INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
Spurious counts and spurious results on haematology
analysers: a review. Part I: platelets
M. ZANDECKI, F. GENEVIEVE, J. GERARD, A. GODON
Haematology Laboratory,
University Hospital of Angers,
Angers, France
Correspondence:
M. Zandecki, Haematology Laboratory, University Hospital of Angers, 4
rue Larrey, 49000 Angers, France.
Tel.: +33 2 41 35 53 53; Fax:
+33 2 41 35 55 99;
E-mail: mazandecki@chu-angers.fr
doi:10.1111/j.1365-2257.2006.00870.x
Received 30 January 2006;
accepted for publication 30 July
2006
Keywords
haematology analysers, automated
count, cell blood count, spurious
count, platelets
SUMMARY
The widespread use of haematology analysers (HA) has led to a major
improvement of cellular haematology, because of quick and accurate
results found in most instances. However, in several situations, spurious
results are observed. Inadequate blood samples, situations induced by the
anticoagulant(s) used, peculiar changes related to the pathology in the
patient, and technical considerations about performances of the various
HA must be considered. Spurious thrombocytopenia occurs in several
circumstances related to the presence of ethylenediamine tetra-acetic
acid (EDTA) used as the anticoagulant. Mechanism of EDTA-dependent
platelet (PLT) agglutination is related to circulating (auto)antibodies
directed against normally hidden epitope(s) in the glycoprotein alpha
IIb/beta IIIa complex from PLT membrane exposed only in the presence
of EDTA. Other spuriously low PLT counts may be related to EDTA,
including PLT rosetting around white blood cells (WBC; satellitism) and
PLT-WBC aggregates, but mechanisms responsible for those latter
phenomena are less well known. Spurious increase of PLT count may
be related to several situations, including fragmented red blood cells,
cytoplasmic fragments of nucleated cells, cryoglobulins, bacteria or fungi,
and lipids. Flags generated in several of these situations alert the operator
on possible abnormal findings and may identify the problem. Analysing
only PLT parameters is not sufficient: in many situations the WBC
differential scattergram is of crucial help for flagging. Flags generated
depend on the software version on the HA used, the performance in
detecting the same anomalies may differ according to which analyser is
used, even those from the same manufacturer. Operators must be aware
of the characteristics of their analyser and be able to recognize and
circumvent anomalous results.
INTRODUCTION
For haematology analysers (HA), blood cells correspond to particles that differ according to various phys-
ical parameters including size, impedance and light
scattering. Quick and accurate results are the rule, in
both normal and abnormal samples. However, in several instances related to abnormal characteristics of
2007 The Authors
4
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
the sample, corresponding either to a peculiar pathology in the patient or to changes induced after sampling, HA may generate erroneous results for one (or
more) parameter(s) of the cell blood count (CBC),
because of performance limitations. Such failures to
determine accurately one or more of the blood components began to be reported as soon as HA began to
replace manual techniques (late 60s). In the early 80s,
improvement of instrument hardware and software
led to a higher degree of analysis of abnormal results.
Quality and control of data increased dramatically in
many ways, including various internal flagging routines generated in order for analytic errors to be
detected more accurately and graphic presentation of
particle analysis for identification and enumeration of
specific blood components. Development of new indices or parameters outside the classical red blood cell
(RBC) indices, such as red cell distribution width
(RDW), mean platelet volume (MPV), percentage of
hypochromic or macrocytic RBC, that will not be discussed extensively here, also led to many studies
regarding their possible use in haematological practice.
Even on the most recent HA, most of the anomalies are related either to a specific condition of the
patient, or to the sampling condition [aggregation of
blood platelets (PLT), white blood cells (WBC) and
red blood cells (RBC) in presence of EDTA for example], or to the principle of the technology used for the
analysis of blood samples. It is important to note that
every HA is affected with at least one part of spurious
measurements, although the degree by which the
count is affected varies. Over the years, manufacturers
have taken these problems into account and are continuously improving the performances of their instruments, and providing educational programme using
oral information for technical and biological staff and
printed or on-line information, corresponding to the
so-called « user’s guide for the automate ». However,
in some smaller HA, the software, histograms and/or
graphs and/or flags are less complex or even absent,
leading to inability to detect at least part of spurious
counts. So, as Bain and Bates (2001) stated « it is
important for instrument operators to be familiar with
the types of factious results to which their instrument
is prone ». Our aim was to give information on the
most current situations leading to the inability of HA
to perform accurate counts for individual blood cell
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS 5
components. The first part of this paper will focus on
abnormal PLT counts, whereas abnormal counts and
measurements related to the other parameters of the
cell blood count (CBC), including WBC, RBC, haemoglobin (Hb), RBC indices, and reticulocytes will be discussed in the second part of this paper.
GENERAL CONSIDERATIONS ABOUT
PLATELET COUNTS
On impedance-type instruments (including: BeckmanCoulter, Miami, FL, USA; ABX, Kyoto, Japan; Abbott,
Abbott Park, IL, USA; Sysmex, Kobe, Japan; Bayer,
Tarrytown, NY, USA; and other instruments) particles
analysed are suspended in an electrolyte solution and
the dilution is passed through an aperture that links
two chambers, one containing a positive and the
other a negative electrode. As cells pass through the
orifice they cause a momentary increase in electrical
resistance, which registers as a pulse. One pulse represents a cell and the size of the pulse is proportional to
the size of the cell. Using this principle PLT and RBC,
which are both analysed in the same channel(s), are
discriminated according to their volume, and volume
histograms are generated next. For PLT, the histogram
generates a log curve if the distribution of PLT volumes fits that of a (log) normal distribution: eventually all particles located under the fitted curve are
considered as PLT. Mean PLT volume ranges from 6
to 10 fl, but impedance-type counters analyse particles
ranging from 2 to 20 fl and, according to the fitted
curve, the upper threshold that discriminates PLT
from RBC may either be at 36 fl or may vary automatically depending on the characteristics of individual blood samples (Sysmex). Instrument flags are
triggered for cases corresponding to inability to separate clearly PLT from RBC. On laser-type HA (Abbott,
Bayer, others) each particle passes through a laser
beam and scatters light that is detected by a photodiode (or related). The amount of light scattered (at
one, two, or even four angles for some HA) is proportional to the area and therefore to the volume of the
particle. PLT are identified on a scatter histogram
based on their volume (1–30 fl) and refractive index
values (1.35–1.40). Some HA provide up to three
counts on the same dilution if required, corresponding
to optical, impedance, and immunological (CD61)
counts (Abbott). Other HA may determine, if
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
M. ZANDECKI ET AL.
M. ZANDECKI ET AL.
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS
required, an optical PLT count together with the reticulocyte count, after the use of a RNA fluorescent
stain (Sysmex). An accurate PLT count is the rule in
most instances, but several situations lead to spurious
results (Table 1).
SITUATIONS LEADING TO SPURIOUSLY
LOW PLT COUNTS
Pseudothrombocytopenia related to EDTA
anticoagulant
Ethylenediamine tetra-acetic acid (EDTA)-dependent
pseudothrombocytopenia (EDP) is an in vitro phenomenon caused by specific proteins from the samples that
react with PLT only in EDTA-anticoagulated blood and
produce PLT clumps (Gowland et al., 1969; Watkins &
Shulman, 1970; Shreiner & Bell, 1973; Berkman et al.,
1991; Bizzaro & Brandalise, 1995) (Figure 1a). HA do
not enumerate PLT from the large clumps and the
number printed corresponds to that from a mixture of
small clumps and unaggregated PLT, leading to PLT
counts as low as 20 · 109/l, whereas the accurate
number is within normal ranges (Cohen et al., 2000).
Anticoagulants other than EDTA (citrate, oxalate and
heparin) are also concerned in several reports
(Watkins & Shulman, 1970; Shreiner & Bell, 1973;
Onder, Weinstein & Hoyer, 1980; Pegels et al., 1982;
Savage, 1984; Payne, 1985; Lombarts & de Kieviet,
1988; Cunningham & Brandt, 1992; Bizzaro, 1995). As
thrombocytopenia discovered in a patient may induce
several procedures including unnecessary bone
marrow aspiration or/and PLT transfusion, recognition
of this phenomenon is important (Payne & Pierre,
1984; Vicari, Banfi & Bonini, 1988; Foresti et al., 1990;
Berkman et al., 1991; Bizzaro & Brandalise, 1995;
Cohen et al., 2000). The most important feature related
to this condition is that it is unaccompanied by any
signs or symptoms of haemorrhage. In some instances,
pseudothrombocytopenia was reported to hide either
true thrombocytopenia (Forscher et al., 1985) or
thrombocytosis (Dahlqvist, Nilsson & Norberg, 1988).
In addition to generating spurious PLT count, PLT
clumps may be as large as WBC and may be enumerated as such by HA (discussed in part II).
