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.

Clinical characteristics and type of thrombophilia in women with pregnancy-related venous thromboembolic disease.

BACKGROUND: Normal pregnancy is characterized by numerous changes in the hemostatic system, creating the hypercoagulable state which increases the risk of venous thromboembolic event (VTE) occurrence. The risk is further increased by the presence of inherited or acquired thrombophilia. OBJECTIVE: In this study, we aimed to determine the prevalence of different types of thrombophilia in women with pregnancy-related VTE, and to investigate the possible connection between the type of thrombophilia and localization of VTE as well as the gestational age of VTE occurrence. PARTICIPANTS AND METHODS: Two hundred and two women with the first episode of pregnancy-related VTE and 130 controls were investigated. The antithrombin, protein C and protein S activity, APC resistance, FVG1691A, and FIIG20210A were determined. None of the investigated women was pregnant at the time of thrombophilia testing, and none was using oral contraceptives. RESULTS: Thrombophilia was diagnosed in 95 patients (47%) and 7 controls (5.4%). The prevalence of FV Leiden, FIIG20210A mutations, antithrombin, PC and PS deficiencies taken together and combined thrombophilia was 22.3, 10.4, 6.9 and 6.9%, respectively. Significantly more frequent antepartum occurrence of VTE (11 vs. 3, p < 0.05) was found in women with natural coagulation inhibitor deficiency. Pulmonary embolism occurred more frequently in nonthrombophilic women (25 vs. 3, p < 0.001). CONCLUSION: Inherited thrombophilia was found to be considerably more frequently present in women with pregnancy- and puerperium-related VTE compared to healthy controls. Women with thrombophilia are at higher risk of developing thromboses localized in the iliacofemoral region, and women without thrombophilia are at higher risk of developing pulmonary embolism. Deficiency in natural coagulation inhibitors is associated with antepartum VTE occurrence.

Relation of functional characteristics and serum alpha-1-antitrypsin (AAT) concentration in patients with PiMM phenotype and chronic obstructive pulmonary disease (COPD).

INTRODUCTION: The relation of AAT phenotype and COPD still raises lots of controversy. In this study we aimed to investigate relation lung function characteristics, AAT serum level and COPD in smoking and non smoking population. PATIENTS AND METHODS: This was a prospective non-randomized study in which we evaluated 45 patients with severe (stage IV) COPD. In all patients we determined AAT phenotype, serum AAT levels and lung function tests. We correlated findings in relation to the smoking status. RESULTS: All patients were MM type homozygotes. Serum AAT concentrations were within the reference values, amounting to 1.66g/l in smokers and 1.80g/l in nonsmokers. There was no significant correlation between serum AAT concentrations and lung function parameters. We have observed the higher mean values of ITGV, RV, TLC and RV/TLC in smokers and a statistically significant difference only in ITGV. CONCLUSION: All of the investigated patients with severe COPD were MM type homozygotes with normal plasma level of AAT. There was no significant correlation between the phenotype and severity of COPD. We did not find significant relation of plasma AAT level and lung function impairment.

Inherited thrombophilia is associated with pregnancy losses that occur after 12th gestational week in Serbian population.

Recurrent fetal loss (RFL) is a significant clinical problem, occurring in 1% to 5% of reproductive females. Inherited or acquired thrombophilia has been diagnosed in 50% to 65% of women with history of unexplained fetal loss. The objective of our study was to determine the prevalence of thrombophilia in women with unexplained RFL in Serbian population and to find out whether the presence of thrombophilia is associated with pregnancy losses that occur later than 12th gestational week. We have examined 147 women with unexplained RFL or intrauterine fetal death and 128 healthy women with at least 1 uncomplicated pregnancy. The antithrombin (AT), protein C (PC), protein S (PS), activated protein C (APC) resistance, factor V (FV) G1691A, factor II (FII) G20210A, and MTHFR C677T were determined. At least 1 inherited thrombophilic defect was found in 54 (36.7%) of 147 women with repeated fetal losses and in 11 (8.59%) of 128 controls (P < .001, OR 6.17, 95% CI 3.06-12.48). The most common thrombophilic abnormalities were homozygosity for MTHFR 677TT, FV Leiden, and FII G20210A. Deficiency of natural anticoagulants occurred in 10 patients, with protein S deficiency being the most frequent one. Thrombophilia was found in 46 of 94 women with RFL that occurred later than the 12th gestational week and in only 8 of 53 with RPL earlier than 12th week (P = .001). Our study has shown the association between the hereditary thrombophilia and RFL that occurred after the 12th gestational week in Serbian population.

Efficacy and safety of nadroparin and unfractionated heparin for the treatment of venous thromboembolism during pregnancy and puerperium.

INTRODUCTION: The optimal treatment of pregnancy associated VTE (venous thromboembolism) has not been established yet. OBJECTIVE: The assessment of the efficacy and safety of low molecular weight heparin (LMWH) nadroparin and unfractionated heparin (UFH) used for the treatment of pregnancy and puerperium related VTE. Primary study goals were to analyze the incidence of recurrent VTE (proximal extension or pulmonary thromboembolism), thrombocytopenia, major and minor hemorrhages and skin allergic reactions. The study also included the incidence of miscarriages, stillbirth and neonatal abnormalities. We also studied the relationship between the presence of thrombophilia and the occurrence of complications during VTE treatment. METHODS: Seventy-two women with antepartal VTE treated with s.c. LMWH during entire pregnancy and 88 women with postpartal VTE initially treated with either s.c. LMWH or i.v.UFH were under follow-up during the entire treatment. Thrombophilia testing included antithrombin, protein C and protein S activity levels, Activated protein C (APC) resistance, LA, ACL, FV Leiden, FII G20210A and MTHFR C677T mutations. RESULTS: Twice a day weight based therapeutic regimen was applied for LMWH and activated partial thromboplastin time (aPTT) adjusted UFH dosages. After 2-6 weeks of antepartal deep vein thrombosis (DVT) treatment the dose of nadroparin was reduced to intermediate level. The duration of LMWH therapy during pregnancy was 1-35 weeks, on average 16 weeks. One case (0.62%) of DVT propagation into the vena cava occurred in a woman with antithrombin deficiency treated with LMWH. Two women (1.25%) had minor bleeding and 5 (3.125%) had minimal bleeding, while 3 (1.9%) had skin allergic reactions. The rate of successful pregnancy outcome was 97.2%. There were no cases of stillbirth or neonatal congenital abnormalities. Thrombophilia was found in 86 women (53.7%). No statistically significant correlation between the presence of thrombophilia and treatment complications were found. CONCLUSION: Nadroparin is both safe and effective for the treatment of DVT during pregnancy and puerperium.