Hematological Parameters,

Coagulation Profile and Outcome in

Patients with Dengue Fever
DR MOHAMMAD USMAN SHAIKH
Assistant Professor, Section of Hematology
Department of Pathology &
Microbiology/Medicine
The Aga Khan University Hospital
 INTRODUCTION
Flavivirius Genus; more than 60 viruses
Mainly arthropods transmission
Thirty viruses can cause human disease
Global perspective: four are important
I- yellow fever 2-Japenese encephalitis 3-tick borne
encephalitis
– Vaccine is available
4- dengue virus

1
Hals re ad SB. D eng ue. In: Warr en, Mah mo ud, eds
 INTRODUCTION
Dengue – homonym for the African ki denga pepo (break bone
fever) – appeared in English literature during Caribbean outbreak.
First detail description by Benjamin Rush in 1780
Dengue shock: first describe in 1897 in Australia
1903: Aedes Egypti recognized as a vector.
1906: Viral etiology established
1944: virus isolation by Sabin
1956: All four serotypes identified by Hammon

• Sabi n A BA m J Tr op Med H yg 1 95 2;1 :30-49

2

3
Hammo n WM cD A m J Tr op Me d H yg 1 97 3;2 2:8 2- 91.
WORLD WIDE INCIDENCE

WHO
 EPIDEMIOLOGY

In Pakistan…
Spectrum of hemorrhagic manifestations in Karachi
(1994-1995) : petechiae, epistaxis, hemetemesis occurred
most frequently5

Epistaxis was the most common feature6

Minor to severe epistaxis, gum bleeding and bleeding

from gastrointestinal tract7

5
Qure shi J A et a l, J Pak Me d A ss oc 19 97
6
Jaw ed K A et al. Pak ar med fo rces Me d J 2 00 1.
7
Nas ee m S e t al Inf ec D is J 2 00 5.
AEDES AEGYPTI
 PATHOPHYSIOLOGY

Replicates in RE system, cytokines response once

patient develops fever.

DSS (dengue shock syndrome) sudden extravasation

of plasma due to increase in vascular permeability
manifested by increase level of TNF-R, IL-8, IFN-
gamma, etc.
PATHOPHYSIOLOGY OF DENGUE FEVER
AND SHOCK SYNDROME
CLINICAL SPECTRUM
 CLINICAL FEATURES
Mostly sub-clinical & self limited.
Severity increase at extreme of age.
Vertical transmission is possible.
CNS involvement rare, although virus isolated from
CSF.
 CLINICAL FEATURES

Incubation period: 4-7 days

Headache, fever, retro orbital pain, backache, bone and
joint pain, weakness, depression and malaise.
Lymphadenopathy and hepatomegaly
Splenomegaly is infrequent.
Symptoms subside after 3 or 4 days; full recovery.
WHO case definitions for DHF:

 Fever
 Hemorrhagic manifestations, including at least a
positive tourniquet test (except in cases of shock),
 Thrombocytopenia (platelet count less than or equal to
100 000/ mm3);
 Hemoconcentration (hematocrit increased by 20% or
more relative to baseline values, or objective evidence of
increased capillary permeability).
 DIAGNOSIS

Specific diagnosis : viral cultures (more reliable in

secondary infections)

Immunodiagnostic methods :
ELISA based test for detection of IgM

PCR techniques.
COAGULATION PROFILE

Coagulation tests : Prolonged Partial Thromboplastin

and Thrombin Times are noted more frequently than
prolonged Prothrombin Times.

Elevated D-Dimer levels.

 TREATMENT
Classical dengue: Supportive
Anti-pyretic (avoid NSAID & Aspirin)
ORS in case of vomiting & diarrhea
Anticipatory & supportive care are life saving & have reduced
fatality rate to 50-100 folds in DHF & DSS.

Normal saline is indicated but over hydration can leads to

pulmonary edema.

Blood, platelets & FFP indicated in significant hemorrhage

No role of Intravenous immunoglobulin & steroids.

