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Review Article

Role of Red cell and Platelet Indices as a Predictive Tool for

Transfusions in Dengue
Ambuja Kantharaj

Department of Transfusion Review of literature and prevalent practices show the importance of red cell indices,

Abstract
Medicine, Manipal Hospital,
Bengaluru, Karnataka, India
Received: September, 2018.
Accepted: October, 2018.
especially hematocrit(HCT )in the diagnosis and prognosis of dengue. Platelet
indices also may act as a tool to assess the prognosis and decide on the need for
red cell and platelet transfusions in dengue. Platelet indices such as platelet count,
mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit
(PCT) are simple indices which can be done by any 3‑part differential cell counter.
However, immature platelet fraction (IPF) can be done only at advanced centres
using more advanced cell counters. In dengue fever, red cell indices give indirect
information on whether the patient is bleeding or going into impending shock. An
increased HCT suggests haemoconcentration and warrants treatment with bolus IV
fluids while a decreased HCT in an unstable patient may indicate bleeding and
act as a predictor for red cell transfusions, whereas it suggests recovery from
disease in a stable patient. Platelet counts have no role in determining need for
transfusion in dengue. Platelet indices give information on whether the platelet
destruction is ongoing (necessitating an impending platelet transfusion) or whether
the bone marrow is responsive and platelet transfusions can be put on hold. An
increase MPV with falling platelets implies destruction of platelet and signals need
for platelet transfusion while a decrease in MPV with low platelets <20,000/ul
coupled with hemorrhagic tendency warrant need for red cell transfusions . An
increase in IPF suggestive of responsive marrow and platelet transfusions could be
possibly put on hold.Low platelet count, low MPV, low PCT, high PDW, and high
P‑LCR may be used as probable indicators for dengue in endemic area and also
as a predictor of severity of dengue infection. However Platelet indices are still
underutilised parameters both by the laboratory personnel as well as the clinicians
due to various reasons like variability or lack of standardization in testing and
reporting. Further platelet indices are not specific for (or predictive of) any
particular pathological condition and large epidemiological, randomized, control
studies are needed to establish utility of these parameters in dengue beyond doubt.
Keywords: Dengue, platelet indices, transfusion in dengue

Introduction dengue shock syndrome (DSS) or dengue hemorrhagic

D engue is a viral disease caused by dengue virus
with four serotypes DEN‑1–DEN‑4 of the
Flavivirus family transmitted through Aedes aegypti
mosquito. More than 70% dengue is seen in lower‑ and
middle‑income countries.[1]
In majority of people, the illness is self‑limiting and called
simple dengue. However, dengue can be complicated by
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fever (DHF) which warrants proper recognition and
treatment without which, outcomes may be severe.
Review of literature and prevalent practices show the
importance of red cell indices, (especially hematocrit
Address for correspondence:
Dr. Ambuja Kantharaj, E‑mail: ambuja.k@manipalhospitals.com
This is an open access journal, and articles are distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to
remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is
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For reprints contact: reprints@medknow.com

How to cite this article: Kantharaj A. Role of platelet and red cell indices
DOI: 10.4103/GJTM.GJTM_39_18 as a predictive tool for transfusions in dengue. Glob J Transfus Med
2018;3:103-8.

