Binding of calcium ions and their effect on clotting of fibrinogen Milano III, a variant with truncated A alpha-chains

• Published in: Blood coagulation & fibrinolysis Vol. 7; no. 3; p. 331
• Main Authors: Furlan, M, Steinmann, C, Jungo, M, Lämmle, B
• Format: Journal Article
• Language: English
• Published: England 01-04-1996
• Subjects: Blood Coagulation; Calcium - metabolism; Fibrinogens, Abnormal - chemistry; Fibrinogens, Abnormal - metabolism; Humans
• ISSN: 0957-5235
• DOI: 10.1097/00001721-199604000-00007

Calcium ions are known to be required for normal polymerisation of fibrin monomers. Normal human fibrinogen has three high-affinity calcium binding sites. Two of these are located in the D-domains whereas the third binding site was tentatively assigned either to the E-domain or to the C-terminal part of the A alpha-chain. Furthermore, binding of calcium to the low-affinity binding sites (n > or = 10) facilitates fibrin monomer polymerisation. In several abnormally clotting fibrinogen variants, the polymerisation defect was partially normalised following addition of calcium ions. In this study, we show normal binding of calcium to fibrinogen Milano III, a homozygous fibrinogen variant with truncated A alpha-chains (A alpha 452 Gly-Pro-Asp-->Trp-Ser-Stop). These results confirm that the C-terminal parts of the A alpha-chains beyond residue 451 Ile are not involved in calcium binding. The thrombin time was severely prolonged and the final clot turbidity was strongly reduced in fibrinogen Milano III. Moreover, calcium ions did not significantly improve the abnormal clotting behavior of this dysfibrinogen. The polymerisation defect in fibrinogen Milano III appears to be due to truncated A alpha-chains as well as to the disulphide-linked albumin.