Homozygous variant of antithrombin III that lacks affinity for heparin, AT III Kumamoto.
Abnormal antithrombin III (AT III) was found in the plasma of a 31-year-old female who suffered from recurrent thrombotic episodes. Heparin cofactor activity was 28% of normal and undetectable when measured by inhibition of thrombin and factor Xa (F.Xa), while both progressive antithrombin and antifactor Xa activities were normal. The concentration of plasma AT III antigen was 37 mg/dl. Analysis by crossed-immunoelectrophoresis (CIE) in the presence of heparin and affinity chromatography on heparin-Sepharose revealed that the propositus' AT III did not bind to heparin. When heparin cofactor II (HC II) was removed from propositus' plasma, heparin cofactor activity of AT III was not detected. Thus, HC II seemed to account for the plasma heparin cofactor activity found in the presence of thrombin. The patient's parents and three of her brothers demonstrated qualitative abnormality of AT III; heparin cofactor activity was 30-50% of normal levels in the presence of both thrombin and F.Xa. These findings indicate that the propositus' AT III lacks affinity for heparin and the mode of its inheritance seems to be autosomal dominant and, hence, the propositus would be a homozygote. For this variant, the name of AT III Kumamoto is proposed.
Okajima
K
K
Department of Laboratory Medicine, Kumamoto University Medical School, Japan.
Ueyama
H
H
Hashimoto
Y
Y
Sasaki
Y
Y
Matsumoto
K
K
Okabe
H
H
Inoue
M
M
Araki
S
S
Takatsuki
K
K
D000328:Adult; D000990:Antithrombin III / Q000235:genetics* / Q000378:metabolism; D001780:Blood Coagulation Tests; D002846:Chromatography, Affinity; D015951:Factor Xa; D005260:Female; D014644:Genetic Variation; D006493:Heparin / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D010375:Pedigree; D015842:Serine Proteinase Inhibitors; D013917:Thrombin / Q000037:antagonists & inhibitors; D013927:Thrombosis / Q000097:blood* / Q000235:genetics
D015842:Serine Proteinase Inhibitors; C060217:antithrombin III Kumamoto; D000990:Antithrombin III; D006493:Heparin; D013917:Thrombin; D015951:Factor Xa