Iron Deficiency Anemia

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Etiology:

The search for a cause of iron deficiency is based on a careful history and thorough physical examination (including a rectal and pelvic exam). Iron deficiency can occur in four circumstances:

– Requirements are increased, particularly during growth and pregnancy;

– The dietary intake is inadequate, especially in countries where the diet is low in animal protein;

– The iron is poorly absorbed;

– Digestive losses are increased when bleeding. The original uterine bleeding and (or) digestive represent the main cause of iron deficiency. A loss of 1 mL of erythrocytes is responsible for a loss of 0.5 mg of iron.

1- increased requirements:

2- Contributed defects:

They can be observed in some countries to defective socio-economic conditions (diet low in animal protein) and in some cases of anorexia nervosa.

3- Malabsorption:

The hyposideremia is a consequence of malabsorption of the proximal small: it can be celiac disease in adults or children.

4. Bleeding:

• genital bleeding: in women of childbearing age, heavy uterine bleeding often explain the occurrence of iron deficiency. It is sometimes difficult to establish from the examination abundance losses. The most common causes are polyps or fibroids, and uterine cancers. This is rarely a disorder of hemostasis, including von Willebrand disease or thrombocytopenia. The presence of an IUD is an aggravating factor in all cases.

• Gastrointestinal Bleeding: the presence of digestive disorders, a recent constipation, epigastric pain, bouts of diarrhea alternating with constipation episodes incite achieve digestive exploration. Looking for blood in the stool is an examination subject to many uncertainties with positive and false negative false: A result can be negative for intermittent bleeding. The results of this review should not change the decision to undertake a digestive exploration.A colonoscopy will be conducted initially in the fifty patients: gastric endoscopy with duodenal biopsies will be preferred from the outset in a younger patient. If both tests are not informative, digestive exploration will be complemented by a small bowel. Gastrointestinal lesion is detected in more than 60% of cases. Malignant tumors are dominated by colonic and gastric adenocarcinomas, malignant non-Hodgkin gastric or small bowel, digestive localizations of Kaposi’s sarcoma. The non-tumor lesions reflux esophagitis, peptic ulcers, angiodysplasia colic, intestinal polyps or angiomatosis HHT. Gastrointestinal bleeding is rarely linked to certain endemic parasitic diseases: hookworm, Schistosomia haematobium). In all cases, it will not incriminate bleeding a nonsteroidal anti-inflammatory drugs, or heparin therapy, which promote bleeding from an unrecognized injury or digestive bleeding too easily attributed to hemorrhoids without having previously conducted a digestive exploration.

• other origin Bleeding: other origin of bleeding is sometimes seen in idiopathic pulmonary hemosiderosis in children, chronic and prolonged intravascular hemolysis (as part of paroxysmal nocturnal hemoglobinuria or mechanical hemolysis in valve patients). The Lasthenie Ferjol syndrome was observed in women practicing hidden blood subtractions.

Pathophysiology:

1- daily dietary iron intake:

Iron metabolism is very balanced. To compensate for losses (skin, digestive and genitourinary) daily iron intake of a 1 to 2 mg daily is required in adult man or woman outside periods of childbearing. This is mainly non-heme form (90%) the iron is provided in the diet (grains, vegetables and fruits). Iron is absorbed primarily in the duodenum and proximal jejunum. The amount absorbed depends on the added amount and its bioavailability. The absorption coefficient is 30 to 40%: it is reduced to 10% in case of iron deficiency anemia. Increase the absorption of non-heme iron, meat, poultry and fish, ascorbic acid and fermented foods (especially sauerkraut). Factors that decrease the absorption of non-heme iron are phytates, tea and calcium.

