1. Frequent blood donations. Iron deficiency anemia may occur in regular blood donors, as well as from daily I/V (phlebotomy) for laboratory analysis in hospitalized patients (nosocomial iron losses). It occurs in hospital conditions from repeated phlebotomies for various medical analyses. In US hospitals, it has been observed that the blood lost due to diagnostic phlebotomy is 12.4 ml/day or 175 ml during the entire hospitalization period. In intensive care units, daily blood loss can reach up to 41.5 ml/day or 762 ml during the entire stay in this service.
Out of 100 studied patients, 36 of them needed blood transfusions due to blood loss from diagnostic phlebotomy. This amount of blood can cause the appearance of iron deficiency anemia in a patient within the limits of the body's iron reserves or worsen an existing iron deficiency anemia. Regular blood donation can be one of the causes of iron loss. Each blood donation of 400-450 ml contains about 250 mg of iron. Just one donation can deplete a woman's iron reserves, while 3 or 4 donations can affect men's reserves.
In many blood centers, measuring Hb is the only index to assess the iron status. By measuring ferritin, it has been seen that iron reserves can decrease by 8% in men and 23% in women after just one donation. With an increase in the frequency of donations, the possibility of developing iron deficiency also increases. After 5 donations in a year, 8% of men and 38% of women have iron deficiency. In this way, giving supplemental iron would reduce the incidence of iron deficiency and should be recommended to individuals who donate more than 1-2 times a year.
2. Loss during and after surgical interventions.
3. Frequent blood withdrawals for analysis, especially in individuals predisposed to Iron Deficiency).
Anemia from self-harm. Encountered more among unmarried, hyperactive, obsessive, intelligent, depressive women who work in the medical service, through different ways of blood loss.
Patients with dialysis develop iron deficiency anemia in 50% of cases. The causes are increased blood loss and frequent laboratory examinations. The amount of iron lost can reach up to 1.5-2 gr/year. G-I blood losses can reach up to 6.27 ml/day in one study. Other factors affecting the negative iron balance include malabsorption of iron caused by the use of aluminum hydroxide to control hypophosphatemia. Supplemental iron should be used in patients undergoing dialysis.
Intravascular Hemolysis
1. March Hemoglobinuria. In a study in the USA, it has been observed that 56% of competitive runners (athletes) have iron deficiency. March hemoglobinuria. It is caused by the destruction of RBCs in the blood vessels, among the small bones of the feet, especially during long marches or runs. Although there are no schistocytes (RBC fragments) in peripheral blood, the data indicate an acute mechanical intravascular hemolysis (mechanical destruction of circulating RBCs). Therefore, there is destruction of RBCs within the blood vessel, with hemoglobinemia and when the level of haptoglobin is exceeded, there will be hemoglobinuria and hemosiderinuria.
Body parts, e.g., the foot, during physical exercises, must forcefully hit a hard surface. Affects men more, especially in their second decade. Perhaps it is related to greater muscle participation in physical exercises and the use of greater force. It occurs more among athletes at the beginning of their careers or when exercises are performed with effort. Athletes with March Hemoglobinuria have a long and fast stride, so hemolysis also depends on the running style.
March Hemoglobinuria also occurs due to protein defects of RBC MP. Besides long walks, fast and competitive runs, anemia is also seen in drummers, karate practitioners, and patients with early-onset dementia, who hit their heads hard every 20-30'.
In 21 out of 24 runners after a race, an increase in iron elimination in feces was observed, peaking 24 hours after the race. In 7 out of 21 runners, the amount of blood lost during the day is 3 ml. It is thought to come from transient ischemia of the Gastrointestinal Apparatus, during intense exercises (when sufficient perfusion with blood is not achieved) because most of the blood is concentrated in the muscles.
2. Hemosiderinuria, hemoglobinuria, and pulmonary hemosiderosis. Hemoglobinuria and hemosiderinuria occur in PNH (Paroxysmal Nocturnal Hemoglobinuria), but can occur in any acute intravascular anemia. Iron is lost with urine in the form of RBC, hemoglobinuria, hemosiderinuria, and myoglobinuria (in crash syndrome). If the urine appears red, but does not contain RBCs, it should be checked for hemoglobinuria, hemosiderinuria, myoglobinuria.
