Hydroxocobalamin is bound to plasma protein to a greater extent than is cyanocobalamin, with the result that there is less free to be excreted in the urine after an injection and rather lower doses at longer intervals are adequate. Thus hydroxocobalamin is preferred to cyanocobalamin, though the latter can give satisfactory results as the doses administered are much greater than are required physiologically. Cyanocobalamin remains available.
The initial dose in cobalamin deficiency anaemias, including uncomplicated pernicious anaemia, is hydroxocobalamin 1 mg i.m. every 2-3 days for 5 doses to induce remission and to replenish stores. Maintenance may be 1 mg every 3 months; higher doses will not find binding sites and will be eliminated in the urine. Higher doses are justified during renal or peritoneal dialysis where hydroxy-cobalamin clearance is increased, and resultant raised plasma methylmalonic acid and homocysteine represent an independent risk factor for vascular events in these patients (see later).
Routine low dose supplements of hydroxyco-balamin, folate and pyridoxine fail to control hyperhomocysteinaemia in 75% of dialysis patients but supraphysiological doses are effective: hyd-roxycobalamin 1 mg/d, folic acid 15 mg/d and pyridoxine 100 mg/d.
After initiation of therapy, patients feel better in 2 days, reticulocytes peak at 5-7 days and the haemoglobin, red cell count and haematocrit rise by the end of the first week. These indices normalise within 2 months irrespective of the starting level. Failure to respond implies a wrong or incomplete diagnosis (coexistent deficiency of another hae-matinic). The initial stimulation of haemoglobin synthesis often depletes the iron and folate stores and supplements of these may be needed. Hypokalaemia may occur at the height of the erythrocyte response in severe cases. It is attributed to uptake of potassium by the rapidly increasing erythron (erythrocyte mass). Oral potassium should be given prior to initiating therapy in a patient with low or borderline potassiuim levels. Once alternative or additional causes of the anaemia have been excluded, inadequate response should be treated by increased frequency of injections as well as increased amount (because of urinary loss with high plasma concentrations). The reversal of neurological damage is slow (and rarely marked) and the degree of functional recovery is inversely related to the extent and duration of symptoms.
Haemoglobin estimations are necessary at least every 6 months to check adequacy of therapy and for early detection of iron deficiency anaemia due to achlorhydria (common in patients with pernicious anaemia > 60 years) or carcinoma of the stomach, which occurs in about 5% of patients with pernicious anaemia.
When injections are refused or are impracticable (rare allergy, bleeding disorder), administration as snuff or aerosol has been effective, but these routes are less reliable. Large daily oral doses (1000 micrograms) are probably preferable; depleted stores must be replaced by parenteral cobalamin before switching to the oral preparation; the patient must be compliant; monitoring of the blood must be more frequent and adequate serum vitamin B17 levels must be demonstrated.
Adverse effects virtually do not occur, but use of vitamin B12 as a 'tonic' is an abuse of a powerful remedy for it may obscure the diagnosis of pernicious anaemia, which is a matter of great importance in a disease requiring lifelong therapy and prone to serious neurological complications. The latter danger is of particular significance when a megaloblastic anaemia due to pernicious anaemia is incorrectly diagnosed as due to folate deficiency; here folic acid, if used alone (see below) may accelerate progression of subacute combined degeneration of the nervous system.
Was this article helpful?
Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...