Running head: Correlation of Leukopeni and Thrombocytopenia with the Clinical Outcome...

Correlation of Leukopenia and Thrombocytopenia

with the Clinical Outcome of Dengue Virus Infection Among Pediatric Patients
Admitted at Ilocos Training and Regional Medical Center, 2015

Michelle Agustin, MD
Department of Pediatrics
Ilocos Training and Regional Medical Center

Correlation of Leukopenia and Thrombocytopenia with the Clinical Outcome of Dengue...

Table of Contents
Introduction......................................................................................................... 3
Objectives........................................................................................................ 6
Significance of the Study...................................................................................... 6
Method............................................................................................................... 7
Participants....................................................................................................... 7
Procedure......................................................................................................... 7
References........................................................................................................... 8

Correlation of Leukopenia and Thrombocytopenia with the Clinical Outcome of Dengue...

Introduction

Dengue disease or Dengue Virus Infection is the most common arthropod-borne viral
(arboviral) illness in humans affecting the tropical and subtropical regions, including the
Philippines (Bravo, Roque, Brett, Dizon, and LAzou, 2014). Around the world, 2.5-3 billion
people live in about 112 countries that experience dengue transmission and that yearly,
approximately 50-100 million individuals are infected. It is caused by infection with 1 of the 4
serotypes of dengue virus, which is a Flavivirus (a genus of single-stranded nonsegmented RNA
viruses). Infection with one dengue serotype confers lifelong homotypic immunity to that
serotype and a very brief period of partial heterotypic immunity to other serotypes, but a person
can eventually be infected by all four serotypes (Singh, et al 2014).
Locally, the highest incidence of dengue disease cases per 100,000 population was
reported in children who are 514 years of age and followed by children 04 years old;
moreover, highest incidences observed by region were in Mindanao. These local trends may be
explained by a improvements in surveillance, growing population, escalating urbanization, as
well as the limited success of vector control measures (Bravo, Roque, Brett, Dizon, & Azou
(2014). Dengue fever (DF) and Dengue Hemorrhagic Fever (DHF) /Dengue Shock Syndrome
(DSS) persist to be large causes of morbidity and mortality in the Philippines especially the
children. Being endemic, clustering dengue cases and outbreaks are actually unpredictable due to
certain factors such as the inability to control and prevent such (Philippine Pediatric Society,
2010).
Infection with any of the four dengue serotypes can produce the full spectrum of illness
and severeness. The range of illness can range from a mild, non-specific febrile syndrome to

Correlation of Leukopenia and Thrombocytopenia with the Clinical Outcome of Dengue...

classic dengue fever (DF), to harsher forms of the disease which are dengue hemorrhagic fever
(DHF) and dengue shock syndrome (DSS) (Centers for Disease Control [CDC], 2014) associated
with headache, myalgia and thrombocytopenia (Tantawichien, 2012. To prevent deaths, advance
clinical recognition of dengue infection and anticipatory or early treatment for those who
develop DHF or DSS (CDC, 2014).
The characteristic clinical manifestations of dengue are fever, headache, malaise,
arthralgia, rash, pruritus, diarrhea, nausea, retro-orbital pain, general, respiratory distress, dry
cough, abdominal pain, vomiting, postural dizziness, and sweating (Kao, King, Chao, Wu, and
Chang, 2005). Epistaxis, gingival bleeding, menorrhagia, gastrointestinal bleeding, intracranial
bleeding, hematuria, effusions and spontaneous bleeding in places of venipuncture can be used
as hematologic warning signs in the development of dengue (Lemes, 2014). Kittigul,
Pitakarnjanakul, Sujirarat, and Siripanichgon, (2007); Kao, King, Chao, Wu, and Chang (2005)
as well as De Paula & Fonseca (2004) agreed that among laboratory results, an increase in
hematocrit, leukopenia, relative lymphocytosis, atypical lymphocytes, low platelet count,
prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) and increased
serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), alkaline
phosphatase and serum gamma-glutamyl transferase (GT) range and decreased serum albumin
may occur.
A study conducted by Asher and colleagues (2001) revealed that leukopenia and
thrombocytopenia are characteristic, but unexplained, features of dengue infection. It has been
suggested that an increased platelet consumption is responsible for thrombocytopenia in dengue
hemorrhagic fever, but the cause of neutropenia is unknown. Moreover,

Correlation of Leukopenia and Thrombocytopenia with the Clinical Outcome of Dengue...

