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Abstract Background Diabetes is well known risk factor for thrombotic events. The association between diabetes and venous thromboembolism is still matter of debate. However, during diabetes an acquired thrombophilia is present and is due to the non-enzymatic glycosilation of clotting inhibitors as antithrombin thus leading to hypercoagulable state. A possibile relationship between the presence of FVL gene variant in type 1 or type 2 diabetes has been hypothysed by several reports in the Literature with non-univocal findings. Patients and methods Retrospectively we analysed nearly 7000 patients referred to our Thrombosis Center for venous thromboembolism (VTE) then we selected 115 patients underwent to the screening for inherited thrombophilia. All selected patients were divided in 2 groups: the first group (group A) included 64 patients with previous VTE and carriers of factor V Leiden, while the second group (group B) included 51 patients with previous VTE and evetually carriers of thrombophilic defects other than factor V Leiden. Patients of group B acted as control group. 75 g oral glucose tolerance Test (OGTT) recommended by WHO was perfomed to all subjects in the study in order to screen subjects with glucose reduced tolerance or subjects with inducible diabetes. Statistical analysis was performed with STATA 6 http://www.stata.com with Student t test for unpaired data, with χ2 test or with Fisher exact test where appropriated; differences were considered to be significant if p < 0.05. Results We did not find sifferences between glycaemia at baseline and after OGTT between patients with VTE carriers of FVL compared to non-carriers of FVL. We found a relevant increase in the prevalence of IGT and diabetes between patients with VTE carriers of FVL compared to non-carriers of FVL although this increase did not raise statistical significance. Discussion our data pointed out an interesting aspect of the linking between FVL gene variant, diabetes and atherothrombosis and other vascular complications, although data on larger population are needed; this aspect may be another relevant topic of research based because also a link between the pathogenesis of venous thrombosis and atherothrombosis has been recently reported in the Literature.

Abstract Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance. Factor V Leiden (FVL) disorder may lead to thrombophilia. Whether a reduction in the activation of Factor V or Factor V Leiden may correct the disposition to thrombophilia is unknown. Therefore we tested SV-IV Peptide 1–16 (i.e. a peptide derived by seminal protein vescicle number IV, SV-IV) to assess its capacity to inhibit the procoagulant activity of normal clotting factor V or Factor V Leiden (FVL). We found that SV-IV protein has potent anti-inflammatory and immunomodulatory properties and also exerts procoagulant activity. In the present work we show that the SV-IV Peptide 1–16, incubated with plasma containing normal Factor V or FVL plasma for 5 minutes reduces the procoagulant capacity of both substances. This is an anticoagulant effect whereas SV-IV protein is a procoagulant. This activity is effective both in terms of the coagulation tests, where coagulation times are increased, and in terms of biochemical tests conducted with purified molecules, where Factor X activation is reduced. Peptide 1–16 was, in the pure molecule system, first incubated for 5 minutes with purified Factor V then it was added to the mix of phosphatidylserine, Ca2+, Factor X and its chromogenic molecule Chromozym X. We observed a more than 50% reduction in lysis of chromogenic molecule Chromozym X by Factor Xa, compared to the sample without Peptide 1–16. Such reduction in Chromozym X lysis, is explained with the reduced activation of Factor X by partial inactivation of Factor V by Peptide 1–16. Thus our study demonstrates that Peptide 1–16 reduces the coagulation capacity of Factor V and Factor V Leiden in vitro, and, in turn, causes factor X reduced activation.

Abstract Background Many available data have suggested that hyperhomocysteinaemia, an established independent risk factor for thrombosis (arterial and venous), may be associated with an increased risk of retinal vein occlusion (RVO). Aim of the study To evaluate homocysteine metabolism in consecutive caucasian patients affected by RVO from Northern Italy. Patients and Methods 69 consecutive patients from Northern Italy (mean age 64.1 ± 14.6 yy) with recent RVO, were tested for plasma levels of homocysteine (tHcy: fasting and after loading with methionine), cyanocobalamine and folic acid levels (CMIA-Abbot) and looking for MTHFR C677T mutation (Light Cycler-Roche) and compared to 50 volunteers, enrolled as a control group. Results Fasting levels of tHcy were significantly higher in patients than in controls: mean value 14.7 ± 7.7 vs 10.2 ± 8 nmol/ml. Post load levels were also significantly higher: mean value 42.7 ± 23.7 vs 30.4 ± 13.3 nmol/ml; Total homocysteine increase was also evaluated (i.e. Δ-tHcy) after methionine load and was also significantly higher in patients compared to control subjects: mean Δ-tHcy 27.8 ± 21.5 vs 21.0 ± 16 nmol/ml (normal value < 25 nmol/ml). Furthermore, patients affected by RVO show low folic acid and/or vitamin B12 levels, although differences with control group did not reach statistical significance. Heterozygous and homozygous MTHFR mutation were respectively in study group 46% and 29% vs control group 56% and 4%. Conclusion our data confirm that hyperhomocysteinaemia is a risk factor for RVO, and also that TT genotype of MTHFR C677T is more frequently associated with RVO: if the mutation per se is a risk factor for RVO remains an open question to be confirmed because another study from US did not reveal this aspect. Hyperomocysteinemia is modifiable risk factor for thrombotic diseases. Therefore, a screening for tHcy plasma levels in patients with recent retinal vein occlusion could allow to identify patients who might benefit from supplementation with vitamins and normalization of homocysteine levels, in fasting and after methionine load.