Iron Deficiency In Women

Iron Deficiency In Women RETTY M. HAHNElVIAN, M.D. A tlending Physician, Chicago Wesley Memorial Hospital; Attending Physician in Internall\f edicine, Chicago M alernily Cenle,.; I nS/TUcior in Medicine, N orlhwestern University Medical School, Chicago, Illinois A.~sociate

IRON DEFICIENCY is commonly encountered in women. It may be thought of as a state in which the total body iron is less than normal, iron deficiency anemia appearing when there is no longer adequate iron available for normal hemoglobin synthesis. Iron deficiency is not itself a disease, but rather an indication of diminished body iron stores. The examination and treatment of a woman with iron deficiency is not completed with the replacement of iron. It is just as important, or in some cases far more important, to determine the underlying cause of the iron depletion.

MECHANISM OF IRON DEFICIENCY

The average adult woman has approximately 4 gm. of iron in her body. Nearly two-thirds of this iron is contained in the circulating erythrocytes, and about onc-fourth, or 1 gm., is stored in reticuloendothelial organs, principally liver, spleen and bone marrow. The remainder is present in myoglobin, enzymes, and in transport in the blood plasma. The body conserves iron very effectively by the reutilization of erythrocyte iron. Hemoglobin is broken down by the reticuloendothelial cells into iron and pigment, the pigment converted to bilirubin which is excreted by the liver, and the iron stored in the form of hemosiderin and ferritin in the reticuloendothelial organs. Iron so stored is available for synthesis of hemoglobin in the bone marrow. Only a small amount of iron (about 1 mg. daily) is lost externally in the skin, hair, nails and stool. Normally, between 1 and 2 mg. arc absorbed daily from the diet. Iroll is absorbed in the duodenum and upper small intestine and transpotted by the iron-binding globulin, transferrin, to the storage sites. Although the exact mechanism controlling iron absorption from the gastrointestinal tract is unknown, the iron deficient individual ordinarily absorbs an increased percentage of the available food iron: whereas the normal person usually absorbs up to 10 per cent of food iron, the iron deficient individual may absorb 20 to 40 per cent or more of the available iron. The usual American diet contains from 10 to 40 mg. of iron. It is thus apparent that the woman who is neither pregnant nor menstruating should not become iron deficient unless she has abnormal

139

140

BETTY

M.

HAHNEMAN

iron loss, that is, loss of blood. The menstruating woman presents a different situation: she loses blood with each menstrual period, the amount varying from person to person and period to period. Although precise evaluation of menstrual blood loss in a given individual is virtually impossible, the blood lost in a "normal" menstrual period is believed to range from 30 to 100 ml., equivalent to 15 to 40 mg. of iron. Therefore, the woman with menstrual periods that are not excessive in amount should be able to absorb sufficient iron from her food to compensate for the menstrual iron loss. However, if excessive blood loss occurs with the menses, the rate of iron absorption from food may no longer be able to keep pace with the iron loss and iron deficiency will then occur. Depending upon the amount of blood lost and the amount of dietary iron absorbed, a period of time varying from a few months to several years may be required before the iron deficit becomes evident as iron deficiency anemia. Pregnancy alters the situation significantly. Although there is no menstrual loss during the time of gestation, the fetus is entirely dependent on the mother for its iron. A normal-term infant's total body iron is approximately 400 mg. Blood loss at delivery and the fetal blood in the placenta constitute additional sources of iron loss, and with the usual 150 to 200 ml. blood loss at delivery, the total iron loss of the average pregnancy may be estimated at 750 mg. Greater amounts will of course be lost with bleeding during pregnancy, excessive blood loss at delivery, and postpartum hemorrhage. One normal pregnancy requires an amount of iron equivalent to 75 per cent of the maternal iron stores of 1 gm. It is apparent, therefore, that repeated pregnancies without replacement of iron lost will result in significant iron deficiency. The development of iron deficiency anemia on the basis of inadequate diet alone is extremely unlikely in adults. In addition to the iron available from meat, vegetable and egg sources, almost all flour produced in the United States for commercial or home use is fortified with iron. Thus only the most unusual diet could be said to be iron deficient, and would have to be consumed over a period of years to result in iron deficiency anemia. Nevertheless, adequate dietary iron is required to avoid anemia in the menstruating woman, and even more in the pregnant person. It is dangerous to assume that iron deficiency in the postmenopausal woman whose diet is poor has been caused by dietary iron lack; this is nearly impossible to achieve under present circumstances. The assumption of iron deficiency on a dietary basis .in this age group may result in overlooking an occultly bleeding neoplasm whose first manifestation may be iron deficiency anemia. LABORATORY DIAGNOSIS OF IRON DEFICIENCY

