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FREQUENCY OF THROMBOCYTOPENIA IN
NEONATAL SEPSIS

SUBMITTED BY:
DR. NADIA GUL
FCPS II RESIDENT

SUPERVISOR
PROF. DR. ASGHAR BUTT
PROFESSOR OF PEDIATRIC MEDICINE
DEPARTMENT OF PEDIATRICS AND CHILD HEALTH
ALLIED HOSPITAL, FAISALABAD
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INTRODUCTION:
Neonatal sepsis is one of the most common causes of mortality among neonates; roughly

leading to 50% of neonatal deaths in developing countries. It occurs in about 20% of neonates

and more than 1% die of this condition.1 Neonatal sepsis includes various systemic infections in

the neonatal period like meningitis, pneumonia, pyogenic arthritis, osteomyelitis, and urinary

tract infections.2

With antimicrobial therapy and good nursing care mortality due to septicemia in the

neonatal period can be prevented. Sepsis in neonates can be classified on basis of time of

appearance into early onset sepsis (EOS) and late onset sepsis (LOS); this helps in determining

the probable organism causing the disease and treatment of choice.3

Thrombocytopenia (low platelet count) is an indicator of neonatal sepsis occurring after

bacterial, viral, fungal and parasitic infections and even after non-infectious causes.4 It is more

common in culture positive sepsis. Studies have shown that maternal hypertension during

pregnancy, intra-vascular thrombosis and neonatal sepsis, especially due to gram-negative

organism, are independently associated with thrombocytopenia. Intra-cranial bleed and

pulmonary hemorrhage are serious complication of severe thrombocytopenia. This bleeding

manifestation is limited to infants with platelet count less than 30000/mm3.5,6 Death occurs after

DIC with bleeding from various sites.7

Charoo BA, et al reported that 59.5% patients with neonatal sepsis had thrombocytopenia

27% babies presented with mild thrombocytopenia, 20% with moderate and 12.5% developed

severe thrombocytopenia.8 Sindhura YS, reported the frequency of thrombocytopenia in neonatal

sepsis patients to be 77.1% (77.8% in EOS, 87.2% in LOS).9 Singh S, et al reported it to be

95.2% neonates with sepsis.10 Bhat SA, et al concluded that among neonates with culture-

positive sepsis incidence of thrombocytopenia was 66.2%; 64.81% in gram-negative sepsis

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patients, 71.4% in gram-positive sepsis patients and 60% fungal sepsis.11 Bhat RY, et al reported

thrombocytopenia at admission in 58.7% septic neonates, which was mild, moderate, and severe

in 39.3%, 25%, and 35.7% respectively and severe thrombocytopenia was highest in Klebsiella

sepsis.12 Ahmad MS, et al reported in his study that thrombocytopenia was present in 24.7%

patients with neonatal sepsis and thrombocytosis in 7.7% patients.13

Qazi I, et al. reported that those septic neonates with leucopenia had 100% mortality and

47.93% of septic neonates had thrombocytopenia, with neonatal mortality directly proportional

to the severity of thrombocytopenia.14

The rationale of this study is that limited local data is available regarding the incidence of

thrombocytopenia in septic neonates. We have designed this study to determine the frequency of

thrombocytopenia in septic neonates and to evaluate the feasibility of thrombocytopenia as a

screening tool for neonatal sepsis in risky neonates. Early detection and treatment of sepsis along

with thrombocytopenia can decrease the length of stay in hospital, time of recovery, and decrease

morbidity.

OBJECTIVE:
To determine the frequency of thrombocytopenia in patients with neonatal sepsis
OPERATIONAL DEFINITIONS:
Neonatal Sepsis:
Neonatal sepsis will be defined as a clinical systemic inflammatory response syndrome in a
neonate with presence of two or more of the following:
1. Tachypnea (more than 60 breaths per minute).
2. Temperature instability < 36°C or more than 37.9°C;
3. Capillary refill time more than 3 seconds;
4. White blood cell count < 5000/µl or more than 34000/µl;
5. C-reactive protein (CRP) greater than 10 mg/dl
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EOS (Early onset sepsis) will be defined as clinical manifestations of sepsis appearing within
72 hours of birth
LOS (Late onset sepsis) will be defined as clinical manifestations of sepsis if seen after 72
hours of birth.