The prevalence rate of EDP was reported as 0.07–
0.20% according to the authors (Payne & Pierre,
1984; Savage, 1984; Vicari, Banfi & Bonini, 1988;
Garcia Suarez et al., 1991; Bartels, Schoorl & Lombarts, 1997; Sakurai et al., 1997). Prevalence was
0.2% in plateletpheresis donors (Sweeney et al.,
1995). For hospitalized patients, 0.1–2.0%, incidence
was reported (Manthorpe et al., 1981; Payne & Pierre,
1984; Savage, 1984; Bragnani et al., 2001). Up to 17%
of patients referred to the outpatient clinic for isolated
thrombocytopenia were in fact found to have EDP
(Silvestri et al., 1995; Cohen et al., 2000). According to
the various reports, EDP may or may not be either
Table 1. Situations leading to altered platelet counts on haematology analysers
Alteration of other parameters
Spurious decrease
PLT agglutination (EDTA, but other anticoagulants may be concerned)
PLT satellitism (mainly related to EDTA)
Around polymorphs
Around other WBC (normal; pathological)
PLT-neutrophil agglutination (mainly related to EDTA)
Large PLT (outside the normal range)
Coagulation within the sample
Overfilling the sample (inadequate mixing)
Spurious increase
Fragmented RBC (schistocytes, severe iron deficiency anaemia, burns)
Cytoplasmic fragments of nucleated cells (leukaemia, lymphoma cells)
Cryoglobulins, cryofibrinogen
Bacteria
Fungi (Candida)
Lipids (samples taken after a meal, lipid drips)
PLT aggregates enumerated as WBC
WBC count spuriously low
Enumerated together with WBC
Abnormal CBC
Abnormal CBC
RBC count spuriously low (anecdotal)
WBC count spuriously increased
WBC and haemoglobin spuriously high
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
6
(a)
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS 7
(b)
Figure 1. (a) EDTA-induced thrombocytopenia. Aggregates observed on peripheral blood smears may contain variable number of PLT within each clump. Some PLT clumps are large enough to be enumerated as WBC by HA. (b)
Platelet satellitism around polymorphs (1). In some instances PLT satellitism is the first part of a peculiar phenomenon that develops within several hours into the sample: PLT migrate to one pole of the polymorph (2), clump
together (3), and eventually leave the polymorph (4) (peripheral blood smear; MGG staining).
slightly more frequent in males and/or in older
patients (Berkman et al., 1991; Garcia Suarez et al.,
1991; Casonato et al., 1994; Bizzaro, 1995; Sakurai
et al., 1997; Bragnani et al., 2001). Patients are either
healthy at the time of presentation or, when diseases
are present, they are heterogeneous (Boehme, Mahmood & Phanuphak, 1980; Veenhoven, Van der Schans
& Nieweg, 1982; van der Lelie, van der Plas-Van
Dalen & von dem Borne, 1984; Solanki & Blackburn,
1985; Garcia Suarez et al., 1991; Casonato et al.,
1994), although some reports hypothesized a possible
relationship with either autoimmune or clinically evident neoplastic pathology (Imai et al., 1983; Bragnani
et al., 2001) but in fully healthy patients no clinical
manifestation of disease occurred, up to 10 years after
follow-up (Bizzaro, 1995). EDP may appear during
the hospitalization period (Berkman et al., 1991; Garcia Suarez et al., 1991; Huss et al., 1995; Gschwandtner et al., 1997), or may be transient (Takeuchi et al.,
1993; Mori et al., 2000), or an increase in the amount
of the related agglutinin may be observed under the
same circumstances (Edelman & Kickler, 1993). EDP
is not restricted to humans and has been reported in a
horse (Hinchcliff, Kociba & Mitten, 1993). EDP has no
relationship with the enhanced PLT activity considered to play a role in the pathogenesis of arterial
thrombosis, such as cerebral and myocardial infarction
(Konstantopoulos et al., 1995). But, in the latter
instance, PLT aggregates may be generated in vivo and
enumerated on HA if the relevant blood samples are
anticoagulated with sodium citrate (Shimizu et al.,
2003).
The first important observation concerning the
mechanism of aggregation in EDP was that serum or
EDTA-plasma not only induced agglutination of PLT
from the patient but also induced agglutination of
EDTA-PLT from nearly all normal individuals
(Watkins & Shulman, 1970; Shreiner & Bell, 1973;
Veenhoven et al., 1979; Onder, Weinstein & Hoyer,
1980; van der Lelie, van der Plas-Van Dalen & von
dem Borne, 1984), with the exception of PLT from
patients with Glanzmann’s disease, suggesting that the
fibrinogen receptor, Glycoprotein (GP) alpha IIb beta
IIIa (GPIIb/IIIa), was involved in EDP (Pegels et al.,
1982; Casonato et al., 1994; Ryo et al., 1994; Bizzaro,
1995; Schrezenmeier et al., 1995). Indirect evidence is
shown with artifactual pseudothrombocytopenia that
develops frequently in patients following exposure to
PLT GPIIb/IIIa receptor antagonists (Christopoulos &
Machin, 1994; Stiegler et al., 2000). Other authors
implicated either a 78-kDa PLT GP related to GPIIb/
IIIa complex (De Caterina et al., 1993), or more precisely GPIIb (Ginsberg et al., 1986; van Vliet, KappersKlunne & Abels, 1986; Fiorin et al., 1998). A new
monoclonal antibody was recently developed that
recognized an epitope on the alpha IIb/beta IIIa
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
M. ZANDECKI ET AL.
M. ZANDECKI ET AL.
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS
integrin, whose accessibility was increased upon EDTA
treatment of PLT (Dabadie et al., 2001). So far, the
most likely hypothesis is that the antigen-binding site,
normally hidden (cryptic) in the GPIIb/IIIa complex is
modified by EDTA or exposed only in the presence of
EDTA. Some authors observed that PLT antibodies
were associated to antiphospholipid antibodies in most
patients tested, suggesting that antibody subpopulations (naturally occurring autoantibodies?) directed
against negatively charged phospholipids could bind
to antigens modified by EDTA on the platelet membrane, and might be responsible for pseudothrombocytopenia genesis (Bizzaro & Brandalise, 1995). In
most instances, no abnormality of PLT function was
reported in association with EDP (Casonato et al.,
1994). Abnormal PLT from myeloproliferative diseases
have been shown to be much more sensitive than
normal ones to clumping in presence of EDTA
(Norberg & Nilsson, 1987).
Agglutinins were shown to be IgG, IgM, or IgA in
33–50%, 10–63%, and 4–40% of cases, respectively
(Watkins & Shulman, 1970; Shreiner & Bell, 1973;
Onder, Weisntein & Hoyer, 1980; Pegels et al., 1982;
Imai et al., 1983; van Vliet, Kappers-Klunne & Abels,
1986; Casonato et al., 1994; Bizzaro & Brandalise,
1995; van der Meer et al., 2002). Agglutinins react
more strongly at room temperature or below (« cold »
agglutinins), but some are temperature independent
or react even better at 37 C. The pathophysiology of
antibody production is unknown: it has been suggested that they could correspond either to natural autoantibodies or to acquired ones, resulting from the PLT
destruction observed in diseases such as septicaemia,
toxaemia of pregnancy, thrombotic thrombocytopenic
purpura, or myelodysplasia (van der Lelie, van der
Plas-Van Dalen & von dem Borne, 1984; Denomme
et al., 1992; Kunicki & Newmann, 1992; Bizzaro &
Brandalise, 1995). In several instances it was shown
that EDP appeared during hospitalization, and particularly after an infection, and that antibodies frequently
bind to PLT from the relevant patient but also to PLT
from all patients, with the exception of PLT from
Glanzmann type I patients (van der Lelie, van der
Plas-Van Dalen & von dem Borne, 1984; Berkman
et al., 1991; Edelman & Kickler, 1993). However, it is
not possible to exclude non-Ig proteins as inducing
EDP in some instances (Mant et al., 1975; Onder,
Weisntein & Hoyer, 1980; Bizzaro & Brandalise,
1995), or other mechanisms, as the interaction of circulating immune complexes with PLT membrane Fc
receptors causing agglutination in presence of EDTA
(Manthorpe et al., 1981).
Agglutination usually occurs within a few minutes
after sampling into EDTA and is more conspicuous in
blood samples kept at room temperature. Aggregates,
as observed in a haematimetric chamber or on stained
smears, are quite variable in size, consisting at times of
three to five PLT but not infrequently in up to 100 PLT
or more (Figure 1a). The most pronounced decreases
in PLT counts were associated with the presence of
large aggregates in one study (Casonato et al., 1994).