© 2018 Global Journal of Transfusion Medicine AATM | Published by Wolters Kluwer - Medknow 103
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Kantharaj: Role of red cell and platelet indices in dengue
[HCT]) in the diagnosis and prognosis of dengue. In
addition, platelet indices also help assess the prognosis
and decide on the need for transfusions.[2,3]
Platelet indices such as platelet count, mean platelet
volume (MPV), platelet distribution width (PDW),
and plateletcrit (PCT) are simple indices which can be
done by any 3‑part differential cell counter. However,
immature platelet fraction (IPF) can be done only at
advanced centers using more cell counters. Platelet
indices are calculated and given by the cell counters
but are often not reported. This is possibly due to
underrecognition of the utility of these parameters
both by the laboratory personnel as well as the treating
physicians. Variability or lack of standardization in
testing and reporting of these parameters could also
be another reason. The clinical significance, reference
values, and usefulness of some of these parameters are
still under investigation.
Platelet Indices
Mean platelet volume
Platelet volume is a marker of platelet function and
activation. It is a calculated measure of platelet
volume expressed in femtoliter (fL). When there is
hypoproduction of platelets, immature platelets are
activated and increase in size by pseudopod formation
leading to increased MPV. Hence, increased MPV can
be used as a marker of production rate and platelet
activation. Normal range of MPV is reported to be
between 7.2 and 11.7 fL. High MPV with ongoing
thrombocytopenia represents peripheral destruction.
Low MPV indicates underproduction/bone marrow
suppression. MPV is inversely related to platelet
counts. When marrow depression is the cause of
thrombocytopenia, a rising trend in MPV heralds platelet
recovery, and platelet transfusions may be put on hold.[4]
MPV is calculated by the formula,
MPV (fL) = ([PCT (%)/platelet count (×109/l)]) × 105.
Plateletcrit
PCT is the platelet equivalent of HCT. It is the volume of
platelets expressed as a percentage of total blood volume
and calculated according to the formula PCT = platelet
count × MPV/10,000. The normal range for PCT is
0.22%–0.24%. PCT parallels the platelet count.
Platelet larger cell ratio
It is an indicator of circulating larger platelets (>12 fL),
expressed as percentage. The normal percentage range
is 15%–35%. It has also been used to monitor platelet
activity. Platelet larger cell ratio (P‑LCR) is inversely
related to platelet count and directly related to PDW and
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MPV. It is decreased in patients with thrombocytosis
and increased in thrombocytopenia. Further, studies
have shown that P‑LCR was significantly decreased
in reactive thrombocytosis compared to neoplastic
thrombocytosis. A greater increase in P‑LCR is seen
in destructive thrombocytopenia than those with
hypoproliferative thrombocytopenia.[5]
Immature platelet fraction
IPF indicates the percentage of immature platelets
containing higher concentration of RNA released into
the circulation. It is measured in the reticulocyte/
optical platelet channel of the 5‑part differential
hematology analyzer, Sysmex XE‑2100 analyzer
(Sysmex Corporation, Kobe, Japan) by flow cytometry,
in which dye penetrates the cell membrane, staining
the RNA in the cytoplasm of immature (or reticulated)
platelets. IPF reference range is established between
1.1% and 6.1% in healthy individuals. An increased
IPF is seen as production of platelets increases and low
IPF indicate suppressed thrombopoiesis. It can be used
as a tool to not only diagnose and monitor severity of
thrombocytopenia but also as a predictor to recovery
of thrombopoiesis in a previously thrombobocytopenic
patient.[6]
Platelet distribution width
PDW directly measures variability in platelet size,
changes with platelet activation, and reflects the
heterogeneity in platelet morphology. It is an indicator
of platelet anisocytosis. PDW is increased in the
presence of platelet anisocytosis. The PDW reported
varies markedly, with reference intervals ranging from
8.3% to 56.6%. There is a direct relation between MPV
and PDW, that is, a high PDW is associated with a high
MPV.[4,7]
PDW and P‑LCR are analyzed from a histogram of
platelet size distribution. The distribution width at the
level of 20% (the peak of the histogram is 100%) is
Table 1: Normal Range of platelet indices
Platelet Definition Normal
indices Range
MPV (fL) Measure of platelet volume expressed 8.6‑15.5
in femtolitre
PDW (fL) Measure of variability in platelet size/ 8.3‑25 
anisocytosis
PDW (%) The distribution width at the level of 8.3‑56.6 
20% in Platelet histogram
PCT (%) Volume of platelets expressed as a 0.22‑0.24
percentage of total blood volume
IPF (%) Percentage of immature platelets 1.1‑6.1
released into the circulation