Most iron deficiency anemia in women is asymptomatic. The diagnosis may be suspected either on the basis of clinical findings or, more often, as a result of routine determination of the hemoglobin level of the blood. Because of the frequency of asymptomatic iron deficiency, even when accompanied by rather severe anemia, it is important that hemoglobin

Iron Deficiency in Women

141

level, and preferably hematocrit as well, be obtained on every woman at least once a year, preferably as a part of an annual examination. Additional determinations should be carried out whenever there is suspicion of anemia. In pregnancy it is important to check hemoglobin more frequently; every two months during the first two trimesters and monthly during the third trimester is advised. Hemodilution usually causes some decrease of hemoglobin and hematocrit levels during pregnancy, but without evidence of iron deficiency. Dilution alone may cause a fall of hemoglobin to 10 gm. per 100 ml. of blood, but usually does not result in this much lowering of hemoglobin levels. The fundamental clinical procedure in the confirmation of iron deficiency anemia is the morphology of the erythrocytes (Fig. 1). When body iron is insufficient for the demands of erythrocyte production, adequate iron is not available for hemoglobin synthesis. The red cells formed are deficient in hemoglobin both absolutely and relatively: there is decreased total hemoglobin in each red cell as manifested by the hypochromia and microcytosis, and the concentration of hemoglobin within each cell is reduced, also producing hypochromia. In mild iron deficiency, microcytosis and hypochromia are the usual changes seen. As anemia becomes more severe, additional evidence of disordered erythropoiesis appears, manifested by poikilocytosis, polychromatophilia, more marked anisocytosis; nucleated erythrocytes may be seen in the peripheral blood film in very marked iron deficiency anemia. Other laboratory findings include decrease of mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC), reflecting the microcytosis and hypochromia. The MCHC is the most significant of the erythrocyte indices as an indication of iron deficiency anemia. It is calculated by dividing hemoglobin (in grams per 100 ml. of blood) by hematocrit, and multiplying by 100. The normal range is 32 to 38 per cent. If the MCHC is significantly reduced, hypochromia

Fig. 1. Erythrocyte morphology in iron deficiency anemia.

142

BETTY

M.

HAHNEMAN

is indicated. This finding should always be confirmed by the examination of a stained blood film. The peripheral blood film may give additional valuable evidence related to the cause of the iron deficiency. Leukocytosis and thrombocytosis are usually present when active bleeding is occurring. An increase in eosinophilic granulocytes should raise suspicion of intestinal parasitic infection in the iron deficient patient, while characteristic changes in granulocytes and erythrocytes may indicate an associated deficiency of vitamin B12 or folic acid. A definite decrease in platelets raises the question of thrombocytopenia as the cause of blood loss. The physician should be aware that there is one other relatively common condition seen in adult women associated with hypochromia which does not represent iron deficiency; this is thalassemia trait. In the latter, hypochromia is accompanied by the characteristic changes of target cells and ovalocytes. Although thalassemia trait has been demOllstrated to occur in a number of ethnic groups, it is most commonly found in the United States in those of Italian or Greek ancestry. Characteristic findings of iron deficiency anemia in the peripheral blood, along with clinical information obtained from history, physical examination and, if indicated, other diagnostic procedures, is usually sufficient to establish the diagnosis of iron deficiency anemia. However, occasions arise when further investigation of the state of the body iron stores is indicated, for example, differentiation of thalassemia trait from iron deficiency in some instances. An excellent evaluation of iron stores may be obtained by the relatively simple and readily available procedure of staining the spread films or histologic sections of bone marrow for iron with the Prussian blue reaction. Normally, blue-stained iron granules will be present and can be seen without difficulty; when the stainable iron is diminished or absent, iron deficiency can be assumed to exist. It is important to use as a control a sample of marrow known to contaill normal amounts of iron, for technical difficulties involving reagents 01' proeedure may result in a false impression of absent marrow iron. Chemical determination of serum iron and iron-binding capacity is a method available in a minority of clinical laboratories at present, but its use is becoming more widespread. This procedure demands very careful attention to details, especially with regard to the use of iron-free glassware and reagents, in order to give reliable results. Therefore the values obtained are only as good as the technique employed-from the moment of drawing the blood specimen to completion of the determination. For these reasons the test is frequently not practical for the practicing physician as a routine clinical diagnostic measure. Accurate interpretation of serum iron level requires simultaneous determination of iron-binding capacity. The normal range for serum iron in most laboratories is approximately 60 to 180 micrograms per 100 m\. of blood, and this normally represents about one-third of the iron-binding capacity of the serum. The earliest change seen in iron deficiency is elevation of iron-binding capacity which occurs before the decrease in serum iron and appearance of anemia. In chronic infection and chronic liver disease decreased serum iron is associated with decreased iron-

