Haematologic Changes in Dengue Viral Infection

8/12/2019 Haematologic Changes in Dengue Viral Infection

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Haematologic Changes

in

Dengue Virus Infection

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Classification


Dengue virus infection

Asymptomatic Symptomatic

Simple fever Dengue fever(DF)

Denguehaemorrhagicfever(DHF)

Withouthaemorrhage

With unusualhaemorrhage

No shock Dengue shocksyndrome

(DSS)


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Juli S - HAEMATOLOGIC CHANGES in DVI

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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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Total WBC

usually normal at the onset of fever

then leucopenia with decreasing neutrophils

lasts throughout the febrile period.



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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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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


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


< 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


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


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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Haematologic Changes in Dengue Viral Infection