aberrant reticulocytes

From: Nebe, Thomas C. (thomas.nebe@ikc.ma.uni-heidelberg.de)
Date: Tue Aug 17 1999 - 05:09:56 EST


Dear Collegues,

I want to comment as we have done some work on retics and flow to validate
the method.  The standard flow method is to gate on red cells in a log log
forward/sidescatter plot and to do a one dimensional histogram for green
fluorecence (eg. as done by the BD reticount software). This is prone to
many errors. The dyes in use are thiazol orange, auramin O, DEQTC or acridin
orange, depending on the patent situation. The absorbing dyes (HeNe
excitation) should not be used.

The false positive cells (non reticulocytes) include:
leukocytes (cave CLL and other leukemias)
nucleated red cells (normoblasts, eg. thalassemia without retics)
large platelets
parasite infected red cells 
and inclusions like Howell Jolly bodies (as already pointed out)

The dual parameter plot FSC vs fluorescence (as done in the Sysmex R3000)
improves this situation a lot.

Our solution we found optimal is to counterstain with the laser dye LDS751
(styryl 8), first introduced by Leon Teerstappen (published in 1988 in
Cytometry 9, 548-556).  This vital DNA stain emits in the red (FL3 channel
in the FACScan etc., 488 nm ecitation) and can be plotted versus green
(FL1).  By this way it is possible to discriminate retics from the cells
mentioned above.  

The method has beeen published: Bertsch T and Nebe CT, Flow-Cytometric
Analysis of Reticulocytes, in: Aspects of the Flow-Cytometric Analysis of
Red Blood Cells, K. Gutensohn, H.-H. Sonneborn and P. Kühnl (eds.), 69-80,
Clin. Lab. Publications (1997)

I fully agree that the analysis of reticulocytes improves the differential
diagnosis of anemias a lot.  It is therefore important not only to measure
the increse but also the decrease of retics and to report absolute numbers
with high precision. This requires dual fluorescence staining and
multidimensional gating.  Some new hematology analyzers present a good
compromise and we include a review of a blood smear in problem cases
(diagnosis).

I appreciate the discussion on this subject.

Regards
Thomas Nebe

Dr.med. C. Thomas Nebe
Universitaetsklinikum Mannheim
Zentrallabor
Theodor-Kutzer-Ufer 1-3
D-68167 Mannheim
*  +49 621 383-3485
*  +49 621 383-3819
e-mail: thomas.nebe@ikc.ma.uni-heidelberg.de
http://www.ma.uni-heidelberg.de/inst/ikc/



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