Macrocytosis – Spurious Causes

Causes of spurious macrocytosis.

Effect of storage time on mean cell volume (MCV). Red blood cells demonstrate time-dependent increase in size/volume during storage because water enters the cells, causing them to swell. This effect is more pronounced at room temperature compared to 4 degrees C. Because the weight of intracellular hemoglobin (and therefore the mean corpuscular hemoglobin [MCH]) remains constant, the mean corpuscular hemoglobin concentration (MCHC) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is important to perform a complete blood count (CBC) promptly after blood collection.

Effect of cold agglutinins on mean cell volume (MCV). Pentameric IgM antibodies bind to red blood cells (RBCs), causing RBC agglutination. This is appreciated on the peripheral smear (right) by the presence of RBC clumps (circled). (and therefore the mean corpuscular hemoglobin [MCH]) remains constant, the mean corpuscular hemoglobin concentration (MCHC) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is important to perform a complete blood count promptly after blood collection.

Effect of cold agglutinins on mean cell volume (MCV). In order to be sized and counted in automated hematology analyzers, red blood cells (RBCs) must pass single file through an orifice that has an electrical current. Each time a cell passes through the aperture it results in an increase in impedance whose magnitude (pulse height) is proportional to the particle volume. This is known as the Coulter principle. Normally, RBCs pass in single file as their numbers are counted and their volume measured. rpuscular hemoglobin [MCH]) remains constant, the mean corpuscular hemoglobin concentration (MCHC) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is important to perform a complete blood count promptly after blood collection.

Effect of cold agglutinins on mean cell volume (MCV). In cold agglutinin disease (CAD), single red blood cells (RBCs) and even some doublets can pass through the aperture, but not clumps of 3 or more cells. Doublets are counted as single cells, resulting in an artifactually increased MCV and decreased RBC count. rpuscular hemoglobin [MCH]) remains constant, the mean corpuscular hemoglobin concentration (MCHC) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is important to perform a complete blood count promptly after blood collection.

Effect of cold agglutinins on mean cell volume (MCV). The red blood cell (RBC) count takes a “double hit” from 1) large clumps not getting through the aperture, and 2) doublets being counted as single cells. The mean cell volume (MCV) is increased from doublets being counted as single cells. rpuscular hemoglobin [MCH]) remains constant, the mean corpuscular hemoglobin concentration (MCHC) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is important to perform a complete blood count promptly after blood collection.

Effect of cold agglutinins on mean cell volume (MCV). The hematocrit (Hct) is calculated from red blood cell (RBC) count and mean cell volume (MCV); since the RBC count is falsely low (disproportionate to the artefactual elevation in MCV), Hct is falsely low. rpuscular hemoglobin [MCH]) remains constant, the mean corpuscular hemoglobin concentration (MCHC) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is important to perform a complete blood count promptly after blood collection.

Effect of cold agglutinins on mean cell volume (MCV). The mean corpuscular hemoglobin concentration (MCHC) is calculated from hemoglobin (Hb) and hematocrit (Hct). The Hb is accurately measured since red blood cells are lysed for the assay to be carried out. Because Hct is falsely low, the MCHC is falsely elevated. rpuscular hemoglobin [MCH]) remains constant, the mean corpuscular hemoglobin concentration (MCHC) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is important to perform a complete blood count promptly after blood collection.

Summary of effects of cold agglutinins on mean cell volume (MCV) and other parameters of the complete blood. Lots of changes to remember! Start with the basics: doublets get through and are counted as one huge single cell (MCV up, RBC down). Triplets and higher don’t get through, so further reduction in RBC count (double hit) – so now we have artificially high MCV and artificially low RBC. Everything else follows from these changes, according to the formulas: Hct = RBC x MCV and MCHC = Hb/Hct.C) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is impo

Effect of hyperglycemia on on mean cell volume (MCV). High glucose may cause
spurious increase in MCV. This may seem counter-intuitive. After all, the red blood cells (RBCs) are surrounded by hypertonic, hyperosmolar plasma. Shouldn’t water follow the osmotic gradient, leak out of RBCs and cause them to shrink? Yes, but that’s in the circulation (in vivo, right vs. left container). What happens when blood is removed from a patient is a different story. When a CBC is performed a small amount of patient blood is added to isotonic diluent; it gets diluted 50,000-fold! As such, the RBCs are suddenly exposed to an isotonic solution, which they experience as hypotonic (see next slide). Water moves into the RBC, causing cell swelling and macrocytosis.

Effect of hyperglycemia on on mean cell volume (MCV). High glucose may cause
spurious increase in MCV. This may seem counter-intuitive. After all, the red blood cells (RBCs) are surrounded by hypertonic, hyperosmolar plasma. Shouldn’t water follow the osmotic gradient, leak out of RBCs and cause them to shrink? Yes, but that’s in the circulation (in vivo, right vs. left container). What happens when blood is removed from a patient is a different story. When a CBC is performed a small amount of patient blood is added to isotonic diluent; it gets diluted 50,000-fold! As such, the RBCs are suddenly exposed to an isotonic solution, which they experience as hypotonic (see next slide). Water moves into the RBC, causing cell swelling and macrocytosis.

Effect of hyperglycemia on on mean cell volume (MCV). Higher mean cell volume (same number of red blood cells) means falsely elevated fractional volume of RBCs (namely, hematocrit [Hct]). rpusan corpuscular hemoglobin [MCH]) remains constant, the mean corpuscular hemoglobin concentration (MCHC) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is important tocular hemoglobin [MCH]) remains constant, the mean corpuscular hemoglobin concentration (MCHC) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is important to perform a complete blood count promptly after blood collection.

Effect of hypernatremia on mean cell volume (MCV). Hypernatremia may cause
spurious increase in MCV for all the same reasons that hyperglycemia does. Both conditions are associated with a hyperosmolar environment in the circulation (in vivo), and a relatively hypotonic environment in diluent (in vitro). rpuscular hemoglobin [MCH]) remains constant, the mean corpuscular hemoglobin concentration (MCHC) must decrease (indicated by the increased proportion of central pallor in the above schematic). For this reason it is important to perform a complete blood count promptly after blood collection.

Effect of extreme leukocytosis on mean cell volume (MCV). White blood cells (WBC) and RBCs are counted in the same channel of an automated counter so that the MCV is actually the mean of both WBC and RBC volumes. Normally, RBCs vastly outnumber WBCs, so the latter have little effect on the MCV. However, when WBC counts are > 100 x 109/L and RBC counts low (for example leukemias), the MCV may be increased by up to 15-20 fL.However, in situations related to high WBC counts (especially when > 100 x 109/L, and low RBC counts (for example leukemias), the MCV may be increased by up to 15-20 fL.