Molecular defect of ‘Prothrombin Amrita’: Substitution of arginine by glutamine (Arg553 to Gln) near the Na+ binding loop of prothrombin

Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism

“…In conclusion, prothrombin Belgrade seems to be a rare prothrombotic condition, but it has been found so far in Serbian, Indian and Japanese populations . It is well known that the risk of thrombosis in families with inherited thrombophilia depends highly on the clinical phenotype of the proband .…”

“…This mutation affects the same Arg596 position, but results in a different amino acid substitution, p.Arg596Gln (prothrombin Belgrade), and likewise leads to antithrombin resistance . The prothrombin Belgrade mutation has been detected as well in one Indian and one Japanese thrombophilic family . Most recently, prothrombin Padua 2 ( F2 c.1786C>T, p.Arg596Trp), also characterized by a mutation at the Arg596 position and the presence of antithrombin resistance, has been described .…”

The first case of antithrombin-resistant prothrombin Belgrade mutation in Japanese

“…So far, Belgrade mutation has been reported only in Serbia and India [4,5] and this is the first case of antithrombinresistant prothrombin Belgrade mutation in Japanese.…”

“…Prothrombin Yukuhashi mutation (c.1787G>T, p.Arg596Leu) found in Japanese thrombophilia pedigree resulted in mutant prothrombin with reduced clotting activity but resistant to inactivation by antithrombin [1][2][3]. Another variant, prothrombin Belgrade mutation (c.1787G>A, p.Arg596Gln) found in Serbia and India is also related to thrombophilia with the same mechanism [4,5]. Here, we report the first Japanese family with ATR caused by prothrombin Belgrade mutation.…”

Optimisation of antithrombin resistance assay as a practical clinical laboratory test: Development of prothrombin activator using factors Xa/Va and automation of assay

“…Following the report on prothrombin Yukuhashi, prothrombin Belgrade ( F2 c.1787G>A, p.Arg596Gln) and prothrombin Padua 2 ( F2 c.1786C>T, p.Arg596Trp) were also reported as an antithrombin‐resistant prothrombin. Currently, patients with the antithrombin‐resistant prothrombin mutation are found in seven unrelated families worldwide (prothrombin Yukuhashi: one Japanese family; prothrombin Belgrade: two in Serbia, one in India, and one in Japan; and prothrombin Padua 2: two Italian families).…”