No benefit of Carbazochrome sodium sulphonate (vascular

permeability reducing agent).
OBJECTIVE

TO A SS ESS THE HEMATOLOGICAL PARAMETERS,

COAGULATION PROFILE AND OUTCOME IN PATIENTS
WITH DENGUE FEVER
PATIENTS AND METHODS

Total number of patients : 210

Study period: January 2001 – December 2006

Study setting: The Aga Khan University Hospital,

Karachi

Inclusion criteria: Febrile illness with dengue IgM

positive

Exclusion criteria: Fever with all other etiologies

Patients & Methods….

Data collection: medical records were reviewed using a

questionnaire.

Parameters:
 Hemoglobin/Hematocrit
 White blood cell count/absolute neutrophil count.
 Platelets.
 Performed on Coulter STKS

 Presence of atypical lymphocytes.

Patients & Methods…

 PT/APTT.
 D-Dimer.
 Performed on SYSMEX 1500

 Requirement of platelet transfusion.

 Dengue IgM antibody : performed by ELISA.

 RESULTS
Total number of cases N=210

Mean age: 29.7years

range:15– 74 years

Male : female ratio – 1.6:1

Frequency of cases during study period
160
140
120
100
80
No of cases
60
40
20
0
2001 2002 2003 2004 2005 2006
 RESULTS

Fever – 96.1%

Fever & Bleeding – 23.1%

HAEMORRHAGIC MANIFESTATIONS IN
DENGUE FEVER

SITE PE RC ENT AG ES (n)

Petechiae 13.9 (29)
Gingival bleed 3.8 (8)
Epistaxis 2.8 (6)
Malena 1.9 (4)
Hemetemesis 1.4 (3)
Menorrhagia 0.9 (2)
Hemoptysis 0.4 (1)
Hematuria 0.4 (1)
HEMATOCRIT VALUES ON ADMISSION
AND DISCHARGE

Hematocrit >48%
ABSOLUTE NEUTROPHIL COUNT

ANC/cumm PE RCENTAGES ( n)

<1500/cumm 31.6 (60)

<500/cumm 5.8 (11)

<200/cumm 1.6 (3)

 Comparison of absolute neutrophil counts.

ANC

On admission

On discharge

PATEINTS
 Thrombocytopenia

Pla tele t co unt Pe rce ntage

Less than 150,000/mm3 90.5%

Less than 100,000/mm3 77%

Less than 50,000/mm3 47.3%

Less than 20,000/mm3 17.4%

 TREND OF PLATELET COUNTS ON
ADMISSION & DISCHARGE

On discharge
PLATELET
COUNT

PATIENTS On admission
 PLATELET TRANSFUSION REQUIREMENTS

n=6 (2.9%)

n=45 (22.1%)

Platelet
transfusion

n=159(77.9%)
Atypical lymphocytes were seen in : 50.5%
(n=106)
Co- infection with plasmodium falciparum:
3.3% (n=7)
Results cont…

Deranged coagulation profile:

 PT: 2.5% (range:10.7 – 29.9)

 APTT: 16.7% (range: 21.1 – 127.7)

D-Dimer : Positive in n=6/14 (42.9%)

Results cont…

OUTCOME:
 Discharged : n=196 (96.6%)

 Deaths : n=7 ( 3.4%)

 COMPARATIVE STUDIES
YEAR SOURCE INC. HCT LEUCOPENIA THROMBOC-
YTOPENIA

20 06 OU R S TUDY 9.8 % 47 .2 % 90 .5 %

Itoda I et al, JAPAN NA 71% 57%

2006
Ayyub M et SAUDI 25% 20% 23%
al, 2006 ARABIA
Baruah J et INDIA 90.9% NA 50%
al, 2006
Salahuddin PAKISTAN 68% 48.6% 100%
N et al,
2005
Abu Baker BANGLADESH 41.89% NA 7.2%
et al, 2000
 CONCLUSIONS

Thrombocytopenia is one of the major reason of

admission.

Platelet transfusions were required in approx 22%.

3.4% mortality was observed in our study.

Hematological parameters –important aid in the

diagnosis of dengue fever.