ORIGINAL  
Niger J Paed 2014; 41 (1):28 –32  
Utuk EE  
The prevalence of thrombocytopenia  
in plasmodium falciparum malaria in  
children at the University of Uyo  
Teaching Hospital, Uyo, Nigeria  
Ikpeme EE  
Emodi IJ  
Essien EM  
DOI:http://dx.doi.org/10.4314/njp.v41i1,5  
Accepted: 23th June 2013  
Abstract Background: Thrombo-  
cytopenia occurring in falciparum  
malaria infection has been docu-  
mented worldwide. However, its  
prevalence varies from place to  
place, and among different popu-  
lation groups studied. There is  
paucity of data on this in Nigerian  
children.  
Objectives: To determine the  
prevalence of thrombocytopenia  
in children presenting with falci-  
parum malaria at the University  
of Uyo Teaching Hospital, Uyo,  
Akwa Ibom State, Nigeria.  
compared with 180 healthy chil-  
dren without malaria parasitaemia  
matched for age and gender. Their  
platelet counts were evaluated  
using the auto-analyser Sysmex  
KX-21N.  
Results: The overall prevalence of  
thrombocytopenia was 5.0%, but it  
was higher in children with severe  
malaria. None of the children in  
the control group had thrombocy-  
topenia.  
Conclusion: The prevalence of  
thrombocytopenia in falciparum  
malaria is low in our setting, but  
higher in children with severe  
manifestations of malaria.  
(
)
Utuk EE  
Ikpeme EE  
Department. of Paediatrics,  
University of Uyo Teaching  
Hospital, Uyo, Akwa Ibom State.  
Nigeria.  
E-mail: utukenoobong@yahoo.com  
Emodi IJ  
Department of Paediatrics,  
University of Nigeria Teaching  
Hospital, Enugu,  
Enugu State, Nigeria.  
Essien EM  
Department of Haematology  
University of Uyo Teaching Hospital,  
Uyo. Akwa Ibom State, Nigeria.  
Method: A prospective cross-  
sectional study from October  
2010 to March 2011 on one hun-  
dred and eighty children with mi-  
croscopically confirmed malaria  
aged six months to fifteen years,  
Keywords: Malaria, Thrombocy-  
topenia, Prevalence, children.  
Introduction  
“normal reference range”, there are some ethnic differ-  
ences, with Caucasian values bein-1g0 higher than those of  
7
Malaria infection remains a major public health problem  
and cause of morbidity and mortality in all age groups.  
the African and Afro-carribeans. It has therefore been  
1
,2  
stressed that each population must establish its own  
“norma7,l10reference values” for use in clinical assess-  
In Nigeria, it accounts for 20 to 30% of infant and child  
mortality, particul2a,3rly in children who are five years of  
age and younger. The lethality of P. falciparum com-  
pared with other species of plasmodium probably stems  
from the parasite density it achieves which is typically a  
hundred times higher than that of other species before its2  
proliferation is curtailed by host defence mechanisms.  
As blood parasites for most of their complex life cycle,  
plasmodia, not surprisingly, produce haematological  
abnormalities that include anaemia, thrombocytopenia,  
splenomegaly and rarely dissemina2t,3e-d6 intravascular co-  
ments.  
The normal reference range of the platelet  
count in the Africa7n-9 population has been established at  
9
100 – 300 x 10 /L. For the Caucasians, it is 150 – 450  
9
2,7,9  
These differences in normal values need to  
x 10 /L.  
be appreciated to avoid fundamental errors in the assess-  
ment and management of patients.  
Thrombocytopenia, a state of reduced circulating plate-  
let count in blood below the normal level can be caused  
by decreased platelet production, increased destruction,  
2
agulation with a bleeding diathesis.  
Values of haema-  
sequestration or a combination of these. A major aeti-  
tological parameters have been shown to be affected by  
factors such as genetics and ethnic differences, sex, age,  
environmental factors like dietary pattern and altitude.  
Since these factors differ depending on the population  
and geographical area studied, it is not surprising that  
differences3-5have been reported in these parameters  
worldwide.  
ologic cause for acquired thrombocytopenia of child-  
hood is increased platelet destruction associated with  
several clinical conditions including protozoal infections  
3
-5  
2,3,6  
such as malaria especially in the tropical regions.  
This association of thrombocytopenia with malaria in-  
fection is well recognized, but prevalence varies with  
levels of malarial endemicity an11d-1i3mmunity, age, malar-  
ial specie and malarial severity.  
