Congenital atresia of the portal vein and extrahepatic portocaval shunt associated with benign neonatal hemangiomatosis, congenital adrenal hyperplasia, and atrial septal defect.

A rare case of congenital atresia of the portal vein and ductus venosus, extrahepatic portocaval shunt, benign neonatal hemangiomatosis, congenital adrenal hyperplasia, and an atrial septal defect is reported. Twenty-two cases of congenital extrahepatic end-to-side shunts have been described before. Although additional anomalies are common in this type of shunt, hemangiomatosis has been described only once. Adrenal hyperplasia has never been reported in this anomaly.

Interaction of fibrinolysis and prothrombotic risk factors in neonates, infants and children with and without thromboembolism and underlying cardiac disease. a prospective study.

UNLABELLED: To evaluate the role of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in children with an estimated risk of vascular occlusion reported to range from 7% to 16%, we conducted a prospective study in infants and children with underlying cardiac disease. One hundred and twenty-five children (neonate - 16 years) were investigated. In 9 infants out of the 125 children vascular occlusion occurred, closely related to cardiac catheterisation and arterial or venous lines during major cardiac surgery. Six of the nine neonates and infants with (n=6) and without (n=3) prothrombotic risk factors showed evidence of a basically impaired fibrinolytic system. Five of the nine infants showed increased PAI-1 clearly correlated to the 4G/4G genotype of the plasminogen activator-1 promoter polymorphism along with elevated t-PA concentration before the first diagnostic cardiac catheterisation was performed. One infant presented with increased t-PA concentration only. Five of the six children with reduced fibrinolytic capacity had further prothrombotic risk factors. CONCLUSION: Data of this study indicate that neonates and infants with underlying cardiac disease and basically increased PAI-1 due to the 4G/4G variant of the PAI-1 promoter polymorphism along with elevated t-PA levels in combination with further prothrombotic risk factors are at high risk of developing early thromboembolism during cardiac catheterisation.

Coagulation and fibrinolysis in children, adolescents, and young adults with inflammatory bowel disease.

BACKGROUND: Patients with Crohn's disease and ulcerative colitis have an increased risk of thromboembolic events. METHODS: Data were collected from 24 patients aged 4.5 to 23 years who had inflammatory bowel disease. Platelet count, antithrombin, fibrinogen, prothrombin fragment F1+2, soluble thrombomodulin, tissue plasminogen activator, D-dimer, and plasminogen activator inhibitor-1 antigen were investigated. In addition the response to activated protein C, the factor V R506Q mutation, protein C, free protein S antigen, and lipoprotein (a) were analyzed. These data were compared with medical treatment, duration, and disease activity, estimated with the Pediatric Crohn's Disease Activity Index or the Clinical Colitis Activity Index. RESULTS: Forty-five percent of our patients showed an increase in fibrinogen, 29% in prothrombin fragment F1+2, and 20% in platelet count, plasminogen activator inhibitor- antigen, and soluble thrombomodulin. Thrombomodulin was higher in active disease than in inactive disease and in Crohn's disease than in ulcerative colitis. Fibrinogen was also higher with Crohn's disease and tended to be higher in active disease than in ulcerative colitis and inactive disease. Plasminogen activator inhibitor-1 antigen was significantly higher in patients with Crohn's disease than in those with ulcerative colitis and was higher in the patient group treated with steroids. CONCLUSION: As has been shown in adults, young patients with active and inactive inflammatory bowel disease were found to have abnormal coagulation and fibrinolysis. The relevance as a thromboembolic risk factor is discussed.

Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly.

AIMS: To determine to what extent the Arg506 to Gln point mutation in the factor V gene and further genetic factors of thrombophilia affect the risk of porencephaly in neonates and infants. METHODS: The Arg506 to Gln mutation, factor V, protein C, protein S, antithrombin, antiphospholipid antibodies and lipoprotein (a) (Lp(a)) were retrospectively measured in neonates and children with porencephaly (n = 24). RESULTS: Genetic risk factors for thrombophilia were diagnosed in 16 of these 24 patients: heterozygous factor V Leiden (n = 3); protein C deficiency type I (n = 6); increased Lp (a) (n = 3); and protein S type I deficiency (n = 1). Three of the 16 infants had two genetic risk factors of thrombophilia: factor V Leiden mutation combined with increased familial Lp (a) was found in two, and factor V Leiden mutation with protein S deficiency type I in one. CONCLUSIONS: The findings indicate that deficiencies in the protein C anticoagulant pathway have an important role in the aetiology of congenital porencephaly.

