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i
CLINICOETIOLOGICAL PROFILE AND OUTCOME OF
ACUTE FEBRILE ILLNESS WITH THROMBOCYTOPENIA
IN CHILDREN-A HOSPITAL BASED PROSPECTIVE STUDY
Dissertation submitted in partial fulfillment of
M.D. DEGREE EXAMINATION
M.D. PEDIATRICS, BRANCH-VII
CHENGALPATTU MEDICAL COLLEGE AND HOSPITAL
CHENGALPATTU
THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY
CHENNAI, TAMILNADU
APRIL 2017
ii
DECLARATION
I Dr. M. ARULGANESH have proposed study titled
“CLINICOETIOLOGICAL PROFILE AND OUTCOME OF
ACUTE FEBRILE ILLNESS WITH THROMBOCYTOPENIA IN
CHILDREN-A HOSPITAL BASED PROSPECTIVE STUDY” in
Department of Pediatrics at Chengalpattu Medical College and Hospital,
I hereby ensure that I will abide by the rules of the institutional ethics
committee.
A PROSPECTIVE STUDY
A bonafide work done by me in the Department of Pediatrics,
Chengalpattu Medical College, Chengalpattu, under the guidance of
Prof. Dr. V. POOVAZHAGI, M.D., D.C.H., Ph.D., Professor,
Department of Pediatrics, Chengalpattu Medical College, Chengalpattu.
(Dr. M. ARULGANESH)
Signature of the candidate
iii
CERTIFICATE
This is to certify that the dissertation titled
“CLINICOETIOLOGICAL PROFILE AND OUTCOME OF
ACUTE FEBRILE ILLNESS WITH THROMBOCYTOPENIA IN
CHILDREN-A HOSPITAL BASED PROSPECTIVE STUDY” is
the bonafide work of Dr. M. ARULGANESH in partial fulfillment of
the requirements for M.D. BRANCH-VII (PEDIATRICS)
examinations of THE TAMILNADU DR.M.G.R MEDICAL
UNIVERSITY to be held in 2017.the period of study was from August
2015- September 2016.
Signature of the H.O.D Dean
Professor and Head Chengalpattu Medical College
Department of Pediatrics Chengalpattu.
Chengalpattu Medical College
Chengalpattu.
iv
CERTIFICATE BY THE GUIDE
This is to certify that the dissertation titled
“CLINICOETIOLOGICAL PROFILE AND OUTCOME OF
ACUTE FEBRILE ILLNESS WITH THROMBOCYTOPENIA IN
CHILDREN-A HOSPITAL BASED PROSPECTIVE STUDY”
submitted by Dr. M. ARULGANESH, M.D. in partial fulfillment for
the award of the degree of DOCTOR OF MEDICINE IN PEDIATRICS
by The Tamilnadu Dr.M.G.R Medical University, Chennai is bonafide
work done by him in the Department of Pediatrics, CHENGALPATTU
MEDICAL COLLEGE, CHENGALPATTU, during the academic year
2015-2017 under my guidance .
PLACE: Chengalpattu Dr. V. POOVAZHAGI, M.D., D.C.H., Ph.D.,
DATE : Professor ,
Department of Pediatrics
Chengalpattu Medical College,
Chengalpattu
v
ACKNOWLEDGEMENT
I take this opportunity to express my respect and heartfelt gratitude
to all my Teachers. First and foremost I would like to express my
sincere gratitude ,heartfelt thanks and appreciation for my guide
Dr.V.Poovazhagi M.D.,D.Ch.,Ph.D., for her unparalleled
encouragement and everlasting patience from the start of my study, my
thesis protocol preparation till the completion of my dissertation. I would
like to express my sincere gratitude and heartfelt thanks to my co-guide
Dr.J.Sathya M.D.,D.Ch., for her valuable suggestions, encouragement
and co- operation provided to me throughout my study.
I would like to express my sincere gratitude to
Dr.N.Gunasekaran M.D.,DTCD., The DEAN of this institution for
allowing me to utilize the facilities in the institution.
I would like to express my sincere gratitude to Dr.M.Jeyakumar
M.D.,DCH., for giving constant support and suggestions for my study. I
would like to express my sincere gratitude to Dr.J.Ganesh M.D.,DCH.,
for his valuable suggestions and guidance for my study. I also like to
express my sincere gratitude to Dr.A.Vijayalakshmi M.D., Professor of
Microbiology for the support provided by her.
vi I express my sincere gratitude and thanks to Dr.S.A.Ravikumar
M.D., Dr.K.Arivoli M.D.,DTCD.,Dr.S.Suresh Kumar M.D.,
Dr.A.Jagadeeswari DCH.,Dr.D.Sree Nandhini, Dr. D.Suresh M.D.,
Dr.R.Diana Grace M.D., for their valuable support and guidance during
the course of Study. I express my gratitude to all my colleagues and
Staff nurses in our Department. I am extremely thankful to all the
children and their parents who have participated in this study.
vii
viii
ix
x
LIST OF CONTENTS
SI
NO TITLE
PAGE
NO
1 INTRODUCTION 1
2 OBJECTIVE 3
3 LITERATURE REVIEW 4
4 METHODOLOGY 18
5 OBSERVATION AND RESULTS 23
6 DISCUSSION 64
7 SUMMARY 72
8 CONCLUSION 75
9 BIBLIOGRAPHY 76
ANNEXURES
a) Proforma
b) Consent form
c) Master chart
xi
LIST OF TABLES
TABLE NO TITLE PAGE
NO
1 Diagnostic criteria 21
2 Age distribution 24
3 Age and sex distribution 26
4 Geographic distribution 28
5. Month wise distribution 30
6 Symptom catergorization 32
7. Symptom categorization according to age 34
8 Examination findings at admission 35
9 Examination finding in different age groups 37
10 Vital signs at admission 38
11 Physiological status at admission 39
12 Physiological status at admission in different age group 41
13 Mean, range, standard deviation of lab parameters. 42
14 Grades of thrombocytopenia 43
15 Comparision of physiological status with grades of thrombocytopenia 45
16 Grades of thrombocytopenia in different etiology 46
17 Frequency of bleeding manifestations 50
18 Bleeding manifestations in different age group 52
xii
TABLE NO TITLE PAGE
NO
19 Types of bleeding manifestations in different etiology 53
20 Grades of thrombocytopenia in different etiology 55
21 Univariate analysis of risk factors among bleeding and non bleeding groups 57
22 Morbidity 59
23 Etiological Profile 61
24 Outcome 63
25 Grades of thrombocytopenia in different Studies 69
xiii
LIST OF FIGURES
FIGURE NO. TITLE PAGE
NO
1 Sex distribution 23
2 Age wise distribution 25
3 Age and sex distribution 27
4 Area distribution 29
5 Month wise distribution 31
6 Symptom categorization 33
7 Examination findings at admission 36
8 Vitals at admission 40
9 Grades of thrombocytopenia 44
10 Severity of thrombocytopenia in undiagnosed fever
47
11 Severity of thrombocytopenia in dengue fever 48
12 Severity of thrombocytopenia in Scrub typhus 48
13 Comparison of severity of thrombocytopenia in common etiology
49
14 Bleeding manifestations 51
15 Bleeding manifestations in different age group 54
16 Bleeding manifestations in different etiologies 56
17 Causes identified among children with thrombocytopenia
62
18 Outcome 63
xiv
ABBREVIATIONS
DHF Dengue hemorrhagic fever
ALOC Altered level of consciousness
WHO World Health Organization
MODS Multi organ dysfunction syndrome
DIC Disseminated intravascular coagulation
ELISA Enzyme linked immune sorbent assay
APTT Activated partial thromboplastin time
ITP Immune thrombocytopenic purpura
ALL Acute lymphoblastic leukemia
PCV Packed cell volume
CSF Cerebro spinal fluid
1
INTRODUCTION
Fever is the most ancient hallmark of disease. Fever is known
as pyrexia from Greek “pyretus” meaning fire. The word Febrile is from
the Latin word Febris, meaning fever. Fever is defined as rectal
temperature of >38° C(100.4° F)1 or axillary temperature of > 37.5°C2
It is a frequent medical sign that implies increase in body temperature to
above normal level. It is considered as one of the natural immune
mechanisms to attain neutralization of perceived threat inside the body.
It is a symptom caused by a variety of illnesses. Fever usually
occurs in response to infection or inflammation. However many other
causes are possible, including drugs , poisons , cancer , heat exposure,
injuries or abnormalities in the brain, or disease of the endocrine
(hormonal or glandular) system.
