Page 633 - Hematology_ Basic Principles and Practice ( PDFDrive )

542 Part V Red Blood Cells

TABLE Causes of Megaloblastosis Not Responding to Therapy TABLE Indications for Prophylaxis With Cobalamin or Folate
39.7 With Cobalamin or Folate 39.8
Wrong Diagnosis Prophylaxis With Cobalamin
Combined folate and cobalamin deficiencies being treated with only Infants on specialized diets a
one vitamin Premature infants
Associated iron deficiency Infants of mothers with pernicious anemia a
Associated hemoglobinopathy (e.g., sickle cell disease, thalassemia) Infants and children of mothers with nutritional cobalamin deficiency
Associated anemia of chronic disease Vegetarianism and poverty-imposed near-vegetarianism a
Associated hypothyroidism Total gastrectomy b
Prophylaxis With Folic Acid c
All women contemplating pregnancy (at least 400 µg/day) d
Pregnancy and lactation, premature infants
present for less than 3 months are usually completely reversible; with Mothers at risk for delivery of infants with neural tube defects e,f
longer duration, there is invariable residual neurologic dysfunction. Hemolytic anemias/hyperproliferative hematologic states
The reversibility of neurologic damage is slow (a maximal response Patients with rheumatoid arthritis or psoriasis on therapy with
may take 6 months). Substantial increments (in recovery) are unlikely methotrexate g
to be gained after the first 12 months of appropriate therapy. However, Patients on antiepileptic drugs
most neurologic abnormalities have improved in up to 90% of Patients with ulcerative colitis
patients with documented subacute combined degeneration. a For vegetarians, prophylaxis with cobalamin (5- to 10-µg tablet/day) orally
should suffice. In all other conditions involving any abnormality of cobalamin
absorption, cobalamin tablets of 1000 µg/day should be administered orally to
Follow-up ensure that cobalamin transport by passive diffusion across the intestine is
sufficient to meet daily needs.
b Consider late development of cobalamin deficiency and iron malabsorption
Patients with neurologic dysfunction from cobalamin deficiency have (prophylaxis with oral cobalamin and iron).
Ensure that the patient does not have a cobalamin deficiency before initiating
traditionally been given more frequent doses of cobalamin (biweekly c long-term folate prophylaxis.
rather than monthly therapy for the first 6 months), despite the lack d For prevention of first occurrence of neural tube defects.
of evidence that this form of therapy is more beneficial. This approach e Previous delivery of a child with neural tube defects (e.g., anencephaly, spina
nevertheless serves a purpose in that improvement in neurologic bifida, meningocele) imparts a 10-fold greater risk for subsequent delivery of
status can be carefully documented. Once maximal responses have infant with neural tube defects.
f
Folic acid (4 mg/day) administered periconceptionally and throughout the first
been established, most patients can be treated with life-long cobala- trimester.
min with a dose that is appropriate for the underlying cause of g To reduce toxicity of the antifolate.
cobalamin deficiency. Follow-up outpatient visits every 6 months
should be instituted to ensure adequate maintenance of hematopoi-
esis, as well as early diagnosis of other diseases commonly associated
with the cobalamin- or folate-deficient state. Patients with pernicious one-quarter of the recommended dietary allowance of folate. A
anemia are prone to developing iron deficiency that arises from poor very brief focused interaction involving physician advice combined
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iron absorption from achlorhydria. Therefore when iron deficiency with a booster phone call and starter bottle of folic acid tablets can
is established, total dose replacement using parenteral iron, such as 1 markedly increase a woman’s regular intake of folic acid (increase
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gram of low-molecular-weight iron-dextran (INFeD) administered by 68% versus 20% in the control group). Although regulations
over an hour, is indicated. 265 for mandatory fortification of wheat flour with folic acid are in
Patients with pernicious anemia have a twofold increase in proxi- place in 53 countries (by 2010), in many cases, these regulations
227
mal femur and vertebral fractures and a threefold increase in distal have not been implemented. Moreover, folate-fortified foods do
forearm fractures. The associated antral enterochromaffin cell hyper- not reach all women of reproductive age adequately, particularly
plasia (driven by hypergastrinemia that accompanies atrophic body the most needy women in the lowest socioeconomic bracket. 228,229
gastritis) can be associated with dysplasia, a risk factor for develop- As a result, the ideal of folate fortification has not been achieved
168
ment of neoplasia. In addition, the loss of oxyntic glands and in developing countries where over 90% of the world’s pregnant
191
replacement by metaplastic pyloric or intestinal glands is a risk factor women still fail to receive optimum folate, and well over one-half
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for gastric cancer. Finally, three studies (from Sweden, the United of the world’s population still does not have easy access to folate-
States, and Denmark) on a total of nearly 15,000 patients with perni- fortified foods. In addition, awareness of the need for folate before
cious anemia have identified an excess risk for gastric cancers within pregnancy remains low in the developing world (in Nepal it is a
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the first few years of diagnosis ; so it is prudent to recommend upper dismal 5%). 273
endoscopy for these patients despite the lack of prospective data The administration of folate and cobalamin in addition to paren-
favoring this approach. teral erythropoietin and parenteral erythropoietin and iron to prema-
274
ture infants significantly improved hemoglobin values ; so this
ROUTINE SUPPLEMENTATION OF should be the standard of care.
Supplementation with folate during pregnancy also helps to
COBALAMIN AND FOLATE prevent premature delivery of low-birth-weight infants, and routine
15
supplementation for premature infants and lactating mothers is also
Routine periconceptional supplementation of folate for normal recommended.
22
women and in 10 times higher doses for women at risk for delivery In addition to hematologic diseases leading to increased folate
22
of subsequent babies with NTDs, provides effective prophylaxis requirements (e.g., autoimmune hemolytic anemia, β-thalassemia),
against the development of NTDs (Table 39.8); this also appears to folic acid supplements reduce the hepatotoxicity and gastrointestinal
223
reduce the risk for congenital heart disease, and isolated cleft lip intolerance of methotrexate in psoriasis 22,275 and rheumatoid arthri-
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(with or without cleft palate) by about one-third. Food fortification tis without impairing the efficacy of methotrexate.
with folic acid (140 µg/100 g flour) has nearly eliminated folate Supplementation with folic acid protects against the development
268
deficiency —the prevalence of low serum folate level decreased from of colorectal neoplasia in high-risk patients with ulcerative colitis. 22
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18.4% to 0.8% with a small (0.3 g/dL) increase in hemoglobin ; For schoolchildren in developing countries, simple community-
it has consistently reduced NTDs 215,270 ; and it is a cost-effective level interventions, such as micronutrient fortification (using a premix
intervention. 228,271 Food fortification was intended to provide only added to school lunches), that build upon the infrastructure of an