Thrombophilia in neonatal renal venous and arterial thrombosis

Abstract

Sirs, Renal venous thrombosis (RVT) is a classical disease in neonates, especially those that are preterm. It is a rare disorder with severe consequences for the affected kidney(s). A recent survey, carried out in Germany over a 2year period, identified 35 proven cases, corresponding to an incidence of 2.2 in 100,000 live births; half of these were premature [1]. Organ scarring was observed in 26 of the 39 affected kidneys. The clinical presentation consists of increased kidney size, macroor microhematuria, reduced urine output, and some degree of renal failure. Renal ultrasonography shows unior bilateral kidney enlargement with little flow and in many cases additional thrombi in the vena cava. The cause of RVT is unclear. The following predisposing factors have been identified in several earlier studies: maternal diabetes, traumatic delivery, prematurity, hyperviscosity, hypovolemia, and hemoconcentration. Recent single case observations have pointed to the association of RVT with activated protein C resistance, especially in bilateral cases [2, 3, 4, 5]. One multicenter case-control study in neonates and infants with abdominal venous thrombosis was published [6]. The odds ratio for RVT was 10.9 in infants with different forms of thrombophilia. Treatment remains controversial in the absence of trials to compare supporting therapy with anticoagulation and/or thrombolysis. Renal artery thrombosis (RAT) in the neonate is far less common than RVT, and there is little information about its incidence. It is strongly associated with umbilical catheters and patent ductus arteriosus [7]. The clinical presentation is rather silent and renal ultrasound findings can be minimal unless Doppler imaging is used. The outcome of the affected kidneys is poor with global atrophy being the rule. To the best of our knowledge, no patients with neonatal RAT and thrombophilia have been reported to date. Thrombophilia is an acquired or genetic state of hypercoagulability; the most common abnormalities being genetic in origin. Established genetic forms predisposing to venous thrombosis are deficiencies of antithrombin, protein C, and protein S, mutations in the promotor of the gene encoding prothrombin and factor V Leiden mutation. Mutations in the gene for methylenetetrahydofolate reductase, which lead to hyperhomocysteinemia, are associated with venous as well as arterial thrombosis. Over the last 25 years, ten patients were followed regularly in our Renal Unit for renal damage as a consequence of renal venous or arterial thrombosis in the neonatal period. There were eight boys and two girls. RVT was diagnosed in five patients, of whom two had bilateral thrombosis. RAT was observed in another five patients and was unilateral in all. The diagnosis of RVT was based on clinical, laboratory, and ultrasound manifestations. All patients had hematuria, thrombocytopenia, and kidney enlargement. The diagnosis of RAT was based on arterial hypertension, reduced kidney size, and poor renal perfusion. The two patients with bilateral RVT developed chronic renal failure. Of the five patients with RAT, three have complete atrophy of the affected kidney and two with a remnant kidney have needed antihypertensive drugs for several years. The investigations for thrombophilia were performed when the patients were aged between 18 months and 22 years. In two patients W. Proesmans · P. van de Wijdeven Renal Unit, Department of Pediatrics, University Hospital, Leuven, Belgium