Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 2183-2184
CORRESPONDENCE
Difficulties in Determining Prophylactic Transfusion Thresholds
of Platelets in Leukemia Patients
 |
LETTER |
To the Editor:
It was recently pointed out that platelet transfusion thresholds of
10,000 platelets/µL, as opposed to 20,000/µL, reduce platelet transfusions by approximately 20% in leukemic patients without increasing any major risk of bleeding.1
Others2,3 have suggested that an even lower transfusion
threshold of 5,000 platelets/µL may be sufficient. We believe that
the main difficulties in determining the suitable threshold for
platelet transfusion are presently caused by (1) the technical
insufficiencies of conventional automated blood analyzers and (2) the
existence of platelet-derived microparticles (or membranes) that can
improve hemostasis.4 Without any consideration of these
factors, determining platelet transfusion thresholds may remain costly
guesswork.
(1) Most instruments used in laboratories to establish the platelet
count do not recognize platelets but are only capable of counting
particles within a defined size limit. Therefore, microcytic
erythrocytes, schizocytes, cell debris, air bubbles, chemical
precipitates, etc, mingle with electronic noise and true platelets,
which, especially at low platelets levels and in the case of
drug-induced leukemic cell destruction, can cause major errors in
platelet counting.5,6 Rebulla et al,1 authors of a recent study, who chose a prophylactic transfusion level of 10,000 platelets/µL and not the lower 5,000 platelet/µL threshold, admitted doing so mainly because they could not trust the accuracy of
platelet counts at low levels in automated blood analyzers.
We have shown in the past that the use of fluorescent platelet-specific
antibodies (ie, anti-CD61, anti-CD41, or anti-CD42b) and multiparameter
flow cytometry in establishing platelet counts can bypass the problems
most blood analyzers have at low platelet levels.5
Immunodetection of cells/plateletes with flow cytometry is no longer an
elusive method but is part of everyday routine in many laboratories.
Manufacturers of automated blood analyzers have recognized this new
trend and are starting to integrate the immunodetection of
cells/platelets into their routine repertoire. This will hopefully
improve the accuracy of automated platelet counts in the future.
(2) Perhaps as important as the accurate enumeration of platelets is
the identification of platelet-derived microparticles that fall below
the normal platelet size-threshold of approximately 2 fL.6
In a survey of 14 patients with acute myelogenous leukemia receiving
myelotoxic chemotherapy, we observed that the levels of
platelet-derived microparticles (defined as the percentage of
CD61+/CD42b+ particles smaller than 2 fL; Fig
1) in the same patient may vary from near
0% to 76% of the total platelet events. Levels of microparticles in
normal controls (n = 10) ranged from 0.4% to 7.9% (mean, 4.8%). At
the time of diagnosis, the percentage of microparticles often distinctly increased (up to 13-fold) above the normal mean. Bleeding episodes were not observed during chemotherapy when counts of normal-size (>2 fL) platelets were between 5,000 and 10,000/µl and
microparticle levels were similar or higher than those of normal-size
platelets. Bleeding episodes (gastrointestinal bleeding and hematuria)
seen in 4 patients during chemotherapy were associated with reduced
platelet microparticle levels (<2%) and total platelet events
of 2,300, 2,700, 3,400, and 4,900/µL, respectively.
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| Fig 1.
Flow cytometric analysis (contour plot) of platelets and
platelet-derived microparticles in a patient with acute myelogenous
leukemia (A) and a normal individual (B) using anti-CD61 and anti-CD42b
antibodies. Whole blood was treated with platelet-specific fluorescent
antibodies as described previously.5
CD61+/CD42b+ events (n = 50,000),
representing platelets and platelet-derived microparticles, were gated
and are shown in forward and side scatter mode. Normal-size platelets
(>2 fL) and platelet-derived microparticles (<2 fL) were defined as
shown in the graph by a size-threshold of 2 fL, established with the
help of fluorescent calibration beads.
|
|
These observations indicate that a platelet transfusion threshold of
5,000/µL formerly suggested by Gmür et al2 (who
used a time-consuming microscopic platelet counting method) is more appropriate than the 10,000/µL platelet threshold suggested recently by Rebulla et al1 provided that automated
technology based on immunodetection is used for platelet counting. This
may lead to a further considerable reduction in platelet transfusions
and costs (despite the possible investment needed to update laboratory equipment). Furthermore, our results suggest that the favorable role of
platelet-derived microparticles in hemostasis needs to be given more
consideration in platelet transfusions.
Wolfram Springer
Alexander von Ruecker
Laboratory
Hematology
University of Bonn
Bonn, Germany
Roswitha Dickerhoff
Kinderklinik St Augustin
St Augustin,
Germany
| |
REFERENCES |
1.
Rebulla P,
Finazzi G,
Marangoni F,
Avvisati G,
Gugliotta L,
Tognoni G,
Barbui T,
Mandelli F,
Sirchia G:
The threshold for prophylactic platelet transfusion in adults with acute myeloid leukemia.
N Engl J Med
337:1870,
1997[Abstract/Free Full Text]
2.
Gmür J,
Burger J,
Schanz U,
Fehr J,
Schnaffner A:
Safety of stringent prophylactic platelet transfusion policy for patients with acute leukaemia.
Lancet
338:1223,
1991[Medline]
[Order article via Infotrieve]
3.
Murphy WG:
Prophylactic platelet transfusion in acute leukaemia.
Lancet
339:120,
1992[Medline]
[Order article via Infotrieve]
4.
Owens MR:
The role of platelet microparticles in hemostasis.
Transfus Med Rev
8:37,
1994[Medline]
[Order article via Infotrieve]
5.
Dickerhoff R,
Von Ruecker A:
Enumeration of platelets by multiparameter flow cytometry using platelet-specific antibodies and fluorescent reference particles.
Clin Lab Haematol
17:163,
1995[Medline]
[Order article via Infotrieve]
6.
Rowan RM:
Platelet counting and the assessment of platelet function
, in Koepke JA
(ed):
Practical Laboratory Hematology.
New York, NY, Churchill Livingston
, 1991
, p 157
