Hematology 2

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Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Hematology 2
Iron Deficiency Anemia
Stages of iron deficiency
normal
iron stores
serum ferritin
(ng/ml)
transferrin
saturation (%)
RBC morphology
normal
50 – 200
negative
iron
balance
↓
< 20
irondeficient
erythropoiesis
↓↓
< 15
iron
deficiency
anemia
↓↓↓
< 15
30 – 40
normal
< 20
< 10
normal
normal
normal
Causes of iron deficiency
Increased demand for iron and/or hematopoiesis
Rapid growth in infancy or adolescence
Pregnancy
Erythropoietin therapy
Increased iron loss
Chronic blood loss
Menses
Acute blood loss
Blood donation
Therapeutic phlebotomy
Decreased iron intake, absorption, or use
Inadequate diet
Malabsorption (sprue, Crohn’s disease, resection)
Acute or chronic inflammation
Iron store measurements
Iron stores
serum ferritin (ng/ml)
0
< 15
1 – 300 mg
15 – 30
300 – 800 mg
30 – 60
800 – 1000 mg
60 – 150
1–2g
> 150
iron overload
> 500 – 1000
1/4
microcytic
hypochromic
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Treatment
 oral iron therapy: 200 – 300 mg elemental iron → absorption of up to
50 mg iron
 parenteral iron therapy (iron dextran – adverse effects, esp.
anaphylaxis in 0.7%, iron gluconate – Ferrlecit safer)
The amount of iron needed:
Body weight (kg) x 2.3 x (15 – patient’s hemoglobin, g/dl) + 500 or 1000 mg
(for stores)
Anemia of acute and chronic disease
 One of the most common forms of anemia. Serum ferritin levels are often
increased. Suppression of erythropoiesis by inflammatory cytokines
(TNF, interferon beta and gamma, IL-1). Anemia of cancer is usually
normocytic and normochromic. In rheumatoid arthritis or chronic
infections, anemia is microcytic and hypochromic.
Acute infection can produce a fall in hemoglobin levels of 2-3 g/dl within one or
two days, which is largely related to hemolysis.
Anemia of renal disease
The level of the anemia correlates with the severity of the renal failure.
Red cells are normocytic and normochromic. Reticulocytes are decreased.
Cause: inadequate production of erythropoietin, reduction in red cell survival.
Serum iron and ferritin levels are usually normal. In dialyzed patients iron
deficiency may develop.
Erythropoietin treatment: 50 – 150 U/kg three times a week subcutaneously.
Megaloblastic anemias
Cobalamin deficiency
1
inadequate intake (vegetarians)
2
malabsorption
a. defective release of cobalamin form food
 gastric achlorhydria
 partial gastrectomy
 drugs that block acid secretion
b. inadequate production of intrinsic factor
 pernicious anemia
 total gastrectomy
c. disorders of teminal ileum
 tropical sprue
2/4
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák




nontropical sprue
regional enteritis
intestinal resection
neoplasms and granulomatous diseases
Folic acid deficiency
1
inadequate intake (alcoholics)
2
increased requirements
 pregnancy
 infancy
 malignancy
 chronic hemolytic anemias
 chronic exfoliative skin disorders
 hemodialysis
3
malabsorption
 tropical sprue
 nontropical sprue
 drugs (phenytoin, barbiturates)
4
impaired metabolism
 inhibitors of dihydrofolate reductase: methotrexate, trimethoprim,
pyrimethamine
 alcohol
Cobalamine deficiency
Symptoms of anemia – weakness, vertigo, tinnitus, palpitations, angina.
Anemia may be very severe but is well tolerated.
Subicterus is common (high erythroid cell turnover in the marrow).
Smooth and sore red tongue. Megaloblastosis of the intestinal epithelium →
malabsorption.
Neurologic manifestations: demyelination, axonal degenereation, neuronal
death → numbness, paresthesia, weakness, ataxia. Disturbances of mentation
up to frank psychosis.
Pernicious anemia – absence of intrinsic factor from either atrophy of the
gastric mucosa or autoimmune destruction of parietal cells.
The incidence of pernicious anemia is increased in patients with other
immunopathologic disease – thyrotoxicosis, myxedema, thyroiditis,
hypoparathyroidism. Antiparietal cell antibody, or anti-IF antibody.
Helicobacter pylori does not cause parietal cell destruction.
Dg: macrocytosis > 100 fl, low reticulocyte count, leukocyte and platelet
count may also be decreased. Neutrophils show hypersegmentation of the
nucleus.
Unconjugated
bilirubin
is
increased.
3/4
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Iron absorption by the intestinal villous cell
Intestinal lumen
Fe+++ → Fe++
DMT-1
Villous
cell
Dcytb
ferritin
Fe++
ferroportin 1
hephaestin
(IREG-1)
Basolateral
surface
Fe++
Fe+++ bound to Tf
4/4
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