|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
N Yoshida, M Okuma, H Hirata, M Matsuda, K Yamazumi and S Asakura
Institute of Hematology, Jichi Medical School, Tochigi, Japan.
A new case of heterozygous dysfibrinogenemia characterized by an amino acid
replacement in the NH2-terminal region of the fibrin alpha-chain was found
in a 27-year-old woman with a bleeding problem. Her one-stage prothrombin
time and activated partial thromboplastin time were slightly prolonged, and
the purified fibrinogen from this patient had a markedly prolonged thrombin
or reptilase time. Release of fibrinopeptides A and B was normal, but the
polymerization of fibrin monomers was impaired. Sodium dodecyl
sulfate-polyacrylamide gel electrophoresis of the purified fibrinogen under
the reduced condition showed no abnormalities in the apparent molecular
weights of its three chains. Reverse-phase high performance liquid
chromatography (HPLC) of the lysylendopeptidase-cleaved purified A
alpha-chains showed a decrease in one peptide compared with the normal
amount and the appearance of an abnormal peptide peak. These peptides were
treated with thrombin and further separated on HPLC. Amino acid sequence
analysis of the abnormal peptide indicated that A alpha proline-18, the
second residue from the NH2-terminus of the fibrin alpha-chain, was
replaced by leucine. The synthetic peptide Gly-Pro-Arg-Pro inhibited both
thrombin- and reptilase-induced fibrin aggregation, but Gly-Leu- Arg-Pro
showed little or no inhibition under the same conditions. The discovery of
this abnormal fibrinogen supports the findings that A alpha proline-18 is
important as part of the polymerization site in the NH2-terminus of the
fibrin alpha-chain. The propositus' mother had the same abnormal
fibrinogen. This unique inherited abnormal fibrinogen was designated as
fibrinogen Kyoto II.
This article has been cited by other articles:
| |||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