Fever rarely occurs without other symptoms or signs. It is mostly
accompanied by specific complaints. Many times it is associated with
thrombocytopenia in children. The normal platelet count is 1, 50,000 -
4, 50,000 cells/cumm 3. Thrombocytopenia is defined as platelet count
less than 1,50,000 cells/cumm3. It results from either decreased
2 production, increased sequestration or destruction of platelets .The
causes for thrombocytopenia are varied from idiopathic, infections to
malignancies. Patients with acute febrile illnesses in a tropical country
like India usually have an infectious etiology and may have associated
thrombocytopenia. Infections like malaria, dengue, typhoid, and
leptospirosis are some common causes of fever with thrombocytopenia.
If we can analyze the low platelet count as one of the diagnostic marker
of some common infections, we can narrow down the differential
diagnosis.
In recent years fever with thrombocytopenia is common clinical
presentation in pediatric wards. Fever and thrombocytopenia causes
significant morbidity in the form of bleeding manifestations,
hemodynamic instability and sometimes leads to mortality. This causes
increased anxiety among parents. Literature shows studies about fever
with thrombocytopenia among adults but not much data exists among
children. But some studies do exist on profile of individual disease like
dengue, typhoid, and malaria with thrombocytopenia in children.
Hence this study was conducted to analyze the clinical and
etiological profile in preference to infective etiology and its outcome
among children admitted at our hospital.
3
OBJECTIVE
• To study the clinical presentation of children with acute febrile
illness associated with thrombocytopenia
• To identify the etiological profile of the children with acute febrile
illness associated with thrombocytopenia
• To study the severity of thrombocytopenia and the disease
outcome
4
LITERATURE REVIEW
Putt Suresh et al,4 conducted a study in April 2015 at
S.V.R.R.G.G.H, Tirupatirap , AndraPradesh aimed at etiology of fever
with thrombocytopenia. Study was undertaken among 50 patients .
Thrombocytopenia without fever were excluded. History, clinical
examination, platelet count and MP smear, dengue serology, widal and
other investigations were done. Thrombocytopenia was common in
malaria followed by undiagnosed fever, dengue, typhoid, scrub typhus.
Bleeding was not common with platelet count >50,000cells/cumm and
severe spontaneous bleeding was unusual with platelet count >20,000
cells/cumm. Transient thrombocytopenia occurred with systemic
infections. Thrombocytopenia occurred in 50% of patients in gram-
negative bacteria sepsis.
Malaria fever was the commonest cause of fever with
thrombocytopenia, in which 16% patients had severe thrombocytopenia
(<50,000 cells/cumm),10% had moderate thrombocytopenia (50,000-
1,00,000cells/cumm) and 10% had mild thrombocytopenia (1,00,000–
1,50,000cells/cumm) especially in falciparum type and it is due to
sequestration, immune mediated destruction with elevated platelet
5 activated immunoglobulin. In dengue fever 12% of patients had severe
thrombocytopenia, 8% had moderate thrombocytopenia and 4% had mild
thrombocytopenia mainly due to immune mediated mechanisms. In
undiagnosed cases, 12% of patients had severe thrombocytopenia, 6%
had moderate thrombocytopenia and 14% had mild thrombocytopenia.
Among all cases 42% of patients had severe thrombocytopenia. The
study concluded that thrombocytopenia was a common lab finding in
fever. It is necessary to do platelet count in all fever cases. Treating the
causative agent will improve the platelet count.
Shankar R Raikar et al,5 done a study at Sir T. Hospital and
Government Medical College, Bhavnagar, Gujarat in 2013 to evaluate
clinical profile, etiological profile and complications of fever with
thrombocytopenia.
Study was conducted in 100 patients . History and complete
examination, basic investigations, specific and special investigation done
as indicated. The most common etiology was dengue followed by
malaria, enteric fever. Male affected more than females. Platelet count
started rising on day 3 and became normal by 4-7 days of admission.
There was no correlation between platelet count and bleeding
6 manifestations, mortality. Thrombocytopenia due to infections was
common in rainy and winter season.
Rekha M.C et al,6 conducted a study in 2013 at MIMS hospital,
Mandya to identify the profile and etiology of febrile thrombocytopenia
in preference to infections. Study was conducted in 328 patients .
History, examination, lab investigations were taken. Data was analyzed
using chi-square test. The most common symptom was fever followed
by myalgia and headache than vomiting and other symptoms. Males and
females were equally affected. More than 70% patients had moderate to
severe thrombocytopenia. Study concluded that viral fever with
thrombocytopenia to be the commonest infection in fever with
thrombocytopenia followed by dengue fever , enteric fever and mixed
infections. Bleeding manifestations were seen with platelet count
<20,000 cells/cumm. Risk factors for bleeding were not reported in this
study.
Praveen Kumar et al,7 done a study in 2011 at Sri Ram Murti
Smarak Institute of Medical Sciences, Bhojpuri, Bareilly, Uttar Pradesh
to identify etiology, clinical presentation of febrile thrombocytopenia
and relation between platelet count and disease outcome. 190 patients
included in this study. History, examination and lab parameters were
7 analyzed. Males are more affected than females. Majority of patients
admitted between July to September. Fever was present in 100%
patients, 30% had GI symptoms, 15% had cough and headache, and 10%
had bleeds.
Common etiology was malaria followed by septicemia, dengue
fever, leukemia, enteric fever. Mortality occurred in 9.6% patients of
which 83% was due to septicemia, 17 % due to complicated malaria.
Mortality was not associated with degree of thrombocytopenia but
related to underlying etiology which causes Multiorgan dysfunction.
Amite A Gandhi et al,8 conducted a study on clinical and
laboratory evaluation of patients with febrile thrombocytopenia in 2015
to identify common etiologies associated and different bleeding
manifestations in relation with platelet count. 112 patients were
included in this study. History, clinical examination, basic and special
Investigations were done as needed. Most common etiology was found
to be malaria followed by dengue, viral fever other than dengue and
septicemia. 57% patients had platelet count of > 50,000 cells/cumm.
30% patients had platelets between 20,000 to 50,000 cells/cumm . 13%
patients had < 20,000 cells/cumm. Petechiae was the most common
bleeding manifestations, majority of them had platelet count of
8 < 50,000cells/cumm. Gum bleeds and gastro intestinal bleeds are less
common than petechiae. Epistaxis and hematuria occurred in very less
number of patients.
Nikalje anand et al,9 done a study in 2013-15 at MGM
Hospital Aurangabad to evaluate clinical outcome of patients presenting
with febrile thrombocytopenia in Marathwada region. This was a
prospective observational study conducted in 150 patients . History,
examination and laboratory evaluation data were analyzed. Patients in
whom definite diagnosis was arrived platelet count was repeated at
discharge. Most common symptom was fever followed by headache and
GI symptoms . 60% of patients admitted with platelet count <
50,000cell/cumm . 35% patients had bleeding manifestations but it was
not related to platelet count . Unknown viral fever was found to be the
commonest etiology; dengue and malaria were the subsequent common
ones. 5% patients expired due to multi organ failure caused by dengue,
mixed malaria and viral fever.
Aisha Sajid et al,10 conducted a case series at pediatric
department, Madina Teaching Hospital/ university medical college
Faisalabad in 2011, to analyze clinical profile of children with dengue
fever. 35 children who fulfilled WHO clinical criteria and who were
9 serologically positive were included in this study. Detailed history,
complete examination and laboratory parameters were analyzed by SPSS
version 19 software. On analysis fever and abdomen pain were the most
common symptoms followed by vomiting and loose stools .
Splenomegaly was present in 94% of patients, pallor in 65%,
hepatomegaly in 54%, bleeding manifestation in 5% patients.
Leucopenia in 14% elevated liver enzymes in 43% of patients. 68% of
patients had moderate thrombocytopenia, only 11% had platelet count
less than 50000 cells/cumm. More than 60% patients improved platelet
count in 5 days. No transfusion was required. No mortality was
documented in this study. 66% children had malaria parasite positivity in
peripheral smear study.
Saba Ahmed et al ,11 conducted cross sectional descriptive study
in serologically positive children with dengue infection in civil hospital,
Karachi in 2006 to study the profile and outcome of dengue fever. 39
children were analyzed in this study. Symptoms and signs, laboratory
parameters were analyzed. Mean age of children affected was 8.3years
(2-15yeaars). Males were more affected than females. Most of the
children presented with fever followed by pain abdomen, vomiting,
rashes, myalgia, gastro intestinal bleeding and epistaxis. Pallor was
10 present in 67% of children. Hepatomegaly in 37% cases and
splenomegaly in 6% of children. Seizures, jaundice, hypotension were
reported in 3%. The study revealed that 86% children had
thrombocytopenia, 57% had anemia, 43% had leucopenia, and 11% had
increased hematocrit. 40% children developed bleeding manifestation,
with petechiae being the commonest. 4% children had bleeding with
normal prothrombin and platelet count; this factor signifies functional
capacities of platelets in dengue can also lead to bleeding manifestation.
