Should Plasma Homocysteine Be Used as a Biomarker of Venous Thromboembolism? A Case—Control Study

Abstract

Mild or moderate hyperhomocysteinemia as a risk factor for venous thrombosis is still a matter of debate. The strength of this study is to bring a body of elements to evaluate whether hyperhomocysteinemia should be used as a biomarker for venous thromboembolism (VTE). These elements consist of a biological evaluation of several hematological risk factors, and an original control group made of patients with a negative Doppler ultrasonography. A total of 151 cases and 155 controls were included. Total plasma homocysteine level, MTHFR C677T polymorphism, inherited abnormalities of the natural anticoagulant system as well as plasma folate and cobalamin levels were determined. A total of 41 (27.2 %) of cases and only 9 (5.8%) of controls had at least one of the coagulation defects studied. No significant difference was observed for total homocysteine levels between the 2 groups: median (interquartile range) = 8.3 (7.2-10.8) micromol/L for cases and 8.4 (7-10.9) micromol/L for controls. We found significantly more plasma folates and/or cobalamin deficiencies in controls (18.3%) than in cases (8.6%). After adjustment for several variables significantly related to risk factors of VTE, hyperhomocysteinemia (>13.2 micromol/L) was not found statistically associated with VTE: odds ratio 1.36 (95% confidence interval, 0.52-3.54). The prevalence of the homozygous 677TT polymorphism in the MTHFR gene was not increased in cases compared with controls. Mild or moderate hyperhomocysteinemia does not seem to be a strong determinant in VTE not only when the control group does not exclusively include healthy persons but also in investigated disease-free (thromboembolic disease) controls.

Hyperhomocysteinemia Prevalence Among Patients With Venous Thromboembolism

“…17 2911 (32) .448 Immobility, n (%) 17 (29) 12 (35) .336 Oral contraceptive use, n (%) 1 (2) 3 (9) .137 Operation, n (%) 18 (31) 9 (27) .434 Smoking history, n (%) 14 (24) 11 (32) .253 Systemic hypertension, n (%) 21 (36) 11 (32) .444 Diabetes mellitus, n (%) 10 (17) 6 (18) .572 Cardiac comorbidity, n (%) 16 (27) 11 (32) . patients with PE if they had genetic analysis results and the results were acquired in only 45% of the patients with PE, which was homozygote mutation in 2 and heterozygote mutation in 8 patients; the remaining 21 patients showed normal results.…”

Three Different Presentation of Same Pathophysiology

“…Tore Amundsen et al, demonstrate that hyperhomocysteinemia is not a frequent cause of DVT (11). Ducros et al, showed that Mild or moderate hyperhomocysteinemia does not seem to be a strong determinant in VTE (12). …”

“…His computed tomography with angiography, revealed venous sinus thrombosis along superior sagital sinus and transverse sinuses with secondary hemorrhagic infarction more on the left side (Figure 1). His Hemoglobin is 15.2 gm/dl and MCV of 106fl and peripheral smear showed macrocytosis with hyper segmented neutrophil, His vitamin 12 level of 92 pmol/L normal (133-675) and homocysteine level of 44.6 umol/L normal (4-12),with treatment his homocysteine level drop to 12.…”

“…Computed tomography showed Portal vein, superior mesenteric, splenic vein thrombosis (Figure 2). His Hemoglobin is 11.2 gm/dl and MCV of 110fl and peripheral smear showed macroovalocytes red cell with hyper segmented neutrophil, His vitamin 12 less than 44 pmol/L normal (133-675) and homocysteine level of 54.4 umol/L normal (4-12), with treatment his homocysteine level drop to 10 and Cobalamin increase to 362.…”

“…Examination revealed that his chest and heart and abdomen were normal, his lower limb was erythematic and tender of both the calf and the thigh with difference of about 4 cm in comparison to the left side, ultra sound Doppler of the right lower limb showed acute thrombosis involve the femoral, popliteal and the posterior tibial veins, His hemoglobin and MCV were normal while his B12 level was low 98 pmol/L normal (133-675) and very high level of homocysteine of 94 umol/L normal (4-12) after treatment with cobalamin his homocysteine level drop to less than ten.…”