Iron Deficiency in Women

143

binding capacity; this may occur in the presence of normal body iron stores and does not imply that iron deficiency is present. CLINICAL DIAGNOSIS IN IRON DEFICIENCY

The pre8ence of iron deficiency in the adult means that iron has been lost from the body. It is mandatory that the physician determine the flource of the iron loss. The basic diagnostic procedures include the complete clinical history and physical examination. Among women in the childbearing period, careful inquiry should be made as to the character, frequency and duration of the menses. Since the average patient has little or no means for determining whether or not her periods are "normal," one should not be satisfied with an affirmative answer to the question, "Do you have a normal flow?" Obstetrical history must include number of pregnancies, multiple pregnancies, presence of anemia during or after pregnancy, bleeding before, during or following delivery, abortions with associated blood loss, and number of blood transfusions received. Previous history of anemia is especially important in women who have had their first pregnancy in their teens, since some of these individuals may have been iron deficient since adolescence. A record of type, duration and time of any treatment for anemia should be made. Bleeding from other sources should be inquired into, and particular attention should be paid in the course of the systemic review to the gastrointestinal tract with regard not only to bleeding and melena but also to symptoms which might be compatible with such lesions as esophageal hiatus hernia or varices, peptic ulcer, or intestinal parasites which can be responsible for blood loss. The physical examination should be complete, with particular attention to the abdomen and the pelvic and rectal examinations. Stool obtained at rectal examination should be tested for occult blood. In considering the findings of the clinical and hematologic examillations, one may be guided by the following: 1. THE PREGNANT WOMAN. Iron deficiency is usually related to iron loss in previous pregnancies, perhaps augmented by pre-existing iron deficiency of adolescence, or by heavy menses. Other sources of blood 108s should not be overlooked, especially if iron deficiency anemia seems out of proportion to that expected from the history, and if there is clinical evidence of other source of bleeding, e.g., history of peptic ulcer. While x-ray examination of the gastrointestinal tract should be undertaken during pregnancy only under the most compelling circumstanee8, other studies such as examination of stools for blood and parasites, proctoscopy, or gastric analysis may mmally be done. An example follows: A 20 year old, Puerto Rican born woman registered for prenatal care at the Chicago Maternity Center in her seventh month of pregnancy. She gave a history of anemia in her previous pregnancy, for which she had been treated with oral iron. Records revealed that on iron therapy her hemoglobin had risen from 4.3 to 10.5 gm./lOO m!., and her hematocrit from 21 to 35 per cent. Post-

144

BETTY

M.

HAHNEMAN

•

Fig. 2. Severe iron deficiency anemia and eosinophilia.

partum, hemoglobin had been 10.5 gm., hematocrit 36 per cent. The postpartum examination had been done 2 months following delivery and 7 months before the current clinic visit. Examination of the blood revealed hemoglobin 4.2 gm., hematocrit 19 per cent, marked hypochromia, anisocytosis, microcytosis, and poikilocytosis of the red cells and 28 per cent eosinophilic granulocytes (Fig. 2). Cathartic stools contained ova of hookworm and trichuris. Antihelmintic therapy and oral iron were administered, with good clinical response.

