Homocysteine Activates Platelets In Vitro

Abstract

is very common, and these has been reported to be a risk factor for arterial and venous thromboses. The study of Leiden thrombophilia established hyperhomocysteinemia (above the 90th percentile) as a risk factor for deep-vein thrombosis. 4 A further metaanalysis showed that a 5 μmol/L elevation in HCY was associated with a 27% higher risk of venous thrombosis in prospective studies and 60% higher risk of venous thrombosis in retrospective studies. Genotype studies of the methylenetetrahydrofolate reductase enzyme showed an association of venous thrombosis with hyperhomocysteinemia. 5In 1964, McDonald et al 6 concluded that HCY, both in vivo and in vitro, increased platelet stickiness associated with arterial and venous thrombosis, but this finding was not confirmed. [7][8][9] In studies of platelet kinetics, a direct relationship was found between HCY concentration and platelet survival. 10Harker et al 7 found that increased platelet consumption in homocysteinemia was interrupted by dipyridamole, but not by heparin anticoagulation, and concluded that platelet thrombus formation on arterial surfaces denuded of endothelium, and not enhanced platelet reactivity, increased platelet consumption.H omocysteine (HCY), a sulfur containing amino acid, is a normal by-product of methionine metabolism. Normal levels of plasma HCY in fasting are considered to be between 5 and 15 μmol/L. Moderate, intermediate, and severe hyperhomocysteinemia refer to concentrations between 16 and 30, between 31 and 100, and >100 μmol/L, respectively.1 Homocystinuria is consistent with severe hyperhomocysteinemia. Homozygous cystathione β synthetase deficiency, causing homocystinuria, is associated with a thromboembolic event in 30% of patients by the age of 20 years, 50% of patients by the age of 30 years, and 60% of patients by the age of 40 years.2,3 Mild and moderately elevated HCY levels (hyperhomocysteinemia)The mechanism of thrombogenicity in hyperhomocysteinemia remains controversial. The authors investigated the association between elevated plasma homocysteine levels, platelet function, and blood coagulation. Blood was collected from healthy subjects and patients with critical limb ischemia. Basal platelet counts and platelet aggregation as well as flow cytometry were performed to assess spontaneous-and agonist-induced platelet aggregation as well as P-selectin and Glycoprotein IIb/IIIa expression at different homocysteine concentrations. Thromboelastography was performed, and platelet shape change was assessed, using a channelyzer, by measuring median platelet volume. Lactate dehydrogenase was measured, to indirectly assess red blood cell membrane integrity, after homocysteine exposure. The study results suggest that platelet activation and hypercoagulability occur after exposure to homocysteine, especially in patients with critical limb ischemia. Homocysteine concentrations of approximately 50 μmol/L appear to be the level at which these changes occur in vitro, and this effect on platelets appears to be indirect.

Complete deficiency of methylenetetrahydrofolate reductase in mice is associated with impaired retinal function and variable mortality, hematological profiles, and reproductive outcomes

“…Hyperhomocysteinemia has been associated with decreased platelet counts in individuals with the MTHFR 677TT genotype (Rongioletti et al 2005). Also, in a study of the activation of platelets by homocysteine in vitro, platelet counts and homocysteine concentration were inversely proportional, an observation attributed to the clumping of activated platelets, rendering them unavailable for counting (Mohan et al 2008).…”

The Relationship of Vitamin B12 Deficiency and Red Cell Distribution Width-Platelet Ratio

“…Therefore, we may propose that homocysteine; RPR and MPV are involved in the course of the inflammation. Similarly, it was indicated that the homocysteine promoted platelet activation [17,18] division of hematopoietic cells consist seen in vitamin B12 deficiency leads to defects in DNA synthesis. RDW indicates heterogeneity and equivalent of anisocytosis of red blood cell.…”

“…It is well known that the level of homocysteine in serum increased in patients with vitamin B12 deficiency. The increasing homocysteine pathway leads to inflammation in patients with vitamin B12 deficiency [17].…”

A curve model for association of serum homocysteine with carotid artery hemodynamics

“…An inverse relationship has been demonstrated between IMT and mean cerebral blood flow velocity (mCBFV), with decreased CBFV corresponding to elevated IMT [21]. In addition, Mohan et al [22] suggested that exposure to Hcy could induce platelet activation and hypercoagulability. Since platelet activating factor can reduce reducing coronary blood flow [23], these results indicate that Hcy may affect hemodynamics.…”

“…The results obtained in this study showed that at Hcy levels below 15 μmol/L, increased Hcy was related to decreased hemodynamics, while Hcy levels higher than 15 μmol/L were positively correlated with hemodynamics. This is due to the fact that Hcy is responsible for the hypercoagulability status of blood [22], and so it can reduce blood flow velocity. Hemodynamics is positively associated with carotid stenosis and carotid stenosis could result from HHcy [25].…”