Thrombocytopenia:
Thrombocytopenia was defined as platelet count < 150000/mm3
MILD: < 150000/mm3
MODERATE: <100,000/mm3
SEVERE: <50,000/mm3

MATERIALS & METHODS:

STUDY SETTINGS:
Pediatric ward unit I, Allied hospital, Faisalabad
STUDY DESIGN:
Cross sectional study
DURATION OF STUDY:
Six (6) months after proper approval of synopsis
SAMPLING TECHNIQUE:
Non-probability consecutive sampling
Sample Size:
Sample size was calculated using WHO sample size calculator
Expected prevalence of thrombocytopenia in septic neonates P = 24.7 %
Confidence level = 95% Absolute precision = 10%
Sample size = 75
INCLUSION CRITERIA:
All neonates aged from birth to 28 days, presenting with clinical signs and symptoms of sepsis
according to operational definition will be included in the study.
EXCLUSION CRITERIA:
1. Mother with history suspected of ITP, SLE / other autoimmune disorders, on medication
during pregnancy (sulfonamides, quinine / quinidine) (thiazides, tolbutamide,
vancomycin, hydralazine, and heparin)
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2. Neonate with history suspected of bleeding disorder in family, trisomies, Turner /

Noonans syndromes, TAR syndrome. Conditions associated with sequestration of
platelets (Kasabach - Merritt syndrome with giant haemangiomas, renal vein thrombosis,
polycythemia, placental vascular thrombi – PIH /preeclampsia /eclampsia).
3. Neonates with severe Rh – HDN (marked erythropoiesis in bone marrow → neutropenia
and thrombocytopenia) Massive bleed from causes like birth trauma, accidental slipping
of cord clamp causing hemodynamic disturbance/ exchange transfusion.
4. Neonate who received IV antibiotics for ≥ 48 hours prior to our study.
5. Patients with congenital heart diseases, congenital anomalies, hypoxic-ischemic
encephalopathy and hyaline membrane disease
6. Neonates with very low birth weight (birth weight <1000 grams), having age >28 days
7. Neonates having maternal history of placental insufficiency
8. Neonates with family history of bleeding manifestations
9. Neonate’s mother with low platelets counts
DATA COLLECTION:
After the approval to carry out this study from the Ethical Review Committee, subjects meeting
the operational definitions and the inclusion criteria will be enrolled in the study after informed
consent from the parents. Blood samples of all the patients included in this study will be obtained
for CBC, CRP levels and blood cultures. Urine samples of all the patients will be sent for routine
examination and culture. Patients will be assessed for manifestations of meningitis and will be
confirmed after lumbar puncture. Cerebrospinal fluid of these cases will be sent for microscopic
examination, gram staining, protein and glucose levels, and cultures. Stomach aspirate of those
patients who were admitted in first 24 hours of life were sent for microscopic examination. Date
of admission, age, diagnosis, WBC count, platelet count, CRP levels, and blood culture reports,
urine routine and culture reports, and if applicable, stomach aspirate and CSF reports, and the
outcome will be recorded. All patients included in this study will be given appropriate
antibiotics. The patients with platelet count < 100000/mm3, will be given platelet transfusion, if
bleeding present. All patients with platelet count < 50000/mm3 will receive platelet transfusion
even in the absence of bleeding. Weight, height, gender and fever (axillary temperature > 99 OF),
will also be noted.
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DATA ANALYSIS:
The data will be analyzed using SPSS version 20. Frequency and percentage will be calculated
for qualitative variables including gender, socioeconomic status, maturity at birth, birth weight,
type of sepsis, presence of thrombocytopenia at admission and severity of thrombocytopenia. For
the quantitative variables like birth weight, gestational age, weight and height at the time of
admission, temperature, platelet count, mean ± SD will be calculated. Effect modifiers like
gender, socioeconomic status, birth weight, gestational age and maturity at birth, type of sepsis
and severity of thrombocytopenia will be stratified to find out the effect of these on the outcome,
through chi square (p < 0.05 will, be considered significant).
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FREQUENCY OF THROMBOCYTOPENIA IN NEONATAL SEPSIS

