Plasma homocysteine in patients with retinal vein occlusion.

PURPOSE: To evaluate total plasma homocysteine (HCY) during fasting and post methionine load test (MLT), serum folate, serum vitamin B12, and methylenetetrahydrofolate reductase (MTHFR) mutation in patients with retinal vein occlusion (RVO) and to examine the association between these risk factors and 2 subtypes of RVO: central (CRVO) and branch (BRVO). METHODS: This case-control study included 91 Italian patients presenting a first RVO and 71 healthy subjects, matched by age, without history of thromboembolic diseases, glaucoma, or malignancy. Homocysteine fasting and after MLT, serum folate level, serum vitamin B12 level, and other laboratory tests were assessed. Genetic analysis for the C677T MTHFR mutation was performed. RESULTS: Multivariate logistic regression analysis indicated that hypertension (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.30-5.30; p = 0.007), higher values of fasting HCY (OR 1.16; 95% CI 1.01-1.33; p = 0.03), and low concentrations of vitamin B12 (OR 0.99; 95% CI 0.995-0.999; p = 0.01) were independently correlated with RVO. Moreover, the main determinants for CRVO risk were hypertension (OR 2.46; 95% CI 1.06-5.72; p = 0.04), high values of fasting HCY (OR 1.20; 95% CI 1.02-1.41; p = 0.03), and low concentrations of vitamin B12 (OR 0.99; 95% CI 0.994-0.999; p = 0.008), whereas for BRVO risk only hypertension was significant (OR 2.74; 95% CI 1.24-6.03; p = 0.01). Genotype distribution of the MTHFR C677T mutation did not reveal any significant difference between patients and controls. CONCLUSIONS: These results suggest that elevated fasting HCY levels, low vitamin B12 levels, and hypertension are associated with a risk of RVO, especially for CRVO. Moreover, our data suggest that only hypertension is associated with BRVO risk.

Prevention of venous thromboembolism in patients with cancer: guidelines of the Italian Society for Haemostasis and Thrombosis (SISET)(1).

BACKGROUND: Prevention of venous thromboembolism (VTE) in cancer patients remains controversial in most clinical settings. PURPOSE: The Italian Society for Haemostasis and Thrombosis (SISET) commissioned a project to develop clinical practice guidelines for the prevention of VTE in patients with malignancy. METHODS: Key questions concerning the prevention of VTE in patients with malignancy were formulated by a multidisciplinary working group consisting of experts in clinical medicine and research. After a systematic review and discussion of the literature, recommendations were formulated and graded according to the supporting evidence. For those questions for which the literature search did not find any definitive answers (due to absence of evidence, low quality evidence and/or contradictory evidence), a formal consensus method was used instead to issue clinical recommendations. RESULTS: The search for "VTE prevention" resulted in 1021 citations; 69 articles were selected and 24 were used for drafting clinical recommendations. Four areas were graded A to C: 1) Need of prevention (pharmacological and/or mechanical) in cancer patients undergoing major abdominal or pelvic surgery and in 2) those with an acute medical disease requiring hospitalization and who are bedridden. Avoid prevention in 3) cancer patients with a central venous catheter and 4) those on chemotherapy, radiotherapy or hormonal therapy, except patients with multiple myeloma treated with thalidomide/lenalidomide plus high-dose dexamethasone, and those with gastrointestinal or lung cancer. Six areas were considered to be clinically important, but lacked evidence from the literature and thus required a formal consensus (grade D): 1) need of prevention during chemo- radiotherapy or hormonal therapy in patients with previous VTE; 2) optimal duration of pharmacological prevention in patients who are hospitalized/bedridden for acute medical illness; 3) optimal duration of pharmacological prevention in patients undergoing major surgery other than abdominal and pelvic; 4) optimal duration of pharmacological prevention in myeloma patients receiving thalidomide plus dexamethasone; 5) presence of cerebral metastasis as a contraindication to pharmacological prevention; 6) prevention in cancer patients undergoing surgery by laparoscopic procedures lasting>30min. CONCLUSION: Results of the systematic literature review and an explicit approach to consensus techniques have led to recommendations for the most clinically important issues in the prevention of VTE in cancer patients.

In retinal vein occlusion platelet response to thrombin is increased.