Shah G.S et al,12 conducted a prospective descriptive study at
Dhaka children hospital, Bangladesh in 2001 to identify clinical and
laboratory profile of dengue infection in children. 100 seropositive cases
in the age group of 8 months to 12 years were analyzed with clinical
manifestations and laboratory parameters. Only 15 % had primary
dengue infection but 85% children with secondary dengue infection.
Mean age of children affected was 8.3 years. Headache, retroorbital pain,
fatigue, arthralgia, vomiting and pain abdomen occurred in equal
frequency in about 98% of children. Serological test was performed by
rapid strip test. Children vaccinated with JE and Yellow fever were
excluded in this study to rule out cross reactivity. Frequencies of clinical
signs were as follows hepatomegaly (77% ) , splenomegaly (23%), skin
11 bleeds (59%) of which > 50% had malena followed by gum bleed and
epistaxis. 57% of the children had platelet count less than 100000
cells/cumm, 88 % had high hematocrit, 16% children had platelet less
than 50,000cells/cumm. There was no correlation between bleeding and
severity of thrombocytopenia suggesting that bleeding in dengue was
due to multifactorial causes. Mortality may be high with prolonged
shock.
Kriti Mohan et al,13 conducted a cross-sectional study in
pediatric hospitals of north India to analyze the occurrence and
severity of thrombocytopenia with bleeding manifestation in childhood
malaria. 185 malaria positive cases included with mean age of 4
years.Data were recorded in preformed proforma and assessed for
thrombocytopenia and bleeding manifestations. Thrombocytopenia
observed in 43 % children of whom 20% had mild thrombocytopenia,
15% had moderate, 8% had severe thrombocytopenia. 5% of children
with thrombocytopenia had bleeding manifestations with malena being
the commonest. No strong association between bleeding and severity of
thrombocytopenia was documented. No significant relation between
severity of malaria and thrombocytopenia was shown in this study.
12 Alphonso J Rodriguez-Morales et al,14 conducted a study on
anemia and thrombocytopenia in children with plasmodium vivax
malaria in hospital Santos Anibal Dominicci , sucre, Venezuela from
2000-2002 . 78 children were evaluated with clinical features and
laboratory investigations. 94% children had fever, 41% had chills and
14% had headache. 95% children presented with anemia of which 10%
had hemoglobin < 5g/dl. Mean hemoglobin level 8.09g/dl , mean platelet
1.27 lakhs/cumm . 25% co existent with malnutrition, 10% with
intestinal parasitosis. 59% children developed thrombocytopenia. No
relation between age and occurrence of anemia and thrombocytopenia.
Hemoglobin and platelet count improved significantly after anti malarial
treatment.
Ahmed Yaramis et al,15 conducted a study in Dicle University
Hospital, Diyarbakir, Turkey to analyze the clinical and laboratory
presentations of typhoid fever. 314 children of age group 6 months to 16
years were included in this study. History, clinical examinations and
laboratory investigations were studied in detail. The study revealed fever
as most common symptom followed by pain abdomen, vomiting,
anorexia and weakness. 42% children had hepatomegaly, 20% had
splenomegaly, 6-8% had abdomen tenderness, lymphadenopathy and
13 encephalopathy. Laboratory analysis revealed high total counts in 78% ,
elevated liver enzymes in 32% , hemoglobulin <12 gm/dl in 38
%,thrombocytopenia in 10 %.
Chitu CH et al,16 conducted a study in Department of
Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan to
identify the profile of Typhoid fever in children . Fever was the most
common presenting symptom followed by vomiting,diarroea,and
abdominal pain. Hepatosplenomegaly was the commonest sign followed
by abdominal tenderness. Thrombocytopenia occurred in 9% ,which
was the commonest cause for complication in the study group followed
by intestinal perforation, rectal bleeding,meningitis.There was no
Mortality in the study. Most children responded well to appropriate
antibiotic therapy and laboratory abnormalities are transient in nature.
Shruthi K Bhalara et al,17 conducted a cross sectional study at
Civil Hospital, Ahmedabad in 2013 to identify the clinical and
etiological profile of thrombocytopenia. 412 patients with fever and
thrombocytopenia were included in the study. After obtaining detailed
history, examination and necessary lab investigations were done.
Bleeding manifestations and complications were monitored throughout
the hospital stay. Platelet counts were repeated daily in moderate
14 thrombocytopenia until values became normal. In the study 31% of
children had mild thrombocytopenia with platelet count of 1,00,000 to
1,50,000 cells/cumm , 29% of children had moderate thrombocytopenia
with platelet count of 50,000 to 1,00,000 cells/cumm , 50% of children
had severe thrombocytopenia with platelet count of <50,000 cells/cumm.
The study revealed dengue fever as the most common etiology for
febrile thrombocytopenia followed by malaria , chronic liver disease,
septicemia and DIC. Among the malarial infections plasmodium
falciparum was most common followed by P.vivax and mixed infection.
46% of thrombocytopenia patients had bleeding manifestations of which
gum bleed was the commonest. Bleeding manifestation was common
with platelet count of <10,000 cells/cumm.
Pankaj B Palange et al,18 conducted a study to analyze the
clinical profile of patients with dengue fever with thrombocytopenia at
Bharati Vidyapeeth Deemed University Medical College and Hospital,
Sangli in 2012. 68 patients were studied with clinical manifestations
and laboratory investigations. Study revealed that males were affected
more than females. Frequency of symptoms were fever (100%), myalgia
& arthralgia (98%), petechiae (92%), rash(87%) and bleeding
manifestations (75%).
15 Shock was seen in 35% patients of whom 17% had compensated
shock and 18% had hypotensive shock of which 20% patients died. 15%
patients who experienced major bleeding manifestations were in shock
at admission. Presence of shock was an important contributing factor to
hemorrhage. In this study 70% patients had platelet count of
<50,000cells/cumm , 27% patients had platelet count of 50,000 to
1,00,000 cells/cumm. Mean platelet count at admission was 46,000
cells/cumm. 16 patients had severe bleeding with platelet count of
20,000 to 49,000cells/cumm but no bleeding in patients with platelet
count <20,000cells/cumm and only 4 patients had bleeding with platelet
count of >50,000 cells/cumm. This signifies that there is no correlation
between platelet count and severity of bleeding manifestations. The
study concluded that shock with severe bleeding and organ dysfunction
was the major factor contributing to mortality. The study also
suggested that preventing the development of shock and rapid
correction of shock is the key to prevent organ dysfunction and
mortality.
Muhammad Ayyub et al,19 conducted a prospective study at
King Abdulla Hospital, Jeddah, Saudi Arabia in 2014 to 2015 to
determine clinical and laboratory profile of dengue fever and disease
16 outcome. 80 serology positive dengue cases were included in the study
and clinical features and laboratory parameters were analyzed. Males
were more affected than females with the ratio of 3:1. Maximum cases
were admitted from the months of June to August. Commonest
clinical presentation was fever followed by myalgia , headache and
vomiting. Rash , hemorrhagic manifestations and positive Hess test
were rare in this study.
Laboratory evaluation revealed thrombocytopenia as the
commonest abnormality followed by leucopenia. Thrombocytopenia
may be due to depression of bone marrow in acute stage of dengue
infection. 60% patients had platelet count of <50,000 cells/cumm and
remaining 40% patients had mild and moderate thrombocytopenia. 66%
patients had elevated liver enzymes, 25% patients had elevated APTT
and 25% patients had increased hematocrit >20% of baseline . This
study confirmed endemic occurrence of dengue fever in Jeddah and
suggested to focus on sustainable community based environmental
control rather than eradication.
Prithviraj patil, et al20 in 2014 conducted a study to evaluate
clinical profile and outcome of patients aged >12 years with febrile
thrombocytopenia at D.Y. Patil hospital, Kolhapur . It was a prospective
17 observational study done in 100 patients. Complete history, clinical
examination and basic and special laboratory investigation for etiology
were done and hospital course was monitored. Platelet count was done
on 0,3,5 days and before discharge if <1,50,000 cells/cumm . Platelet
counts were repeated until increasing trend in the count was documented.
The study data revealed malaria (54%) was the most common etiology
followed by viral fever(17%) , dengue(15%) , enteric fever(6%), and
septicemia(4%). Bleeding manifestations mostly occurs with <50,000
cells/cumm and major bleeds in patients with <20,000 cells/ cumm .
Petechiae is most common manifestation followed by hematuria and
rectal bleed. 95% improved and 5% mortality was documented and was
mainly due to septicemia followed by malaria, viral fever. Treatment of
cause and supportive therapy yields good outcome.