The difference between hemoglobinuria and myoglobinuria is easily made with 60% ammonium sulfate, which precipitates Hb but not Mb. Hemosiderin is detected intracellularly. Most of these patients have little or no plasma haptoglobin. Pulmonary hemosiderosis can cause significant iron loss as hemosiderin from the lungs.
Normally, iron losses in urine are < 0.1 mg/day. In case of intravascular hemolysis, losses can reach 3-11 mg/day, in the form of hemosiderinuria. In the case of PNH, there's an iron loss with hemoglobinuria of 1.8-7.8 mg/day.
3. Cardiac patients with malfunctioning valve prostheses, repairs of heart walls, intracardiac myxomas. In the early days of artificial valve implantation (heart surgery), this mechanism of AF development was common in university hospitals. Now, with the use of better prostheses, it has become a less common problem. In less severe hemolytic anemias, there is no significant hemoglobinuria.
Unknown cause (idiopathic hypochromic anemia). When no apparent cause for the development of iron deficiency and its clinical consequences is found, the term "idiopathic hypochromic anemia" is used. In this group, the entire clinic and laboratory are those of iron deficiency anemia, but only the cause of the iron deficiency is not found.
50% of Iron Deficiency Anemias in adult females (during the reproductive period) are related to menstrual cycle losses, gastrointestinal losses, and pregnancy.
Often there is a combination of causes (multifactorial).
The patient usually seeks medical attention when the Hb value reaches 7-8 gr/dl, because it develops gradually and the Cardiovascular System adapts to this Hb value (with an increase in heart rate, blood ejection volume, etc.).
A single blood loss causes posthemorrhagic anemia which is normochromic, normocytic. AF (hypochromia, microcytosis) will be caused by chronic and small blood losses. EPO is stimulated to increase Hb production until iron depots are depleted. When depots are depleted, Hb synthesis is impaired and hypochromic, microcytic erythrocytes are produced.
The maximum changes (thus in peripheral blood we will have only the hypochromic, microcytic cell population) in RBC cellular indicators occur in about 120 days (the lifespan of an erythrocyte), i.e., for 4 months as long as it takes for the normochromic, normocytic RBC population produced before depletion of iron depots to be completely replaced by hypochromic microcytes. During this period, there will be two populations normochromic, normocytic and hypochromic microcytic (at least when there are no deficiencies of other vitamins (Vitamin B12, Folic Acid, Vitamin E, etc.).
The replacement of populations (thus on the slide we will see hypochromic, microcytic erythrocytes) will be accompanied by an increase in RDW (in the device). If in the peripheral blood analysis there is a more pronounced decrease in Hb than the decrease in RBC and MCV stays within normal values or slightly lower than normal, consider the presence of two erythrocyte populations (microcytic and macrocytic), thus also consider Folic Acid deficiency.
Therefore, in the description of the morphology of the red series (in the peripheral blood smear stained with Gimsa) we distinguish microcytic, hypochromic erythrocytes and some elements of poikilocytosis, where Pencil cells (Eleptocytes) predominate.
A bone marrow examination is not necessary, it is done when other pathologies are suspected. Perl's staining is negative (unlike in refractory anemias), because the Fe reserves are empty.
Iron in serum and iron binding capacity. In peripheral blood, sideremia (< 60 γ/dl) and ferritinemia (< 20 ng/ml or μg/l ) are low. The most important indicator is ferritinemia, which is the best evaluator of iron depots.
The best evaluation of iron depots is done with ferritinemia (10% of ferritin circulates in serum, as ferritinemia). Values lower than 12 (for some 15 or 20) g/l are equivalent to iron deficiency anemia (iron in the composition of macrophages of the bone marrow and liver is decreased or absent). WHO defines iron deficiency when the ferritin value is lower than <12 µg/L in children < 5 years and less than <15 μg/L in those ≥ 5 years.
Overall iron stores are calculated based on the current ferritin value (which represents only 10% of all iron depots) ≈ (8 - 10) x ferritin (ng/mL)
Iron stores (mg) ≈ (8 to 10) x ferritin (ng/mL)