P‑LCR (%) Percentage of circulating larger 15‑35
platelets (>12 fL)
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Kantharaj: Role of red cell and platelet indices in dengue
Figure 1: Role of hematocrit in dengue
defined as PDW, and the percentage of platelets with a
size of more than 12fL was defined as P‑LCR.
Mean platelet component (MPC)
Mean platelet component is a measure of mean
refractive index of the platelets calculated by the new
generation of blood cell analyzers (ADVIA 120 and
ADVIA 2120) and provides direct information on density
and granularity of platelets. Recent studies suggest that
this parameter could correlate with the platelet activation
state and become a potential predictive parameter for
acute ischemic complications or thrombotic risk.[4,8]
Composite platelet index (CPLI)
This is a conceptual index derived by multiplying
platelet count (as decimal) with the mean platelet volume
(e.g., platelet count of 1.5 × 105 mm3 and MPV of
10 fL, composite platelet index (CPLI) = 1.5 × 10 = 15)
which can be used as an indicator of risk of bleeding.
The rationale behind this index is fresh and large
platelets would be more functional and hence counter
the disadvantage of lower platelet count to certain
extent. This means for a given platelet count, higher
CPLI indicates higher MPV and hence better function
and protection from bleeding.[9]
Normal ranges of platelet indices are shown in
Table 1.[10]
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Pathophysiology of Dengue Hemorrhagic
Fever
Hemorrhage in dengue is the result of low platelets
and coagulopathy. Low platelets are due to direct bone
marrow suppression of thrombopoiesis by dengue virus
or destruction of platelets by anti‑NS1 antibodies.
Platelet transfusions have a limited role in the
management of dengue[2,3] and transfused platelets are as
much likely to be destroyed by these antibodies as one’s
own platelets. Only indication for platelet transfusions in
dengue is overt or internal mucosal bleeding. However,
patient and doctors alike want platelet transfusions when
the count drops below 10,000–20,000/ul.
Pathophysiology of Dengue Shock
Syndrome
Dengue virus causes increased capillary permeability
and plasma leakage into extravascular space, leading to
hemoconcentration.
Red cell indices give indirect information on whether the
patient is bleeding (needing red cell transfusion) or going
into impending shock (needing bolus intravenous [IV]
fluids). Platelet indices give information on whether the
platelet destruction is ongoing (necessitating an impending
platelet transfusion) or whether the bone marrow is
responsive and platelet transfusions can be put on hold.
Role of Red Cell and Platelet Indices in
Dengue
Role of red cell indices
Hematocrit
HCT forms the most important indicator in recognizing
dengue complications. Increase in HCT over the baseline
suggests hemoconcentration and possibly impending
shock. This is caused by fluid leakage from capillaries
that are seen in dengue. Such patients are more likely to
develop DSS and need aggressive management with IV
fluids.
Decrease in HCT in an unstable patient is suggestive
of hemorrhage and may indicate internal bleeding
secondary to DHF, whereas a decrease in HCT in a
stable patient suggests recovery from disease [Figure 1].
Therefore, a baseline HCT must be established in all
patients with viral fevers.[2]
In the absence of baseline values the population mean
may be used.
Role of reticulocyte production index
Reticulocyte production index (RPI) is believed to be
good surrogate marker to predict the responsiveness of
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Kantharaj: Role of red cell and platelet indices in dengue
Figure 2: Role of mean platelet volume in dengue
the bone marrow. A good correlation is seen between
the increase in RPI and increase in postdengue platelet
count.
Patients with an RPI greater than the cutoff (RPI >3)
indicate a good bone marrow regenerative capacity and
that the platelet count would eventually increase.[11]
Role of Platelet Indices
Platelet count
Thrombocytopenia may be seen in dengue patients by
day 4 or 5 of illness. The exact pathophysiology of
thrombocytopenia in dengue is uncertain.
It could be due to direct bone‑marrow suppression of
thrombopoiesis modulation of endothelial cell by dengue
virus destruction of platelets by Anti‑NS1 antibodies
directed against the virus cross‑reacting with the
platelets.
However, transfused platelets are as much likely to be
destroyed by these antibodies as one’s own platelets and
hence platelet transfusions have a limited role in the
management of dengue.[12]
Mean Platelet Volume in Dengue
Increase in MPV seen in dengue is the result of platelet
activation and pseudopod formation. Further, in case of
106 Global Journal of Transfusion Medicine AATM ¦ Volume 3 ¦ Issue 2 ¦ July-December 2018
functional marrow, there is release of immature platelets