2- Iron Reserves in adults:

The body iron (55 mg / kg in men and 45 mg / kg in women, a stock from 3 000 to 4000 mg) is distributed mainly (60-70%) in hemoglobin of erythrocytes . One ml of red blood cells contained 0.5 mg of iron. The iron in myoglobin, cytochromes mitochondria, or other enzymes containing iron, is about 10% of the iron stores. The rest, about 20 to 30% is stored as ferritin, mainly in hepatocytes, erythroblasts and macrophage cells. In the blood, iron is bound to transferrin majority: it represents less than 0.1% of the content in body iron. At the membrane level, iron bound to transferrin binds to the transferrin receptor, which is then internalized. After endocytosis, the iron is released and recycled apotransferrin. Iron belongs to a labile pool: it is transferred either to a functional site, or to its storage protein, ferritin. It is in the cell under the control of a regulatory protein, IRF (iron regulatory protein). This protein in reverse modulates the receiver of transferrin and that ferritin. If the cell iron load decreases, the RFID increases the number of transferrin receptor, thereby promotes the entrance of iron in the cell and reduces the synthesis of ferritin.Iron stores depend on age and physiological conditions.

• Impact of age:

– At birth, the newborn has an iron stock 70 mg / kg, distributed to 50% hemoglobin and 50% as ferritin;

– During the first months, the infant’s iron requirements are very high due to a significant increase in blood volume.However, the milk diet is low in iron. The newborn is obliged to draw on its reserves: it is at risk of iron deficiency, when he was born with insufficient reserves (premature twins born to a deficient mothers …)

– After 6 months, food becomes less milk and is similar to that of adults. The daily food intake usually covers the needs of that period;

– After puberty, iron requirements are of the order of 1 mg and are compensated by food intake.

• Impact of physiological conditions:

– Women of childbearing period. The rules (30 to 50 ml per cycle) are lose 15 to 25 mg of iron per month. Pregnancy also induces an estimated specific additional needs 750 1 000 mg;

– Sports. Some sports activities, particularly prolonged foot race (marathon runners) are likely by repeated gastrointestinal bleeding induce iron deficiency observed more frequently in women;

– Blood donations. Each blood donation of 400 mL causes depletion of 200 mg of iron. French law allows four blood donations, which corresponds to the daily needs of about 3 mg. An iron deficiency in blood donors is more frequently seen in women of childbearing age.

3- Steps to iron deficiency:

The first stage is that of the isolated iron deficiency. The stock of body iron reserves are gradually reduced. When reserves are exhausted, iron deficiency sounds on erythropoiesis in a second time. Finally, in a third step, when the deficiency is prolonged, it is microcytic iron deficiency anemia.

Diagnosis:

1- To establish the diagnosis of iron deficiency:

It is based, in most cases, on simple biological criteria. A blood count abnormalities alone without iron deficiency is asserted if the serum ferritin is below normal reference values. Serum ferritin is the indirect reflection of the iron stock in the body. One mg / L serum ferritin is 8-10 mg of iron stores in the body. The values ​​of serum ferritin are dependent on sex: they are in men between 30 ng / mL (low value) and 150 ng / mL (high value). In women, the lower limit is often lower, between 10 and 12 ng / mL. More reduced iron stores in women explain these differences.At this early stage of iron deficiency, it is a decrease in serum iron and transferrin increased. Changing these parameters becomes difficult to interpret if associated inflammatory reaction. When iron stores are depleted, iron deficiency is heard on erythropoiesis. The changes are:

– Decrease in the percentage of transferrin saturation <0.16;

– Increased erythrocyte protoporphyrin;

– Increase the dispersion index of the volume of red blood cells expressed on automatic blood cell counters with the value red blood cells distribution width (RdW)

– Microcytosis with a mean corpuscular volume (MCV) of less than 80 mm3, often associated with anemia (hemoglobin less than 130 g / L in men and 110 g / L in women). The profound anemia develops gradually, which explains his usual tolerance due to compensatory mechanisms involved Clinical signs are late. It is fatigue, difficulties in ensuring physical or intellectual efforts of neurosensory events (dizziness, tinnitus), disorders of nail growth (koilonychia), atrophic glossitis, dysphagia with Plummer-Vinson syndrome, Geophagy of pagophagia or Trichophagia;

– A moderate increase in the number of platelets is normal (500 to 600 x 109 / L);

– Myelogram is unnecessary and is not justified in the diagnosis of iron deficiency with or without effects on erythropoiesis.