PLT clumps are resistant to RBC lysis agents, and on
HA which show a WBC differential scattergram,
clumps are plotted as a cloud of particles of low to
moderate size (Figure 2). If PLT clumps reach the size
of WBC, falsely elevated WBC counts may be observed
(see part II). HA do not identify these clumps as a definite population of WBC, leading the instrument to
generate a flag (PLT clumps, large or giant PLT, or related). Of crucial importance is that alarms are mainly
related to inaccuracy to determine WBC count or inability to determine WBC differential rather than related
to the inaccuracy to analyse PLT on the PLT channel(s)
(Solanki & Blackburn, 1983; Payne & Pierre, 1984;
Vicari, Banfi & Bonini, 1988; Bartels, Schoorl & Lombarts, 1997). So, PLT clumps are usually detected on
HA which analyse WBC populations in order to perform a WBC differential, whereas HA, which do not
perform WBC differential frequently overlook PLT
clumps. Bartels, Schoorl and Lombarts (1997)
observed that, in situations corresponding to EDP,
WBC histograms generated a specific flag for PLT
clumps in nearly all instances (90% sensitivity and
100% specificity), whereas analysis of PLT into the
PLT channel(s) generated less frequently abnormal
findings or specific alarms. In up to 10% of cases, normal PLT and WBC histograms are displayed and EDP is
overlooked (Cunningham & Brandt, 1992).
Immediate dilution without any anticoagulant or
collecting blood using the Unopette system (Becton
Dickinson, Franklin Lakes, NJ, USA) (or related)
containing ammonium oxalate and a haematimetric
chamber (phase contrast microscopy) obviate the
phenomenon. Heparin is not suitable, but an easy
alternate is analysis of samples anticoagulated with
10% trisodium citrate (meaningful count is obtained
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
8
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS 9
Figure 2. WBC scattergram form on normal patient (left) and another one showing EDTA-induced PLT aggregates
(right). PLT aggregates generate a rocket of particles of small and intermediate size (outing from the origin from
the X–Y display), leading to inability to perform accurate identification of WBC (Bayer Advia 120). Ly, lymphocytes; LUC, large unstained cells; Mo, monocytes; PMN, polymorphonuclear neutrophils; Eo, eosinophils.
after mathematical correction because of the dilution),
although clumping may also occur on such samples
(Rabinovitch, 1984; Garcia Suarez et al., 1991; Bizzaro,
1995). In some instances, agglutination was noted as
abolished or less evident for samples both drawn and
maintained at 37 C (Watkins & Shulman, 1970; Fiorin
et al., 1998), but agglutination occurring at room temperature cannot be reverted by warming and leads in
most instances to increase in PLT clumping (Watkins &
Shulman, 1970; Cornbleet, 1983; Payne & Pierre,
1984; van Vliet, Kappers-Klunne & Abels, 1986). Various other anticoagulants have been proposed to circumvent aggregation, including ACD (Lombarts & de
Kieviet, 1988), mixture of citrate, pyridoxal, and Tris
(Lippi et al., 1990), theophillin (Ohnuma, Shirata &
Miyazawa, 1988; De Caterina et al., 1993), MgSO4
(Nakamoto et al., 1986), or addition of aminoglycosides
that both dissociate the aggregates and prevent the
phenomenon (Sakurai et al., 1997).
Pseudothrombocytopenia related to satellitism
around WBC
PLT satellitism, or satellitosis or rosetting, is an in vitro
phenomenon related to the adherence of PLT to
mature polymorphonuclear neutrophils (PMN; Figure 1b), and occasionally to other cells (Figure 3), PLT
surrounding WBC in EDTA-anticoagulated blood samples (Zeigler, 1974; Mende, Doring & Thomas, 1975).
This phenomenon is rare (1 of 12 000 blood counts;
Bizzaro, Goldschmeding & von dem Borne, 1995),
sometimes related to an autoimmune process, but in
most instances unrelated to any specific disease (LazoLangner et al., 2002). Its clinical significance is not
known. Cryofibrinogen has been associated to the phenomenon in one report (McGregor et al., 1980), and
thrombospondin has been involved in the mechanism
in another report (Christopoulos & Mattock, 1991). In
other reports, after the use of either anti-IgG antibodies or specific absorption to remove IgG fraction, IgG
were involved as mediators, implicating or not Fcgamma receptors from PMN (Zeigler, 1974; Greipp &
Gralnick, 1976; Bodensteiner, Talley & Rosenfeld,
1987; Yamanaka et al., 1993; Bizzaro, Goldschmeding
& von dem Borne, 1995; Lazo-Langner et al., 2002).
GPIIb/IIIa from PLT membrane was involved in the
mechanism (Yamanaka et al., 1993; Bizzaro et al.,
1995), but also an IgG autoantibody directed against a
cryptic antigen, sharing community with both GPIIb/
IIIa from the PLT and Fc-gamma receptor III (CD16)
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
M. ZANDECKI ET AL.
M. ZANDECKI ET AL.
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS
(b)
(a)
Figure 3. (a) Platelets surrounding lymphocytes in a patient known for chronic lymphocytic leukaemia. (b) Neutrophil–Platelet aggregates; that latter situation is related to PLT satellitism around polymorphs: PLT are ‘bridges’
between PLT-neutrophil rosettes, generating peculiar clumps, differing from neutrophil aggregates, as no PLT is
observed within the latter (peripheral blood smears; MGG staining).
from the PMN, possibly unmasked in presence of
EDTA, has been suggested (Bizzaro, Goldschmeding &
von dem Borne, 1995). Phagocytosis of PLT by PMN
has been reported, either after optical or electron
microscopical study of the rosettes, but is not a consistent finding (Mende, Doring & Thomas, 1975; White
et al., 1978; Payne, 1981; Bizzaro, 1991), and may be
related to PLT dysfunction observed in some cases
(White et al., 1978; Yoo, Weems & Lessin, 1982).
When PLT satellitism occurs the PLT count is moderately reduced (from 50 to 100 · 109/l), leading to
pseudothrombocytopenia in some but not in all cases.
Flagging is not consistent, and in most cases it is generated after analysis of the WBC differential scattergram, mainly because PMN are abnormally located on
the graphs, being either difficult to separate from
lymphocytes (impedance-type HA) or looking larger
than usual (laser-beam HA). An alarm corresponding
to WBC with high peroxidase value may be generated
on Bayer HA. In our experience with this anomaly,
changes may vary with time within the blood sample:
satellitism is observed within a few minutes after collecting the blood sample, followed by a progressive
migration of PLT to one pole of the PMN after 1–3 h,
mimicking a clump of PLT stuck to the PMN and,
eventually, after 4–6 h, clumps of PLT unbind from
the PMN, leaving PMN free of PLT on the one hand
and PLT clumps free in the blood on the other hand
(Figure 1b). According to the time elapsed from samp-
ling to analysis, satellitism or PLT aggregates may be
the abnormal finding observed as well.
Besides rosetting around PMN, satellitism around
both PMN and monocytes in EDTA samples was
reported (Greipp & Gralnick, 1976). Heparin was also
involved as generating rosetting around monocytes
(Cohen et al., 1980). PLT satellitism was also reported
around basophils but not other cells in a chronic
myelocytic leukaemia patient (Liso & Bonomo, 1982),
and around eosinophils (Fabryova, Burgi & Brugger,
1991; Lazo-Langner et al., 2002). PLT satellitism to
lymphocytes (Figure 3a) or to lymphoma cells was
also reported, the mechanism either involving or not
involving Ig and CD16 as mediators in the latter
instances (Fabryova et al., 1991; Muglia & Davis,
1997; Espanol, Muniz-Diaz & Domingo-Claros, 2000;
Cesca, Ben-Ezra & Riley, 2001). Other situations
related to EDTA have been described under the term
« satellitism », but such situations corresponded either
to lymphocytic clumps (Juneja, Wolf & McLennan,
1992) or to RBC surrounding either lymphocytes or
mature PMN in the presence of EDTA (Feizi et al.,
1973; Sherwood, Shulman & Pierre, 1998).
EDTA-dependent platelet-neutrophil
agglutination
Large aggregates containing hundreds of PLT and
>100 PMN were observed, that seemed to be the end
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
10
point of an evolving process initiated by a typical
satellitism of PLT around PMN (Ahmed, Minnich &
Michael, 1978; Lombarts et al., 1992; Moraglio, Banfi
& Arnelli, 1994) (Figure 3b). As the number of cases
reported is low, studies dealing with that artifact are
scarce and do not allow any definite conclusion
about the mechanism of clumping to be drawn,
namely what differs with classical PLT satellitism
around PMN (Ahmed, Minnich & Michael, 1978;
Lombarts et al., 1992; Moraglio, Banfi & Arnelli,
1994). In one patient who demonstrated both PLT
aggregation and PLT-PMN agglutination, PLT-PMN
clumping was not abolished by dithiothreitol,
occurred only at room or low temperature, and was
restricted to EDTA anticoagulant, three conditions
that were not fulfilled for PLT aggregation, suggesting
that PLT clumps on the one hand and PLT-PMN
agglutination on the other hand corresponded to two
different phenomena (Moraglio, Banfi & Arnelli,
1994). If PLT-PMN clumps are large they are not
detected by HA. Depending on the severity of clumping, the WBC differential is likely in most cases to be
affected to certain degrees, and usually an accompanying WBC flag will be generated to alert the
operator. Spurious PLT counts are likely in most
cases. Examination of a peripheral blood film at low
magnification is compulsory for each leukopenic
sample from an unknown patient or when WBC
count falls dramatically: a step of examination at low
magnification is often necessary to demonstrate the
clumps. In one instance spurious WBC count was
the consequence of both diminished number of PMN
(located within clumps) and artifact of PLT aggregates
that falsely elevated the WBC count (Moraglio, Banfi
& Arnelli, 1994).
