Dengue- Blood and Blood
Products
Jameela Sathar
Hospital Ampang
Haemostatic Changes in Dengue
1. Vasculopathy/ Endothelial activation
- Hess’s test is an early sign
- Plasma leakage
2. Thrombocytopenia
3. Coagulation abnormalities
Mitrakul C 1987
Endothelial activation
lumen
DV-ab
C
DV-ab
C
C
C
IL
IL
IL
EC
C
Complement: C3a, C5a-C9
IL
Interleukin
Dengue-infected monocytes
Plasma leak
Raised haematocrit

Early evidence of plasma leakage
Platelet activation
lumen
DV-ab
DV-ab
Plt
Plt
Plt
endothelium
Plt
vWF
Thrombocytopenia

Platelet count begins to fall towards the end of
febrile stage


Lowest during leakage phase
Main mechanism: platelet activation
Coagulation activation
lumen
DV-ab
DV-ab
T
T
Plt
Plt
T
thrombin
fibrinogen
T
Plt
VIIa
vWF
TF
Coagulation Abnormalities
Prolonged APTT: 54.6%
Prolonged PT:
33.3%
Variable but no significant reduction in coagulation factors
II, V, VII, VIII, IX, XII and X
These do not mean that patient has DIC!
Other factors: ? Contact factor deficiency or presence of
inhibitor
Isarangkura PB 1987
Coagulation Abnormalities

In general, only mild and improves after fluid
replacement or cease spontaneously after
recovery of illness

However prolonged shock can lead to acidosis
and DIC resulting in occult or overt bleeding
and end-organ damage
Thrombocytopenia and coagulation
abnormalities do not reliably predict
bleeding in dengue infection
Chaudhary R 2006; Mairahu AT 2003; Krishnamurti C 2001;
Coagulation Abnormalities
48 children with DSS in Vietnam:

Reduced levels of anticoagulant proteins:



PC, PS, AT
Due to plasma leakage and loss
Increased levels of:




Thrombomodulin
Tissue factor
PAI-1
Due to endothelial activation
Wills 2002
Coagulation Abnormalities

Prospective cohort study
42 Thai children with dengue (20 DF; 22 DHF)

Endothelial cell activation assays were higher in DHF






 thrombomodulin
 t-PA
 TF
 ADAMTS
Abnormal vWF multimers were only seen in DHF patients
Sosothikul 2007
Increased markers of endothelial
activation may promote microvascular
thrombosis and end-organ damage
Esmon CT 2004
Use blood and blood
products with caution and
only when indicated
Management of bleeding in dengue

Mild bleeding eg. gums, vagina, epistaxis or
petechiae usually cease spontaneously and do not
require blood or platelet transfusion

Transfusion of blood and/or blood products in
dengue is indicated only when there is evidence of
significant bleeding (occult or overt)
WHO 1997
Significant occult bleeding

Haematocrit not as high as expected for the degree
of shock to be explained by plasma leakage alone

A drop in HCT without clinical improvement
despite adequate fluid replacement (40-60 ml/kg)

Severe metabolic acidosis and end-organ
dysfunction despite adequate fluid replacement
Lum LC 2002
Significant bleeding- which blood
products?

Blood transfusion with whole blood or packed cell
(preferably less than 1 week old)

± blood products if in DIC or uncontrolled
bleeding
Management of UGIT bleed

Endoscopy and endoscopic injection therapy in
upper GIT haemorrhage increases the risk of
bleeding and should be avoided

Blood transfusion if significant bleeding
Chiu YC 2005
What are the risk factors for
significant bleeding?
Risk factors for hemorrhage in
severe dengue Lum et al, J Ped 2002
Clinical /laboratory
parameter
Group 1
(significant
hemorrhage)
(n=22)
Group 2
(no/mild
hemorrhage)
(n=92)
P value
Age (mean) (years)
6.1 + 4.0
5.9 + 3.5
0.8
Male : Female ratio
1:1
1:0.9
0.9
Platelet count (x 109/L)
72 + 54
71 + 50
0.9
Lowest platelet count
23 + 18
28 + 21
0.4
Serum sodium (mmol/L)
127 + 6
130 + 6
0.49
Risk factors for hemorrhage in severe dengue
Clinical/Laboratory
features
Odd
ratio
95% CI
b
P value
Encephalopathy
0.01
0.00-41.89
-4.40
0.289
Mottling
0.08
0.00-15.50
-2.50
0.350
Hypotension
2.28
0.18-28.19
0.08
0.521
Duration of shock
2.11
1.13-3.92
0.75
0.019
HCT at admission
Liver failure
Renal failure at adm
Prothrombin time ratio
Abnormal glycemia
Partial thromboplastin time
0.72
1.8x104
1.44
0.10
2.71
1.03
0.55-0.95
0.50-6.80x108
0.10-249.90
0.00-46.89
0.22-33.68
0.98-1.07
-0.33
9.83
0.37
-2.30
1.00
0.03
0.020
0.067
0.889
0.454
0.437
0.262
Lum et al, J Ped 2002
Results

