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Dengue- Blood and Blood Products

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... Transfusion-related acute lung injury TTI: Transfusion-transmitted infections Wrong blood Infective risks of blood/ blood products Virus Units transfused ... – PowerPoint PPT presentation

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Title: Dengue- Blood and Blood Products


1
Dengue- Blood and Blood Products
  • Jameela Sathar
  • Hospital Ampang

2
Haemostatic Changes in Dengue
  • 1. Vasculopathy/ Endothelial activation
  • - Hesss test is an early sign
  • - Plasma leakage
  • 2. Thrombocytopenia
  • 3. Coagulation abnormalities

Mitrakul C 1987
3
Endothelial activation
lumen
C
C
C
C
IL
IL
IL
EC
C
Complement C3a, C5a-C9
Plasma leak
Interleukin
IL

Dengue-infected monocytes
4
Raised haematocrit
  • Early evidence of plasma leakage

5
Platelet activation
lumen
Plt
Plt
Plt
Plt
endothelium
6
Thrombocytopenia
  • Platelet count begins to fall towards the end of
    febrile stage
  • Lowest during leakage phase
  • Main mechanism platelet activation

7
Coagulation activation
lumen
T
Plt
T
T
Plt
Plt
TF
T
thrombin
fibrinogen
8
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
9
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

10
Thrombocytopenia and coagulation abnormalities do
not reliably predict bleeding in dengue infection
Chaudhary R 2006 Mairahu AT 2003 Krishnamurti C
2001
11
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
12
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
13
Increased markers of endothelial activation may
promote microvascular thrombosis and end-organ
damage
Esmon CT 2004
14
Use blood and blood products with caution and
only when indicated
15
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
16
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
17
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

18
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
19
What are the risk factors for significant
bleeding?
20
Risk factors for hemorrhage in severe dengue Lum
et al, J Ped 2002
Clinical /laboratory parameter Group 1 (significant hemorrhage) (n22) Group 2 (no/mild hemorrhage) (n92) P value
Age (mean) (years) 6.1 4.0 5.9 3.5 0.8
Male Female ratio 11 10.9 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
21
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 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
Lum et al, J Ped 2002
22
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
23
Prevention of hemorrhage in DHF
  • Early recognition of shock
  • Prompt correction of shock to prevent acidosis
    which leads to bleeding

24
Preventive transfusions in DSS is it necessary?
Lum et al, J Ped, 2003
25
Clinical parameter Treatment groups Treatment groups Treatment groups
Clinical parameter Received bld prod (n60) Did not receive bld prod (n46) 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
26
Behaviour of transfused platelets in DSS
Patient no 52 No of transfusions113
LCS Lum et al, 2003
27
Life-threatening complications of blood/ blood
products
  • Bacterial contamination
  • TRALI Transfusion-related acute lung injury
  • TTI Transfusion-transmitted infections
  • Wrong blood

28
Infective risks of blood/ blood products
Virus Units transfused
HIV 1500,000
HCV 1150,000
HBV 1 50,000
(prior to NAT testing)
29
There is no role for prophylactic transfusion
with platelets and fresh frozen plasma in dengue
patients
30
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

31
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

32
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

33
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

34
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

35
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

36
Thank You
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