[An elderly case of congenital prekallikrein deficiency]

Abstract

The proband is a 69-year-old woman with purpura and subcutaneous hematoma.We investigated this patient with prekallikrein (PK) deficiency, using both standard coagulation study and molecular genetic analysis of the PK gene. In a coagulation study, the prothrombin time (PT) was normal but the activated partial thromboplastin time (APTT) was prolonged. Preincubation of normal plasma with APTT reagent caused shortening of abnormal clotting time. Plasma PK activity was <1%. Her parents were cousins. Molecular genetic analysis showed a homozygous Gly401Glu substitution in exon 11 in the PK gene. This mutation has already been reported in a Japanese patient as PK Tokushima. Gly401 is positioned in PK light chain, which encodes the serine protease domain. The disulfide binding is formed between Cys400 and Cys416, thus Gly401 is located next to His415, which is one of the activation peptides and is important in supporting the correct conformation of proteins. Therefore, we suggest that this mutation may prevent formation of disulfide binding and reduce enzyme activity. In conclusion, in the elderly case with prolonged APTT, we should consider the contact factor deficiency and determine PK activity apart from the abnormality of coagulation factor VIII, IX, XI and XII activities.