1. What’s New in Hematology?
Dengue Hemorrhagic Fever
Ampaiwan Chuansumrit, M.D.
Department of Pediatrics
Faculty of Medicine Ramathibodi Hospital,
Mahidol University, Bangkok, Thailand
2. Hematocrit (Hemoconcentration)
Serotypes DF DHF I DHF II DSS OFIs
Number of patients 51 43 36 19 15
Max Hct (%) 39.5 + 4.0 43.5 + 3.9 44.7 + 4.3 44.9 + 8.1 36.6 + 6.1
Min Hct (%) 34.6 + 3.8 3.6 + 4.0 35.7 + 4.7 32.8 + 3.9 31.0 + 5.9
Mean increment of Hct (%) 14.4 21.1 26.0 37.7 18.8
DF, dengue fever; DHF, dengue hemorrhagic fever; DSS, dengue shock syndrome; OFIs, other febrile illnesses
5. Elevated Soluble Thrombomodulin in the Febrile Stage
Related to Patients at Risk for Dengue Shock Syndrome
Day of illness Day of illness
SolubleThrombomodulin(ng/ml)
Butthep P, et al. Pediatr Infect Dis J 2006;25:894-7.
11. Mean Levels of IL-6,IL-8,IL-10 and IFN-γ
(A)
DF
DHF I
DHF II
DSS
OFIs
Day -2 Day -1 Day 0 Day +1 Day +2 Conval
Day of illness
0
10
20
30
40
50
60
70
80
90
100
IL-6(pg/ml)
(B)
DF
DHF I
DHF II
DSS
OFIs
0
50
100
150
200
250
300
350
IL-8(pg/ml)
Day of illness
Day -2 Day -1 Day 0 Day +1 Day +2 Conval
(C) (D)
DF
DHF I
DHF II
DSS
OFIs
Day of illness
20
40
60
80
100
120
140
160
180
IL-10(pg/ml)
0
Day -2 Day -1 Day 0 Day +1 Day +2 Conval
DF
DHF I
DHF II
DSS
OFIs
Day -2 Day -1 Day 0 Day +1 Day +2 Conval
Day of illness
0
50
100
150
200
250
300
IFN-γ(pg/ml)
Butthep P, et al. Pediatr Infect Dis J 2012; 31:e232-8.
13. Dengue Virus Antigen in Peripheral
Blood Mononuclear Cell
• Dengue virus antigens are found in most PBMC samples of
dengue infected patients on Day -3 to Day -1, Day 0 and cont
inue until Day +1 to Day +3
Chunhakan S, et al. Pediatr Infect Dis J 2009;28:1085-8.
14. 100
80
60
40
20
0
Day -1 Day 0 Day +1 Conval
Day of defervescence
UnstimulatedTNF-αexpression(%)
* ** *
DF
DHF I
DHF II
DSS
OFIs
100
80
60
40
20
0
Day -1 Day 0 Day +1 Conval
Day of defervescenceLPS-stimulatedTNF-αexpression(%)
* ** *
Unstimulated TNF-α Expression (%)
LPS-stimulated TNF-α Expression
(%)
Chunhakan S, et al. Int J Vas Med 2015:917143.
15. Unstimulated IL-1 β Expression (%) LPS-stimulated IL-1β Expression (%)
DF
DHF I
DHF II
DSS
OFIs
10
8
6
4
2
0
Day -1 Day 0 Day +1 Conval
Day of defervescence
UnstimulatedIL-1-βexpression(%)
*
*
*
*
100
80
60
40
20
0
Day -1 Day 0 Day +1 Conval
Day of defervescence
LPS-stimulatedIL-1βexpression(%)
*
*
*
*
Chunhakan S, et al. Int J Vas Med 2015:917143.
16. Host Genetics
• Alleles of susceptibility or resistance
– HLA class I and II
– Tumor necrosis factor-α
– CD209
– OAS gene
17. Association of -308 A of TNF-α and Bleeding
Case Frequency
With bleeding 38 9/76 = 11.8%*
Without bleeding 63 5/126 = 4.0%*
*P = 0.045
Chuansumrit A, et al. Pediatr Inter Child Health 2013;33:97-101.
18. Oligoadenylate Synthetase (OAS) Gene
• OAS gene related to interferon alpha/beta
• The very first line of antiviral innate immune
response against arbovirus
• OAS 1 splicing variant: susceptible to plasma
leakage and shock
• OAS 3 missense variant: protection against shock
Simon-Loriere E, et al. J of Infectious Disease 2015; pii: Jiv321.