The phenomenon described above is related to
EDTA and appears in vitro: it is quite different from
the PLT-WBC aggregates that may appear in vivo in
several inflammatory and thrombotic conditions, the
latter related to enhanced expression of P-selectin
after PLT activation (Hu et al., 2003). A flow cytometric assay was proposed to enumerate these PLT-WBC
aggregates (Li, Goodall & Hjemdahl, 1999).
Large platelets
In normal and in many pathological situations a few
PLT demonstrate a high volume and for that reason
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS 11
HA may consider particles up to 30 or 36 fl in volume
(or up to 60 fl for some laser-beam analysers) as PLT.
According to the instrument and to the blood sample,
some very large PLT (>30–40 fl) may be missed, or
not. In pathological situations, such as in myeloproliferative or in myelodysplastic syndromes, one must
take care of some PLT as large as WBC that are not
identified as such, and at times enumerated as RBC or
WBC (Norberg & Nilsson, 1987; see part II). However,
missing large PLT is a real challenge in thrombocytopenic states, as true PLT count is of crucial importance
for the management of bleeding. In these instances,
even if considerable improvement has been made on
discriminating large PLT from other particles (fitted
curve, changing threshold between PLT and RBC,
multi angle scatter, refractive index), some problems
owing to PLT counting persist. In some instances,
namely if the number of large PLT is high, alternative
approaches using immunologic markers have been
proposed, that require the use of fluorescent flow
cytometers, either optimized for that routine clinical
use, or dedicated and integrated to the HA (Ault et al.,
1997; Harrison et al., 2000; Kunicka et al., 2000; Sandhaus et al., 2002).
Technical considerations regarding sampling
Preanalytical variables may contribute to anomalous
results. The venepuncture site may lead to spuriously
low counts, corresponding to samples diluted because
of proximity to a drip or taken from a line. Whatever
the anticoagulant used, an increase in its concentration within the sample (less blood drawn because of
difficult venepuncture, or difficult sampling in newborns; also discussed in part II) or a delay between
sampling and analysis may change PLT volume, leading to an inability of the HA to generate a fitted
curve or to ascertain the criteria used to define particles as PLT (volume and refractive index; Wynn et al.,
1995).
Overfilling of blood collection vacuum tubes has
been reported to generate a spuriously low PLT count,
because of an inadequate sample mixing: after several
aspirates progressive return to nearly accurate results
occurred (Pewarchuk, VanderBoom & Blajchman,
1992). Delay in contact between whole blood and the
anticoagulant, or difficult venepuncture, may initiate
coagulation and generate PLT clumps.
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
M. ZANDECKI ET AL.
M. ZANDECKI ET AL.
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS
Figure 4. Schistocytes are small RBC fragments which
size may reach that of large platelets (arrow). Most
impedance-type haematology analysers analyse PLT
according to their volume and print next a ‘fitted’
curve (arrowhead), the latter allowing discrimination
with small RBC and accurate count (Coulter STKS
II).
SITUATIONS LEADING TO SPURIOUSLY
ELEVATED PLT COUNTS
Fragmented RBC
Accurate PLT and RBC counts are determined both on
the same channel(s), but the size of particles (and
refractive index for laser beam HA) clearly differs in
normal subjects. For impedance-type HA a fitted
curve of PLT histogram is generated to improve accuracy and in most patients discrimination between
large PLT and small RBC is achieved (Figure 4). However in presence of RBC with extremely low volume,
wrong fitted curves may be generated in some cases,
namely in severe microcytic iron deficiency anaemia
(Savage, Lucas & Hoffman, 1983; Savage & Hoffman,
1985), microangiopathic haemolysis with a large
number of schistocytes (Cornbleet & Kessinger, 1985),
or microspherocytosis because of acute burns (Akwari,
Ross & Stass, 1982), leading to spuriously elevated
PLT counts. In such situations altered RBC counts
have also been reported (see part II). In acute burns
RBC may be split into a large number of very small
fragments, which disturb PLT count, leading to a
peculiar PLT histogram (Figure 5) similar to that
observed with the presence of other very small particles, such as bacteria or cryoglobulins (see later). On
Beckman-Coulter HA the threshold between PLT and
RBC is fixed at 36 fl, whereas on Sysmex and some
Abbott HA that threshold may vary automatically to
ascertain better the « valley » between the peak of
PLT and that of RBC, improving discrimination
between PLT and small RBC in some instances. On
laser-beam HA (Abbott, Bayer) a two dimensional
method determining both volume and refractive index
of PLT or fluorescent staining of platelets (Sysmex)
allows an accurate partition between PLT, large PLT,
small RBC, and RBC fragments in most samples. Some
HA enumerate PLT using impedance and optical
methods, and report both results on the same ticket
(Abbott, Sysmex), whereas one HA can perform optical, impedance, and immunological (CD61) counts on
the same sample, if required (Abbott). Confirmation
of PLT result, either by analysing the blood film, or
manual count, or using another sample and another
method of counting, such as flow cytometry
(Dickerhoff & Von Ruecker, 1996), should be
Figure 5. After acute burns several changes may be observed on RBC, including spherocytes (arrowheads) and very
small RBC fragments (small schistocytes, arrows) (left; peripheral blood smear, MGG staining). Small schistocytes
are enumerated together with PLT, leading to a peculiar PLT histogram showing an excess of small particles (right;
Coulter counter STKS II).
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
12
performed at least in each following circumstances: PLT
curve failing to return to baseline at 20 fl, population of
microcytes appearing on the PLT histogram, exaggeratedly elevated mean PLT volume (MPV) or RBC distribution width (RDW; Savage & Hoffman, 1985).
Cytoplasmic fragments of nucleated cells
Beside RBC fragments or schistocytes, part of the
cytoplasm of abnormal cells was reported as leading
to the elevation of PLT counts, including leukaemic
blasts, monoblasts, or lymphoblasts (Armitage, Goeken & Feagler, 1978; Malcolm, Monks & Katz, 1978;
Hammerstrom, 1992; Li & Salhany, 1999; Kakkar &
Garg, 2005). Particles originating from leukaemic
cells were also reported during the leukaemic phase
of poorly differentiated lymphocytic lymphoma, both
at diagnosis and during chemotherapy (Stass et al.,
1979) (Figure 6), and in hairy cell leukaemia (Stass
et al., 1977; Ballard & Sidhu, 1981). In some of the
above-mentioned cases, cytochemistry (butyrate
esterase), immunocytochemistry (peroxidase, CD61),
or electron microscopy was performed that demonstrated the leukaemic origin of that particles, and
that only a few particles were true PLT. In some
situations, related mainly to acute myeloid leukae-
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS 13
mias, spurious PLT counts could be related to buds
that could develop on the surface of PMN, generating
pseudo-PLT, difficult to distinguish from PLT on
blood smears, but easier to demonstrate at electron
microscopic level because of their myeloperoxidase
positivity (Merz, 1983).
Routine stained smears show that these cytoplasmic parts of nucleated cells are much more heterogeneous in size and content than PLT (Figure 6). The
incidence of this abnormality is far from being small,
as shown in a recent study, which found at least
some ‘pseudoplatelets’ on May Grünwald-Giemsa
stained smears in 43 of 169 (25.4%) patients with
acute leukaemia, corresponding in seven (4.1%)
patients to a corrected PLT count <15 · 109/l,
whereas the mean automated PLT count was
39 · 109/l (range: 21–75; Van der Meer et al., 2003).
In some reports PLT transfusion was mentioned to
be delayed because of spuriously elevated counts,
and the authors proposed that, as high or normal
PLT counts are infrequent in acute leukaemias, they
should be considered as spurious and verified using
another method of counting, namely if bleeding
symptoms are present (Hammerstrom, 1992; Li &
Salhany, 1999). In many but not in all instances a
flag is generated but, as the HA cannot identify these
cytoplasmic fragments as such, various kinds of flags
may be printed, including: thrombocytopenia, large
PLT, RBC ghosts, or other flags related to the inability to produce a fitted curve.
