Dengue- Blood and Blood Products

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Dengue- Blood and Blood Products

• Jameela Sathar
• Hospital Ampang

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Haemostatic Changes in Dengue

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

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

Dengue-infected monocytes
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Raised haematocrit

• Early evidence of plasma leakage

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Platelet activation
lumen
Plt
Plt
Plt
Plt
endothelium
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Thrombocytopenia

• Platelet count begins to fall towards the end of
  febrile stage
• Lowest during leakage phase
• Main mechanism platelet activation

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Coagulation activation
lumen
T
Plt
T
T
Plt
Plt
TF
T
thrombin
fibrinogen
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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
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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

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

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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
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What are the risk factors for significant
bleeding?
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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
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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
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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
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Prevention of hemorrhage in DHF

• Early recognition of shock
• Prompt correction of shock to prevent acidosis
  which leads to bleeding

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Preventive transfusions in DSS is it necessary?
Lum et al, J Ped, 2003
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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
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Behaviour of transfused platelets in DSS
Patient no 52 No of transfusions113
LCS Lum et al, 2003
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Life-threatening complications of blood/ blood
products

• Bacterial contamination
• TRALI Transfusion-related acute lung injury
• TTI Transfusion-transmitted infections
• Wrong blood

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

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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

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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

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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

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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

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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

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Thank You