Clinical significance of determining plasma homocysteine: case-control study on arterial and venous thrombotic patients.

AIM: To determine the differences in plasma homocysteine levels between three MTHFR 677 genotype subgroups in patients with thrombosis and in controls, as well as between patients with thrombosis and controls with the same MTHFR 677 genotype. METHODS: This case-control study was conducted in Clinical Center of Vojvodina, Novi Sad, from June to December 2011. We included 65 patients with either arterial or venous thrombosis (mean age, 40.97 ± 11.38 years) and 65 controls with no history or clinical evidence of any thrombotic event (mean age, 41.23 ± 11.12 years). Patients and controls were age- and sex-matched. RESULTS: In comparison with controls, thrombotic patients had significantly higher homocysteine levels (12.81 ± 4.94 µmol/L vs 9.82 ± 3.68 µmol/L; P<0.001) and significantly higher incidence of hyperhomocysteinemia (55% vs 22%; P<0.001; odds ratio [OR]=4.521). There were no significant differences in homocysteine levels between homozygous carriers, heterozygous carriers, and non-carriers of the MTHFR 677 mutation in either thrombotic patients (12.97 ± 5.40 µmol/L vs 12.55 ± 5.71 µmol/L vs 13.27 ± 1.71 µmol/L; P=0.100) or controls (10.07±2.50 µmol/L vs 10.25 ± 4.84 µmol/L vs 9.20 ± 2.44 µmol/L; P=0.651). However, in comparison with controls, homozygous carriers in thrombotic patient group did not have significantly higher levels of homocysteine (12.97 ± 5.40 µmol/L vs 10.07 ± 2.50 µmol/L; P=0.072), but heterozygous carriers (12.55 ± 5.71 µmol/L vs 10.25 ± 4.84 µmol/L; P=0.020) and non-carriers (13.27 ± 1.71 µmol/L vs 9.20 ± 2.44 µmol/L; P<0.001) did. There was no significant difference in homocysteine levels between patients with arterial and venous thrombosis (12.76 ± 3.60 µmol/L vs 12.86 ± 5.51 µmol/L; P=0.990) and between patients with one thrombotic event and those with recurrent thrombotic events (12.14 ± 3.20 µmol/L vs 15.25 ± 8.51 µmol/L; P=0.254). CONCLUSION: Plasma homocysteine levels have a greater clinical significance in the prevention of thrombosis and managing its complications than MTHFR 677 genotyping.

Changes of serum VEGF concentration after intravitreal injection of Avastin in treatment of diabetic retinopathy.

PURPOSE: Avastin (bevacizumab) intravitreal injections are widely used for treatment of diabetic retinopathy. The aim of our study was to analyze effect of 1.25 mg of intravitreal Avastin on serum concentration of vascular endothelial growth factor (VEGF) in diabetic patients. METHODS: Participants were 10 diabetic patients on insulin therapy, without any other eye or systemic disease, and no kidney disfunction. Both eyes of diabetic patients were injected simultaneously with 1.25 mg of intravitreal Avastin, as a first step in treatment of nonproliferative diabetic retinopathy with clinically significant macular edema (4 patients), and of proliferative diabetic retinopathy (6 patients). Fluorescein angiography was performed prior to and laser therapy followed 1 month after Avastin treatment. VEGF concentration in patients serum was measured by ELISA technique: on the day of the Avastin administration, and 1, 7, and 28 days after intravitreal injection. RESULTS: In all analyzed participants, 24 hours after Avastin treatment, serum levels of VEGF were lower then basal (preinjection value). Maximal reduction of serum VEGF was noted on the 7th postoperative day. Twenty-eight days after, VEGF level in serum was raised, without completely reaching basal preoperative concentrations in most patients. CONCLUSIONS: Intravitreal injections of anti-VEGF drugs have an effect on decreasing systemic VEGF values. Rhythm of changes in serum VEGF concentrations and lowest detected concentration on the seventh postinjection day are according to pharmacokinetics of Avastin in serum and vitreous, reported by similar studies. The small number of patients involved in this pilot study implicates the need for further studies.

Fibrinolytic parameters, lipid status and lipoprotein(a) in ischemic stroke patients.

INTRODUCTION: Ischemic stroke is the third leading cause of mortality and morbidity in most countries in the world. Impaired fibrinolysis, as well as disordered lipid metabolism have been recognized as risk factors for this disease. OBJECTIVE: To study some of fibrinolytic parameters, lipid status and lipoprotein(a) - Lp(a) in ischemic stroke patients in Serbia and to examine associations between Lp(a) and fibrinolytic parameters. METHODS: Sixty ischemic stroke patients (case group, mean age 63.48 +/- 9.62 years) and 30 age and sex matched healthy controls (control group, mean age 60.2 +/- 7.96 years) were studied. RESULTS: A significantly longer euglobulin clot lysis time (219.7 +/- 78,8 min. vs 183.5 +/- 58,22 min; p = 0.005) and higher levels of plasminogen activator inhibitor-1 (PAI-1) (48.5 +/- 17.1 ng/ml vs 27.1 +/- 10.1 ng/ml; p = 6.2 x 10(-11)), tissue-type plasminogen activator antigen (t-PA) (11.1 +/- 7.14 ng/ml vs 6.0 +/- 3.66 ng/ml; p = 5.2 x 10(-5)) and D-dimer (382.27 +/- 504.22 ng/ml vs 116.12 +/- 88.81 ng/ml; p = 0.0002) were found in cases compared to controls. There were no significant differences in fibrinogen levels (4.30 +/- 0.84 g/l vs 4.09 +/- 0.64 g/l; p = 0.23) or plasminogen activity (92.67 +/- 11.37% vs 96.87 +/- 9.48%; p = 0.085). There was no significant difference in Lp(a) concentration between cases and controls (0.15 +/- 0.11 g/l vs 0.12 +/- 0.11 g/l; p = 0.261). However, in the cases, but not in the controls, multivariate analysis of associations between fibrinolytic parameters and Lp(a) showed the highest correlation between t-PA and PAI-1, and the latent effect of Lp(a) on t-PA and PAI-1. CONCLUSIONS: Our results show that there are important differences in the characteristics of the fibrinolytic mechanism in ischemic stroke patients compared to healthy population. The major differences are prolonged euglobulin clot lysis time and elevated PAI-1 and t-PA antigen in ischemic stroke patients. In addition, Lp(a) appears to be involved in the inhibition offibrinolysis in ischemic disease through a mechanism unrelated to its serum concentrations.