2- Circumstances may make it difficult biological diagnosis:

They are three in number:

– In case of inflammation, it is difficult to identify a possible component to deficiency anemia. Serum ferritin is increased, the lowered serum iron and transferrin lowered;

– In case of iron deficiency associated with folate deficiency, microcytosis is absent;

– In a patient treated with polyglobulique bled, it is necessary to respect the deficiency.

3- microcytosis:

It can be the witness of a thalassemia trait. Although ethnic backgrounds suggest this diagnosis, we must correct iron deficiency possibly associated before making a hemoglobin electrophoresis. Iron deficiency may mask an increase in the fraction of hemoglobin A2 (characteristic of b-thalassemia trait).

Treatment:

1- Curative treatment:

List of the main treatments containing iron
List of the main treatments containing iron

It is twofold: to restore iron stores in the body and remove the cause of the deficiency.

• Restore iron reserves replacement therapy: the restoration of the body’s iron stores is achieved by treatment with oral iron salts. The reference salt is sulfate: other salts exist, all as effective as each other (see table). There are many preparations, which in reality essentially differ in their content of metal iron. The dosage is 2 to 3 mg / kg of metal iron per day, preferably between meals. However, in about one third of cases, digestive disorders as nausea, epigastric, fullness appear 30 to 60 minutes after administration. Taking iron with meals to reduce gastrointestinal intolerance. In all cases, a black coloring stool appears: the patient must be prevented. Treatment should be continued for a period of six months or until correction of serum ferritin. Only such a strategy will avoid the risk of short-term recurrence.

Treatment with iron, by injection, is not useful and should be reserved exclusively for poor compliance or in case of major digestive malabsorption.

• Treat the cause of iron deficiency. It must in any case treat the cause of iron deficiency (see treatment of digestive tumors of uterine cancer) and reduce factors that aggravate iron deficiency.

2- Preventive treatment:

It seeks to reduce iron deficiency risk factors in high-risk patient groups. Diet rich in animal protein and especially meats.

1 mg / kg / day in pregnant women from the fourth month of pregnancy, unless the ferritin assay is high and can suggest hemochromatosis.

2-3 mg / kg for infants on the third or fourth month, especially in cases of premature or in case of iron deficiency in the mother. 1 to 2 mg / kg for one month after each blood donation, especially in women of childbearing age.

Highlights to understand:

• Iron deficiency is the result of an imbalance between excessive losses and inadequate intake to compensate for these losses. Iron stores depend on the age and certain physiological conditions (periods of genital activity, sports …).

• If these reserves are reduced, resulting in iron deficiency with appearance of microcytic anemia with low ferritin.

• To restore the reserve replacement therapy should be sufficiently prolonged. It should be also preventive in at risk patient groups.

Important points of the question:

Iron deficiency and microcytic anemia that results are the witness of an imbalance between excessive losses and inadequate intake to compensate for these losses. Digestive and uterine bleeding is the leading cause of iron deficiency. The decrease in ferritin is the first step of iron deficiency: it is the witness of lower iron stores in the body.Decreasing the percentage of transferrin saturation, microcytosis and anemia appear secondarily. A sufficiently prolonged replacement therapy, associated in all cases the treatment of the cause of iron deficiency, avoid the risk of relapse. The identification of high-risk patient groups (growth periods menstruation, frequent sports …) allows preventive treatment adapted.

Strong Points to remember:

• Iron deficiency is a common problem in hematology. It causes microcytic anemia associated with low levels of serum ferritin. It is high in most cases of digestive origin or uterine bleeding. Replacement therapy should be prolonged enough to prevent a recurrence: it must be associated with the removal of the cause of iron deficiency.The preventive treatment in high-risk patients should be systematic

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