Factor V Leiden, protein C, and lipoprotein (a) in catheter-related thrombosis in childhood: a prospective study.

OBJECTIVE: To determine the association between catheter-related thromboses and hereditary causes of thrombophilia, including the factor V Leiden mutation, deficiencies of protein C or protein S, or increased lipoprotein (a). STUDY DESIGN: To evaluate the incidence of genetic risk factors for familial thrombophilia in catheter-related thrombosis, 163 consecutively admitted infants and children (cardiac disease and catheter placement [C] n = 140; Broviac catheter [B] n = 23) were prospectively investigated. In addition, an age-matched, healthy control group undergoing elective surgery (S: n = 155) was investigated. RESULTS: Heterozygous factor V Leiden mutation was diagnosed in 20 of the 318 study subjects (C: n = 5; B: n = 4; S: n = 11), homozygous factor V Leiden mutation was found in two subjects (C: n = 1; S: n = 1), protein C deficiency type I was diagnosed in nine subjects (C: n = 4; B: n = 1; S: n = 4), and five subjects showed increased lipoprotein (a) (C: n = 3; S: n = 2). The frequency of thrombosis (C: n = 13; B: n = 5) in patients with familial thrombophilia was significantly higher (p < 0.0001; chi square: 27.79) in the catheter groups (15 of 17 subjects) than in control subjects after minor elective surgery (none of 18). Fifteen of the 18 infants with thrombosis had congenital thrombophilia; two children with congenital thrombophilia did not have documented thrombosis, and three infants with vascular occlusion had no inherited predisposition to thrombophilia. CONCLUSIONS: Genetic risk factors for familial thrombophilia play an important role in the manifestation of catheter-related thromboembolism in children.

Inherited defects of the protein C anticoagulant system in childhood thrombo-embolism.

Childhood thrombo-embolism is mostly the result of inherited thrombophilia or vascular insults combined with risk factors such as peripartal asphyxia, fetopathia diabetica, exsiccosis, septicaemia, central lines, congenital heart disease, cancer, trauma, surgery or elevated antiphospholipid antibodies. Inherited thrombophilia includes mainly defects of the protein C pathway, resistance to activated protein C, protein C or protein S deficiency. Resistance to activated protein C, in the majority of cases caused by the point mutation Arg 506 Gln of the factor V gene, has emerged as the most important hereditary cause of thrombo-embolism in adults and children. However, since an acquired risk of thrombo-embolic complications frequently masks the inherited deficiency in affected children, children with thrombo-embolism should have adequate laboratory evaluation for inherited coagulation disorders, especially the protein C pathway. Until more data on childhood thrombo-embolism are available, treatment recommendations will continue to be extrapolated from guidelines for adults.

Left atrial thrombus in a 10-month-old boy--successful thrombolysis with recombinant tissue-type plasminogen activator after open-heart surgery: review of the literature.

A 10-month-old boy with major left atrial thrombus following cardiac surgery was treated with intravenously administered recombinant tissue-type plasminogen activator (rt-PA; Actilyse, Thomae-Behring, Germany). The left atrial thrombus was diagnosed by Doppler echocardiography 8 days after complete correction of a ventricular septal defect. rt-PA therapy was administered over a 10-day period. Significant hemopericardium occurred 50 h after the start of thrombolytic therapy. rt-PA infusion was discontinued for 20 h to insert a pericardial drainage. The initial rt-PA dose was 0.1 mg/kg over 10 min followed by a continuous daily infusion of 1.7 mg/kg together with low-dose heparin. Thrombolytic therapy was restarted 20 h after pericardial drainage was inserted. The daily rt-PA dose was gradually raised to 3 mg/kg (total dose: 18 mg/kg). On day 7 and 8 a clear decrease in P-plasminogen and P-antithrombin occurred, requiring additional fresh frozen plasma and P-antithrombin concentrate substitution. One day later, without further side effects, complete thrombolysis occurred. Although hemopericardium demanded discontinuation of thrombolytic therapy, rt-PA administration, closely monitored by Doppler echocardiography, was continued, leading to complete thrombolysis of the left atrial thrombus in the early postoperative period. We consider the literature dealing with rt-PA thrombolysis in infancy we discuss this case report.