18
METHODOLOGY
This was a prospective observational study conducted at the
Department of Pediatrics, Chengalpattu Medical College over a period
of 12months from September 2015 to August 2016, among children in
the age group 1 month to 12 years. In this study all children admitted
with history of fever for 5 days or more with thrombocytopenia were
included. Neonates, children with afebrile thrombocytopenia, ,known
ITP, children with already with diagnosed hematological malignancies
or marrow disorders, children on anti- platelets drugs and
pseudothrombocytopenia were excluded. Pseudothrombocytopenia 21 is
a relatively uncommon phenomenon caused by ex vivo agglutination of
platelets. As a result of platelet clumping, platelet counts reported by
automated counters may be much lower than the actual count in the
blood because these devices cannot differentiate platelet clumps from
individual cells. Children were recruited for the study,after informed
written consent from parents or care givers at admission , Assent was
obtained from children who were more than 7 years of age. Age, gender
and geographical location of these children were noted in the pretested
preformed. Detailed history included the duration of fever, headache,
19 myalgia, gastro intestinal symptoms, cutaneous or gastro intestinal or
other bleeds like hematuria and epistaxis , breathing difficulty, seizures,
edema, puffy face, oliguria and antibiotic exposure prior to
hospitalization . Following this, children were subjected for a detailed
clinical examination . Clinical features at admission were recorded. The
parameters included fever, heart rate, respiratory rate, blood pressure,
capillary refill time, hepatomegaly, eschar, splenomegaly,
lymphadenopathy, petechiae and ALOC. Tourniquet test 22 was
Performed by inflating a blood pressure cuff to a point midway between
systolic and diastolic pressure for 5 minutes. The test is considered
positive when 10 or more petechiae per square inch are observed.
In DHF the test usually gives a definite positive with 20
petechiae or more . The test may be negative during the phase of
profound shock. It usually becomes positive, sometimes strongly
positive after recovering from shock. Following clinical examination,
all children were subjected to the investigations as per the unit protocol.
The investigations included Complete blood count, peripheral smear
study, urine albumin, blood urea, serum creatinine, liver enzymes and
serum bilirubin, xray chest depending upon detailed examination on
suspicion of tropical infections MP smear, dengue IgM , scrub typhus
20 IgM ELISA , widal test , leptospirosis IgM were performed along with
blood culture and urine culture. Children with suspected hematological
malignancy underwent bone marrow examination. CSF study was not
undertaken in any child with thrombocytopenia. However if viral
encephalitis was a suspicion CSF analysis was done after recovery from
thrombocytopenia as per our unit policy. Children in the study group
were followed up till outcome for complications like shock, bleeding
manifestations, hepatic failure, renal failure, respiratory distress, cardiac
failure , pulmonary edema and multi organ failure. Platelet count and
hematocrit were monitored frequently during complications like shock
and bleeds in the pediatric intensive care unit (PICU). Platelet count
were repeated on alternate days in hemodynamically stable children
until it reached 1,50,000 cells/cumm, for the purpose of this study. Need
for any blood product transfusion was documented. Platelet transfusion
was not routinely undertaken among children in our unit. Presence of
DIC or need for surgical or invasive interventions were considered as
the indication for transfusion of platelets in our unit.
Final diagnosis was arrived in these children based on clinical and
/ or laboratory features for the common pediatric infections and other
conditions as shown in table no( 1).Children with acute febrile illness
21 but could not be placed in any of the common diagnosis either clinically
or by investigations were labeled as undiagnosed fever for this study
category. Outcome was defined as recovery to hospital discharge or
death.
Table 1: Diagnostic Criteria Used In This Study
S.NO. DISEASE DIAGNOSIS
1. Malaria Peripheral smear / Rapid diagnostic test positivity
2. Dengue fever Dengue IgM positivity
3. Scrub typhus Presence of Eschar and/or Scrub typhus IgM positivity
4. Enteric Fever Serial rise in widal titres/ enteric culture positivity
5. Leukemia , ITP Peripheral smear, Bone marrow examination
6. Septicemia Blood culture
7. Viral encephalitis
CSF , MRI Brain
8. Undiagnosed fever
Absence of a clinical clue with negative investigations
22 The study was approved by the institutional ethics committee.
Data were entered in Excel Spreadsheet and analyzed using SPSS
software Version 16. Simple calculations like Percentages, Proportions
and Mean values were derived.
Appropriate statistical tests like Chi- Square test, T test were used
to compare the study parameters among the children with bleed and
those without bleed. Data was analyzed for any statistical significance
with a P value < 0.05 being considered significant.
23
OBSERVATION AND RESULTS
This study included 100 children with fever and
thrombocytopenia. Since the study subjects n = 100, this will be
mentioned as n= percentage in the result section in all statistical analysis
involving the entire study group. Demographics that like age , gender
and location of the patient were analysed using simple statistics like
proportions.
1. Sex distribution
Among the 100 children gender distribution revealed 52 % male
and 48 % female with male female ratio of 1.1: 1 as depicted in the pie
diagram figure.1
Figure 1: Sex distribution
52%
48% MALE
FEMALE
24 2. Age distribution:
Study group comprised of children between 1 month to 12 years
of age. They were categorized as infants, toddlers, preschool children
and school children.
Table No. 2 Age Distribution
Age Frequency / Percent
< 1 year 7%
1 -3 years 10%
3-5 years 16 %
>5 years 67%
Out of 100 children 67% were more than 5 years, 16 % were 3 to
5 years, 10 % were 1 to 3 years, 7 % were infants. Infants and toddlers
contributed to less than one fifth of the study group in comparison to
the preschool children and school going children .Two thirds of study
group was constituted by children beyond 5 years . The same has been
shown in figure.2
25
Figure 2: Age wise distribution
7% 10%16%
67%
0%
10%
20%
30%
40%
50%
60%
70%
80%
<1year 1-3years 3-5years >5 years
26 3. Age and Sex distribution
Male and female children in various age group in this study is
shown in the table no.3.
Table No.3 Age and Sex Distribution.
Age Males (N- 52) N(%)
Females (N-48) N(%)
Infants 5(9.6) 2(4.1)
Toddlers 4(7.7) 6(14.3)
Preschool children 5(9.6) 11(22.2)
School children 38(74.1) 29(60.4)
In infants and school children males were more affected than
females contrast to Toddlers and Preschool children where females were
more affected. The same has been shown in figure no.3.
27
Figure 3: Age and Sex distribution
9.60%7.70%
9.60%
73.10%
4.20%
12.50%
22.90%
60.40%
0%
10%
20%
30%
40%
50%
60%
70%
80%
<1year 1-3years 3-5years >5 years
MALE
FEMALE
28 Geographic area distribution:
Since Chengalpattu Medical College is the only available tertiary
care institute, this caters to the needs of a number of nearby villages
from various health union districts . The study group had children from
different localities as shown in table no 4.
Table No.4. Geographic Area Distribution
Place Frequency / Percent
Chengalpattu 22
Vandavasi 18
Kanchipuram 15
Maduranthagam 13
Uthiramerur 10
Cheyar 9
Thirukazhukundram 6
Thiruporur 5
Cheyyur 2
Majority of children came from Chengalpattu (22),18 children
from Vandhavasi, 15 from Kanchipuram, 13 from Madhuranthagam, 10
from Uthiramerur, 9 from Cheyyar, 6 from Thirukalukundram, 5 from
Thiruporur, 2 from Cheyyur. Majority of these areas are located within
30 kilometers from Chengalpattu. The same as depicted in figure 4.
29
Figure 4 : Geographic distribution
13%
15%
18%
10%
22%
9%
6%
2%5%
MADURAM
KPM
VANDVASI
UTMRUR
CPT
CHYR
TKM
CHEYUR
TRPORUR
30 Though thrombocytopenia occurs uniformly in any common
pediatric illness, seasonal variation of the common infections did reveal
predominance of children with thrombocytopenia during certain months
of the year. Month wise distribution revealed 90% of the study group
presenting between the months of August and November.
Table No.5. Month Wise Distribution
Month of admission Frequency / Percent
September 22
October 31
November 22
December 1
January 0
February 1
March 0
April 0
May 0
June 5
July 2
August 15
The same has been depicted in figure .5
31
Figure 5: Month wise distribution
22%
31%
22%
1%0%
1%0% 0% 0%
5%
2%
15%
0%
5%
10%
15%
20%
25%
30%
35%
Percent
32 Clinical features of children presenting with thrombocytopenia
revealed predominant GI symptoms followed by myalgia. Rash as a
presentation was encountered in 6% of the children.
Table No.6 Symptom Catergorization
Symptom Frequency / percent
GI symptoms 42
Headache, myalgia 27
GI bleeds 11
Altered sensorium 11
Cutaneous bleeds 9
Other bleeds Seizures 6
Rash( Erythema) 6
Oliguria 3
Seizures 3
In this study 42% children had GI symptoms, 27% children had
headache and myalgia, and 22% children had GI bleed and altered
sensorium . The same has been represented in figure 6.