Comment. In this patient, rapid recurrence of severe iron deficiency anemia following good response to treatment seven months earlier led to suspicion of an etiologic factor in addition to pregnancy, and eosinophilia pointed to the possibility of intestinal parasites. 2. THE NONPREGNANT, MENSTRUATING WOMAN. Previous pregnancies and excessive uterine bleeding are the most common causes of iron deficiency in this group. As in the pregnant woman, associated factors should not be overlooked. Anemia out of proportion to apparent blood loss, iron deficiency of relatively recent onset when there has been no apparent change in menses or recent pregnancy, symptoms referable to the gastrointestinal tract, and increasing age of the patient should all raise the question of unrecognized bleeding. Repeated stool examinations for occult blood are desirable, and proctoscopy and gastrointestinal radiologic studies should be done in these circumstances. The following case is an example: A 23 year old woman presented herself for a routine check-up. She had never been known to be anemic, had not been pregnant, and had had no excessive menstrual bleeding or change in the menstrual flow. Examination of the stool for occult blood was positive, and hemoglobin was 10.5 gm. per 100 m!. of blood and the hematocrit 36 per cent, with hypochromia and microcytosis of the red cells. Despite the absence of gastrointestinal complaints, x-ray examination was done and a duodenal ulcer crater demonstrated. Good response followed medical management of the ulcer and oral iron therapy.

Iron Deficiency in Women

145

Comment. Not only was the cause of the anemia determined in this patient, but serious additional disease discovered and brought under proper management. 3. THE POSTMENOPAUSAL WOMAN. Iron deficiency developing after menopause has serious implications and demands immediate evaluation for occult bleeding, particularly from the gastrointestinal tract, if no other localizing symptoms or findings are noted. Proctoscopy and gastrointestinal x-rays are mandatory, even in the asymptomatic patient, for the incidence of carcinoma, especially of the colon, is high in this group. Examination of urine for blood is also of importance, with intravenous pyelography included if there is microscopic or gross hematuria, flank pain, or mass. The following case illustrates this concept: A 61 year old white housekeeper was seen at the Northwestern University Medical School Clinics because of a small mass on the vulva. Physical examination was entirely normal, and there were no complaints other than the vulvar tumor. Hemoglobin was 7.6 gm. per 100 ml. of blood and hematocrit 28 per cent. The red blood cells were hypochromic and microcytic, with moderate anisocytosis and poikilocytosis. Gastrointestinal examinations revealed a constricted area in the right colon. Right hemicolectomy was performed and the pathologic diagnosis was well differentiated adenocarcinoma of the cecum.

Comment. Thorough investigation of this patient's anemia was probably lifesaving for this woman, who remains well and without clinical or radiologic evidence of recurrence of tumor (it is now two years since her surgery). 4. COEXISTING ANEMIA OF DIFFERENT ETIOLOGY. Iron deficiency anemia does not exclude the presence of an additional type of anemia, and the physician must not concentrate on the iron deficiency so intensively that he does not consider this possibility. The clues are usually found in history, physical examination, and in the peripheral blood. Information which may be obtained from the patient includes past and/or family history of anemia, jaundice or gallstones, history of chronic disease of the urinary or respiratory tract or liver, bone pains, fever, weight loss, sore tongue. Physical findings of icterus, splenomegaly of more than minimal degree, lymph node enlargement, hepatomegaly, chronic leg ulcers, and defective position or vibration sense should arouse suspicion. Abnormalities of the blood film such as spherocytosis, macrocytosis, unusual poikilocytosis, thrombocytopenia, leukocytosis, changes resembling those seen in leukemias, and large granulocytes which are hypersegmented should be noted. Types of disorder which may be found include: a. Hemolytic states due to congenital abnormalities of hemoglobin or erythrocyte formation (e.g., hereditary hemoglobinopathies) or related to drug administration b. Aplastic or hypoplastic states, of unknown cause or induced by physical or: chemical agents c. Anemia of chronic renal disease or chronic infection

146

BE'I'TY

M.

HAHNEMAN

d. Leukemia, acute or chronic e. Megaloblastic anemia: in older women, pernicious anemia, in pregnancy, megaloblastic anemia of pregnancy

An example follows: A 27 year old white woman, gravida 8, para 5, with 2 abortions, was admitted to the prenatal clinic of the Chicago Maternity Center with hemoglobin 6 gm. per 100 ml., hematocrit 22 per cent. She was in the eighth month of her pregnancy. Examination of blood films showed hypochromia, anisocytosis, microcytosis, poikilocytosis, occasional oval macrocytes, and hypersegmentation of the nuclei of some large polymorphonuclear neutrophils. Bone marrow examination revealed erythrocytic hyperplasia with megaloblastic changes in many of the nucleated cells of the erythrocytic series. She was treated with oral iron and folic acid, but delivered prematurely a .5 pound male infant before hematologic remission occurred; she did, however, have reticulocytosis of 18 per cent on the seventh day following beginning of therapy. TREATMENT

