THERAPEUTIC NOTE Successful use of recombinant factor VIIa for management of severe menorrhagia in an adolescent with an acquired inhibitor of human thrombin L Giovannini 1 , A Appert 2 , F Monpoux 1 , F Fischer 2 , P Boutte 1 and N Sirvent 1 Service de Pe ´diatrie 1 and Laboratoire Central d’He ´matologie 2 , Ho ˆpital de l’Archet, CHU Nice, France Giovannini L, Appert A, Monpoux F, Fischer F, Boutte P, Sirvent N. Successful use of recom- binant factor VIIa for management of severe menorrhagia in an adolescent with an acquired inhibitor of human thrombin. Acta Pædiatr 2004; 93: 841–843. Stockholm. ISSN 0803-5253 Antibodies directed against human thrombin are exceedingly rare, having only been reported in adult patients with underlying diseases. Consensus on the most appropriate management has not yet been reached. A 12-y-old girl presented with intractable menorrhagia several days after an acute infectious episode. Laboratory tests revealed disturbed clotting tests: prothrombin index 17%, activated partial thromboplastin time >150 s, thrombin time >120 s, and failure to achieve correction with a normal pooled plasma. Further studies demonstrated the presence of an antibody directed against human thrombin. Viral serology revealed a 1/128 titre for adenovirus. Massive haemorrhage was unresponsive to standard treatments, but intravenous administration of recombi- nant factor VIIa resulted in a successful outcome. Conclusion: This is the first report of an anti-human thrombin antibody associated with severe bleeding in a child. Recombinant factor VIIa could represent a novel therapeutic approach for such patients. Key words: Thrombin inhibitor, child, adenovirus, recombinant factor VIIa N Sirvent, Service de Pe ´diatrie, Ho ˆpital de l’Archet, CHU Nice, 151 route de Saint Antoine de Ginestie `re, 06202 Nice Cedex 3, France (Tel. 33 4 92 03 60 64, fax. 33 4 92 03 65 78, e-mail. sirvent.n@chu-nice.fr) Haemorrhage is a well-recognized and potentially fatal complication of acquired thrombin autoantibodies. Such antibodies rarely occur, having only been reported in adult patients with various underlying diseases (1). No consensus has yet been reached on the most appropriate management of bleeding complications. Activated recombinant human coagulation factor VII (rFVIIa, NovoSeven 1 ) is used primarily for prophy- lactic or curative treatment of haemorrhage in haemo- philiacs with inhibitors. Recently, the indications for rFVIIa have been broadened to include treatment of severe bleeding associated with acquired coagulopa- thies of unknown origin (2). We report herein the first paediatric case of successful use of rFVIIa for manage- ment of intractable menorrhagia in a 12-y-old girl with acquired anti-human thrombin inhibitor. Case report A previously healthy 12-y-old girl presented with uncontrolled menorrhagia 4 d after an acute infectious episode including fever, diarrhoea and acral rash. Physical examination was unremarkable. She had no personal or family history suggestive of a bleeding disorder, and was not receiving any medication known to inhibit platelet function. Initial laboratory evaluation showed a haemoglobin level of 5 mmol/l and a normal platelet count. Coagulation assays were performed on STAR (Diagnostica Stago), using PTTAutomate 10 (Diagnostica Stago) reagent for APTT, NEOPLAS- TINE CI (Diagnostica Stago) for prothrombin index and THROMBIN 2 (Diagnostica Stago) for thrombin time. Results were as follows: prothrombin index 17%, activated partial thromboplastin time (aPTT) >150 s, thrombin time (TT) >120 s, normal fibrinogen level. Clotting factor levels were slightly decreased (Table 1). The search for lupus anticoagulant directed against prothrombin was negative. The reptilase time was normal, but the aPTT and TT failed to correct when the patient’s plasma was mixed with an equal volume of normal pooled plasma, suggesting the presence of a thrombin inhibitor. Immediate transfusions of packed red cells (one unit)  2004 Taylor & Francis. ISSN 0803-5253 Acta Pñdiatr 93: 841±843. 2004 DOI 10.1080/08035250410027616