Systemic or Venous Thromboembolism Antithrombin Dublin ( p . Val 30 Glu ) : a relatively common variant with moderate thrombosis risk of causing transient antithrombin deficiency

Antithrombin is the primary haemostatic anticoagulant due both to the broad range of target procoagulant proteases and to its efficient mechanism of inhibition (1). Accordingly, complete deficiency caused embryonic lethality in mice (2), and resulted in spontaneous venous thrombosis in larvae of zebrafish (3). In humans, severe but also moderate antithrombin deficiency significantly increases the risk of thrombosis (4, 5). Actually, antithrombin deficiency was the first thrombophilic defect identified in 1965 by Olav Egeberg (6), and so far the strongest known thrombophilic factor (7). However, it is confusing why the incidence of congenital antithrombin deficiency is so low (below 1 %) in consecutive patients with venous thrombosis (8). Increasing evidence suggests that the incidence of antithrombin deficiency may be underestimated, particularly by the inability of current screening methods to detect pathological variants (9–13). Another mechanism that might increase the number of cases with thrombosis with underlying antithrombin defects might be the presence of a transient deficiency of this key anticoagulant. Actually, acquired antithrombin deficiency is also involved in thrombosis (14). We suggest that mutations affecting SERPINC1, the gene encoding antithrombin, might also cause transient antithrombin deficiency. Accordingly, we sequenced SERPINC1 in patients with a diagnosis of antithrombin deficiency even though a second analysis did not confirm the deficiency. Stroke, Systemic or Venous Thromboembolism