33
Figure 6: Symptom categorization
The clinical presentation was analyzed with respect to the
different age groups and this revealed predominant GI symptoms across
all age groups. Analysis of the distribution of symptoms in various age
groups was undertaken to look for any variation as shown in table no.7
0
5
10
15
20
25
30
35
40
45
27
42
911
6
3
8
11
6
Present
34
Table.7. Symptom distribution in different age groups
Symptom < 1yr (n =7) N(%)
1 to 3 yrs (n=10) N(%)
3 to 5yrs (n=16) N (%)
>5 yrs (n=67) N(%)
Headache, myalgia
0 0 5(31%) 22(33%)
GI symptoms 4(57%) 6(60%) 6(37%) 26(39%)
Cutaneous bleeds 1(14%) 2(20%) 2(12%) 4(5.9%)
GI bleeds 2(28%) 0 1(6%) 8(11.9%)
Other bleeds like gum bleed, epistaxis.
0 1(10%) 1(6%) 4(5.9%)
Seizure 2(28%) 0 0 1(1.4%)
Breathlessness 3(43%) 1(10%) 1(6%) 3(4.4%)
Oliguria 2(28%) 1(10%) 2(12%) 4(5.9%)
Rash (erythema) 1(14%) 1(10%) 1(6%) 3(4.4%)
Altered sensorium 6(85%) 1(10%) 0 4(5.9%)
85 % of infants presented with altered sensorium in comparision
to the children more than 5 years . GI bleeds ,breathlessness, oliguria
and seizures were also occurred in increased frequency among infants.
35 Examination findings at admission has been tabulated in table
no.8
Table No 8.Examination findings at admission
Signs Frequency/ percentage (n=100)
Fever during hospital stay 88
Hepatomegaly 62
Facial puffiness 48
Pallor 37
Lymphadenopathy 25
Splenomegaly 25
Petechiae 14
Eschar 10
Jaundice 1
Out of 100 children studied, 88 children were febrile at admission
with temperature of >100.4 F. 50 % of the children had facial puffiness,
one third of them had pallor ,one fourth had lymphadenopathy and two
third had hepatomegaly. Petechiae,eschar and splenomegaly were less
common.
36
Figure 7 : Examination findings at admission
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%88%
37%
25%
1%
14%
62%
25%
48%
10%
PRESENT
37
Table No. 9.Examination findings in different age groups
Signs <1 yr (n-7) N(%)
1 - 3 yrs (n-10) N(%)
3 – 5 yrs (n-16) N(%)
>5 yrs (n-67) N (%)
Fever 7(100%) 10(100%) 13(81%) 58(86%)
Pallor 7(100%) 7(70%) 6(37%) 17(25%)
Lymphadenopathy 1(14%) 4(40%) 5(31%) 15(22%)
Petechiae 1(14%) 0(0%) 1(6%) 12(18%)
Hepatomegaly 4(57%) 8(80%) 12(75%) 38(57%)
Splenomegaly 2(28%) 6(60%) 6(37%) 11(16%)
Eschar 0(0%) 2(20%) 5(31%) 9(13%)
More than two third of children < 3 years of age had pallor at
admission, 75 % of toddlers and preschool children presented with
hepatomegaly,two third of toddlers presented with splenomegaly and
about one third of preschool children had eschar than other groups
38
All children in the study groups were evaluated with their vital
signs at admission and the findings are tabulated in table no.10
Table .10. Vital signs at admission
Vitals Minimum Maximum Mean Standard deviation
Heart rate / min 64 200 121.33 25.403
Respiratory rate / min
18 72 29.29 8.093
Systolic BP mmHg 62 136 98.214 14.983
Diastolic BP mmHg
20 74 44.568 9.021
Among the study group 1 child had respiratory distress and
subsequently required ventilator support for respiratory failure and
septic shock.
39 Physiological status at admission revealed the following findings .
Table no .11. Physiological status at admission
Parameter Frequency / Percent
Compensated shock 22
Narrow pulse pressure 19
Tourniquet Test positive 19
ALOC 14
Wide pulse pressure 11
Hypotensive shock 4
In this study pulse pressure <20 mmHg was defined as narrow
pulse pressure, pulse pressure >40 mmHg was defined as wide pulse
pressure. Among 100 children, 26 % developed shock of which 22%
children had compensated shock and 4% children had hypotensive
shock. 14% children presented with altered sensorium. Abnormal pulse
pressure was noted in 30% children of which 19% children had narrow
pulse pressure, 11% children had wide pulse pressure. The same has
been shown in the following figure 8.
40
Figure 8: Vital signs at admission
22%
24%
14%
19%
11%
19%
0%
5%
10%
15%
20%
25%
30%
Compensatedshock
Hypotensiveshock
ALOC Positive TT Wide PP Narrow PP
Present
41
Table 12 : Physiological status at admission in different age groups
Parameter < 1 year (n-7)
1 to 3 years (n-10)
3 to 5 years (n-16)
>5 years (n-67)
Compensated shock
3(42%) 1(10%) 3(19%) 15(22%)
Hypotensive shock
1(14%) 0(0%) 1(6%) 2(3%)
Wide pulse pressure
1(14%) 3(30%) 1(6%) 6(9%)
Narrow pulse pressure
3(42%) 0(0%) 4(25%) 10(15%)
ALOC 5(71%) 1(10%) 1(6%) 7(10%)
Tourniquet test positive
1(14%) 1(10%) 3(12%) 14(20%)
ALOC, narrow pulse pressure and compensated shock were more
common in infants. Tourniquet test positivity was commonly seen in
school going children.
42 Table No:13. Summarizes the range ,mean and standard deviation
of the common lab parameters of the study group
Parameters Minimum Maximum Mean Standard deviation
Total count (cells/cumm)
1700 74000 8540.00 10725.425
Hemoglobin (grams/dl)
4.3 16.2 11.237 2.1899
Hematocrit (%) 14 48 34.801 6.3928
Highest PCV 16 48 35.532 5.799
Slowest PCV 14 44 31.221 4.9228
Platelet count(cells/cumm) at admission
5000 270000 75920 48762.3
Lowest platelet count(cells/cumm)
5000 130000 52580 29720.985
SGOT(IU/L) 12 52 26.40 7.742
SGPT(IU/L) 14 46 27.65 7.004
S.Bilirubin (mg/dl)
0.6 2.0 0.908 0.16
Urea (mg/dl) 15 54 23.97 7.881
Creatinine (mg/dl)
0.4 2.0 0.674 0.1952
43 Severity of thrombocytopenia was graded based on the platelet
counts. Platelet count was graded as mild ,moderate,severe and analysis
was done as shown below
Grades of Thrombocytopenia :
Platelet count between 1,00,000 cells/cumm and 1,50,000
cells/cumm is mild thrombocytopenia, platelet count between 50,000
cells/cumm and 1,00,000 cells/cumm is moderate thrombocytopenia and
platelet count below 50,000 cells/cumm is severe thrombocytopenia 23 .
The same is shown in table no.14.
Table no 14.Grades of thrombocytopenia
Grade of thrombocytopenia Frequency /Percent
Mild 10
Moderate 43
Severe 47
Most of the children had severe thrombocytopenia(47%),
44
Figure.9 Grades of thrombocytopenia
10
43
47
mild moderate severe
45
Table 15. comparision of physiological status with severity of
thrombocytopenia
Parameters Mild thrombocytopenia
(n-10)
Moderate thrombocytopenia
(n-43)
Severe thrombocytopenia
(n-47)
Compensated shock
1(10%) 8(19%) 13(28%)
Hypotensive shock
0(0%) 0(0%) 4(8%)
Wide pulse pressure
2(20%) 6(14%) 3(6%)
Narrow pulse pressure
0(0%) 5(12%) 12(25%)
Tourniquet test positive
0(0%) 7(16%) 12(25%)
In this study, compensated shock, hypotensive shock, narrow
pulse pressure and positive tourniquet test were common with severe
thrombocytopenia.
46
Analysis was undertaken to identify the severity of
thrombocytopenia in different illness among the study group .This is
summarized in table no.16
Table no .16.Grades of thrombocytopenia in specific etiology
Etiology Mild thrombocytopenia
(n=10)
Moderate thrombocytopenia
(n=43)
Severe thrombocytopenia
(n=47%)
Undiagnosed fever
4 (8%) 16 (36%) 26(56%)
Dengue fever
0 13 (43%) 17(57%)
Scrub typhus 4 (25%) 8(50%) 4(25%)
ALL 0 4 (100%) 0
Malaria 1 (100%) 0 0
Enteric fever 0 1 (100%) 0
Viral encephalitis
0 1 (100%) 0
septicemia 1 (100%) 0 0
47 Among the children affected by undiagnosed fever 56% had
severe Thrombocytopenia, 36 % had moderate thrombocytopenia, 8 %
had mild thrombocytopenia . The same has been shown in figure.10.