Studies from various  
Genetic factors are shown to sig7n-9ificantly contribute to  
variance in all blood cell lines. Thus within the wide  
authors in different regions of the world have also  
shown that considerable overlap exists in  
2
9
thrombocytopenic values which occur in both unc1o1m-13pli-  
cated and severe falciparum malarial infections. In  
weeks of presentation were excluded. Children with  
systemic diseases e.g leukaemia and other malignancies  
that involve the bone-marrow and those with an obvious  
focus of infection, with a positive blood culture exami-  
nation were all excluded. Controls were afebrile appar-  
ently healthy children, matched for age and gender who  
showed no signs of any systemic disease and had no  
parasitologic evidence of malaria. They were selected  
from children attending child welfare clinic for growth  
monitoring and those presenting for immunization. Also  
children who presented to the out-patient clinic for  
school entry medical examination were recruited.  
non-endemic countries such as United Kingdom, France,  
Sweden, studies done showed a varying prevalence rate  
of thro1m4-b17ocytopenia in malaria to be between 64% -  
8
7.3%.  
In a study in Dakar, Senegal where malarial  
transmission is hypo-endemic, that8 is, low and seasonal,  
1
a prevalence of 56.2% was seen. In holoendemic ma-  
laria countries like Pakistan, India, Kenya, Cameroon,  
and Nigeria, varying prevalence rates have been9-2d1ocu-  
1
mented to be as low as 13% and as high as 90%.  
The  
prevalence of thrombocytopenia with falciparum parasi-  
taemia has been mostly documented in adult populations  
of semi-immune and non-immune individuals, but there  
have been few documentation for children in the tropical  
region of Africa, more so in Nigeria, where malaria is  
endemic. This study was therefore designed to establish  
A clinical history was obtained from the care-giver and/  
or the patient and included the onset and duration of  
0
fever (temperature 37.5 Celsius) and associated symp-  
toms. Uncomplicated malaria was established by micro-  
scopically confirmed malaria parasitaemia with no  
symptoms of severity. Children with repeated convul-  
the preva7-l9e,1n9ce of thrombocytopenia (platelet count <100  
9
x 10 /L)  
in children aged six months to fifteen years  
o
with falciparum malaria infection as seen in a locality in  
Nigeria. The practice of paediatrics in the tropics does  
not always permit a detailed diagnostic work-up for  
every child with haematological manifestations therefore  
research on the prevalence and aetiologic patterns is  
important. It will serve as a guide to improve clinical  
treatment and outcome.  
sions, hyperpyrexia (axillary temperature39.5 celsius),  
respiratory distress, oliguria (urinary output < 1ml/kg/  
hr), cardiovascular shock, jaundice, severe prostration,  
haemoglobinuria, severe anaemia (Haemoglobin<5g/dl),  
hyperparasitaemia (involving > 5% of erythrocytes),  
hypoglycaemia (serum glucose < 2.2mmol/l), acidosis  
(bicarbonate <,4 15mmol/l) were classified as having se-  
3
vere malaria. Children presenting with an episode or  
repeated episodes of convulsions had a lumbar puncture  
done for cerebro-spinal fluid analysis to exclude bacte-  
rial meningitis. A complete physical examination was  
done. Level of consciousness was assessed using the  
Blantyre’s score for children younger than two years and  
Glasgow score for older children.  
Subjects and Methods  
The study was carried out in the Children Out-patient  
(
CHOP) clinic, Children Emergency Unit (CHEU) and  
the Paediatric ward of the University of Uyo Teaching  
Hospital (UUTH), Uyo in Akwa-Ibom State. The Teach-  
ing Hospital is the only tertiary health institution in the  
state, and is located on the outskirts of Uyo, six kilome-  
tres from the centre of the city. Uyo, the capital city of  
Akwa-Ibom State is located in the South-south region of  
Nigeria. It lies between latitudes 4’33 and 5’33 North,  
longitudes 7’35 and 8’35 east, and falls within the tropi-  
cal zone where the anopheline mosquito habitat exists.  
Thick and thin blood films for malaria parasite were  
prepared directly from capillary blood and the slides  
stained on the same day with the Giemsa stain. Each  
blood film was examined microscopically using the  
100X objectives and the 7X eyepieces as these give a  
brighter and clearer image. The parasite density was  
determi2ned using the method by Greenwood and Arm-  
2
strong who found this method to be more accurate and  
quicker than counting the parasites against white cells.  
The platelet count were determined using the fully auto-  
mated blood cell analyser (Sysmex KX-21N). For any  
samples which contained a significant proportion of  
giant platelets, small platelets or did not show any plate-  
let count, indicated by a flag signal from the machine,  
the manual counting method was performed for confir-  
mation.  
Approval for the study was obtained from the hospital’s  
Ethics committee before commencement. A written and  
verbal informed consent was obtained from each child if  
up to twelve years old and above or from the parents/  
guardian(s) for younger children.  
