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Haemostatic system compounds not routinely studied, have been evaluated to define the individual risk of VTE (venous thromboembolism) and to influence the prognosis using selective drugs. Significantly high values of fibrinogen, free-TFPI, F1 + 2 fragments and TAT complexes on coagulation side and PAI-1 and TAFI on fibrinolysis side have been detected. Thrombin seems to have a role in the inhibition of TAFI dependent fibrinolysis not inhibited by heparin.

Recent findings have indicated the association between APC-resistance and cerebrovascular disease. These reports prompted us to investigate whether resistance to APC could be found in patients suffering from stroke.Therefore, we studied APC-resistance in 50 young adults (or =45 yrs) with a history of ischemic stroke. Eleven out of fifty cerebrovascular subjects showed APC-resistance, while 2 had PC deficiency and 3 PS deficiency. No deficiencies in the anticoagulant protein AT III and in fibrinolytic proteins were found. The family history demonstrated a distribution of APC-resistance compatible with dominant autosomal inheritance. The plasma concentration of prothrombin fragment 1+2 (F1+2), which is a marker of hypercoagulable states, was also measured in patients and family members of resistant subjects (n = 38).DNA analysis showed factor V R506Q mutation (Leiden mutation) in 11 patients and their relatives with poor response to activated protein C detected by APTT tests. Of 11 investigated subjects with APC-resistance, 9 were heterozygotes and 2, with the lowest APC-ratio values, were homozygotes for factor V mutation. Among 38 relatives, 22 showed a poor response to APC and according to the APC-ratio values, 18 were heterozygotes and 4 homozygotes for FV Leiden mutation. The mutation, in heterozygous form, was also found in 2% of our normal population (n = 100). The plasma concentration of F1+2 was significantly higher both in 11 individuals carrying the FV:Q506 mutation and in 39 patients without APC-resistance compared to that found in the control group. However, the patients with FV:Q506 mutation showed the highest values in F1+2. In the studied family members F1+2 plasma levels were within normal values.Our findings indicate a possible involvement of APC-resistance in the pathogenesis of cerebral thrombosis in young adults and agree with the hypothesis that individuals with APC-resistance have an imbalance between pro-and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.

Recent findings have indicated the association between activated protein C (APC)-resistance and cerebrovascular disease. These reports prompted us to investigate whether resistance to APC could be found in patients suffering from transient ischaemic attacks or stroke. Therefore, we studied APC-resistance in 14 young adults belonging to three different families with a history of transient ischemic attacks (TIAs) and stroke. Nine out of fourteen subjects showed APC-resistance but no deficiencies in the anticoagulant proteins AT III, PC and PS. The family history demonstrated a distribution of APC-resistance compatible with dominant autosomal inheritance. A rapid screening method to detect factor V R506Q (Leiden) mutation without sequencing or restriction enzyme digestion has been set-up after biochemical analyses. DNA analysis showed a guanine to adenine transition at nucleotide 1,691 in patients and their relatives with poor response to activated protein C detected by APTT tests. Of 14 investigated subjects and their family members, 5 were normals, 6 were heterozygotes and 3 were homozygotes for factor V mutation. The mutation, in heterozygous form, was also found in 1.3% of our normal population (n = 75). Our findings indicate a possible involvement of APC-resistance in the pathogenesis of arterial thrombosis in young adults.

The aim of this study was to investigate the role of natural cascade inhibitors in Juvenile Transient Ischemic Attacks. Fifty patients with anterior or posterior brain attacks were studied. One hundred healthy subjects matched for sex and age were randomly assigned to a control group. All had a physical examination and radiologic work-up. Computerized tomography showed no ischaemia either with or without contrast medium. Digital angiography of epiaortic and intracerebral vessels was unremarkable patients non controls ever had war-farin therapy. Antithrombin III, protein C and plasminogen were determined by functional methods. Protein S was assayed by a functional clotting method based on prolonged PT. The activated protein C resistance test was performed and a poor response to activated protein C was verified in patients. Our findings show protein S, protein C and antithrombin III type I deficiency with a functional activity70% compared to controls. Eight of fifty patients (16%) had low protein S levels, 5 (10%) had low protein C, 2 (4%) had low antithrombin III and 1 (2%) plasminogen deficiency. A significant (p0.01) difference in activated protein C ratio was seen for controls and patients. These results suggest that screening for natural anticoagulants in young people suffering from transient ischemic attacks could be beneficial and should be encouraged.