title: Milder clinical presentation of haemophilia A with severe deficiency of factor VIII as measured by one-stage assay.
abstract: During the course of investigations we encountered 11 patients with haemophilia A who had severe factor VIII deficiency as measured by one-stage assay but had surprisingly mild clinical presentation. Four of these patients had either a brother, nephew or maternal uncle with severe clinical manifestations. Two patients had low protein S levels, and one was heterozygous for the factor V Leiden mutation. One patient had a combined deficiency of protein C and antithrombin III. Four patients had a two-stage factor VIII assay value that was much higher than the one-stage assay value. Five patients were heterozygous for the MTHFR gene C677T polymorphism, of whom two patients were also deficient for protein S and one had two-stage factor assay values higher than the one-stage assay values. The patient who was both factor VIII deficient and heterozygous for factor V Leiden had mild clinical presentation as compared to his maternal uncle who was only factor-VIII deficient. The maternal cousin of the same patient was heterozygous for factor V Leiden and had suffered two thrombotic episodes. Thus, the present study advocates that the physiological inhibitors of blood coagulation also play an important role in cases of haemophilia A in the final outcome of haemostasis in vivo.
authors.affiliation: Institute of Immunohaematology, KEM Hospital Campus, Parel, Mumbai, India. mohanty@bom5.vsnl.net.in
authors.forename: K
authors.initials: K
authors.lastname: Ghosh
authors.forename: S
authors.initials: S
authors.lastname: Shetty
authors.forename: D
authors.initials: D
authors.lastname: Mohanty
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005165:Factor V / Q000235:genetics; D005169:Factor VIII / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006467:Hemophilia A / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation
chemical_list: C095381:factor V Leiden; D005165:Factor V; D005169:Factor VIII