic acid (50mg/d), betaine (50mg/kg/d), and vitamin B12 (500mg/d). She was detached from mechanical ventilation on the seventh day of life; however, she needed mechanical ventilation again on day 15. Despite all supportive efforts, the patient died because of nosocomial sepsis on day 22. During the follow-up, the number and the size of the skin necroses were stable. Maternal and fetal factor V Leiden mutation is the most common mutation that is known to cause tendency for thrombosis.3,4 Genetic prothrombotic risk factors, especially when they exist in combination, play an important role in abdominal venous thrombosis seen in neonatal period and in infants.5 Thornburg et al6 reported on a full-term infant presenting at 7 days of life with HSV pneumonitis, a tricuspid valve thrombus, and a subsequent pulmonary embolus. The infant was found to be heterozygous for the prothrombin G20210A mutation and homozygous for the methylenetetrahydrofolate reductase C667T mutation and was treated with lowmolecular weight heparin. Our patient, who carried homozygous MTHFR C677T and heterozygous prothrombin G20210A mutations, presented with a rare symptoms such as intrauterine skin lesions. In conclusion, skin bruising and necrosis during delivery, which is mostly attributed to birth trauma, may be the sign of underlying inherited thrombophilia.