Oliveira, Pontes, Cunha, Fres, and Nascimento (2009) stressed that leukopenia,
thrombocytopenia, lymphocytopenia, and atypical lymphocytes were main hematologic findings
in dengue. For Kittigul, Pitakarnjanakul, Sujirarat, and Siripanichgon (2007), leukopenia is a
common finding, whereas thrombocytopenia may occasionally be observed in DF, especially in
those with hemorrhagic signs. However, according to Wu et al. (2000) and Durbin et al. (2008)
explained that the fall of WBC count occurs since dengue viruses attack the epidermal dendritic
cells which in turn migrate toward lymph nodes and subsequently infects macrophages,
monocytes and other subtypes of WBC. The fall in platelet count is primarily caused by the
induced bone marrow suppression (Kafeel, 2011) by the dengue virus as well as the anti-platelet
antibodies causing platelet deterioration by an immune mediated mechanism (Kyle, Beatty and
Harris (2007) as cited from Rasool, Ahmad, Masood, and Khan (2014).
CDC (2014) suggests that new-onset leukopenia (WBC <5,000 cells/mm3) with a
lymphocytosis and an increase in atypical lymphocytes signify that the fever will likely dissipate
within the next 24 hours and that the patient is entering into the Critical Phase. Subsequently,
high (>38.0C) to normal or subnormal temperatures, thrombocytopenia (100,000 cells/mm3)
with a rising or elevated hematocrit (20% increase from baseline), new hypoalbuminemia or
hypocholesterolemia, new pleural effusion or ascites, and signs and symptoms of impending or
frank shock, are biomarkers that imply the patient has already entered the Critical Phase.
The interplay between the two significant blood counts are descriptively observed during
the dengue course, but only few studies would provide us with data regarding their correlation.
Rasool, Ahmad, Masood, and Khan (2014) found in their retrospective study of relating WBC
and platelet count during only the recovery phase of dengue hemorrhagic fever that there is a
positive correlation of the two earlier mentioned blood counts. Furthermore, they also discovered

Correlation of Leukopenia and Thrombocytopenia with the Clinical Outcome of Dengue...

that during the dengue fever infection in DHF, the WBC count decreases first and then platelets
count follows in a descending fashion, and when recovering from dengue, WBC count increases
first while platelet count is still falling but will actually increase in a progressive approach.
Consequently, it still cannot conclude from previous studies that the trends of leukopenia
in relation to thrombocytopenia may be agreed upon a certain correlation (positive, none, or
negative) in conjunction with different factors or their destruction, suppression, recycling and/or
synthesis throughout the course of the dengue disease. And with this problem, the conduction of
this research material shall provide the avenue to identify the gap.
Objectives
To determine the correlation of leukopenia and thrombocytopenia with the clinical
outcome of dengue virus infection among pediatric patients.
Specific Objectives
1. To identify the specific pattern of leukopenia and thrombocytopenia in patients diagnosed
with dengue virus infection.
2. To determine the relationship of leukopenia and thrombocytopenia in patients with dengue
virus infection
3. To correlate the relationship of leukopenia and thrombocytopenia with the severity of dengue
virus infection.
Significance of the Study
Determining the possible significant correlation of leukopenia and thrombocytopenia
would further improve recognition of dengue cases. It will also an avenue to identify severe
dengue and carry out more focused close monitoring and prompt, appropriate management, such
as in providing guidance on appropriate and timely fluid management and the use of blood and
blood products, though it also includes the prevention of complications. The output of this

Correlation of Leukopenia and Thrombocytopenia with the Clinical Outcome of Dengue...

research might provide a stepping stone for future studies and that it might provide ideas for
further understanding the significance of the correlation in improving the management of dengue
patients.

Method
Participants
Total enumeration was utilized with the general inclusion of medical records of patients
admitted at Ilocos Training and Regional Medical Center, a tertiary hospital in La Union,
Philippines within the period of January to December of 2013. These patients, 0-18 years of age
were admitted as a case of Dengue Fever or Dengue Hemorrhagic Fever based on the latest
WHO criteria.
Procedure
Data were collected using a proforma designed to collect laboratory track records and
other clinical information of the patient role during the course of treatment and then concerned
argument were statistically analyzed. A retrospective cohort study of above mentioned secondary
data was mainly utilized to analyze the white blood cell and platelet counts of patients diagnosed
with DF or DHF throughout the stages of the disease course.

Correlation of Leukopenia and Thrombocytopenia with the Clinical Outcome of Dengue...

References
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Vaughn, D.W. (2001). Platelet Phagocytosis And Neutrophil Apoptosis Might Account
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Bravo, L., Roque, V.G., Brett, J., Dizon, R., and LAzou, M. (2014). Epidemiology of Dengue
Disease in the Philippines (20002011): A Systematic Literature Review. PLoS Neglected
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