from the bone marrow which are larger in size and could
be another reason for increased MPV.
When platelet production is decreased, young platelets
become bigger and more active, and MPV levels increase.
Increase in MPV together with a stable platelet count
possibly indicates recovery whereas a persistently
elevated MPV together with ongoing thrombocytopenia
is suggestive of active disease causing platelet
destruction with possible need to prepare for platelet
transfusions.
Decreased MPV has been noted in patients with
hemorrhagic tendencies. Decreased MPV with severe
thrombocytopenia (<20,000 platelets/Ul) could be an
ominous sign in dengue and could indicate need for red
cell transfusion [Figure 2].[13,14]
Immature platelet fraction in dengue
Increased IPF is suggestive of an active responsive
marrow, whereas a low IPF possibly indicates suppressed
thrombopoiesis.
In a study by Suman et al., it was observed that in
thrombocytopenic patients, a cutoff value of IPF  ≥6.25
indicated that there is a 67% chance that there will be
a rise in platelet count by 20,000 platelets/UL within
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Kantharaj: Role of red cell and platelet indices in dengue
48 hours. A cutoff value of 10.6 or more indicated
that there is 100% chance of platelet recovery by
20,000 platelets/UL within 48 hours and hence
transfusion decision could be put on hold.[15]
In another study by Dadu et al., it was seen that 93.75%
of the patients show platelet recovery within 24–48 h if
the IPF was more than 10%.[16]
Plateletcrit, Platelet Distribution Width,
Platelet Large‑cell Ratio in Dengue
PCT is directly related to platelet counts, whereas
P‑LCR is inversely related to platelet count
and an increased P‑LCR is seen in destructive
thrombocytopenia (more likely in dengue). PDW
is reported to be higher in dengue fever patients
compared to controls. A study by Mukker et al. showed
that PDW and PCT values were significantly altered
in dengue fever patients with platelet counts below
20,000/ul compared to control group of patients with
platelet count more than 1 lakh.[17] Studies have shown
that a high PDW >13 Fl is associated with dengue
fever, whereas a PDW >15 Fl, a high P‑LCR (>42%),
and low PCT (<0.15%) are more sensitive for DHF.  In
conclusion, Low platelet count, low PCT, and high
PDW may be used as predictors of severity of dengue
infection.[18]
Summary
In dengue:
1. Increased HCT suggests hemoconcentration
and warrants treatment with bolus IV fluids
(10–20ml/kg/h)
2. Decreased HCT in an unstable patient may
indicate bleeding and act as a predictor for red cell
transfusions, whereas it suggests recovery from
disease in a stable patient
3. Platelet counts have no role in determining need for
transfusion in dengue
4. An increase MPV with falling platelets implies
destruction of platelet and signals need for platelet
transfusion
5. A decrease in MPV with low platelets <20,000/ul
coupled with hemorrhagic tendency warrant need for
red cell transfusions
6. Low platelet count, low MPV, low PCT, high PDW,
and high P‑LCR may be used as probable indicators
for dengue in endemic area
7. Low platelet count, low PCT, and high PDW may be
used as a predictor of severity of dengue infection
8. An increased P‑LCR is seen in destructive
thrombocytopenia (more likely in dengue)
9. P‑LCR is inversely related to platelet count
10. An increase in IPF suggestive of responsive marrow
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and platelet transfusions could be possibly put on
hold.
Conclusion
Platelet indices (PI)  may act as predictive tools in the
diagnosis and predicting outcomes in dengue fever.
Clinicians and transfusionists need to be sensitized about
the utility and limitations of these indices in day‑to‑day
and clinical practice. Transfusion decisions based on these
indices may also help in rationalizing the need for red
cell and platelet transfusions in dengue and thereby allay
anxiety of the clinician and improve preparedness of the
blood center to provide necessary blood components for
transfusion. However, platelet indices are not routinely
used in clinical practice, probably because they are not
tested for or reported routinely. IPF is one parameter
that is being increasingly used to assess the recovery
from thrombocytopenia in dengue but can be done
only on 5‑part differential machines making it difficult
for routine implementation in all laboratories/hospitals.
Further, platelet indices are not specifc for (or predictive
of) any particular pathological condition.[19] Most of these
studies are retrospective in small study populations and
the cutoff values have not been validated prospectively.
Hence, large epidemiological, randomized, control
studies are needed to establish utility of these parameters
in dengue beyond doubt.[20]
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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