Children aged six months to fifteen years of age with  
fever or a history of fever of not longer than seven days  
duration before presentation in hospital with parasi-  
tologic evidence of malaria were included. Also in-  
cluded were children with fever and at least one or more  
features of severe malaria, as well as those who had not  
received any anti-malarial drug in the preceding two  
weeks of presentation to hospital. Any child who had  
received any cytotoxic drug and other drugs that inter-  
fere with platelet counts e.g non-steroidal anti-  
inflammatory drugs (NSAIDS) such as aspirin, Ibupro-  
fen etc, within ten days of presentation, as well as those  
who had received any anti-malarial treatment within two  
Thrombocytopenia was def2i3n-2e5d in this study as a platelet  
9
count < 100,000 x 10 /L.  
Severe thrombocytopenia  
9 2  
was defined as a platelet count < 50,000 x 10 /L. Aero-  
bic and anaerobic blood cultures were done on each  
child. Random blood sugar was also done using a One-  
Touch Ultra-2 glucometer (Life scan model Inc.  
Milpitas, CA.USA 95035) on every child presenting  
with clinical features of severe malaria. Values less than  
2.2mmol/l were considered as hypoglycaemia.  
3
0
Statistical analysis  
Overall, nine (5.0%) of the 180 subjects in this study  
had thrombocytopenia, defined as platelet count < 100 x  
10 /L. There was no individual with thrombocytopenia  
9
Statistical analysis was performed using the SPSS  
(
Statistical Analysis for Social Sciences) 17.0 software.  
among the controls. Of the 156 subjects presenting with  
uncomplicated malaria, three (1.9%) had thrombocyto-  
penia, while six (25.0%) of the 24 subjects with severe  
malaria had thrombocytopenia. Of these, one subject  
(0.6%) had severe thrombocytopenia (defined by a  
Qualitative variables were expressed as number and  
percentage while quantitative variables were expressed  
as mean (X) and standard deviation (S).The arithmetic  
mean as a measure of central tendency, and the standard  
deviation (S) as a measure of dispersion where applied.  
The student t-test was used to compare the mean values  
of the quantitative variables between the subjects and  
the controls. For non-normally distributed quantitative  
variables, the Wilcoxon rank sum test was employed.  
The Chi-square test was used in finding a difference in  
the qualitative variables. A p-value of less than 0.05 (p <  
9
platelet count < 50 x 10 /L). This difference was statisti-  
cally significant [(p < 0.001) Table 2a]. Comparatively,  
using a reference thrombocytopenic cut-off value of 150  
9
x 10 /L in this study, twenty-three (12.8%) of the 180  
subjects would be seen to have thrombocytopenia. Of  
these, thirteen (54.2%) presented with severe malaria  
and ten (6.4%) with uncomplicated malaria. This was  
also statistically significant [(p < 0.001) Table 2b].  
0
.05) was considered statistically significant.  
Table 2a: Prevalence of thrombocytopenia (<100,000) in  
clinical malaria  
Results  
Platelet  
Subjects  
Total  
P-value  
0.001  
count  
Uncompli-  
cated N %  
Severe  
N %  
9
(
x10 /L)  
A total of one hundred and eighty (180) subjects, and  
one hundred and eighty (180) controls were studied. The  
group of children aged one to five years were the most,  
constituting 73.3% of subjects. The mean age of the  
subjects, 3.75 ± 4.20 years and that of control group  
>
100,000  
153 (98%) 18 (75%) 171 (95%)  
6 (25.0%) 9 (5%)  
<100,000 3 (1.9%)  
3
.78 ± 4.26 were comparable (p=0.96). The gender dis-  
Table 2b: Prevalence of thrombocytopenia (<150,000) in  
clinical malaria  
tribution and weight of subjects and controls were also  
comparable (p = 0.89). The mean temperature of sub-  
jects at presentation was 37.8 ± 0.84 and their mean  
duration of fever was 3.27 ± 1.58 days. No child in the  
control group had fever.  
Platelet  
Subjects  
Total P-value  
count  
x10 /L)  
Uncompli-  
cated N%  
Severe  
N %  
9
(
>
<
150,000 146(93.6%) 11(45.8%) 157(87.2%)  
150,000 10 (6.4%) 13(54.2%) 23(12.8%) 0.001  
The mean malaria parasite count in subjects was  
2
5,650.28 ± 88,312.04, with a range of 500 to 725,500  
parasites/µl. P. falciparum was the only specie found in  
all the subjects. The control children had no parasitae-  
mia. Platelet count was higher in the control group. This  
was statistically significant [(p = 0.0008) Fig I]. The  
platelet count range in subjects with uncomplicated ma-  
Discussion  
9
The low prevalence of 5.0% of thrombocytopenia in  
falciparum malaria found in this study is comparable to  
the 13.75% found by Jeremiah and Uko in Port-  
laria was 70 - 596 x 10 /L significantly greater than the  
9
range, 44 – 565 x 10 /L in subjects with severe malaria  
(
Table 1).  
