Recombinant factor VIIa (rFVIIa, Novoseven®) has been shown to induce hemostasis in hemophilia patients with inhibitors against factor VIII or factor IX independent of factor VIII/factor IX. rFVIIa initiates hemostasis by forming a complex with tissue factor (TF) exposed as a result of vessel wall injury. Pharmacologic doses of rFVIIa can enhance thrombin generation. Recombinant activated factor VII (rFVIIa, Novoseven®) is in regular clinical use in haemophilia B patients with high-titer inhibitors to coagulation factor IX (FIX) since 1996 [1]. Potential adverse event of rFVIIa therapy is pathological blood clotting. However, when rFVIIa is used in labeled indications such adverse event is rare and did not appear to be dose-related. The incidence of serious thromboembolic events after treatment with rFVIIa in hemophilia patients with inhibitors appears to be much less than 1%, with only three cases reported in children, all of them with hemophilia A and predisposing factors [2]-[4].

We present the patient with hemophilia B and high titer inhibitors to coagulation FIX who was treated with rFVIIa for severe life-threatening hematuria. Although hematuria was successfully treated, renal thromboembolic adverse event associated with unsuspected vascular anomalies resulted in severe renal damage. To our knowledge, this is the first case of tromboembolic event connected with rFVIIa therapy with this set of symptoms presented exclusively on kidney with underlying vascular anomalies. The second normal kidney was fully spared.

The risk of clot formation is low even if rFVIIa was given in higher doses (>300 mcg/kg BW) [5],[6]. But the treatment with high doses of rFVIIa on an off-label basis significantly increases the risk of arterial but not venous thromboembolic events among the elderly [7]. In the literature we found a report of a woman with Glanzmann Thrombasthenia with haematuria and clotting in renal pelvis after rFVIIa administration. In this case, the major reason for rFVIIa administration was intraoperative bleeding, during laparotomy for pelvic inflammatory disease. It is well known that inflammatory process activate "kinin-kallikrein" system and that leads to increased clotting [8].

Our patient had multiple renal vascular anomalies. Multiple renal arteries are not uncommon. Various reports estimate its incidence up to 32%, usually on the right side with very rare occurrence of triple arteries supplying one kidney [9]-[12]. Anatomical variations of multiple renal veins are less common with incidence ranging between 0.8 and 6% [13]. Both anomalies occur far more commonly on the right side [9],[13],[14]. Anomalies occurring in both arteries and vein together are extremely rare. To our knowledge, this is the first report of combination of both multiple arterial and vein kidney anomalies of one kidney while the other kidney had normal circulatory system. As we did not exceed recommended rFVIIa dosage and as right kidney was spared, the contribution of such vascular anomaly to the thromboembolic incident of the left kidney is a reasonable assumption. According to radionuclide examinations the main site of lesion and clotting event was intrarenal vascular bed, primarily in glomerular region, while tubular region was less affected. Renal damage secondary to pelvicaliceal obstruction is less likely.

Such an extremely rare troboembolic event in patients with hemophilia B certainly do not compromise safe administration of rFVIIa. However, caution is necessary if hematuria requires administration of rFVIIa. US color doppler renal imaging before and after drug administration should be sufficient as an early warning.

Written informed consent was obtained from the patient’s parents for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.