In Dengue fever, severe thrombocytopenia was more common and
scrub typhus had moderate thrombocytopenia.
Figure . 10 Severity of thrombocytopenia in undiagnosed fever
In dengue fever 57 % had severe thrombocytopenia, 43% had
moderate Thrombocytopenia.
8%
36%56%
mild
moderate
severe
48
Figure.11 Severity of thrombocytopenia in dengue fever
In scrub typhus positive cases 50 % had moderate
thrombocytopenia, 25 % had mild, and 25 % had severe
thrombocytopenia
Figure12.Severity of thrombocytopenia in scrub typhus
0%
43%
57%
mild
moderate
severe
25%
50%
25%
mild
moderate
severe
49
Figure.13 comparison of severity of thrombocytopenia in common
etiologies
0%
10%
20%
30%
40%
50%
60%
Mild Moderate Severe
8%
36%
56%Undiagnosed fever
Dengue fever
Scrub typhus
50
Bleeding manifestations among children with thrombocytopenia is
summarized in table 17. Among the bleeding manifestations petechiae
were the commonest bleeding manifestation.
Table No. 17 . Bleeding Manifestations
Bleeding manifestation Frequency/percent(n-31)
Petechiae 14 (46 %)
GI bleeds 11( 35%)
Other bleeds 6 (19%)
Among children with bleeding manifestation 46% had petechiae,
35% had GI bleeds and remaining 19 % children had other bleeds like
episatxis,hematuria, gum bleeds, subconjuntival hemorrhage.The same
has been depicted in figure no.14.
51
Figure .14 : bleeding manifestations
35%
19%
46%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
GI bleeds Other bleeds Petechiae
Series1
52
Table no.18.Bleeding manifestation in different age groups:
Age group With bleeding Without bleeding
< 1 year(n-7) 3(43%) 4(57%)
1 – 3 years(n-10) 1(10%) 9(90%)
3– 5 years(n-16) 3(19%) 13(81%)
>5 years(n-67) 24(36 %) 43(64%)
Bleeding manifestations were most common in infants followed
by school going children and rare in toddlers.
53
Table no.19. Type of bleeding manifestation in different age group:
Bleeding
manifestation
<1 year
(n=3)
1 – 3 years
(n=1)
3 – 5 years
(n=3)
>5 years (n=24)
GI bleeds 2(67%) 0 1(33%) 8(33%)
Other bleeds like
epistaxis, gum bleed
0 1(100%) 1(33%) 4(17%)
Petechiae 1(33%) 0 1(33%) 12(50%)
Among different bleeding manifestations GI bleeds were more
common in infants in contrast to school going children where petechiae
was the commonest. The same has been illustrated in the figure no.15.
54
Figure 15.Bleeding manifestation in different age groups
Platelet count was analysed in individual subgroup of major
infections in this study group and is summarized in table.20.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
<1 yr 1-3 yrs 3-5 yrs >5 yrs
67%
0%
33% 33%
0%
100%
33%
17%
33%
0%
33%
50%
GI bleeds
Other bleeds
Petechiae
55
Table no.20.Grades of thrombocytopenia in different etiologies
Diagnosis
Bleeding manifestat
ion
No of children with mild
thrombocytopenia
No of children with moderate thrombocytop
enia
No of children with severe
thrombocytopenia
Dengue (n=30)
7 (23%) 0 1(14%) 6(86%)
Scrub (n=16) 4(25%) 1(25%) 1(25%) 2(50%)
Undiagnosed fever (n=46)
13(28%) 0 2(15%) 11(85%)
Among 30 children with dengue fever 7 had bleeding
manifestation (23%),among 16 children with scrub typhus 4 had
bleeding manifestations (25 %) and among 46 children with
undiagnosed fever 13(28%) had bleeding manifestations. In reference
to etiology, bleeding manifestations were more common in undiagnosed
fever (28%) followed by scrub typhus (25%) and dengue fever (23%).
Bleeding manifestations were more common in children with severe
thrombocytopenia.
56
Figure.16. Bleeding manifestation in different etiologies
Univariate analysis of risk factors for bleeding in children with
acute febrile illness and thrombocytopenia were evaluated. The study
parameters are compared between two groups with bleeds and without
bleeds .The results were summarized in table no.21.
28%
25%
23%
0%
5%
10%
15%
20%
25%
30%
undiagnosed fever scrub typhus dengue fever
bleeding manifestations
bleeding manifestations
57
Table.no.21 . Univariate analysis of risk factors for bleeding in children
s.no Parameters With Bleeds
Without Bleeds
Chi- Square
P value
1. Gender M F
11(21.2%) 18(37.5%)
41(78.8%) 30(62.5%)
3.239 0.080
2. Age <5yr >5yr
9(27.3%) 20(29.9%)
24(72.7%) 47(70.1%)
0.070 1.000
3. GI symptoms yes no
14(33.3%) 15(25.9%)
28(66.7%) 43(74.1%)
0.660
0.504
4. Compensated shock Yes No
10(45.5%) 19(24.4%)
12(54.5%) 59(75.6%)
3.709
0.066
5. Hypotensive shock Yes no
2(50%)
27(28.1%)
2(50%)
69(71.9%)
0.892
0.577
6. Tourniquet test Positive Negative
12(63.2%)
17(21%)
7(36.8%) 64(79%)
13.292
0.001
7. Platelet count <50,000cells/cumm >50,000cells/cumm
20(40%)
9(18%)
30(60%) 41(82%)
4.857
0.020
8. Platelet rising time < 3 days >3 days
19(23.5%) 10(52.6%)
62(76.5%)
9(47.4%)
6.362
0.022
9. Duration of Thrombocytopenia < 5days >5days
23(79.3%) 6(20.7%)
60(84.5%) 11(15.5%)
0.394
0.564
58
S. No
Parameters
Mean value ± SD F Sig
Bleeding group Non Bleeding group
1. Total count (cells/cumm) 7113.7 ± 4392 9122 ± 12401.131 0.720 0.398
2.
SGOT (IU/L) 26.38 ± 7.42 26.41 ± 7.92 0.000 0.986
3. SGPT(IU/L) 28.10 ± 6.26 27.46 ± 7.32 0.170 0.681
4. Platelet count at admission (cells/cumm)
59900 ± 39589 79300 ± 48856 3.605 0.061
5. Lowest Platelet count (cells/cumm)
37900 ± 20613 58600 ± 30888 10.917 0.001
The above analysis revealed statistically significant association
between bleeding manifestation and positive tourniquet test, lowest
platelet count with p value of 0.001 for both parameters.
The above analysis revealed the children without bleeds had an
earlier rise in platelet count (< 3 days of hospitalization) in comparison
to those with bleeds, this was statistically significant with p value-
0.0221
The above analysis also shows statistically significant risk for
bleeding with platelet count of < 50,000 cells/cumm with p value of
0.020
59 Other study parameters analyzed in this study were duration of
fever, duration of thrombocytopenia, PICU stay and hospital stay. The
range, mean and standard deviation is represented in the table no .22.
Table no .22. Morbidity
Duration in days Minimum Maximum Mean Standard deviation
Fever 5 16 7.34 2.442
Thrombocytopenia 1 14 4.07 2.056
PICU stay 1 12 2.28 2.055
Hospital stay 2 19 6.90 2.611
In this study fever duration were ranged 5-16 days(mean -7.34
days), duration of thrombocytopenia ranged between 1-14days ( mean -
4.07days), PICU stay ranged from 1-12 days ( mean -2.28 days ) and
hospital stay ranged from 2-19 days (mean- 6.9 days).
60 Final diagnosis was arrived based on the criteria as mentioned in
the methodology section. Infective etiology was the commonly identified
cause and nearly 45 % of them could not be classified into any of the
common illness. Majority of them may be viral or other causes of fever
with thrombocytopenia . A repeat evaluation for common infections
might have helped to identify more common causes however the
invasive blood sampling tests were not repeated for this reason in
children who had recovered. The inclusion of bone marrow analysis
would have thrown more light into the etiology of thrombocytopenia
especially in the undiagnosed fever group. However this being an
invasive procedure was not undertaken for ethical reasons unless
clinical examination and diagnosis warrented the same. This is a
limitation of the present study.
