Haematologic Changes in Dengue Viral Infection
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Transcript of Haematologic Changes in Dengue Viral Infection
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Haematologic Changes
in
Dengue Virus Infection
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Classification
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Dengue virus infection
Asymptomatic Symptomatic
Simple fever Dengue fever(DF)
Denguehaemorrhagicfever(DHF)
Withouthaemorrhage
With unusualhaemorrhage
No shock Dengue shocksyndrome
(DSS)
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Manifestasi klinis IVD (WHO, 2011).
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DF
/DHF Grade Symptoms LaboratoryDF
Fever with two or more of the
following signs; headache, retro-
orbital pain, Myalgia, arthralgia.
Luecopenia occasionally
Thrombocytopenia may be
present, no evidence of
plasma leakage.
DHF IAbove signs plus positive
tourniquet test.
Thrombocytopenia
20%
DHF IIAbove signs plus spontaneous
bleeding
Thrombocytopenia
20%.
DHF III
Above signs plus circulatory failure
(rapid weak pulse, pressure, coldclammy skin, restlessness and
capillary refill time >3sec)
Thrombocytopenia20%
DHF IVProfound shock with undectable
blood pressure and pulse
Thrombocytopenia
20%.
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Dengue infection: Immunopathogenesis
Immune deviation
Cytokine over-production
Dengue virus-induced vasculopathy
Dengue virus-induced coagulopathy
Anti-platelet autoantibody
Anti-endothelial cell autoantibody
Molecular mimicry
Dengue virus infects monocytes and B cellsJuli S - HAEMATOLOGIC CHANGES in DVI 8
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Complete Blood count (CBC) is an importantpart of the diagnostic workup of patients.
Comparison of various finding in CBCincluding peripheral smear can help the
physician in better management of the patient
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The laboratory findings during an acute DF episode
Mild hematocrit rise (10%)
may be found
as a consequence of dehydrationassociated with
high fever,
vomiting, anorexia
poor oral intake.
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Haemoconcentration :
Haemoglobine
Haematocrit increased
Red blood cell count
MCV
MCH NOT increased
MCHC
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The laboratory findings during an acute DF episode
Total WBC
usually normal at the onset of fever
then leucopenia with decreasing neutrophils
lasts throughout the febrile period.
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The laboratory findings during an acute DF episode
Platelet counts
usually normal
Mild thrombocytopenia (100 000 to 150 000/mm3) iscommon
50% of DF : platelet count < 100 000 cells/mm3
severe thrombopenia (
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The laboratory findings during an acute DF episode
Serum biochemistry is usually normal
AST levels may be elevated.
It should be noted that analgesics, antipyretics,
anti-emetics and
antibioticscan interfere with
liver function
blood clotting.Juli S - HAEMATOLOGIC CHANGES in DVI 15
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DF DHF DSS
DIC
BLEED
ACIDOSIS
ORGANDYSFUNCTION
Vascular
Permeability
HCTAlbuminPerdarahanspontanPlt
RL (+)
Plt
VasculerEC damage
Viremia : masa inkubasi hari ke 3 demam
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TOURNIQUET TEST
How to perform?
Inflate the BP cuff on theupper arm to a point midwaybetween the SBP & DBP for 5min.
A positive test : 20petechiae per 6.25 cm2
(1 inch2)
Note: Helpful in the early febrile
phase (< 3 days) esp. whenthe platelet count is stillnormal
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OVERALL ASSESSMENT
InvestigationSerial FBC and HCT
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Leucopaenia followed by progressive
thrombocytopaenia (dengue infection)
Rising HCT accompanying progressive
thrombocytopaenia (DHF)
In the absence of a baseline HCT level, aHCT value of >40% in female adults and >46%
in male adults should raise the suspicion of
plasma leakage
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Thrombocytopenia
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< 100x10/L
Begins to fall in the febrile stage
Lowest in the shock stage
Can reach a nadir of less than 10 x 10 /L
Starts to rise by the second afebrileday andnormalizes by 7 days
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Thrombocytopenia
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Mechanism of thrombocytopaenia
Decreased productionand increased peripheral destruction
Immune complexes on platelets
Shortened survival of transfused platelets
Cross reactive platelet antibodies
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Platelet dysfunction
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Impaired
ADP-induced platelet aggregation
ADP-releasing ability
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Viraemia
HI AbIgG
Fever C
Symptoms
Haemorrhage
Shock
Platelet 10/L
Hct %
Days after onset of fever
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Gambaran Klinis, Laboratoris dan Serologis IVD (WHO, 2009)
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Monitoring
Hematocrit or Hb :
every two hours for the first six hours then
every four hoursuntil the patient is stable.
