Q&A column

Editor: Frederick L. Kiechle, MD, PhD

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Q. What is the appropriate way to measure or identify microcytosis or macrocytosis?

A.December 2022—Mean corpuscular volume (MCV) is a measure of the average or mean volume or size of the total RBC population. MCV is used to indicate microcytosis (average RBC size smaller than the normal range) or macrocytosis (average RBC size larger than the normal range).

In contrast, modern hematology analyzers that are based on the principle of flow cytometry provide the volume and hemoglobin content of individual RBCs. On the Siemens Healthineers Advia 120 analyzer, having greater than 2.5 percent of the RBCs with a volume of less than 60 fL indicates microcytosis. The degree of microcytosis is graded as 1+ for 2.5 to 6.4 percent, 2+ for 6.5 to 10.5 percent, and 3+ for more than 10.5 percent of RBCs with a volume of less than 60 fL. Macrocytosis, on the other hand, is defined as greater than 2.5 percent of the RBCs with a volume of more than 120 fL but graded 1+, 2+, or 3+ in the same manner.¹

The routine evaluation of peripheral smears involves grading microcytosis and macrocytosis based on MCV ranges, such as normal, 80 to 99 fL; mild microcytosis, 70 to 79 fL; moderate microcytosis, 60 to 69 fL; or severe microcytosis, less than 60 fL. RBCs are usually not counted per microscopic field for grading purposes. A 2015 article by Constantino describes a similar MCV grading system as well as a 1+/2+/3+ grading system.²

1. Kakkar N, Makkar M. Red cell cytograms generated by an ADVIA 120 automated hematology analyzer: characteristic patterns in common hematological conditions. Lab Med. 2009;40(9):549–555.
2. Constantino BT. Reporting and grading of abnormal red blood cell morphology. Int J Lab Hematol. 2015;37(1):1–7.

Archana Agarwal, MD
Medical Director, Hematopathology and Special Genetics
ARUP Laboratories
Clinical Professor
University of Utah School of Medicine
Salt Lake City, Utah
Member, CAP Hematology/Clinical Microscopy Committee

Tim Skelton, MD, PhD
Medical Director, Core Laboratory and Laboratory Informatics
Lahey Hospital and Medical Center
Burlington, Mass.
Member, CAP Hematology/Clinical Microscopy Committee

Q. A six-year-old female with B-cell acute lymphoblastic leukemia and Rh-negative blood is being treated with myeloablative chemotherapy to achieve durable remission or as a bridge to stem cell transplantation, during which supportive transfusions will include repeated platelet transfusions over many weeks. Clinicians are concerned that the patient could become alloimmunized to the D antigen, which, in turn, could affect her ability to eventually bear children.

Apheresis platelets contain a small but finite amount of RBC contaminants, which are not usually quantitated. An optimal strategy to prevent anti-D alloimmunization is to use Rh-negative platelets, but they are often in short supply and cannot be ordered stat in a timely enough manner to ensure every platelet transfusion episode is Rh-negative. We considered using Rh immune globulin (RhIg). However, we recognize that commercial RhIg is designed to prevent D alloimmunization in the setting of obstetric fetal-maternal bleeding.

Is there an optimal dose for RhIg or suggested timing of administration to prevent anti-D alloimmunization in this setting?

A.The risk of rhesus D (RhD) alloimmunization in RhD-negative patients who receive RhD-positive platelets is very low. However, alloimmunization may be significant for females with childbearing potential because it could lead to hemolytic disease of the fetus and newborn.^1,2 Because of this low but possibly impactful risk, it is preferable to provide RhD-negative platelets for RhD-negative patients who have childbearing potential. Some transfusion services will consider implementing alloimmunization mitigation strategies if RhD-positive platelets are transfused, while others will not because the risk of alloimmunization is low.³

RhIg has been evaluated and used successfully to prevent D alloimmunization in RhD-negative women who are carrying an RhD-positive or RhD-unknown fetus. Clinical studies of RhIg have defined dosing, timing of administration, and efficacy in this context.⁴ However, to our knowledge, clinical studies have not evaluated RhIg dosing, timing, and efficacy in the context of preventing RhD alloimmunization after platelet transfusions.