Intrauterine Death of Twin II Associated With Hereditary Thrombophilia

At 34 weeks gestation she went into premature labour and both twins were delivered vaginally. The first twin (male) was cephalic presentation and born with Apgar scores of 5 and 8 at 1 minute and 5 minutes respectively and weighed 2.54 kg. The second twin (female), also cephalic presentation diagnosed as an intrauterine death (IUD) and a macerated stillborn weighing 1.94 kg was delivered. Two separate placentae confirmed dichorionicity, but were not sent for histopathology. The autopsy on the stillbirth confirmed an anatomically normal female baby. There was significant maceration in keeping with IUD more than 7 days before delivery but failed to reveal any congenital malformations. The only abnormality found at autopsy was extensive renal vein thrombosis (RVT) with calcification which suggested possible primary thrombotic disorder in the fetus such as protein C deficiency. On further inquiry into the family history, the father of the baby was found to have congenital protein C deficiency. This was first diagnosed when he had a thrombotic episode after surgery for Crohn’s disease at the age of 20. He is currently on Warfarin therapy and is under the care of the Haematologist. A similar problem was also recorded in his mother (grandmother of the baby). The possible link between the symptomatic heritable thrombophilic defect in the family and the extensive renal vein thrombosis resulting in IUD of twin II was appreciated and the family was referred to the Haematologist for further screening for congenital thrombophilia. It was later discovered that the mother of the children has also inherited congenital protein S deficiency. The maternal family history was not available as she had been adopted as a child. Among the two boys, one is positive for congenital protein C deficiency and the other one is positive for protein S deficiency. It is possible that the twin II might have inherited both protein C and S deficiency resulting in extensive venous thrombosis leading to IUD. Discussion This is thought to be the first case reported in the literature where the entire family is affected with congenital thrombophilia transmitted to the offsprings. This case also illustrates the need to think of inherited thrombophilia as a primary cause of prenatal extensive RVT. Inherited thrombophilia is known to be associated with an increased risk of thrombosis. The heritable defects which are at present accepted as proven to be associated with familial venous thrombosis are deficiency of antithrombin (AT), protein C (PC) or protein S (PS), Activated Protein C Resistance (APCR) and Factor V (FV) Leiden mutation. Women with a family history of these defects are at an increased risk of pregnancy-associated venous thrombosis and increased risk of fetal loss and other vascular complications of pregnancy1. Renal vein thrombosis (RVT) occurs at any time in the neonatal period and also has been described in-utero. Prenatal RVT is a less common entity found incidentally on prenatal imaging2,3or at autopsy. Calcification due to RVT has been reported as early as the first day of life, indicating a prenatal origin3,4. In neonates, RVT occurs as an acute and life-threatening event as a result of perinatal stress, most frequently dehydration. Predisposing factors for neonatal RVT include asphyxia, shock, traumatic delivery, dehydration, polycythaemia, sepsis, congenital heart disease, congenital renal vein defects and rarely primary renal disease. It is more common in babies of diabetic mothers or when maternal