Challenging Bleeders - A Symposium for Haemostasis Specialists: Proceedings of the Edinburgh Haematology Symposium; November 8-9 2002, Edinburgh, UK: ReviewFour factor deficiencyThomas, Angelaa; Stirling, DavidbSection Editor(s): Ludlam, Christopher Author Information aRoyal Hospital for Sick Children and bRoyal Infirmary of Edinburgh, Edinburgh, UK. Correspondence and requests for reprints to Angela Thomas, MBBS, PhD, FRCPE, FRCPath, FRCPCH, Royal Hospital for Sick Children, Edinburgh, UK, EH9 1LF Tel: +44 (0)131 536 0433; fax: +44 (0)131 536 0430; e-mail: firstname.lastname@example.org Blood Coagulation & Fibrinolysis: June 2003 - Volume 14 - Issue - p S55-S57 Buy Abstract Four factor deficiency is variably associated with mild to fatal bleeding. We describe a 3-month-old boy, born of consanguineous parents, who presented with a right subdural haematoma and a clotting screen showing a prothrombin time (PT) > 100 s, an activated partial thromboplastin time (aPTT) > 150 s, a fibrinogen of 0.4 g/l, and fibrinogen degradation products < 1 μg/ml. He was given 300 U of factor IX concentrate (containing factors II and X) and 1 mg of vitamin K intravenously. Forty-five minutes later, clotting tests showed a PT of 24 s, an aPTT of 31 s and a fibrinogen of 2.6 g/l. The patient was found to be deficient in all the vitamin K-dependent factors: factors II, VII, IX and X, protein C and protein S. A 14-base deletion was found in intron 1 (bases 1056-1069) of the γ-carboxylase gene. The patient and his elder sister were homozygous for this deletion, whereas both parents were heterozygous. The deletion destroys a reverse palindromic sequence (TTGAGGCAA) of the type often associated with cis-acting elements. Our results suggest that this element may be involved in the regulation of γ-carboxylase expression. Expression studies are being completed so that this region can be definitively ascribed as a cis-acting element involved in gene regulation. © 2003 Lippincott Williams & Wilkins, Inc.