61
Table no.23.Etiological profile
Diagnosis Frequency Percentage
Undiagnosed Fever 46 46
Dengue Fever 30 30
Scrub Typhus 16 16
Acute Lymphoblastic
Leukemia
4 4
Enteric Fever 1 1
Viral Encephalitis 1 1
Septicemia 1 1
Malaria 1 1
In this study ,the most common etiology was found to be dengue
fever which is 30% followed by Scrub typhus in 16% . Acute
lymphoblastic leukemia was seen in 4% children. Enteric Fever, viral
encephalitis, septicemia and malaria all occurred in 1% .Nearly 46 % of
the children had undiagnosed febrile illness. The same has been depicted
in figure:17.
62
Figure.17: causes identified among children with thrombocytopenia.
46%
30%
16%
4%
1% 1% 1% 1%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Series1
63 OUTCOME:
Table No.24.Outcome of the study
Parameters Numbers
Recovered to discharge 95
Expired 1
Referral 4
Among 100 children, 95 children were improved with appropriate
treatment, 4 children referred for hematological malignancy evaluation
and management, 1 child died of septicemia and multiorgan
dysfunction.
Figure.18. outcome
0
20
40
60
80
100
improvedreferred
expired
95
41
Series1
64
DISCUSSION
As discussed in literature, fever with thrombocytopenia has varied
clinical presentation and diverse etiology. In this study clinical profile ,
etiological profile of febrile thrombocytopenia and its outcome were
studied.
1. Sex
In this study male female ratio was almost equal, with male
female ratio of 1.1:1 which is comparable with Rekha .M.C et al 5,
Praveen Kumar et al 6 and Saba Ahmed et al11 studies that also had
male female ratio of 1.2:1. This is an observation in my study as well as
other studies
2. Age
In this study the mean age of children affected was 8.5 ± 2.95
years. Saba Ahmed et al11 and Shah G.S et al 12 studies also had a mean
age of 8.3 ± 3.5 years. In the present study infants and toddlers were
less in comparison to the preschool children and school going children.
65 3. Geographic area
In the present study most of the children came from
Chengalpattu , Vandhavasi and Kanchipuram.
4. Seasonal variation
In the present study 90% of the children presented between the
months of August and November. Praveenkumar et al 6 study
revealed a major distribution of cases between July to September and
Muhammad
Ayub et al19 study documented increased prevalence of cases
between June to August. These study results were nearly comparable to
the present study. This could be universal phenomenon where certain
infective conditions like dengue and scrub are known to have seasonal
presentation.
5. Clinical presentation
In the present study majority of children presented with gastro
intestinal symptoms followed by headache, myalgia, GI bleeds and
altered sensorium. Praveen Kumar et al6 and Saba Ahmed et al12 studies
also revealed GI symptoms were the commonest followed by headache
and bleeds in Praveen Kumar et al 6 study and rashes in Saba Ahmed
66 12et al study. Ahmed Yaramis et al 15, Aisha Sajid et al10, Chitu CH et
al16 studies also showed GI symptoms was the commonest in more than
two third cases. These studies results were comparable with the
present study.
In contrast Shah GS et al12 and Nikalje anand et al 8 studies
showed headache was the commonest than GI symptoms.
6. Clinical signs
In the present study 88% children were febrile at admission . Two
third children had hepatomegaly, one third children had pallor , one
fourth had splenomegaly and one sixth had petechiae at admission .
Shah G.S12 et al study revealed hepatomegaly in three fourth children,
splenomegaly in one fourth of children and petechiae in half the study
group. Ahmed Yaramis et al 15 study shows hepatomegaly in two fifth
of children, splenomegaly in one fifth and altered sensorium in 6%
children . These study results were comparable with present study. In
contrast Saba Ahmed et al 11study showed pallor was the commonest
presentation with 67 % followed by hepatomegaly in 37 % and
splenomegaly in 6 % children and Aisha Sajid et al10 study showed
that splenomegaly was the commonest presentation in 94% children
followed by pallor in 65 % of children and hepatomegaly in 64%.
67 7. Vital signs
In the present study mean heart rate was 121.33 ± 25.4
beats/minute, mean respiratory rate was 29.29 ± 8.1 breaths / minute.
Mean systolic blood pressure was 98.214 ± 14.9 mm Hg and mean
diastolic blood pressure was 44. 568 ± 9.021 mmHg. 22% children
had compensated shock and 4% children had hypotensive shock of
which one child had respiratory failure and required ventilatory
support. Shock was commonly associated with severe thrombocytopenia.
Pankaj B Palange et al 18study results showed shock in 35% cases of
which 17 % had compensated shock and 18% had hypotensive
shock which is nearly comparable to the present study. Occurrence of
hypotensive shock indicates late presentation. This could be due to
various factors like parental ignorance, lack of access to health care
facility and inappropriate treatment.
8. Thrombocytopenia
In the present study among 100 children 47% had severe
thrombocytopenia , 43% had moderate thrombocytopenia and 10%
had mild thrombocytopenia . Muhammad Ayub et al19 study revealed
severe thrombocytopenia in 60% children , moderate
thrombocytopenia in 20% and mild thrombocytopenia in 20%.
68 Shruthi k Bhalara et al 17 study showed severe thrombocytopenia in
50%, moderate thrombocytopenia in 29 % and mild
thrombocytopenia in 21% children . Pankaj B Palange et al19 study
revealed severe thrombocytopenia in 60%, moderate
thrombocytopenia in 27 % and mild thrombocytopenia in 13%.
These studies are comparable to the present study. In contrast Kriti
Mohan et al13 study showed that mild thrombocytopenia 48% ,
moderate thrombocytopenia in 35% and severe thrombocytopenia
17% of children, Shah G.S et al revealed mild thrombocytopenia in
54 %, moderate thrombocytopenia in 40% and severe
thrombocytopenia in 16% of children and Aisha Sajid et al 10 study
result showed moderate thrombocytopenia in 68%, mild
thrombocytopenia in 21% and severe thrombocytopenia in 11% .
Puttasuresh et al3 study showed that thrombocytopenia in Malaria due
to sequestration and immune mediated destruction with elevated platelet
activated immunoglobulins and thrombocytopenia in Dengue fever due
to immune mediated mechanism. Muhammed Ayub et al 19 study
revealed marrow depression in acute stage of Dengue infection causes
thrombocytopenia.
69 Table. 25: Severity of thrombocytopenia in different studies
Study Mild thrombocytopenia
Moderate thrombocytopenia
Severe thrombocytopenia
Muhammed Ayub et al
20% 20% 60%
Pankaj B Palange et al
13% 27% 60%
Shruti K Bhalara et al
21% 29% 50%
Kriti Mohan et al
48% 35% 17%
Shah G.S et al 54% 40% 16%
Aisha Sajid et al
21% 68% 11%
This study 10% 43% 47%
9. Bleeding manifestations
In the present study petechiae was the commonest one which
accounts for 46 % followed by GI bleeds 35% and other bleeds
like epistaxis, subconjunctival hemorrhage , gum bleeds collectively
accounts for 19%. Among bleeding manifestations GI bleeds were
common in infants in contrast to school going children where
petechiae was the common one . Saba Ahmed et al11 study result
showed petechiae in 40 % of the study group . Prithviraj et al20
and Amitha G Gandhi et al 7 studies also showed that petechiae
70 was the commonest bleeding manifestation followed by gum bleeds ,
epistaxis, hematuria and GI bleeds. The above study results were
comparable with the present study. In contrast Shah G.S et al 12 and
Kriti Mohan et al 13 study results revealed GI bleeds were more
common than petechiae and other bleeds and Shruthi K Bhalara et
al 17 study showed gum bleeds was the commonest one.
In the present study bleeding manifestations were more
common in children with severe thrombocytopenia with platelet
count of less than 50, 000 cells / cumm. Shruthi K Bhalara et al17
and Prithvi Raj et al20 studies also shows that bleeding
manifestations were more common with platelet count less than
50,000 cells/cumm. In contrast pankaj K Palange et al18, Kriti
Mohan et al 13, Shah G.S et al12 , Nikalje Anandh et al8 , Shankar
Raikar et al 4 study results revealed that there was no relation
between platelet count and bleeding manifestations.
In the present study mean platelet rising time 2.7 days which
is comparable with Shankar Raikar et al 4 study which shows mean
platelet rising time is 3 days .
Mean duration of thrombocytopenia in this study is 4.07 ±
2.056 days which is comparable with Aisha Sajid et al10 study
where mean duration of thrombocytopenia was 5 days.
71 10. Etiology
In the present study undiagnosed fever was the commonest
etiology for fever with thrombocytopenia followed by Dengue
fever, Scrub typhus, leukemia, Malaria , Enteric fever and Septicemia.