Sr. no.: ______________ Reg. No. __________

Name:___________________ Age:__________`

Address: ___________________________________________________

Socioeconomic Status: Poor / Middle / Upper class

Gender: □ Male □ Female Birth weight: _______Kg

Classify by weight: LBW / Normal Weight / Macrocosmic

At Birth: Gestational Age in weeks: ________weeks

Gestational Age: Term / Preterm / Post-term

SGA / LGA

AT PRESENTATION:

Type of Sepsis: EOS / LOS

Weight: _______ kg Temp: _______ F Height: _______cm
Platelet Count on Admission: __________________
WBC Count: ___________ CRP Level: ________

MAIN OUTCOME VARIABLE:

Thrombocytopenia: Yes / No
Severity of Thrombocytopenia: Mild / Moderate / Severe
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References:

1
Sindhura YS, Reddy KR. A study of neonatal thrombocytopenia in neonatal sepsis.

Inter J Contemporary Med Res 2017; 4: 77-83.

2
Aggarwal R, Nupursarkar, Deorari AK, Paul VK. Sepsis in the newborn. Indian J Pediatr

2001;68:1143-7.
3
Ahmed Z, Ghafoor T, Waqar T, Ali S, Aziz S, Mahmud S, Diagnostic value of C- reactive

protein and haematological parameters in neonatal sepsis,JColl Physicians Surg Pak.

2005;15:152-6.
4
Sola MC, Del Vecchio A, Rimsza LM. Evaluation and treatment of thrombocytopenia in the

NICU. Clinics in Perinatology. 2002;27:655-79.

5
Baer VL, Lambert DK, Henry E, Christensen RD. Severe thrombocytopenia in the NICU.

Pediatrics 2009; 124:e1095-100.

6
Ree IMC, Fustolo-Gunnink SF, Bekker V, Fijnvandraat KJ, Steggerda SJ, Lopriore E.

Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors. PLoS One. 2017

4;12:e0185581.
7
Arif SH, Ahmad I, S. Ali M, Khan HM. Thrombocytopenia and Bacterial Sepsis in Neonates

Indian J Hematol Blood Transfus. 2012; 28:147–51.

8
Charoo BA, Iqbal J, Iqbal Q, Mushtaq S, Bhat AW, Nawaz I. Nosocomial sepsis-induced late

onset thrombocytopenia in a neonatal tertiary care unit: A prospective study. Hema/Onco Stem

Cell Therapy 2009; 02: 349-53.

9
Sindhura YS, Reddy KR. A study of neonatal thrombocytopenia in neonatal sepsis.

Inter J Contemporary Med Res 2017; 4: 77-83.

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10
Singh S, Agrawal A, Mohan U, Awasthi S. Prevalence of thrombocytopenia in neonates

admitted in NICU with culture proven sepsis. Int J Contemp Pediatr. 2018; 5: 743-8.
11
Bhat SA, Naik SA, Rafiq W, Tariq S. Incidence of thrombocytopenia and changes in various

platelet parameters in in neonates with blood culture positive sepsis. Int J Pediatr. 2015; 3: 757-

66.
12
Bhat RY, Kousika P, Lewis L, Purkayastha J. Prevalence and severity of thrombocytopenia in

blood culture proven neonatal sepsis: a prospective study. Arch Pediatric Inf Dis 2018; 6.
13
Ahmad MS, Waheed A. Platelet counts, MPV and PDW in culture proven and probable

neonatal sepsis and association of platelet counts with mortality rate. JCPSP 2014 ; 24: 340-4.
14
Qazi I, Bashir C, Mushtaq S, Ahmad A, Baba AR. Thrombocytopenia and other hematological

parameters in culture positive neonatal sepsis and their impact. J Pediatr Infect Dis. 2013;8: 25-9.