Microorganisms
Figure 6. Parts of cytoplasm from lymphoma cells
(arrows) may be found within blood stream: such
fragments are at times difficult to distinguish from
PLT, both by HA and after microscopic examination
(diffuse large B-cell lymphoma in relapse; MGG
staining).
Bacteria may induce falsely elevated PLT counts,
because of their presence in vivo (Gloster et al., 1985;
Kakkar, 2004). Although it is a rare situation, even
in septic patients, some bacteria may be observed on
the peripheral blood smear and are associated with
positive blood cultures (Marshall, Theil & Brandt,
1990). Histogram of PLT volumes is abnormal and
shows a shift towards low sized particles, corresponding to bacteria or to bacterial clumps (Figure 7). In
our experience with infected patients, abnormal PLT
histograms related to bacteria were always associated
with bacteria observed on the peripheral blood film
and to extreme clinical situations. An intermediate
situation is that related to bacterial overgrowth in
the blood sample from infected patients, because of
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
M. ZANDECKI ET AL.
M. ZANDECKI ET AL.
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS
Figure 7. Bacteria or bacterial aggregates may be enumerated together with PLT and appear as a peak of
particles of small size (2 fl or less). In this patient
(septicaemia) the fitted curve was established and
PLT count was not overestimated (Coulter counter
STKS II).
the delay between sampling and analysis (Kakkar,
2004). An unsterile tube used for blood sampling
may cause bacterial overgrowth. In this situation,
the PLT count and PLT histogram are altered,
whereas clinical condition of the patient is unrelated
to infection.
Fungi may show the same size as PLT and may be
observed on peripheral blood smears (Arnold, Jowzi &
Bain, 1999). They were reported recently as increasing PLT counts in thrombocytopenic patients infected
by Candida (Latif et al., 2003).
In one patient treated for malaria, small RBC infected by trophozoites of Plasmodium falciparum were misinterpreted as PLT by a HA, leading to a spuriously
normal PLT count (Crabbe, Van Poucke & Cantinieaux, 2002).
Lipids
In patients with hyperchylomicronemia, in samples
taken after a meal, or after parenteral nutrition therapy, lipids may form small droplets in vitro, that disturb PLT counts (Nicholls, 1983; Savage, 1989;
Cantero, Conejo & Jimenez, 1996), and/or haemoglobin, RBC parameters, and WBC counts (discussed in
part II). Some authors compared the effects of
hyperchylomicronemia on PLT counts performed by
two types of HA: they observed a moderate increase
of PLT count for the analyser using an optical method
for counting when compared with the one using an
electrical impedance method that seemed unaffected
(Cantero, Conejo & Jimenez, 1996; Kabutomori,
Iwatani & Kabutomori, 1999). If the increase was
reported as low and unimportant in patients with normal counts (rise in 2–40 · 109/l), it could not be neglected in those patients with low PLT counts,
especially the leukaemic ones treated with L-asparaginase, a drug known as inducing lipid abnormalities
(Cantero, Conejo & Jimenez, 1996; Kabutomori et al.,
1999). Lipids possess a high refractive index and can
generate abnormal signals located near PLT or at the
same place as the so-called debris (corresponding to
small RBC or RBC ghosts in normal subjects). On
some HA that analyse WBC on two channels, reagents
used in each channel are not equally sensitive to
lipids and, according to the amount and composition
of lipids, discrepancy between WBC counts from both
channels may be observed (Bayer Advia 2120; Sysmex). Specific flagging and scattergram review are
key items to appreciate the potential interference of
lipids on CBC. Methods were reported to discard specifically lipids from the sample, but some led themselves to spurious PLT counts, either low or elevated
(Nicholls, 1983). Changes more or less superimposable
to those observed with lipid droplets were reported
after the use of perfluorocarbon emulsions (Cuignet
et al., 2000).
Cryoglobulins, cryofibrinogen and related
Cryoglobulins may lead to spuriously elevated PLT
counts and in a few instances to altered RBC counts,
but were put forward first as generating erroneous
WBC counts (Emori, Bluestone & Goldberg, 1973).
Cryoprecipitates disturb measurements according to
their size: if precipitates are small enough, they may
lead to very high spurious PLT counts, and up to
eight times elevation may be observed (Fohlen-Walter et al., 2002). Anomalies are more obvious on HA
that act at room temperature (Figure 8), but those
which use heated reagents are not fully devoid of
changes (Bayer Advia 120). As the mechanism leading to spurious elevation of PLT and WBC counts is
similar, both changes will be discussed together in
part II of this report. Spuriously elevated PLT counts
may also be observed relating to the presence of cryofibrinogen but, as for cryoglobulins, WBC counts
are frequently affected, and changes related to that
peculiar condition will also be discussed in part II of
this report.
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
14
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS 15
Figure 8. Cryoglobulins may precipitate during the dilution procedure into the HA, and the small particles are enumerated together with PLT. On impedance-type HA (Coulter STKS II) the small size of particles generates a shift to
the left of the PLT histogram (up left). On laser-beam HA (Bayer ADVIA 120) the PLT scattergram is overloaded
with particles of various sizes, the largest ones accumulating at the top of the scattergram (down left). After warming the sample at 37 C cryoglobulin dissolves, and prompt analysis leads to full disappearance of abnormalities (up
right and down right, for the relevant HA, respectively).
Miscellaneous
Air bubbles, which have resulted from mechanical
leaks, being introduced into flow cells and to impedance apertures, can cause spurious counts. Also reagent contamination and debris build up into the
analyser can cause erroneous counts. Cleaning and
background counting procedures as well as quality
control are stressed to prevent these events.
Previous generation HA
Some HA of previous generations, such as Hemalog 8
(Technicon-Bayer), measured PLT counts on whole
blood after lysis of RBC, leaving abnormal intraerythrocytic particles free, which could be enumerated as
PLT. So, nuclei of nucleated red blood cells, Howell
Jolly bodies, malarial parasites, and Pappenheimer
bodies were reported to disturb PLT count in such
instances (Morton et al., 1980). Other changes, such
as aggregated RBC stroma secondary to haemolytic
action of RBC antibodies were also reported as eleva-
ting PLT counts on the same HA (Malcolm, Monks &
Katz, 1978; Morton et al., 1980).
Concluding remarks
Preanalytical and analytical variables should be considered first within the laboratory, including human
errors in sample identification, site of venepuncture
(adjacent to a drip or out of a line), or inadequate
mixing prior to analysis. Instrument malfunction,
inability to recognize quality control failure, cleaning
and background counting procedures are also of considerable importance before pointing out spurious
results from the HA.
EDTA-dependent thrombocytopenia is certainly
one of the most frequent anomalies associated with
spurious counts on HA: an alarm or a flag is not consistent and, in previously unknown patients with low
PLT count by automated cell-counting, looking for at
least PLT clumps (blood smear, haematimetric chamber) is required. Samples should not be heated to
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
M. ZANDECKI ET AL.
M. ZANDECKI ET AL.
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS
dissociate aggregates and in many instances another
blood sample will be helpful. Many other situations
may induce spurious PLT counts, either high or low
(Table 1) but, even if we consider one given mechanism for spurious count, the depth of the deviation
between the true and the spurious result will differ
from one patient to the other. As reported in Table 1,
if some changes are restricted to PLT, in several situations spurious PLT counts are or may be associated
with other abnormalities of the CBC (see also part II).
Beside the anomalies described above, others are certainly unexplained (Savage, 1989) and unreported.
An important finding is that, in many cases, flags or
REFERENCES
Ahmed P., Minnich V. & Michael J.M.
(1978) Platelet satellitosis with spurious
thrombocytopenia and neutropenia.
American Journal of Clinical Pathology
69, 473–474.
Akwari A.M., Ross D.W. & Stass S.A.
(1982) Spuriously elevated platelet
counts due to microspherocytosis.
American Journal of Clinical Pathology
77, 220–221.
Armitage J.O., Goeken J.A. & Feagler J.R.
(1978) Spurious elevation of the platelet count in acute leukemia. JAMA 239,
433–434.
Arnold J.A., Jowzi Z. & Bain B.J. (1999)
Candida glabrata in a blood film. British
Journal of Haematology 104, 1.
Ault K.A., Mitchell J., Knowles C. & Van
Hove L. (1997) Implementation of the
immunological platelet count on a
hematology analyser: the Abbott CellDyn 4000. Laboratory Hematology 3,
125–128.
Bain B.J. & Bates I. (2001) Basic haematological techniques. In: Dacie and
Lewis Practical Haematology (eds S.M.
Lewis, B.J. Bain & I. Bates), pp. 19–46.
Churchill , Livingston.
Ballard H.S. & Sidhu G. (1981) Cytoplasmic fragments causing spurious platelet counts in hairy cell leukemia:
ultrastructural
characterization.