Prithvi Raj et al ,20 Rekha M.C et al5 and Nikhalje Anand et al8
study results shows undiagnosed fever was the commonest etiology
followed by dengue fever and enteric fever. These studies were
comparable with present studies. Shankar Raikar et al4 and Shruti K
Bhalara et al17 studies revealed that Dengue fever was the
commonest etiology followed by malaria and sepsis, these studies
were also comparable with present study in reference to diagnosable
etiology. In contrast Putta Suresh et al3, Praveen Kumar et al6 and
Amita G Gandhi et al 7studies showed malaria as commonest
etiology followed dengue and undiagnosed fever.
11. Outcome
In this study 95 % improved and discharged,4 children referred for
hemato oncological consultation and one child expired due to associated
septicemia and MODS.
72
SUMMARY
Fever with thrombocytopenia is common clinical problem in
pediatric wards. Literature shows very minimal data on febrile
thrombocytopenia in children , even though there are some studies on
profile of individual diseases like dengue fever, typhoid fever, malaria
in children. Hence this study was conducted to analyze clinic etiological
profile in preference to infective etiology and outcome of children with
febrile thrombocytopenia. This was a prospective observational study
conducted in Pediatric Dept, Chengalpattu Medical College from August
2015 to September 2016.100 children between 1 month to 12 years of
age who fulfilled the criteria of fever for 5 days or more with
thrombocytopenia were included in the study and newborn, children
with afebrile thrombocytopenia ,known ITP and hematological
malignancy, pseudothrombocytopenia were excluded. After informed
written consent detailed history, clinical examination and necessary
laboratory investigation were undertaken. Study parameters were
documented in Excel spread sheet and analyzed using SPSS version 16
software. This study demonstrated no gender difference in the study
population .Analysis of different age group revealed two third study
73 group comprised of children more than 5 years. Comparision of different
age group and gender was done which showed in infant and school going
children males are more affected. Geographic and Seasonal analysis
revealed more than 50 % children from Chengalpattu, Vandhavasi,
Kanchipuram and 90 % of study group presented between months of
August and November. Clinical features and Physiological status at
admission were analysed for frequency and occurence in different age
groups which revealed altered sensorium, GI bleeds, seizures and
oliguria were common in infants. Hepatomegaly was seen in two third
children, facial puffiness in 50 % ,pallor in 30 % and shock in 25 %
children.Shock was frequent in infants along with narrow pulse pressue
and ALOC. Tourniquet test was positive in 19 % children mostly in
>5years .Thrombocytopenia were graded as per WHO criteria of which
47 % had severe and 43 % had moderate thrombocytopenia. Severe
thrombocytopenia was commonly associated with bleeding
manifestations. Among bleeding manifestations petechiae was the
commonest followed by melena and other bleeds, bleeding
manifestations were common among infants, school going children.
Bleeding manifestations were common in undiagnosed fever followed by
dengue fever. Univariate analysis of clinical signs and lab parameters
among the bleeding and non bleeding group was undertaken. The
74 analysis revealed significant association between bleeding manifestation
and positive tourniquet test and low platelet count, severe
thrombocytopenia .Early rise in platelet count ( < 3 days) was seen in
non bleeding group compared to bleeding group. In this study
undiagnosed febrile illness was the commonest etiology followed by
dengue fever and scrub typhus. Mortality in febrile thrombocytopenia is
1% . This was due to sepsis ,MODS. No blood product transfusion was
given for children in this study group.
75
CONCLUSION
Ø Febrile Thrombocytopenia is a benign illness in children
Ø GI symptoms are the commonest presenting feature.
Ø 65 % of them presents with hepatomegaly and 50% with facial
puffiness
Ø Shock and ALOC are common in infants with thrombocytopenia
Ø Severe thrombocytopenia is associated with bleeding
manifestations
Ø Petechiae is the commonest bleeding manifestation in children
with thrombocytopenia.
Ø No blood product transfusion was required in children with febrile
thrombocytopenia
Ø Treatment of primary condition improves the platelet count and
this much more earlier in children without bleeding
Ø Even though study group came across platelet count as low as
5000 cells/cumm, shock and bleeding manifestations mortality
was only 1 % , and that too due to associated septicemia.
This shows the benign nature of the condition.
76
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83 CHENGALPATTU GOVERNMENT MEDICAL COLLEGE AND
HOSPITAL
DEPARTMENT OF PEDIATRICS
SI No:
IP NO:
Name: <1 yr 2 – 5 yrs >5 yrs 5-10yrs
Age:
Sex:
Region:
HISTORY:
Yes no duration Fever
Headache,myalgia
GI symptoms
Cutaneous bleeds
GI bleeds
Other bleeds
Brethlessness
Edema
ALOC
Seizures
Neck stiffness
Oliguria
Rash
h/o antibiotic exposure
84 ON EXAMINATION:
yes No Febrile Pallor Petechiae Ecchymosis Lymphadenopathy Hepatomegaly Sleenomegaly Eschar Ascities Jaundice
Cardinal signs yes no Tachypnoea Bradypnoea Tachycardia Bradycardia Wide pulse pressure ALOC Compensated shock Hypotensive shock Tornique test
investigations elevated decreased Normal total count Hb
Hematocrit
MP SMEAR
urine routine
urine c/s
Widal
MSAT
85 weil felix
Dengue
NEC
Chest X RAY
Date
Hb/PCV
Date
Smear platelet
CBC platelet
increased decreased normal
SGOT
SGPT
s.bilirubin
Urea
Creatinine
peripheral smear thrombocytopenia
peripheral smear hemolysis
86 Tranfusion yes no platelets FFP PRBC
· HOSPITAL STAY:
· DURATION OF FEVER:
· DURATION OF THROMBOCYTOPENIA:
· GRADE OF THROMBOCYTOPENIA:
· VENTILATORY SUPPORT:
· INOTROPE SUPPORT:
· FINAL OUTCOME:
FINAL DIAGNOSIS :
87
PATIENT CONSENT FORM STUDY DETAIL: “CLINICOETIOLOGICAL PROFILE AND OUTCOME OF ACUTE FEBRILE ILLNESS WITH THROMBOCYTOPENIA IN CHILDREN-A HOSPITAL BASED PROSPECTIVE STUDY”
STUDY CENTER:
CHENGALPATTU MEDICAL COLLEGE & HOSPITAL, C HENGALPATTU PATIENT NAME: PATIENT AGE: IDENTIFICATION NUMBER: FATHER’S NAME: I confirm that I have understood the purpose of procedure for the above study. I have the opportunity to ask the question and all my questions and doubts have been answered to my satisfaction. I understand that my child participation in the study is voluntary and that I am free to withdraw my child at anytime without giving any reasons, without my legal rights being affected. I understand that investigator, regulatory authorities and the ethics committee will not need my permission to look at my health records both in respect to the current study and any further research that may be conducted in relation to it, even if withdraw from the study, I understand that my child identity will not be revealed in any information released to third parties or published, unless as required under the law. I agree not to restrict the use of any data or results that arise from the study. I agree my child to take part in the above study and to comply with the instructions given during the study and faithfully cooperative with the study team and to immediately inform the study staff if my child suffer from any deterioration in my health or wellbeing or any unexpected or unusual symptoms. I hereby give consent for my child to participate in this study. I hereby give permission to undergo complete clinical examination and diagnostic test on my child . Signature/Thumb impression: Place: Parent name and address: Date: Signature of the investigator: Place: Study investigator’s name: Date:
88
CHILD ASSENT FORM
STUDY DETAIL: CLINICOETIOLOGICAL PROFILE AND OUTCOME OF ACUTE FEBRILE ILLNESS WITH THROMBOCYTOPENIA IN CHILDREN-A HOSPITAL BASED PROSPECTIVE STUDY STUDY CENTER: CHENGALPATTU MEDICAL COLLEGE & HOSPITAL, CHENGALPATTU PATIENT NAME: PATIENT AGE: IDENTIFICATION NUMBER: I confirm that I have understood the purpose of procedure for the above study. I have the opportunity to ask the question and all my questions and doubts have been answered to my satisfaction. I understand that my participation in the study is voluntary and that I am free to withdraw at anytime without giving any reasons, without my legal rights being affected. I understand that investigator, regulatory authorities and the ethics committee will not need my permission to look at my health records both in respect to the current study and any further research that may be conducted in relation to it, even if withdraw from the study, I understand that my identity will not be revealed in any information released to third parties or published, unless as required under the law. I agree not to restrict the use of any data or results that arise from the study. I agree to take part in the above study and to comply with the instructions given during the study and faithfully cooperative with the study team and to immediately inform the study staff if I suffer from any deterioration in my health or wellbeing or any unexpected or unusual symptoms. I hereby give consent to participate in this study. I hereby give permission to undergo complete clinical examination and diagnostic test . Signature/Thumb impression: Place: Patient name and address: Date: Signature of the investigator: Place: Study investigator’s name: Date: