Pernicious anemia is a common cause of vitamin B12 deficiency, due to a lack of intrinsic factor, a protein produced by the stomach cells and necessary for absorption of vitamin B12 in the terminal ileum, the last segment of the small intestines. The hallmarks of pernicious anemia are macrocytic anemia (anemia with enlarged red blood cell size), neurological symptoms, and atrophic gastritis (wearing off of the inner lining of the stomach); however, venous and arterial thromboses (blood clots that form in the arteries and veins) have also been reported as presenting symptoms.
The link between B12 deficiency and thrombosis can be explained by the elevation of plasma homocysteine, which may result from nutritional deficiencies of vitamin B6, vitamin B12, or folic acid, or from genetic abnormalities that result in the synthesis of abnormal enzymes. As a result, homocysteine piles up in the blood and reaches abnormal levels.
Homocysteine is a non-protein α-amino acid; it is a homologue of the amino acid cysteine that can be recycled or converted into cysteine with the aid of B-vitamins. A high level of homocysteine makes a person more prone to injury of the inner linings of blood vessls (endothelial injury), which leads to vascular inflammation, which in turn may lead to atherogenesis (formation of atherosclerotic plaques), which can result in ischemic injury. Hyperhomocysteinemia, a higher than usual level of homocysteine, is therefore a possible risk factor for coronary artery disease (disease of the blood vessels that nourish the heart muscles). Coronary artery disease occurs when an atherosclerosis leads to occlusion (blockage) of the coronary arteries. Hyperhomocysteinemia has been correlated with the occurrence of blood clots, heart attacks and strokes, though it remain not well understood whether hyperhomocysteinemia is an independent risk factor for these conditions.