- marrow production defects (hypoproliferation)
- red cell maturation defects (ineffective erythropoiesis)
- decreased red cell survival (blood loss/hemolysis).
Complete Blood Count
- MCHC = mean cell hemoglobin concentration; MCV = mean cell volume.
- hematocrit – fraction of packed red cells over total blood volume, determined indirectly from the red cell count and MCV.
- (MCHC) -quotient of hemoglobin divided by hematocrit.
- MCV useful in classifying the anemias caused by decreased red cell production
- Microcytic (small red blood cells) anemias have low MCV values and often low MCHC. Microscopically-small and often pale red cells.
- macrocytic anemias-MCV increased, microscopically– large, oval cells (macro-ovalocytes).
- Hemolytic anemias: hemolytic anemias are either normocytic or slightly macrocytic , because of many young red cells that are relatively large. Severe forms of thalassemia are an exception; there, microcytic red cells may be accompanied by brisk hemolysis. Reticulocyte Count
Useful for distinguishing anemias secondary to decreased red cell production from those caused by hemolysis
- index <2.5àproblem with morphology of Red cellà production problem of red blood cell (hypoproliferative) or formation (maturation)
- Index>2.5àdamage due to hemolysis/hemorrhage, due to increase of young cells from bone marrow
- normal individuals – 1%, red cell lifespan of approximately 120 days.
- The rate of red cell production can be assessed with absolute reticulocyte count, the product of the percentage of reticulocytes and the red cell count.
- normal blood contains about 50,000 reticulocytes/mm3.
- Need to consider distribution of reticulocytes between bone marrow and peripheral blood. When erythropoiesis is robust, marrow reticulocytes enter the circulation prematurely. “shift reticulocytes” appear larger than average on a routine (Wright-stained) blood smear, have a lavender hue, called polychromatophilia. Because the circulation of shift reticulocytes in the peripheral blood is prolonged, the reticulocyte count should be divided by two. Correction should always be made if normoblasts are encountered in the peripheral blood
- Failure to produce red cells is reflected in an inappropriately low reticulocyte count. In contrast, a significant elevation of reticulocytes is suggestive of hemolysis
Examination of the Blood Smear
- Important to examine this in addition to CBC and RC, especially with patients with hemolysis.
- Helps determine characteristic cell abnormalities in red cell morphology characteristic of hemolytic anemias.
- The presence of abnormal white cells may be the first clue to a lymphoproliferative or primary bone marrow disorder.
- variations in red cell size (anisocytosis), varioation in shape (poikilocytosis),
Bone Marrow Examination
Bona Marrow Examination: informative in the diagnosis of anemias of underproduction, those accompanied by abnormalities in white cells and/or platelets, suggesting a problem with hematopoiesis.
- assessment of the quantity and quality of red cell precursors may identify a defect in cell production due to either hypoplasia (misdevelopment) or ineffective erythropoiesis.
- marrow biopsy is required for estimating overall cellularity. The ratio of myeloid (M) to erythroid (E) precursors is normally about 2 : 1
- may be artifactually increased by the inclusion of circulating leukocytes.
- ratio is increased in patients with infection, a leukemoid reaction, or neoplastic proliferation of myeloid cells.
- Rarely, a high M/E ratio is due to selective aplasia of the red cell precursors.
- decreased M/E ratio indicates erythroid hyperplasia.
- Erythroid maturation is normal in hemolysis and hemorrhage, but it is disordered when erythropoiesis is ineffective, such as in megaloblastic and sideroblastic anemias and in β-thalassemia major or intermedia.
- presence of cellular infiltrates such as those found in leukemia, lymphoma, or multiple myeloma. demonstration of tumor, fibrosis, or granuloma usually requires a bone marrow biopsy, not just a bone marrow aspiration.
- 75% of all cases of anemia are hypoproliferative.
- majority of hypoproliferative anemias are due to mild to moderate iron deficiency or inflammation
- characterized by normocytic, normochromic red cells, but microcytic, hypochromic cells may be observed with mild iron deficiency or long-standing chronic inflammatory disease.
- Key laboratory tests to distinguish between forms: serum iron and iron-binding capacity, evaluation of renal and thyroid function, a marrow biopsy or aspirate to detect marrow damage or infiltrative disease, and serum ferritin to assess iron stores. An iron stain of the marrow will determine the pattern of iron distribution.
- low reticulocyte production index, macro- or microcytosis on smear, and abnormal red cell indices suggests a maturation disorder.
- nuclear maturation defects, associated with macrocytosis, and cytoplasmic maturation defects
- iron parameters are helpful in the differential diagnosis
Blood Loss/Hemolytic Anemia
- associated with red cell production indices 5 times normal
- Typically normocytic or slightly macrocytic, reflecting the increased number of reticulocyte