Archives of Internal Medicine 141, 942–
944.
Bartels P.C., Schoorl M. & Lombarts A.J.
(1997) Screening for EDTA-dependent
alarms are generated because of abnormal finding on
the WBC differential scattergram: HA which do not
analyse WBC subpopulations are unable to detect
some spurious results.
ACKNOWLEDGEMENTS
We are indebted to Mathilde LINARD for kindly
reviewing English manuscript.
CONFLICT OF INTEREST
No conflict of interest.
deviations in platelet counts and
abnormalities in platelet distribution
histograms in pseudothrombocytopenia.
Scandinavian Journal of Clinical and
Laboratory Investigation 57, 629–636.
Berkman N., Michaeli Y., Or R. & Eldor
A. (1991) EDTA-dependent pseudothrombocytopenia: a clinical study of 18
patients and a review of the literature.
American Journal of Hematology 36,
195–201.
Bizzaro N. (1991) platelet satellitosis to
polymorphonuclears:
cytochemical,
immunological and ultrastructural characterization of eight cases. American
Journal of Hematology 36, 235–242.
Bizzaro N. (1995) EDTA-dependent pseudothrombocytopenia: a clinical and epidemiological study of 112 cases, with
10-year follow-up. American Journal of
Hematology 50, 103–109.
Bizzaro N. & Brandalise M. (1995) EDTAdependent
pseudothrombocytopenia.
Association with antiplatelet and antiphospholipid
antibodies.
American
Journal of Clinical Pathology 103, 103–
107.
Bizzaro N., Goldschmeding R. & von dem
Borne A.E. (1995) Platelet satellitism is
Fc gamma RIII (CD16) receptor-mediated. American Journal of Clinical
Pathology 103, 740–744.
Bodensteiner D., Talley R. & Rosenfeld C.
(1987) Platelet satellitism: a possible
mechanism. Southern Medical Journal
80, 459–461.
Boehme W.M., Mahmood T. & Phanuphak
P.
(1980)
Pseudo-
thrombocytopenia
associated
with
vasculitis. American Journal of the
Medical Sciences 279, 125–128.
Bragnani G., Bianconcini G., Brogna R. &
Zoli G (2001) Pseudothrombocytopenia:
clinical comment on 37 cases. Minerva
Medica 92, 13–17.
Cantero M., Conejo J.R. & Jimenez A.
(1996) Interference from lipemia in cell
count by hematology analysers. Clinical
Chemistry 42, 987–988.
Casonato A., Bertomoro A., Pontara E.,
Dannhauser D., Lazzaro A.R. & Girolami A. (1994) EDTA dependent pseudothrombocytopenia
caused
by
antibodies against the cytoadhesive
receptor of platelet gpIIB-IIIA. Journal
of Clinical Pathology 47, 625–630.
Cesca C., Ben-Ezra J. & Riley R.S. (2001)
Platelet satellitism as presenting finding
in mantle cell lymphoma. A case report.
American Journal of Clinical Pathology
115, 567–570.
Christopoulos C.G. & Machin S.J. (1994)
A
new
type
of
pseudothrombocytopenia:
EDTA-mediated
agglutination of platelets bearing Fab
fragments of a chimaeric antibody. British Journal of Haematology 87, 650–
652.
Christopoulos C. & Mattock C. (1991) Platelet satellitism and alpha granule proteins. Journal of Clinical Pathology 44,
788–789.
Cohen A.M., Lewinski U.H., Klein B. &
Djaldetti M. (1980) Satellitism of Platelets to Monocytes. Acta Haematologica
64, 61–64.
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
16
Cohen A.M., Cycowitz Z., Mittelman M.,
Lewinski U.H. & Gardyn J. (2000) The
incidence of pseudothrombopcytopenia
in automatic blood analysers. Haematologica (Budab) 30, 117–121.
Cornbleet J. (1983) Spurious results from
automated hematology cell counters.
Laboratory Medicine 14, 501–514.
Cornbleet P.J. & Kessinger S. (1985)
Accuracy of low platelet counts on the
coulter S-plus IV. American Journal of
Clinical Pathology 83, 78–80.
Crabbe G., Van Poucke M. & Cantinieaux
B. (2002) Artefactually-normal automated platelet counts due to malariainfected RBC. Clinical and Laboratory
Haematology 24, 179–182.
Cuignet O.Y., Wood B.L., Chandler W.L.
& Spiess B.D. (2000) A second-generation blood substitute (Perfluorodichlorooctane
emulsion)
generates
spurious elevations in platelet counts
from automated hematology analyzers.
Anesthesia and Analgesia 90, 517–522.
Cunningham V.L. & Brandt J.T. (1992)
Spurious thrombocytopenia due to
EDTA-independent cold-reactive agglutinins. American Journal of Clinical
Pathology 97, 359–362.
Dabadie M., Valli N., Jacobin M.J., Laroche-Traineau J., Barat J.L., Ducassou
D., Nurden A.T. & Clofent-Sanchez G.
(2001) Characterisation, cloning and
sequencing of a conformation – dependent monoclonal antibody to the alphaIIb beta3 integrin: interest for use in
thrombus detection. Platelets 12, 397–
405.
Dahlqvist S.R., Nilsson T.K. & Norberg B.
(1988) Thrombocytosis in active rheumatoid arthritis. Relation to other parameters of inflammatory activity and
confounding effect of automated cell
counting. Clinical Rheumatology 7,
335–341.
De Caterina M., Fratellanza G., Grimaldi
E., Variale V., Scopacasa F., Di Maro G.
& Formisano S. (1993) Evidence of a
cold immunoglobulin M autoantibody
against 78-kD platelet glycoprotein in a
case of EDTA-dependent pseudothrombocytopenia. American Journal of
Clinical Pathology 99, 163–167.
Denomme G.A., Smith J.W., Kelton J.G.
& Bell D.A. (1992) A human monoclonal antibody to platelet glycoprotein
IIb derived from normal human lymphocytes. Blood 79, 447–451.
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS 17
Dickerhoff R. & Von Ruecker A. (1996)
Enumeration of platelets by multiparameter flow cytometry using platelet-specific antibodies and fluorescent
reference particles. Clinical and Laboratory Haematology 18, 163–172.
Edelman B. & Kickler T. (1993) Sequential measurement of anti-platelet antibodies in a patient who developed
EDTA-dependent
pseudothrombocytopenia. American Journal of
Clinical Pathology 99, 87–89.
Emori H.W., Bluestone R. & Goldberg L.S.
(1973) Pseudo-leukocytosis associated
with cryoglobulinemia. American Journal of Clinical Pathology 60, 202–204.
Espanol I., Muniz-Diaz E. & DomingoClaros A. (2000) The irreplaceable
image: platelet satellitism to granulated
lymphocytes. Haematologica 85, 1322.
Fabryova V., Burgi W. & Brugger E.
(1991) Platelet satellitosis. Vnitrni
Lekarstvi 37, 563–571.
Feizi T., Wernet P., Kunkel H.G. & Douglas S.D. (1973) Lymphocytes forming
red cell rosettes in the cold in patients
with chronic cold agglutinin disease.
Blood 42, 753–762.
Fiorin F., Steffan A., Pradella P., Bizzaro
N., Potenza R. & de Angelis V. (1998)
IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to
platelet membrane glycoprotein IIb.
American Journal of Clinical Pathology
110, 178–183.
Fohlen-Walter A., Jacob C., Lecompte T. &
Lesesve J.F. (2002) Laboratory identification of cryoglobulinemia from automated
blood cell counts, fresh blood samples,
and blood films. American Journal of
Clinical Pathology 117, 606–614.
Foresti V., Parisio E., Tronci M., Casati O.,
Zubani R. & Pedretti D. (1990) EDTAinduced
pseudothrombocytopenia.
Recenti Progressi in Medicina 81, 661–
662.
Forscher C.A., Sussman I.I., Friedman
E.W., Solomon V. & Spaet T.H. (1985)
Pseudothrombocytopenia masking true
thrombocytopenia. American Journal of
Hematology 18, 313–317.
Garcia Suarez J., Merino J.L., Rodriguez
M., Velasco E. & Moreno M.C. (1991)
Pseudothrombocytopenia:
incidence,
causes and methods of detection. Sangre 36, 197–200.
Ginsberg M.H., Lightsey A., Kunicki T.J.,
Kaufmann A., Marguerie G. & Plow
E.F. (1986) Divalent cation regulation
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
of the surface orientation of platelet
membrane glycoprotein IIb. Journal of
Clinical Investigation 78, 1103–1111.
Gloster E.S., Strauss R.A., Jimenez J.F.,
Neuberg R.W., Berry D.H. & Turner E.J.
(1985) Spurious elevated platelet counts
associated with bacteremia. American
Journal of Hematology 18, 329–332.
