An in-depth focused study of specific cases of patients with recurrent
thrombosis may help to identify novel circumstances, genetic and acquired factors contributing to the development of this disorder. The aim of this study was to carry out a detailed and sequential analysis of samples from a patient suffering from early and recurrent venous and arterial
thrombosis. We performed thrombophilic tests, biochemical, functional, genetic and glycomic analysis of
antithrombin and other
plasma proteins. The patient carried a new type I
antithrombin mutation (p.Ile218del), whose structural relevance was verified in a recombinant model. Experiments with
N-glycosidase F and
neuraminidase suggested a nearly full desialylation of
plasma proteins, which was confirmed by mass spectrometry analysis of
transferrin glycoforms. However, partial desialylation and normal patterns were detected in samples collected at other time-points. Desialylation was noticeable after arterial events and was associated with low
antithrombin activity, reduced platelet count and glomerular filtration rate. This is the first description of a global and transient desialylation of
plasma proteins associated with
thrombosis. The decrease in the strong electronegative charge of terminal
glycans may modulate
hemostatic protein-
protein interactions, which in combination with a strong prothrombotic situation, such as
antithrombin deficiency, could increase the risk of
thrombosis.