Page 627 - Hematology_ Basic Principles and Practice ( PDFDrive )

536 Part V Red Blood Cells

233
TABLE Beneficial Effects of Homocysteine-Lowering Therapy neuropsychiatric dysfunction is a valuable reminder that those on
39.5 on Nonhematopoietic Systems folate prophylaxis need periodic follow-up for symptoms and signs
Using Folic Acid, Cobalamin, Pyridoxine Supplementation (Grade A Studies) of supervening cobalamin deficiency.
Reduction in hip fracture 208,a
Reduction in the progression of carotid intima media thickness 209,a (a Folate Malabsorption With Normal Intestinal Mucosa
surrogate marker of early subclinical arteriosclerosis)
Reduction in age-related macular degeneration 210,a Hereditary Folate Malabsorption
Reduction in rate of brain atrophy 177,a
Improvement in cognitive function 178,211,212,a Hereditary folate malabsorption, which is caused by loss of function
Using Folic Acid Supplementation (Grade A Studies) mutations in the PCFT gene, has been detected in 19 different fami-
Reduction in stroke 213,a lies; in the USA, those of Puerto Rican descent share a common
234
Reduction in the rate of cognitive decline among healthy older mutated allele. Loss of PCFT is associated with inability to trans-
adults 211,a port folate across the intestine and into the brain, resulting in low
Reduction in age-related (sensorineural) hearing loss 214,a serum and cerebrospinal fluid folate values with megaloblastic anemia,
Reduction in first occurrence of NTDs 215,216,a chronic diarrhea, and neurodevelopmental defects with seizures and
Reduction in recurrence of NTDs 217,a mental retardation; this syndrome responds to high-dose parenteral
Reduction in phenytoin-induced gingival hyperplasia 218,a folinic acid that bypasses and overcomes the transport defects.
Beneficial Effects of Folic Acid Fortification of Food (Population-Based Affected patients can also present with a syndrome of reversible
Studies) subacute combined immunodeficiency syndrome with hypogam-
235
Reduction in NTDs 219–221 (anencephaly, spina bifida, encephalocele, maglobulinemia and recurrent infections. If diagnosed early in
meningocele, iniencephaly) infancy, hereditary folate malabsorption responds well to parenteral
Reduction in cleft lip with or without cleft palate 222 5-formyltetrahydofolate and can allow normal development into
Reduction in severe congenital heart disease 222,223 (endocardial cushion adulthood. 236
defects, conotruncal defects)
Reduction in congenital pyloric stenosis, stenosis of the ureteropelvic Folate Malabsorption With Intestinal
junction, limb reduction defects 222
Reduction in stroke mortality 224 Mucosal Abnormalities
Decreased risk for preterm births, 225 low birth weight, and small-for-
gestational-age babies Tropical Sprue
a Paper with randomized controlled trial data; grade A studies.
NTD, Neural tube defect. Residents of, and visitors to, endemic areas in the tropics can acquire
15
a disorder characterized by small intestinal malabsorption. General-
ized, nonspecific small bowel malabsorption leads to a wide spectrum
of clinical manifestations arising from defective absorption of fat,
Moreover, folate-fortified foods do not reach all women of reproduc- carbohydrate, albumin, calcium, folate, and in later stages, cobala-
15
tive age adequately, particularly the most needy women in the lowest min. There is abrupt onset of explosive, intermittent, or continuous
socioeconomic bracket. 228,229 So the ideal of folate fortification has diarrhea, abdominal distention, and pain, associated with anorexia,
not been achieved and over 90% of pregnant women worldwide still vomiting, and extreme fatigue. Stools are fluid or semisolid and fre-
191
do not receive sufficient folate, and over one-half of the world’s quently contain mucus and blood. This stage is followed weeks to
population still does not have easy access to folate-fortified foods. months later by nutrient deficiency. Later, as steatorrhea continues,
Contrary to the assertion in the American Dietetic Association’s megaloblastosis dominates the clinical picture. In the short term,
230
position paper on vegetarianism, there is an insufficient body of malabsorption leads to folate deficiency, but later in the chronic
evidence to confidently assert that women in the United States of (longer than 3 years) phase of the disease, cobalamin malabsorption
childbearing age who consume a balanced vegetarian diet with contributes additional clinical manifestations of cobalamin neuropa-
15
abundant green leafy vegetables will obtain sufficient folate and thy. There is some degree of villous atrophy and loss of intestinal
therefore not be at risk for giving birth to babies with NTDs. Until functional surface. Although less severe than in nontropical sprue, it
robust evidence from clinical trials is available to support this associa- is more extensive, involving the entire small intestine.
230
tion’s position paper, a prudent approach is to recommend that all After investigations for associated iron, cobalamin, and folate
women who are vegetarians must take cobalamin and folate deficiencies, therapy with folate and a broad-spectrum antibiotic
supplements. (e.g., tetracycline) is indicated together with symptomatic treatment
of diarrhea and vomiting; fluid, mineral, and electrolyte imbalance;
and other associated nutritional deficiencies. 15
Folates and Intrinsic Hematologic Disease The endemic nature of this disorder in the tropics (and in certain
15
households) and the beneficial response to antibiotics all suggest an
Because folate is necessary for hematopoiesis, folate requirements are infectious origin. However, the dramatic response to folate, which is
increased when there is significant compensatory erythropoiesis in curative in the first year in about 60% of cases (this cure is cited to
15
response to peripheral RBC destruction, abnormal hematopoiesis, or be almost diagnostic of the disease), has not been explained. It is
infiltration by abnormal cells in marrow. The recognition that folate unlikely that pure folate deficiency is the primary cause, because
deficiency developing in hemolytic disorders can lead to an acute nutritional folate deficiency does not result in tropical sprue; the
aplastic crisis has led to recommendations favoring routine prophy- clinical response to antibiotics suggests a close interplay among a
lactic administration of folate. A recent metaanalysis of 19 studies pathogenic infectious agent, endogenous flora, and the folate status
231
have put to rest the concern of iron-folate and malarial progression of the enterocyte.
and a Cochrane analysis identified no evidence that this is a problem
when combined with antimalarial drugs and insecticide-treated bed
232
nets. Sadly however, this dictum is not followed for the vast major- Nontropical Sprue
ity of children living in malarial regions. An unexpected increase in
transfusional requirement or a fall in platelets can also suggest folate Nontropical sprue (i.e., celiac disease, gluten-induced enteropathy) is
15
deficiency. The case of a patient with sickle cell disease on long-term the most common cause of intestinal malabsorption in temperate
folate who developed pernicious anemia and presented with zones. It results from a possibly inherited sensitivity to gluten (a