Carbohydrate-deficient glycoprotein syndromes (CDGS) are genetic multisystemic metabolic disorders characterized by a defect of the carbohydrate moiety in a large number of glycoproteins. Several plasma coagulation factors and inhibitors abnormalities in association with transient neurological deficits and recurrent stroke-like episodes have been reported in these patients type 1 thus suggesting that a hypercoagulable state is prevalent in CDGS (Musso R. et al, Thrombos Haemost 76: 502-4, 1996). We here provide evidence that a chronic generation of thrombin and plasmin can also occur in CDGS. Two Sicilian adolescent patients, 1 female (12 yrs old) and 1 male (15 yrs old), belonging to unrelated families, with the clinical pictures of CDGS type 1 (squint, mental retardation, cerebellar ataxia, skeletal deformities) were reinvestigated. Recurrent paresthesia and hemiparesis have been registered during their clinical course. According to our overall haemostatic study we evaluated the prothrombin fragment (F1+2) and fibrinopeptide A (FPA) by ELISA technique (commercial kits from Behring Institute, Scoppito), plasma D-dimer (ELJSA Diagnostica Stago, Asnieres), thrombin-antithrombin complexes (TAT) and plasmin-antiplasmin (PAP) complexes(ELISA, Behring Institute) as markers of “in vivo” thrombin/plasmin generation and fibrinolysis, Activated PC resistance (APCR) by photometric method (Immuno, Pisa) using an ACL-3000 Plus (Instrumentation Laboratory, Milan) was also assayed as a novel test to detect risk for venous/arterial thrombosis. Our results showed for the first time a marked increase of prothrombin fragment F1+2 in the patients (5.5-4.9 nM/ml vs 1.37± 0.31 nM/ml in controls) and FPA (7.3-8.1 ng/ml vs ≤3 ng/ml). D-dimer plasma levels (781-625 ng/ml vs 225 ± 110 ng/ml) were elevated as well as TAT complexes (4.1-4.7 μg/L vs 2.1 ± 0.3 μg/L). No rise of PAP complexes (215-207 μg/ml vs 188 ± 105.7 μg/ml) was observed. Interestingly, in both of the patients APC response was decreased(1.81-2.03 vs 3.91 ± 0.36 in healthy controls). The present findings further demonstrate that the measurement of plasma markers of thrombin formation “in vivo” would confirm the prothrombotic tendency in this congenital metabolic disease.