Development of a new laboratory test to evaluate antithrombin resistance in plasma

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

“…Protein S, protein C, and antithrombin deficiencies were not detected, and none of previous observations identified the causes of this hereditary thrombophilia. We conducted ATR kinetic assay [6] and F2 genome analysis and found that the relative residual thrombin activity after adding antithrombin of this patient was significantly higher than that of normally pooled plasma (Fig. 1b).…”

“…Whereas current conventional laboratory tests cannot detect ATR in the plasma, our novel laboratory test of ATR is useful even in warfarinized patients [6]. Further studies including more ATR patients would enable us to assess suitable anticoagulant therapy for ATR patients.…”

High prophylactic LMWH dose successfully suppressed hemostatic activation in pregnant woman with a new prothrombin c.1787G > A mutation

“…Molecular testing showed the F2 c.1787G N A mutation, located in the last exon of the prothrombin gene resulting in the Arg596Gln replacement (prothrombin Belgrade) [2]. Plasma tests in accordance with previously published methods [8] revealed that she had antithrombin resistance diathesis (Supporting Information File).…”

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

“…The Ox activator‐based manual ATR kinetic assay was conducted as reported previously . The assay comprised the following three steps: (i) prothrombin activation, (ii) thrombin inactivation and (iii) residual thrombin activity assessment.…”

“…Global coagulation tests (eg prothrombin time or activated partial thromboplastin time) cannot detect the antithrombin‐resistant prothrombin abnormality in heterozygote patients . Previously, we have established a manual operation assay specialised in detecting ATR . This manual operation assay has a prothrombin activator step by Oxyuranus scutellatus (Ox) venom; however, currently, it is difficult to obtain Ox venom because it is not marketed in some countries including Japan.…”