Alpha1-antitrypsin Pittsburgh in a family with bleeding tendency

• Published in: Haematologica (Roma) Vol. 94; no. 6; pp. 881 - 884
• Main Authors: Hua, Baolai, Fan, Liankai, Liang, Yan, Zhao, Yongqiang, Tuddenham, Edward G D
• Format: Journal Article
• Language: English
• Published: Italy 01-06-2009
• Subjects: Adolescent; Adult; alpha 1-Antitrypsin - genetics; Blood Coagulation Tests; Blood Protein Electrophoresis; DNA Mutational Analysis; Factor X - metabolism; Factor XI - metabolism; Factor XII - metabolism; Family Health; Female; Hemorrhagic Disorders - blood; Hemorrhagic Disorders - diagnosis; Hemorrhagic Disorders - genetics; Heterozygote; Humans; Male; Mutation; Pedigree
• ISSN: 1592-8721
• DOI: 10.3324/haematol.2008.004739

We describe a 16-year-old girl and her 41-year-old father who both had a bleeding tendency, dramatic prolongation of all standard clotting assays, undetectable levels of plasma protein C activity, and low or borderline levels of factors X, XI and XII. Plasma and serum electrophoresis revealed a minor peak following the main alpha(1) globulin peak, of which the proportion was increased. Platelet aggregation by thrombin (final concentration 1 U/mL) was absent in both patients, but this inhibition can be overcome by increasing the concentration of thrombin (4 U/mL). The molecular defect responsible for these coagulation abnormalities was identified by genomic sequencing. Both patients are heterozygous for alpha(1)-antitrypsin Met 358 to Arg (alpha(1)-antitrypsin Pittsburgh). Seven other members of this pedigree had normal coagulation tests and do not carry the same genetic mutation. This unique family with alpha1-antitrypsin Pittsburgh sheds some light on the study of this extremely rare mutation and its inheritance.