INTRODUCTION: Retinal vein occlusion is a major cause of ocular morbidity. The precise mechanism leading to thrombosis in retinal vein occlusion has not yet been clearly elucidated. Several risk factors have been identified, including hypertension diabetes, history of cardiovascular disease, hypercholesterolemia, hyperhomocysteinaemia, increased ocular pressure and glaucoma. Although thrombus formation in the vein plays a significant role in the onset of retinal vein occlusion, the relationship between platelet aggregation and retinal vein occlusion remains to be clarified. MATERIALS AND METHODS: In the present study the platelet response to thrombin in a selected group of retinal vein occlusion patients was investigated. Retinal vein occlusion patients were compared to a group of healthy subjects matched for age, sex, clinical and metabolic characteristics. In resting and activated platelets of both groups of subjects total protein tyrosine phosphorylation, p38MAPK and cytosolic phospholipase A(2) phosphorylation, arachidonic acid release, intracellular calcium levels, thromboxane B(2) and superoxide anion formation were measured. RESULTS: Results show that platelets of patients were more responsive to thrombin than healthy subjects. In resting or in thrombin stimulated platelets of patients total protein tyrosine phosphorylation, p38MAPK and cytosolic phospholipase A(2) phosphorylation were increased. Also arachidonic acid release, thromboxane B(2) and superoxide anion formation were higher in patients than in healthy subjects. In addition intracellular calcium rise induced by thrombin was increased in patients. CONCLUSIONS: Altogether data suggest that platelet hyperaggregability inducing thrombus formation might be an important factor in the onset and/or development of retinal vein occlusion.

Platelet activation by collagen is increased in retinal vein occlusion.

Retinal vein occlusion (RVO) is the most common retinal vascular disorder second to diabetic retinopathy. The main risk factors in patients with RVO are hypertension, diabetes, hyperlipidemia, increased blood viscosity and glaucoma. The pathogenesis of RVO has not yet been clarified. In these events platelets could play a very important role. In the present study the platelet response to collagen was deeply investigated. Experiments were carried out on a selected group of RVO patients, which were compared to a group of healthy subjects matched for age, sex, clinical and metabolic characteristics. In resting and activated platelets of both groups of subjects p72syk phosphorylation, phospholipase Cgamma2 phosphorylation, protein kinase C activation, intra-cellular calcium levels and nitric oxide formation were measured. Results show that platelets of patients were more responsive to collagen or ADP than healthy subjects and that the response was significantly different (p < 0.0005) at low concentrations of these agonists. In platelets of patients stimulated with collagen increased phosphorylation of p72syk and phospholipase Cgamma2 was found. Also protein kinase C was more activated in patients. In addition intracellular calcium rise induced by collagen was significantly higher in patients than in healthy subjects. RVO patients showed a lower basal level of nitric oxide both in resting and stimulated platelets compared to healthy subjects. Altogether these results suggest that the platelet hyperaggregability described in patients might be an important factor in the development of RVO contributing to the thrombogenic effects.

2-Phenyl-3-(quinolizidin-1-yl)-5-substituted indoles as platelet antiaggregating agents.

A set of ten 2-phenyl-3-(quinolizidin-1-yl)-5-substituted indoles was prepared through the Fischer cyclization of lupinyl- and epi-lupinylphenylketone 4-substituted phenylhydrazones. Compounds were tested for antiaggregating activity on human platelets activated by adenosine diphosphate (ADP), collagen and adrenaline. At 2.5 x 10(-4) M concentration most compounds strongly inhibited the aggregation induced by all the agonists considered and many of them still displayed good activity at 0.625 x 10(-4) M concentration. The least active (1c) and one of the most active (1d) compounds were also tested for antiaggregating activity on rabbit platelets activated by ADP, PAF and sodium arachidonate. Both the compounds were active against ADP and PAF, but only 1d inhibited the arachidonate-induced aggregation (100% at 8 x 10(-6) M concentration) and increased the bleeding time in mice. The same compounds were subjected to a general pharmacological screening and found to display several activities; of particular interest was the dose dependent reduction of serum cholesterol and heparin precipitating betalipoproteins in hypercholesterolemic mice exerted by 1c, which was still significant at the oral dose of 10 mg/kg.