Thomas J Cramer1, Kristin Anderson2, Karanjia Navaz3, Justin M Brown4, Laurent O Mosnier5, Annette von Drygalski6. 1. University of California San Diego, Department of Medicine, 9500 Gillman Drive, San Diego, CA 92093, USA. Electronic address: t.j.cramer@hotmail.com. 2. University of California San Diego, Department of Medicine, 9500 Gillman Drive, San Diego, CA 92093, USA. Electronic address: knanders@gmail.com. 3. University of California San Diego, Department of Neurosciences, 9500 Gillman Drive, San Diego, CA 92093, USA. Electronic address: nkaranjia@ucsd.edu. 4. University of California San Diego, Department of Surgery, 9500 Gillman Drive, San Diego, CA 92093, USA. Electronic address: jmbrown@ucsd.edu. 5. The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: lmosnier@scripps.edu. 6. University of California San Diego, Department of Medicine, 9500 Gillman Drive, San Diego, CA 92093, USA; The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: avondrygalski@ucsd.edu.
Abstract
BACKGROUND: In congenital Factor (F) VII deficiency bleeding phenotype and intrinsic FVII activity levels don't always correlate. Patients with FVII activity levels <30% appear to have a higher bleeding propensity, but bleeding can also occur at higher FVII activity levels. Reasons for bleeding at higher FVII activity levels are unknown, and it remains challenging to manage such patients clinically. CASE: A 19year old male with spontaneous intracranial hemorrhage and FVII activity levels of 44%, requiring emergent surgical intervention and a strategy for FVII replacement. Genotyping showed the rare heterozygous FVII 9729del4 mutation. Bleed evacuation was complicated by epidural abscess requiring craniectomy, bone graft procedures, and prolonged administration of recombinant human (rh) activated FVII (FVIIa). The patient recovered without neurological deficits, and remains on prophylactic low dose treatment with rhFVIIa in relation to risky athletic activities. CONCLUSION: For clinicians, it is important to recognize that effects of rhFVIIa within these pathways are independent of its contribution to blood clot formation and cannot be assessed by clotting assays. Reduced FVII levels should therefore not be dismissed, as even a mild reduction may result in spontaneous bleeding. Treatment of mild FVII deficiency requires a careful case-by-case approach, based on the clinical scenario.
BACKGROUND: In congenital Factor (F) VII deficiency bleeding phenotype and intrinsic FVII activity levels don't always correlate. Patients with FVII activity levels <30% appear to have a higher bleeding propensity, but bleeding can also occur at higher FVII activity levels. Reasons for bleeding at higher FVII activity levels are unknown, and it remains challenging to manage such patients clinically. CASE: A 19year old male with spontaneous intracranial hemorrhage and FVII activity levels of 44%, requiring emergent surgical intervention and a strategy for FVII replacement. Genotyping showed the rare heterozygous FVII 9729del4 mutation. Bleed evacuation was complicated by epidural abscess requiring craniectomy, bone graft procedures, and prolonged administration of recombinant human (rh) activated FVII (FVIIa). The patient recovered without neurological deficits, and remains on prophylactic low dose treatment with rhFVIIa in relation to risky athletic activities. CONCLUSION: For clinicians, it is important to recognize that effects of rhFVIIa within these pathways are independent of its contribution to blood clot formation and cannot be assessed by clotting assays. Reduced FVII levels should therefore not be dismissed, as even a mild reduction may result in spontaneous bleeding. Treatment of mild FVII deficiency requires a careful case-by-case approach, based on the clinical scenario.
Authors: Roger J S Preston; Eva Ajzner; Cristina Razzari; Stalo Karageorgi; Sonia Dua; Björn Dahlbäck; David A Lane Journal: J Biol Chem Date: 2006-07-25 Impact factor: 5.157
Authors: Muriel Giansily-Blaizot; Régis Verdier; Christine Biron-Adréani; Jean-François Schved; M A Bertrand; J Y Borg; V Le Cam-Duchez; V LeCam-Duchez; M E Briquel; H Chambost; K Pouymayou; F Dutrillaux; R Favier; I Martin-Toutain; E Verdy; V Gay; J Goudemand; R Navarro; A Durin; R d'Oiron; T Lambert; G Pernod; C Barrot; J Peynet; B Bastenaire; P Sie; N Stieltjes; M F Torchet; P de Moerloose Journal: Haematologica Date: 2004-06 Impact factor: 9.941
Authors: D S Millar; G Kemball-Cook; J H McVey; E G Tuddenham; A D Mumford; G B Attock; J C Reverter; N Lanir; L A Parapia; J Reynaud; E Meili; A von Felton; U Martinowitz; D R Prangnell; M Krawczak; D N Cooper Journal: Hum Genet Date: 2000-10 Impact factor: 4.132