Overview Vitamin B12 (cobalamin) deficiency is a common cause of megaloblastic anemia, a variety of neuropsychiatric symptoms, and elevated serum homocysteine levels, especially in older persons. The recognition and treatment of vitamin B12 deficiency is critical since it is a reversible cause of bone marrow failure and demyelinating nervous system disease
| Definitions Anaemia (Anemia): The World Health Organization defines anaemia as a haemoglobin (Hb) concentration below 13 g/dl (130 g/L) in men over 15 years of age, below 12 g/dl (120g/L) in non-pregnant women over 15 years of age, and below 11 g/dl (110g/L) in pregnant women Iron deficiency anaemia: Most common type of anemia, and it occurs when your body doesn't have enough of the mineral iron Microcytic anemia Defined as the presence of small, often hypochromic, red blood cells in a peripheral blood smear and is usually characterized by a low mean cell volume (MCV) (<83 micron3). Iron deficiency is the most common cause of microcytic anemia. Normocytic anaemia: defined by a normal mean corpuscular volume (MCV), but the hemoglobin and hematocrit are decreased. Usually a result of hemolytic anaemia or anaemia of chronic disease Mactocytic anaemia (Macrocytosis): defined as a mean corpuscular volume greater than 100 fL, is frequently encountered when a complete blood count is performed. The most common etiologies are alcoholism, vitamin B12 and folate deficiencies, and medications. |
Vitamin B12 is found in meat, fish, and dairy products. NOT in plants. The liver can store Vitamin B12 and stores are sufficient for up to 5 years. The daily requirement of vitamin B12 is about 2.4 μg.
| Side note Vitamin B12 is found almost exclusively in animal-based foods and is therefore a nutrient of potential concern for those following a vegetarian or vegan diet. Vegans, and anyone who significantly limits intake of animal-based foods, require vitamin B12-fortified foods or supplements. |
| Remember Vitamin B12 (cobalamin) is a water-soluble vitamin that is crucial to normal neurologic function, red blood cell production, and DNA synthesis. |
Decreased ileal absorption
Decreased intrinsic factor
Genetic
Inadequate intake
| Alcohol abuse |
Prolonged medication use
Clinical manifestations of megaloblastic anemia include pallor, tachycardia, weakness, fatigue, and palpitations. The specific mechanism by which vitamin B12deficiency affects the neurologic system is unknown
| Remember There are extensive hepatic stores of vitamin B12. There may be a five- to 10-year delay between the onset of deficiency and the appearance of clinical symptoms |
| Remember Peripheral neuropathy is the most common symptom of vitamin B12 deficiency. Folate deficiency alone typically has no neurological symptoms. |
| DIFFERENTIAL DIAGNOSIS OF MACROCYTIC ANAEMIA (MACROCYTOSIS) | ||
| Macrocytic Anaemia | Clinical Features | Investigations |
| Vitamin B12 deficiency | paresthesias related to peripheral neuropathy, poor or strict vegan diet, lack of socioeconomic resources, bowel-related symptoms (including diarrhea), or a history of bowel surgery for weight loss. Findings on physical examination may include neurologic signs such as ataxia, decreased proprioception, and vibratory sensation. Patients may also have poor dentition or nonspecific oral stomatitis or glossitis. | Serum Vitamin B12. |
| Alcohol excess | Physical findings consistent with alcoholism include gynecomastia, caput medusae, and jaundice. | The mean corpuscular volume is generally less than 110 fL with chronic alcohol use. Abstinence from alcohol rapidly corrects the elevated mean corpuscular volume |
| Reticulocytosis | Family History of haemotological syndromes (sickle cell disease, hereditary spherocytosis, G6P dehydrogenase deficiency). Examination may reveal hepatosplenomegaly in hemolysis or other physical manifestations of blood loss (e.g., conjunctiva, mucosal pallor | Peripheral smear will reveal evidence of hemolyzed RBCs (e.g., bite cells, helmet cells) |
| Myeloproliferative disorders | Splenomegaly, hepatomegaly, fatigue | Bone marrow biopsy is required to establish this diagnosis |
| Hypothyroidism | Mental sluggishness, obese, fatigue, sleepy | Thyroid function test |
| Folate deficiency | Serum folate levels are not useful. RBC folate levels is more accurate. | |
| Side note In differentiating the cause of megaloblastic anemia, a methylmalonic acid level that is within normal range also points toward a diagnosis of folate deficiency, especially if the serum vitamin B12 level is within the normal range. Note that homocysteine levels will be elevated with vitamin B12and folate deficiencies. |
Both the clinical recognition of vitamin B12 deficiency and confirmation of the diagnosis by means of testing can be difficult.
| Remember Classic hematologic expression of vitamin B12 deficiency is a megaloblastic macrocytic anemia characterized by an elevated mean corpuscular volume and mean corpuscular hemoglobin, and a peripheral smear containing macroovalocytes and hypersegmented neutrophils |
| Think Serum vitamin B12 levels can be normal even in vitamin B12 deficiency. This is because during periods of stress, the body will produce more transcobalamin (carrier protein for VB12). Measuring methylmalonic acid is thus more sensitive. |
| Side note Exclusively breastfed children of mothers with vitamin B12 deficiency are at increased risk of failure to thrive, hypotonia, ataxia, developmental delays, anemia, and general weakness |
Complications
Prognosis Vitamin B12 deficiency can cause devastating neurological disease and severe haematological disorders. Early diagnosis and prompt treatment may reverse neurological disease. Unfortunately, many cases are irreversible and clinical disease may not respond to adequate therapy
Overview Pernicious Anaemia is a condition where there is lack of intrisinc factor, a glycoprotein responsible for the absorption of Vitamin B12. Vitamin B12 (Cobalamin) is an essential vitamin responsible for many physiological process in our body. Vitamin B12 deficiency causes megaloblastic anaemia and maybe accompanied by neurological abnormalities.
Clinical Presentation
Differential Diagnosis
Investigations
Aetiology Pernicious Anaemia is associated with the following:
Pathophysiology
Symptomatic Treatment For patients with pernicious anaemia or malabsorption, lifelong vitamin B12 therapy is indicated.
Asymptomatic (poor diet, vegan) Treatment
Complications
Prognosis
Early diagnosis and treatment is important to prevent severe neurological and haematological deficits. Patients usually do well with treatment.