The proper therapeutic agent in iron deficiency is iron. This statement appears too simple to need emphasis, but at the present time many patients with iron deficiency are treated with improper, expensive, unnecessary and even dangerous preparations which have no rational place in the therapy of iron defieieney. No known agent will increase the effeetiveness of iron in the treatment of uncomplicated iron deficiency anemia. If the patient's iron defi(~iency is associated with another type of anemia, or other disease, only specific adequate treatment of the associated condition will help the patient's response to iron. Despite widespread publicity in the medical literature regarding the potential dangers of "shotgun" preparations for the treatment of anemia, these combinations continue to be prescribed. Their use not only reveals the physieian's lack of knowledge of basic principles of therapy but also shows disregard for the patient's health as well as for her purse. In addition to iron, of eourse, any etiologic factor or associated disease requiring therapy should be treated in the proper manner. This may require one or more of a wide range of measures, surgical or medical, depending upon the individual situation. Iron is administered orally as either ferrous sulfate or ferrous gluconate. Each is available in U.S.P. preparations as 300 mg. tablets and should be administered in divided doses. Three tablets daily are usually adequate, although from four to six tablets may be given when iron need is great. Iron salts should be given after meals in order to minimize their tendency to cause gastric irritation. If gastrointestinal symptoms are anticipated or appear following the initiation of full-dosage therapy, gradual administration is almost always satisfactory: the patient is instructed to take one tablet daily, after eating, for one to three days, and then to increase by one tablet everyone to three days until the desired dosage is reached. With postprandial and graduated initial administration, it is rare to encounter a patient who experiences gastro-

Iron Deficiency in Women

147

intestinal irritation sufficient to prevent adequate therapy. No acceptable evidence is available to indicate that any other salt or form of ferrous iron is better tolerated or better absorbed than the official D.S.P. preparations of ferrous sulfate and gluconate. Oral iron should be continued in therapeutic dosage for two to four weeks following achievement of normal hemoglobin levels; this permits adequate replacement of the previously depleted iron stores. Therapy may then be stopped and the patient observed at three months, then at intervals of six months, unless the clinical situation dictates more frequent observation. In iron deficiency anemia of pregnancy, therapy at full dosage should be continued until delivery and for two to four weeks postpartum. Inability to absorb iron from the gastrointestinal tract is an extremely rare occurrence, and is practically never encountered as a selective defect, that is, without evident clinical and laboratory signs of associated malabsorption of other nutritional factors such as is seen in sprue, advanced regional enteritis, or following extensive small bowel resection. Parenteral Iron Therapy

Intravenous iron preparations have been available for many years. Recently an intramuscular iron-dextran complex for intramuscular use was placed on the market but was subsequently withdrawn pending studies of toxicity. A number of serious, and several fatal reactions to parenteral iron have been reported; to this danger may be added increased expense, greater discomfort, and necessity for the patient to travel to physician, clinic or hospital for its administration. Parenteral iron is indicated, and should be used, only in selected patients in whom demonstrated iron deficiency exists and in whom oral iron will not be of avail or when rapid response to iron is required. Such patients are not commonly encountered, but may include the following: 1. Pregnant women 6 weeks or less from term with iron deficiency anemia in which the hemoglobin is less than 8.5 gm. per 100 m!. 2. Patients with iron deficiency associated with malabsorption syndromes sueh as sprup or small bowel resection who do not absorb oral iron 3. Patients with serious gastrointestinal disease, such as chronic ulcerative colitis, who are iron deficient and whose symptoms are exacerbated by oral iron salts

The effects of long-term iron overload in the normal human are not known at present. Since the patient has no way of excreting excess iron, it is important that parenteral iron dosage be calculated with regard to the individual patient and her degree of iron deficiency. A useful and simple formula is that presented by Brown et aLl: Kormal humoglobin (gm.) - Initial hcmoglobin (gm.) X 0.255

The result of this calculation gives dosage in grams. In pregnancy, it is advisable to add 0.5 gm. to this total because of the increased iron requirements in the pregnant woman. Total dosage ordinarily should not exceed 2.5 gm.

148

BETTY

M.