Accurate record of intake and output including the
type of fluid given should be made.
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SUMSUM TULANG
Supresi haemopoietic 4
5 hari post infeksi Menghilangnya CFU-GM hiposeluler megakariosit,
eritroblast dan myeloid pada awal serangan akut.
Macrophage Inflamatory Protein- 1 (MIP-1), IL-6, IL-8. Patogenesis :
1. Infeksi langsung pada progenitor haemopoietic
oleh virus dengue.
2. Infeksi sel stroma oleh virus dengue
3. Perubahan regulasi sumsum tulang cytokin
MIP-1 bersifat haemato depressive.Juli S - HAEMATOLOGIC CHANGES in DVI 31
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TINJAUAN PUSTAKA
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Gambar 2.6Supresi sutul akibat IVD; (a) Interaksi awal sutul dengan virus
gangguan produksi sitokinsupresi hematopoisis; (b) respon imun seluler
mengeliminasi elemen sutul yang terinfeksi virus (hiposelularitas sutul);
(c) kembalinya hematopoisis melalui ekspansi poolsel progenitor
pada kavitas sutul (La Russa, 1995) 32
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TROMBOSITOPENIA Supresi haemophoetic sumsum tulang
Peripher :
1. Destruksi trombosit interaksi antibodi & antigen VD di
permukaan trombosit.
2. Kerusakan dinding endothel akibat VD Interaksi trombosit
dengan kolagen sub endotel agregasi dan lysis trombosit.
3. IL-6 IgM antiplatelet antibodies destruksi trombosit
4. Peningkatan kebutuhan / pemakaian
DYSFUNGSI TROMBOSIT
TROMBOSIT
Degranulasi trombosit ADP (-)
1. Primer hypoagregasi
2. Sekunder tidak ada responsJuli S - HAEMATOLOGIC CHANGES in DVI 33
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LEKOSIT
Jumlah normal lekositosis akhir serangan
lekopenia, netropenia, limpositosis dan atypicallimposit (+).
Jumlah limfosit pada DHF lebih besar 15 - 20%
dibandingkan DF
Jumlah lekosit kembali normal 2
3 hari setelah
fase pemulihan.
Sutaryo (1991) Sensitivitas dan spesifisitas LPB
- pada hari ke 4 : 68 % dan 86 %
- pada hari ke 5 : 81 % dan 83 %
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Lymphoplasmacytoid lymphocyte
Plasmacytoid lymphocyte,
Blue lymphocyte
reactive lymphocyte
with dark bluecytoplasmJuli S - HAEMATOLOGIC CHANGES in DVI 35
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2- Dysfunctional
anticoagulant
mechanisme(AT, PC)
Fibrinformation
3- Impaired Fibrinolysis
(hyperactivite PAI-1)Microvascularthrombus
TF
TF-VIIa
Xa-Va
IXa-VIIIa
1- Activation of
coagulation(TF mediated)
Thrombine
PATHOGENETIC
MECHANISMS of DIC
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Monitoring
Hematocrit or Hb studies should be
performed every two hours for the first six
hours then every four hours thereafter until
the patient is stable.
Accurate record of intake and output
including the type of fluid given should be
made.
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Screening test : PT, APTT, TT, fibrinogen
Coagulation Activation : TAT, sFM, FPA, D Dimer
Fibrinolysis Activation : FDP, D Dimer
Inhibitor consumption : AT, PC, PS
Thrombocyte count
HEMOSTATIC MARKERS
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Peripheral blood in DIC : fragmentocytes and activated platelet
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l