Gowland E., Kay H.E.M., Spillman J.C. &
Williamson J.R. (1969) Agglutination of
platelets by a serum factor in the presence of EDTA. Journal of Clinical
Pathology 22, 460–464.
Greipp P.R. & Gralnick H.R. (1976) Platelet to leukocyte adherence phenomena
associated
with
thrombocytopenia.
Blood 47, 513–517.
Gschwandtner M.E., Siostrzonek P., Bodinger C., Neunteufl T., Zauner C., Heinz
G., Maurer G. & Panzer S. (1997) Documented sudden onset of pseudothrombocytopenia.
Annals
of
Hematology 74, 283–285.
Hammerstrom J. (1992) Spurious platelet
counts in acute leukaemia with DIC
due to cell fragmentation. Clinical and
Laboratory Haematology 14, 239–243.
Harrison P., Horton A., Grant D., Briggs
C. & MacHin S. (2000). Immunoplatelet
counting: a proposed new reference
procedure. British Journal of Haematology 108, 228–235.
Hinchcliff K.W., Kociba G.J. & Mitten
L.A. (1993) Diagnosis of EDTA-dependent pseudothrombo-cytopenia in a
horse. Journal of the American Veterinary Medical Association 203, 1715–
1716.
Hu H., Varon D., Hjemdahl P., Savion N.,
Schulman S. & Li N. (2003) Plateletleukocyte aggregation under shear
stress: differential involvement of selectins and integrins. Thrombosis and Haemostasis 90, 679–687.
Huss B., Kretschmer V., Schnabel M.,
Weiner L. & Ulshofer B. (1995) Pseudothrombocytopenia: case reports and
review of the literature. Infusionstherapie und Transfusionsmedizin 22, 303–
309.
Imai H., Nakamoto Y., Miki K., Miyakuni
T. & Miura A.B. (1983) Pseudothrombocytopenia and IgA-related platelet agglutinin in patients with IgA
nephritis. Nephron 34, 154–158.
Juneja S., Wolf M. & McLennan R.
(1992) Clumping of lymphoma cells in
peripheral blood induced by EDTA.
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
M. ZANDECKI ET AL.
M. ZANDECKI ET AL.
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS
Journal of Clinical Pathology 45, 538–
540.
Kabutomori O., Iwatani Y. & Kabutomori
M. (1999) Effects of hypertriglyceridemia on platelet counts in automated
hematologic analysis. Annals of Internal
Medicine 130, 452.
Kakkar N. (2004) Spurious rise in the
automated platelet count because of
bacteria. Journal of Clinical Pathology
57, 1096–1097.
Kakkar N. & Garg G. (2005) Cytoplasmic
fragments of leukaemic cells masquerading as platelets in an automated haematology analyser. Journal of Clinical
Pathology 58, 224.
Konstantopoulos K., Grotta J.C., Sills C;,
Wu K.K. & Hellums J.D. (1995) Shearinduced platelet aggregation in normal
subjects and stroke patients. Thrombosis
and Haemostasis 74, 1329–1334.
Kunicka J.E., Fischer G., Murphy J. &
Zelmanovic D. (2000) Improved platelet
counting using two-dimensional laser
scatter. American Journal of Clinical
Pathology 114, 283–289.
Kunicki T.J. & Newmann P.J. (1992) The
molecular immunology of human platelet proteins. Blood 80, 1386–1404.
Latif S., Veillon D.M., Brown D., Kaltenbach J., Linscott A.J., Oberle A. & Cotelingam J.D. (2003) Spurious automated
platelet count. Enumeration of yeast
forms as platelets by the Cell-Dyn 4000.
American Journal of Clinical Pathology
120, 882–885.
Lazo-Langner A., Piedras J., RomeroLagarza
P.,
Lome-Maldonado
C.,
Sanchez-Guerro J. & Lopez-Karpovitch
X. (2002) Platelet satellitism, spurious
neutropenia, and cutenaeous vasculitis:
casual or causal association? American
Journal of Hematology 70, 246–249.
Li S. & Salhany K.E. (1999) Spurious elevation of automated platelet counts in
secondary acute monocytic leukemia
associated with tumor lysis syndrome.
Archives of Pathology and Laboratory
Medicine 123, 1111–1114.
Li N., Goodall A.H. & Hjemdahl P. (1999)
Efficient flow cytometric assay for platelet-leukocyte aggregates in whole blood
using fluorescence signal triggering.
Cytometry 35, 154–161.
Lippi U., Schinella M., Nicoli M., Modena
N. & Lippi G. (1990) EDTA-induced platelet aggregation can be avoided by a
new anticoagulant also suitable for
automated complete blood count. Haematologica 75, 38–41.
Liso V. & Bonomo L. (1982) Platelet satellitism to basophils in a patient with
chronic myelocytic leukaemia. Blut 45,
347–350.
Lombarts A.J.P.F. & de Kieviet W. (1988)
Recognition and prevention of pseudothrombocytopenia and concomitant
pseudoleukocytosis. American Journal
of Clinical Pathology 89, 634–639.
Lombarts A.J., de Kieviet W., Franck P.F.
& Baars J.D. (1992) Recognition and
prevention of two cases of erroneous
haemocytometry counts due to platelet
and white blood cell aggregation. The
use of acid citrate dextrose as an auxiliary anticoagulant. European Journal
of Clinical Chemistry and Clinical Biochemistry 30, 429–432.
Malcolm I.D., Monks P. & Katz M. (1978)
Spurious thrombocytosis in acute myelocytic leukemia. New England Journal
of Medicine 298, 1260.
Mant M.J., Doery J.C., Gauldie J. & Sims
H. (1975) Pseudothrombocytopenia due
to platelet aggregation and degranulation in blood collected in EDTA. Scandinavian Journal of Haematology 15,
161–170.
Manthorpe R., Kofod B., Wiik A., Saxtrup
O. & Svehag S.E. (1981) Pseudothrombocytopenia. In vitro studies on
the underlying mechanism. Scandinavian Journal of Haematology 26, 385–
392.
Marshall B.A., Theil K.S. & Brandt J.T.
(1990) Abnormalities of leukocyte histograms resulting from microorganism.
American Journal of Clinical Pathology
93, 526–532.
McGregor D.H., Davis J.W., Liu P.I., Gates
E. & Pointdexter A.R. (1980) Platelet
satellitism:
experimental
studies.
Laboratory Investigation 42, 343–355.
Mende S., Doring M. & Thomas X. (1975)
Spurious thrombocytopenia caused by
granulocyte platelet rosettes. Klin
Wochenschr 53, 343–345.
Merz B. (1983) Newly identified particle
may explain spurious platelet count.
Journal of the American Medical Association 249, 3146–3147.
Moraglio D., Banfi G. & Arnelli A. (1994)
Association of pseudothrombocytopenia
and pseudoleukopenia: evidence for different pathogenic mechanisms. Scandinavian Journal of Clinical and
Laboratory Investigation 54, 257–265.
Mori M., Kudo H., Yoshitake S., Ito K.,
Shinguu C. & Nogushi T. (2000) Transient
EDTA-dependent
pseudothrombocytopenia in a patient with
sepsis. Intensive Care Medicine 26,
218–220.
Morton B.D., Orringer E.P., LaHart L.A. &
Stass S.A. (1980) Pappenheimer bodies.
An additional cause for a spurious platelet count. American Journal of Clinical Pathology 74, 310–311.
Muglia B. & Davis B.H. (1997) Platelet
satellitosis to lymphoma cells: case
report and literature review. Laboratory
Hematology 3, 112–116.
Nakamoto K., Sugibayashi S., Terauchi S.,
Hada A., Munakata M., Teraoka A.,
Komiyama Y., Egawa H. & Murata K.
(1986) Platelet count in EDTA-dependent
pseudothrombocytopenia- application of MgSO4 as an anticoagulant. Rinsho Byori. Japanese
Journal of Clinical Pathology 34, 167–
173.
Nicholls P.D. (1983) Erroneous platelet
counts on the Coulter Model S Plus
counter after correction for hyperlipaemia. Medical Laboratory Sciences 40,
69–71.
Norberg B. & Nilsson T.K. (1987) Platelet
clumping in Ph-negative myeloproliferative syndromes. Acta Medica Scandinavica 222, 459–464.
Ohnuma O., Shirata Y. & Miyazawa K.
(1988) Use of theophylline in the investigation of pseudothrombocytopenia
induced by edetic acid (EDTA-2K).
Journal of Clinical Pathology 41, 915–
917.
Onder O., Weinstein A. & Hoyer L.
(1980) Pseudothrombocytopenia caused
by agglutinins that are reactive in blood
anticoagulated with chelating agents.
Blood 56, 177–182.
Payne C.M. (1981) Platelet satellitism: an
ultrastructural study. American Journal
of Pathology 103, 116–128.