HAHNEMAN

Blood Transfusion in Iron Deficiency

Blood transfusion is rarely necessary in the treatment of iron defieieney anemia, and should never be employed unless there is urgent need for rapid restoration of hemoglobin levels. The well known serious hazards of blood transfusion (including hemolytic reaetion, isosensitization and serum hepatitis) may be compared to the minimal hazards of oral iron. Patients developing iron deficiency usually do so slowly, and ordinarily become well acclimated to the lowered hemoglobin. Therefore, the hemoglobin level itself does not constitute an indication for transfusion. Many women are seen with hemoglobin levels ranging from 4 to 8 gm. per 100 m!. who have become iron deficient as a result of repeated pregnancies and/or increased menstrual bleeding who suffer few or no symptoms; these women need not be transfused in the absence of other indication for rapidly raising the hemoglobin level. In transfusing patients with iron deficiency anemia, care should be taken not to overload the circulation; this is more likely in the elderly or cardiae woman whose vascular system may be incapable of accommodating a rapid inerease in blood volume. Unless recent blood loss has occurred or there is need to supply serum proteins, it is preferable to use transfusions of red cells rather than whole blood. Blood transfusion should be employed without hesitation when dearly indicated. The usual indications are: 1. Pregnant women less than four weeks before expected delivery date who have iron deficiency anemia of less than 8.5 gm. of hemoglobin per 100 ml. of blood. 2. Patients with recurrent or concurrent hemorrhage whose source of bleeding predisposes to continuing or recurrent hemorrhage, c.g., a patient with bleeding peptic ulcer, iron deficiency anemia and recent hematemesis who is likely to bleed again while medical or surgical management is being undertaken. 3. Patients with arteriosclerotic heart disease and marked myocardial ischemia with severe iron deficiency anemia. (These individuals must be transfused with extreme care.) 4. Those in whom surgical therapy may not reasonably be delayed for the period necessary for response to oral iron, e.g., ectopic pregnancy, malignancy, bowel obstruction.

RE-EVALUATION

The woman who has been placed on iron therapy should be followed by means of hemoglobin and hematocrit determinations. Although the reticulocyte count rises following administration, usually reaching maximal levels in 10 to 15 days, it is not ordinarily necessary to follow this response. In mild iron deficiency and in pregnancy, one may not note a marked reticulocyte peak (in the former) or it may be delayed (in the latter instance), despite adequate therapeutic response. In the nonpregllant woman a significant rise in erythroid values is seen by the end of three weeks of therapy. Normal levels are usually attained in from four to eight weeks, depending in part on the initial hemoglobin and hemato-

Iron Deficiency in Women

149

crit levels. In the pregnant woman, a month may be required for signifieant increase. Failure to achieve adequate respom;e to treatment requires re-evaluation of the patient's status. The following possibilities should be kept in mind: 1. She may not be taking her medieation, or may be taking less than the prescribed dosage. This is a very common cause of failure of response, and careful questioning is often required to elicit correct information. A woman who will answer "Yes" to the inquiry, "Have you been taking your pills?" is often found, on detailed questioning, to have taken one tablet or less daily. 2. Continuing blood loss may be present. This is particularly important in excessive uterine bleeding and gastrointestinalloss. 3. Infection, uremia or chronic inflammation may be present. These conditions may inhibit response to iron despite the presence of iron deficiency. Chronic pulmonary disease, hepatic or renal infection may be responsible. Asymptomatic urinary tract infection frequently exists in the pregnant patient; response to iron will usually occur rapidly following adequate treatment of the infection. 4. The iron deficient pregnant patient who has only a partial response to iron should be investigated for evidence of megaloblastie anemia of pregnancy. This usually occurs in the third trimester, is more frequent in multiparas, and in those with multiple pregnancies. Peripheral blood films show macrocytosis and large, hypersegmented neutrophilic granulocytes, and bone marrow examination reveals evidence of megaloblastie erythropoiesis. SUMMARY

Iron deficiency is eommon in women, especially in pregnancy and the menstrual years. Iron deficiency anemia may be properly diagnosed, in the vast majority of cases, by examination of the peripheral blood film. Etiology of the iron deficiency should be established. The anemia itself is almost always best treated with oral ferrous iron salts alone, although in some situations parenteral iron or blood transfusion may be required. Etiologie factors should be treated as indicated. When proper response to iron is not achieved, the patient should be re-evaluated and the reason for lack of response determined. REFERENCE 1. Brown, E. B., Moore, C. V., Reynafarje, C. and Smith, D. E.: Intravenously Administered Saccharated Iron Oxide in the Treatment of Iron Deficiency Anemia. J.A.M.A. 14-4-: 1084-1089, 1950. 670 N. Michigan Avenue Chicago 11, Illinois