1
9
Harcourt. This finding may be as a result of the throm-  
9
bocytopenic cut-off range of 100 x 10 /L used in both  
Table 1: Platelet counts in subjects with uncomplicated versus  
studies. Besides this, the children in that community  
study done in Port-harcourt were asymptomatic for ma-  
laria, which may otherwise, have had more profound  
effect on their platelet counts. Both studies were carried  
out in the south-south region of Nigeria, with similar  
levels of malaria transmission. The low prevalence rates  
obtained in both studies, may be due to the early acqui-  
sition of malarial immunity by many children in these  
holo-endemic study settings which confers a protective  
effect again7st severe manifestations including thrombo-  
severe malaria  
9
Clinical Malaria  
Platelet ( x 10 /L)  
P- value  
Range  
Mean ± SD  
Uncomplicated 70 596 313.95 ± 117.98  
Severe 44 565 192.54 ±141.62  
P < 0.001  
Controls  
Subjects  
1
cytopenia. This immunity seems to vary in children  
3
from region to region and may be a possible factor re-  
sponsible for the low prevalence observed in both  
studies.  
The higher prevalence of 23% to 59.7% documented in  
other stu23d,2i4es carried out in the south-western part of  
were in contrast with that obtained from this  
Box and Whisker Plot showing the distribution of platelet count in Subjects and Controls  
Nigeria  
3
1
study. These differences in prevalence may be partly  
explained by the different age distributions of the chil-  
dren studied, the clinical severity of malaria in the  
groups studied, and the platelet cut-off reference ranges  
used by the different authors. These studies were hospi-  
tal-based, had more children with severe malaria in-  
cluded and children with bacterial infections were not  
excluded. These may have contributed greatly to their  
higher prevalence rates of thrombocytopenia, consider-  
ing the synergistic effect of these facto2r3s,24on depression  
The significantly lower platelet count in the children  
with malaria parasitaemia than those in the control  
group is an3 observation similar to that made by Aking-  
2
24  
bola et al and Iwalokun et al in Lagos, Nigeria. Like-  
wise, the normal platelet count values seen in the control  
chi3ldren in this study as also observed by Akingbola et  
2
al all serve to affirm the adverse effect of malaria para-  
sitaemia on platelet count values. The reduced platelet  
lifespan and platelet destruction in acute malaria, which  
partly results from the binding of malaria antigen unto  
platelets is perhaps responsible for the above findings.  
This observation was found to be irrespective of the  
malaria2t1ransmission level or specie in the areas  
studied.  
of platelet count values. These authors  
also both in-  
explicably used a thrombocytopenic cut-off range of 150  
9
x 10 /L in defining thrombocytopenia, rather than the  
9
accepted normal range of 100 x 10 /L used in present  
study, being9,1t9he standard reference range for the African  
population.  
Children with severe manifestations of malaria had sig-  
nificantly lower platelet counts than those with uncom-  
plicated malaria in this study23s,i2m4 ilar to previous reports  
Outside Nigeria, higher prevalence rates of 49% and  
2
5
5
8% were a6lso documented among children in Kenya  
in other Nigerian children.  
Reduction in platelet  
2
and Gabon respectively, who live in similar tropical  
settings with stable malaria and perennial transmission.  
count values, which is a more frequent finding in severe  
forms of malaria, would have been responsible for the  
lower platelet counts seen in the children in this study.  
9
A higher cut-off of platelet reference value of 150 x 10 /  
L was also used in these studies. This seems to have  
contributed significantly to the higher prevalence docu-  
mented. As compared to this study, a high8er prevalence  
1
was also obtained from children in Dakar (56.2%) and  
Conclusion  
1
6
France (45.6%), being areas of hypo-endemic and non-  
endemic transmission of malaria respectively. This may  
be because children in these hypo and non-endemic ar-  
eas o2,f16,t1r8ansmission are mostly non-immune to ma-  
In conclusion, although the overall prevalence of throm-  
bocytopenia in children with falciparum malaria in our  
locality is low, it is significantly higher in children with  
severe manifestations of malaria than in the uncompli-  
cated type. It is recommended where possible, to evalu-  
ate and monitor the platelet counts in children presenting  
with clinical features of severe malaria. It would also be  
beneficial to use standardized normal reference values  
representing children living in similar geographical set-  
tings.  
laria.  
They are therefore at a higher risk of severe  
clinical manifestations of malaria, with its attendant  
lowering effects on platelet count values. Besides, the  
prospective study in Dakar was done over a prolonged  
period of seventeen months, and children with severe  
malaria comprised a greater percentage (74.7%) of the  
study population. This probably explains the low platelet  
count values. This re-inforces the importance of a close  
monitoring of the platelet counts in children visiting  
from non-endemic settings, since they are at greater risk  
of thrombocytopenia.  
Conflict of interest: None  
Funding: None  
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