dengue- blood and blood products
DESCRIPTION
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. DV-ab. DV-ab. - PowerPoint PPT PresentationTRANSCRIPT
Dengue- Blood and Blood Products
Jameela SatharHospital 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
DV-ablumen
Endothelial activation
DV-ab
Plasma leak
CC
C
ILIL
ILC
C
IL
Complement: C3a, C5a-C9
Interleukin
ECEC
Dengue-infected monocytes
Raised haematocrit
Early evidence of plasma leakage
DV-ab
endothelium
lumen
Platelet activation
DV-ab
vWF
PltPltPltPlt
Thrombocytopenia
Platelet count begins to fall towards the end of febrile stage Lowest during leakage phase
Main mechanism: platelet activation
DV-ab
lumen
Coagulation activation
DV-ab
VIIavWF
fibrinogen
thrombin TF
T
T
T
Plt
PltPlt
T
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?
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 Lum et al, J Ped 2002
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 0.72 0.55-0.95 -0.33
0.020
Liver failure 1.8x104 0.50-6.80x108
9.83 0.067
Renal failure at adm 1.44 0.10-249.90 0.37 0.889
Prothrombin time ratio
0.10 0.00-46.89 -2.30 0.454
Abnormal glycemia 2.71 0.22-33.68 1.00 0.437
Partial thromboplastin time
1.03 0.98-1.07 0.03 0.262
Risk factors for hemorrhage in severe dengue
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
Time (hours) after transfusion
1211109876543210
Mean
% c
han
ge i
n p
late
let
cou
nt
aft
er
tran
sfu
sion
400
300
200
100
0
Patient no =52No of transfusions=113
LCS Lum et al, 2003
Life-threatening complications of blood/ blood products Bacterial
contamination
TRALI: Transfusion-related acute lung injury
TTI: Transfusion-transmitted 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