Bleeding is not related to degree of
thrombocytopenia

Bleeding is related to the duration of shock due to
plasma leakage
Lum et al, J Ped 2002
Prevention of hemorrhage in DHF

Early recognition of shock

Prompt correction of shock to prevent acidosis
which leads to bleeding
Preventive transfusions in
DSS – is it necessary?
Lum et al, J Ped, 2003
Clinical parameter*
Treatment groups#
Received bld prod
(n=60)
Did not receive
bld prod (n=46)
P value
Duration of shock (hours)
4.0
4.0
0.918
% increase in hematocrit
53.0
42.0
0.239
Lowest platelet count (x 109/L)
20.5
22.0
0.127
Highest PTR
1.2
1.1
0.207
Highest PTT (sec)
77.7
71.3
0.347
FFP transfused (ml/kg)
20.0
0
0.000
Total platelets transfused
(units/kg)
0.2
0
0.000
Total fluid balance (ml/kg)
121.0
107.0
0.045
Days of thrombocytopenia
5.0
4.0
0.395
Days of hospitalization
7.0
5.0
0.000
^Incidence (%)of bleeding
60.0
43.5
0.136
Incidence (%)of pulmonary
edema
30.0
6.5
0.006
Behaviour of transfused platelets in DSS
Mean % change in platelet
count after transfusion
400
Patient no =52
No of transfusions=113
300
200
100
0
0
1
2
3
4
5
6
7
8
9
10
11
12
Time (hours) after transfusion
LCS Lum et al, 2003
Life-threatening complications of blood/
blood products

Bacterial contamination

TRALI: Transfusionrelated acute lung injury

TTI: Transfusiontransmitted infections

Wrong blood
Infective risks of blood/ blood products
Virus
Units transfused
HIV
1:500,000
HCV
1:150,000
HBV
1: 50,000
(prior to NAT testing)
There is no role for prophylactic
transfusion with platelets and fresh
frozen plasma in dengue patients
No role for prophylactic transfusion of
platelets or FFP

Do not produce sustained changes in the coagulation
status and platelet count in patients with DHF/DSS

Do not change or reduce the bleeding outcome in DHF

Inappropriate transfusion of blood products increases
the risk of pulmonary oedema and respiratory
embarrassment
Adjunctive therapy

Insufficient evidence to support use in dengue of




Recombinant activated factor VII (rFVIIa) in significant
bleeding
ivIG
Steroids
The coagulation system is activated in dengue and
infusion of activated factor concentrates may
increase the risk of thrombosis
Summary

The process of coagulation and platelet activation is
an intrinsic part of the disease

Significant bleeding occurs following prolonged
shock and acidosis

It is important to recognise and correct hypovolemia
to prevent shock which leads to acidosis and
DIC/bleeding
Summary

There is evidence that prophylactic platelet
transfusion is not useful

There is no role for FFP as a plasma expander

Blood transfusion is indicated if there is evidence
of significant bleeding
Pitfalls in the management of DHF

Focus on platelet count instead of hematocrit

Too much focus on bleeding instead of plasma leakage

Too much emphasis on lab results rather than the
clinical condition of the patient

Late recognition of shock and inadequate resuscitation
Pitfalls in the management of DHF

Not recognising that Hct does not drop to low levels even
in significant bleed

Transfusion of blood only when the Hct falls to a low level
may be too late

Too much reliance on platelet and FFP transfusion to
control bleeding

Inappropriate and unnecessary transfusion of platelets and
FFP will lead to fluid overload
Thank You