Plasma Homocysteine and Hematological Factors in Patients with Venous Thromboembolic Diseases in Kuwait

Abstract

Background: Venous thromboembolic disease (VTE) is a common cause of morbidity in Kuwait, but the risk factors have not been studied. Hyperhomocysteinemia has been suggested as one of the risk factors. We postulate that hyperhomocysteinemia acts synergistically with hematological variables to increase VTE risk. This study evaluates the roles of hyperhomocysteinemia and hematological variables in patients with VTE. Methods: We measured fasting plasma total homocysteine (tHcy), activated protein C resistance, protein C (PC), protein S (PS) and antithrombin (AT) in 201 patients with VTE and 166 healthy controls. We also measured factor VIII, factor II, lupus anticoagulant, anticardiolipin, serum vitamin B₁₂, folate, creatinine, lipid profile, glucose, full blood count and red cell folate. The glomerular filtration rate (GFR) was calculated from creatinine. Results: When patients on warfarin were excluded, 13.1% of patients (18 out of 137) had a deficiency in PC, 16.8% (23 out of 137) had a deficiency in PS, and when patients on heparin were excluded, 8.3% of patients (14 out of 168) had low AT. Spearman’s rank correlation analysis showed that tHcy had significant correlations with age, creatinine and PS, and significant inverse correlations with GFR, high-density lipoprotein cholesterol and serum folate. Partial correlation analysis after correcting for age and sex showed that tHcy retained a significant correlation with creatinine, GFR and serum folate. Binary logistic regression analyses of the determinants of hyperhomocysteinemia included age, creatinine, GFR and serum folate. Multivariate logistic regression analysis showed significant association of tHcy with VTE (OR = 5.6; p < 0.0001) in the presence of known risk factors for VTE. Conclusion: We conclude that elevated tHcy is a significant risk factor for the development of VTE, and therefore, it should be included in the workup for patients at risk of VTE, but the determinants of tHcy should be kept in mind.

Hyperhomocysteinemia Prevalence Among Patients With Venous Thromboembolism

“…24 In this study, the prevalence of hyperhomocysteinemia is found to be higher than the prevalence that was presented in several previous reports that varied between 7.9% and 25% in patients with VTE. 25 –27 As well, the mean plasma total homocysteine level of the control group was slightly higher than some of the previous reports, which showed plasma homocysteine levels between 10 and 12 µmol/L in Turkish healthy individuals. 28,29 There may be several reasons for the higher plasma homocysteine levels in our patient and control study population.…”

“…Our results are in accordance with previous reports that observed an increased risk of VTE in hyperhomocysteinemia between 2.1-and 5.6-fold. 26,36 Another interesting result of the current study is the increased levels of plasma homocysteine among patients with PE compared with DVT (23 + 13.7 vs 16 + 5.8; P < .05). There is limited data comparing plasma homocysteine levels among patients with DVT and PE in the current literature.…”

Red cell or serum folate: what to do in clinical practice?

“…The two markers appeared to perform similarly, with a trend toward better performance of serum folate ( Table 1 ). Regression against homocysteine Marouf et al [ 60 ] Men with venous thromboembolism 91 Significant Not significant Marouf et al [ 60 ] Women with venous thromboembolism 110 Not significant Not significant Cheng et al [ 53 ] General population 130 Significant Not significant Dierkes et al [ 61 ] General population 336 Significant Significant Golbahar et al [ 56 ] Subjects with coronary artery disease and matched controls In our own analysis, we investigated the ability of serum and red cell folate to predict elevated plasma homocysteine levels ( ≥ 15 μ mol/L) in 320 randomly selected patient samples sent to our hospital laboratory. Among patients with a normal serum vitamin B 12 concentration and eGFR, serum folate demonstrated a significantly higher area under the receiver operating characteristic curve (AUC) for predicting increased plasma homocysteine concentration.…”

Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study

“…Though our MR data does not show a significant association between high level with VTE, the p -value is around the border of suggestive significance ( p = 0.078) and suggested a trend toward increasing VTE risk. Likewise, there is no indication of elevated homocysteine in increasing the VTE risk, which suggested that the association seen between homocysteine and VTE might be due to confounders ( 45 ).…”