New data on FII, FV, FIX and thrombomodulin defects: blood keeps clotting in normal and in peculiar ways

ABSTRACT

Objective: To present the clinical and laboratory implications of defects or variants of some clotting factors and of thrombomodulin that were discovered during the past few years.

Methods: Data concerning new aspects of FII, FV, FIX and thrombomodulin defects were investigated. This involved the dysprothrombinemias, the East Texas or short FV disorder, a FIX defect and a thrombomodulin abnormality.

Results: the recently reported clotting defects or variants are: (1) the thrombophilic dysprothrombinemias due to Arg596 mutations (Prothrombin Yukuhashi, Belgrade and Padua 2) which are characterized by absence of bleeding and presence of venous thrombosis; (2) the short FV defects due to Ser356Gly (FV East Texas) or Ala863Gly (FV Amsterdam) mutations characterized by a mild bleeding tendency with normal FV and other clotting factors, increased TFPI and no thrombosis; (3) the abnormal FIX (FIX Padua) due to the Arg338Leu mutation which is associated with high levels of FIX activity, lack of bleeding and venous thrombosis; (4) the thrombomodulin Cys537Stop mutation associated with a mild bleeding tendency despite normal clotting factors but increased plasma levels of soluble thrombomodulin and no thrombosis.

Conclusions: these new coagulation defects have great implications in the clinical and laboratory approach to the coagulation disorders. They have demonstrated that a prothrombin defect may be associated with thrombosis, that a mild bleeding tendency may occur despite normal Factor V levels and that high levels of plasmatic thrombomodulin may be associated with mild bleeding.

KEYWORDS:

• Bleeding
• thrombosis
• clotting factors
• thrombomodulin
• natural inhibitors

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported in part by the ‘Associazione Emofilia ed altre coagulopatie delle Tre Venezie’.