Payne B.A. (1985) EDTA-induced pseudothrombocytopenia: recognizing a laboratory artifact. Postgraduate Medical
Journal 77, 75–76.
Payne B.A. & Pierre R.V. (1984) Pseudothrombocytopenia: a laboratory artifact
with potentially serious consequences.
Mayo Clinic Proceedings 59, 123–125.
Pegels J.G., Bruynes E.C., Engelfriet C.P.
& von dem Borne A.E. (1982) Pseudothrombocytopenia: an immunologic
study on platelet antibodies dependent
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
18
on ethylene diamine tetra-acetate.
Blood 59, 157–161.
Pewarchuk W., VanderBoom J. & Blajchman M.A. (1992) Pseudopolycythemia,
pseudothrombo cytopenia, and pseudoleukopenia due to overfilling of blood
collection vacuum tubes. Archives of
Pathology and Laboratory Medicine
116, 90–92.
Rabinovitch A. (1984) Anticoagulants,
platelets and instrument problems.
American Journal of Clinical Pathology
82, 132–137.
Ryo R., Sugano W., Goto M., Takada M.,
Saigo K., Hashimoto M. & Yamaguchi
M. (1994) Platelet release reaction during EDTA-induced platelet agglutinations and inhibition of EDTA-induced
platelet agglutination by anti-glycoprotein II b/III a complex monoclonal
antibody. Thrombosis Research 74, 265–
272.
Sakurai S., Shiojima I., Tanigawa T. &
Nakahara K. (1997) Aminoglycosides
prevent and dissociate the aggregation
of platelets in patients with EDTAdependent
pseudothrombocytopenia.
British Journal of Haematology 99,
817–823.
Sandhaus L.M., Osei E.S., Agrawal N.N.,
Dillman C.A. & Meyerson H.J. (2002)
Platelet counting by the coulter LH 750,
sysmex XE 2100, and advia 120: a comparative analysis using the RBC/platelet
ratio reference method. American Journal of Clinical Pathology 118, 235–241.
Savage R.A. (1984) Pseudoleukocytosis
due to EDTA-induced platelet clumping.
American Journal of Clinical Pathology
81, 317–322.
Savage R.A. (1989) Analytic inaccuracy
resulting from hematology specimen
characteristics. Three cases of clinically
misleading artifacts affecting white
blood cell and platelet counts. American
Journal of Clinical Pathology 92, 295–
299.
Savage R.A. & Hoffman G.C. (1985) Spuriously high platelet counts. American
Journal of Clinical Pathology 84, 406–
407.
Savage R.A., Lucas F.V. & Hoffman G.C.
(1983) Spurious thrombocytosis caused
by red blood cell fragmentation. American Journal of Clinical Pathology 79,
144.
Schrezenmeier H., Muller H., Gunsilius
E., Heimpel H. & Seifried E. (1995)
Anticoagulant-induced
pseudo-
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS 19
thrombocytopenia and pseudoleucocytosis. Thrombosis and Haemostasis 73,
506–513.
Sherwood T., Shulman I. & Pierre R.
(1998) Satellitosis of erythrocytes about
mature neutrophils. Laboratory Hematology 4, 207–210.
Shimizu M., Yamamoto M., Miyashi H.,
Shinohara Y. & Ando Y. (2003) Simple,
rapid, and automated method for detection of hyperaggregability of platelets
using a hematology analyzer. American
Journal of Hematology 72, 282–283.
Shreiner D.P. & Bell W.R. (1973) Pseudothrombocytopenia: manifestation of a
new type of platelet agglutinin. Blood
42, 541–549.
Silvestri F., Virgolini L., Savignano C.,
Zaja F., Velisig M. & Baccarani M.
(1995) Incidence and diagnosis of
EDTA-dependent
pseudothrombocytopenia in a consecutive outpatient population referred for isolated
thrombocytopenia. Vox Sanguinis 68,
35–39.
Solanki D.L. & Blackburn B.C. (1983)
Spurious leukocytosis and thrombocytopenia. A dual phenomenon caused by
clumping of platelets in vitro. JAMA
250, 2514–2515.
Solanki D.L. & Blackburn B.C. (1985)
Spurious
thrombocytopenia
during
pregnancy. Obstetrics and Gynecology
65, 174–178.
Stass S.A., Holloway M.L., Slease R.B. &
Schumacher H.R. (1977) Spurious platelet counts in hairy cell leukemia.
American Journal of Clinical Pathology
68, 530–531.
Stass S.A., Holloway M.L., Peterson V.,
Creegan W.J., Gallivan M. & Schumacher H.R. (1979) Cytoplasmic fragments causing spurious platelet counts
in the leukemic phase of poorly differentiated lymphocytic lymphoma. American Journal of Clinical Pathology 71,
128–133.
Stiegler H., Fischer Y., Steiner S., Strauer
B.E. & Reinauer H. (2000) Sudden
onset of EDTA-dependent pseudothrombocytopenia after therapy with
the glycoprotein IIb/IIIa antagonist c7E3
Fab. Annals of Hematology 79, 161–164
Sweeney J.D., Holme S., Heaton W.A.,
Campbell D. & Bowen M.L. (1995)
Pseudothrombocytopenia in plateletpheresis donors. Transfusion 35, 46–49.
Takeuchi T., Yoshioka K., Hori A.,
Mukoyama K., Ohsawa A. & Yokoh S.
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
(1993) Cytomegalovirus mononucleosis
with mixed cryoglobulinemia presenting
transient
pseudothrombocytopenia.
Internal Medicine 32, 598–601.
van der Lelie J., van der Plas-Van Dalen
C.M. & von dem Borne A.E. (1984) Platelet autoantibodies in septicaemia. British Journal of Haematology 58, 755–
760.
van der Meer W., Allebes W., Simon A.,
van Berkel Y. & de Keijzer M.H. (2002)
Pseudothrombocytopenia: a report of a
new method to count platelets in a
patient with EDTA- and temperatureindependent antibodies of the IgM type.
European Journal of Haematology 69,
243–247.
van der Meer W., MacKenzie M.A., Dinnissen J.W.B. & de Keijzer M.H. (2003)
Pseudoplatelets: a retrospective study of
their incidence and interference with
platelet counting. Journal of Clinical
Pathology 56, 772–774.
van Vliet H.H., Kappers-Klunne M.C. &
Abels J. (1986) Pseudothrombocytopenia: a cold autoantibody against platelet glycoprotein GPIIb. British Journal
of Haematology 62, 501–511.
Veenhoven W.A., van der Schans G.S.,
Huiges W., Metting-Scherphuis H.E.,
Halie M.R. & Nieweg H.O. (1979) Pseudothrombocytopenia due to agglutinins.
American Journal of Clinical Pathology
72, 1005–1008.
Veenhoven W.A., Van der Schans G.S. &
Nieweg H.O. (1982) Monoclonal immunoglobulins with affinity for platelets
and their relationship to malignant lymphomas. Cancer 49, 40–42.
Vicari A., Banfi G. & Bonini P.A. (1988)
EDTA-dependent pseudothrombocytopaenia: a 12-month epidemiological
study. Scandinavian Journal of Clinical
and Laboratory Investigation 48, 537–
542.
Watkins S.P. & Shulman N.R. (1970) Platelet cold agglutinins. Blood 36, 153–
158.
White L.A. Jr, Brubaker L.H., Aster R.H.,
Henry P.H. & Adelstein E.H. (1978) Platelet satellitism and phagocytosis by
neutrophils: association with antiplatelet antibodies and lymphoma. American
Journal of Hematology 4, 313–323.
Wynn R.F., Davies S.V., Williams K. &
Trevett D.G. (1995) The effects of time
from venepuncture and choice of anticoagulant on mean platelet volume esti-
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
M. ZANDECKI ET AL.
M. ZANDECKI ET AL.
ABNORMAL PLATELET COUNTS ON HAEMATOLOGY ANALYSERS
mations. Clinical and Laboratory Haematology 17, 173–176.
Yamanaka J., Kawai Y., Shimizu N.,
Takeuchi K., Shimazaki C., Osada E.,
Sugisaki N., Yamamoto M., Watanabe
K. & Iri H. (1993) Study on platelet
satellitism. Rinsho Byori. Japanese
Journal of Clinical Pathology 41, 1141–
1145.
Yoo D., Weems H. & Lessin L.S. (1982)
Platelet to leukocyte adherence phenomena. (Platelet satellitism) and phagocytosis by neutrophils associated with
in vitro platelet dysfunction. Acta Haematologica 68, 142–148.
Zeigler Z. (1974) In vitro granulocyte–
platelet formation mediated by an IgG
immunoglobulin. Haemostasis 3, 282–
287.
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 4–20
1751553x, 2007, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2257.2006.00870.x by Cochrane Peru, Wiley Online Library on [28/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
20