LETTER TO THE EDITOR A new report of FVII-inhibitor in a patient suffering from severe congenital FVII deficiency M. BORHANY,* C. DELBES, † M. GIANSILY-BLAIZOT, † M. ZUBAIR, ‡ M. S. AHMED, ‡ N. FATIMA* and T. SHAMSI* *Department of Haematology, Haemostasis & Thrombosis, National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, Pakistan; †D epartement d’h ematologie biologique, CHU de Montpellier, H^ opital Saint Eloi, Montpellier, France; and ‡Military Hospital Rawalpindi, Rawalpindi, Pakistan Congenital factor VII (FVII) deficiency is a rare, auto- somal recessive bleeding disorder affecting both males and females. It is characterized by increased bleeding after surgery and trauma in mildly affected individu- als, and by spontaneous, severe and even life-threaten- ing bleeding in those severely affected [1]. Optimal replacement therapy for FVII deficiency consists of recombinant-activated FVII (rFVIIa) or plasma-derived FVII (pdFVII) concentrates. Both therapeutic options are safe and effective [2]. The rationale behind the use of rFVIIa in congenital FVII deficiency is based on the fact that it provides a source of the missing protein in a low-volume preparation, and is devoid of other human proteins and potential blood-borne pathogens. The recommended dose of rFVIIa in FVII-deficient patients is between 15 and 30 lg kg 1 body weight, every 4–6 h [3]. Although rare, the formation of anti- bodies against FVII is an important concern of replacement therapy [4]. Here, we present the case of a severe FVII-deficient patient who developed inhibi- tors directed against rFVIIa after replacement therapy. The patient (a female born in 2005) first presented at the age of 8 years after sustaining a fracture of the left wrist requiring surgical correction. After removal of plaster of Paris, she started having multiple epi- sodes of swelling, pain, tenderness and restricted movement revealing haemarthrosis. She also reported an episode of uncontrolled bleeding after tooth extrac- tion. Severe isolated FVII deficiency was diagnosed with a FVII:C level of 1% measured. Subsequently, rFVIIa treatment was started at a dose of 15 lg kg 1 every 6 h. Bleeding stopped, but after 2 weeks of rFVIIa treatment, the patient suddenly developed haematoma in the right calf and multiple haemarthro- sis. She then developed haematuria, gum-bleeding, severe myalgia and multiple bruises leading to an increase in the rFVIIa dose to 30 lg kg 1 . Following this her haemoglobin dropped from 11 to 7 g dL 1 , and the patient was transfused with packed red cells and fresh frozen plasma (FFP) 15 mL kg 1 every 12 h. However, she showed no response to the treat- ment. Vitamin K injections were also administered i.v. for 3 days. Screening for FVII inhibitors was per- formed using an adapted Bethesda assay [5]. Inhibi- tory activity of a 1:1 mixture was measured after an incubation period of 2 h at 37°C revealing a titre of 11 BU. This high titre led us to stop rFVIIa infusions and start treatment with steroids, azathioprine, immu- noglobulin and FEIBA to treat acute bleeding episodes (Fig. 1). Lupus anticoagulant and other markers of an- tiphospholipid syndrome including anticardiolipin antibody and an autoimmune profile were all negative. Despite the treatment, the patient’s condition deterio- rated clinically. The patient did not have any signifi- cant bleeding history except one or two episodes of bruises after trauma and there was no history of Correspondence: Munira Borhany, St 2/A block 17 Gulshan-e-Iqbal KDA Scheme 75300 24, Karachi, Pakistan. Tel.: +92333 2317521; fax: +92 21 34821504; e-mail: muniraborhany@gmail.com Accepted after revision 31 March 2015 11 3 1.1 2 3 3 3 0 2 4 6 8 10 12 0 3 6 9 12 15 18 21 Inhibitor level (BU) Time (months) * rFVIIa stopped,patient was on immunosuppressants,FFP, FIEBA and steroids Patient had severe bleeding,rFVIIa was started at 15 μg kg –1 dose but no response acheived then rFVIIA stopped again. Fig. 1. Detection and course of FVII:C inhibitor in a patient with severe FVII deficiency as recorded by a FVII:C inhibitor assay following the Beth- esda method. *Patient had persistent bleeding and was diagnosed as a case of severe factor VII deficiency, FVII:C level was 1% and was treated with recombinant activated FVII (rFVIIa). rFVIIa started at a dose of 15 lg kg 1 six hourly for 2 weeks, and increased to 30 lg kg 1 but had no response. Inefficacy of rFVIIa treatment suggested the occurrence of FVII inhibitors. © 2015 John Wiley & Sons Ltd 1 Haemophilia (2015), 1–3 DOI: 10.1111/hae.12708