CHRONIC REACTION IN

TRANSFUSION

Maria C Shanty Larasati

Hematology Oncology Working Group

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CURICULUM VITAE
Maria Christina Shanty Larasati
Division of Hematology Oncology
Department of Child Health
Airlangga University – Dr Soetomo Hospital Surabaya

Education
• Undergraduate : Faculty of Medicine Airlangga University - 1999
• Pediatrician : Faculty of Medicine Airlangga University - 2009
• Consultant : Faculty of Medicine Airlangga University - 2016
Training
• Basic and Intermediate Course of Palliative Care 2012
• Application Training and Trouble Shooting (Apheresis) 2012
• International Hemophilia Training Centre (IHTC) Fellowship Program Blood Bank
Centre Kuala Lumpur 2014
• Training Course Thalassemia Disease Management Forum Thailand 2015
• South East Asia Haemophilia Training Academy Malaysia 2016

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 TRANSFUSION REACTION
Hemolytic : acute/immediate reaction
delayed/chronic reaction

Non hemolytic :
- Fever
- Urticaria
- Anaphylactic reaction
- Overload

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 TRANSFUSION REACTION
Hemolytic : acute/immediate reaction
delayed/chronic reaction

Non hemolytic :
- Fever
- Urticaria
- Anaphylactic reaction
- Overload

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 TRANSFUSION REACTION
Hemolytic : acute/immediate reaction
delayed/chronic reaction

Non hemolytic :
- Fever
- Urticaria
- Anaphylactic reaction
- Overload

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 TRANSFUSION REACTION…
Hemolytic : acute/immediate reaction
delayed/chronic reaction

> 24 hours
Occur from a few days, weeks, and months

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 TRANSFUSION REACTION…
Hemolytic : acute/immediate reaction
delayed/chronic reaction

> 24 hours
Occur from a few days, weeks, and months
Immunologic
Non immunologic

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 TRANSFUSION REACTION…

Immunologic
1. Delayed Hemolytic Transfusion Reactions (DHTRs)
2. Alloimmunization
3. Transfusion associated Graft Versus-Host Disease (Ta-GVHD)
4. Transfusion-related Immunomodulation (TRIM)
5. Post-Transfusion Purpura (PTP)
6. Iron Overload

Non immunologic
1. Hepatitis B; C; A
2. HIV, CMV, malaria
3. Bruselosis, Tripanosomiasis, Parvovirus
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 CHRONIC REACTION IN TRANSFUSION
1. Delayed Hemolytic Transfusion Reactions (DHTRs)
• RBCs antigen can produce Ig G alloantibodies when exposed
to the complete antigen
• DHTRs occur from a few days to two weeks after a blood
transfusion
• Manifest as clinical features of acute hemolysis
(hemoglobinuria, jaundice, and pallor) combined with
symptoms suggesting severe vaso-occlusive crisis (pain, fever,
acute chest pain)

Susan, 2003; Jeffery, 2005; George, 2006; Mariane 2011

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CHRONIC REACTION IN TRANSFUSION…
• Destruction of both the donor’s and recipient’s RBCs leads to
an abrupt drop in hemoglobin level
• Screening test may show alloantibody reactivation
• The pathophysiology of this syndrome remains unclear,
especially when there is no detectable antibody  negative
immunological tests don’t exclude DHTRs
• A recent study suggests accelerated apoptosis of donor RBCs
• Corticosteroid and/or IVIg therapy has been reported to
ensure recovery from DHTRs
• Recently, two studies reported the use of rituximab

Mariane 2011
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CHRONIC REACTION IN TRANSFUSION…
Eryptosis

RBC destroyed by macrophages

Phospholipase A2, hydrolyze phosphatidylserine-exposing RBCs

Accelerated RBC destruction & hemolysis

The role of concomitant inflammation is under debate

Risk factors for DHTRs in patients without detectable antibodies
are unknown
Mariane 2011
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Pathophysiological mechanism of DHTRs

Kate, 2011; Narcisse, 2013

CHRONIC REACTION IN TRANSFUSION…
2. Alloimmunization
• RBCs alloantibodies  patients received repeat transfusions
• Occurs in up to 30% of chronically transfused patients
• Alloimmunization occur from a week to months
• The risk of RBCs alloimmunization 1% to 1.4% per unit of
transfusion
• Repeat transfusion can produce the antibodies to Rh system,
Kell (K), Duffy (Fy) and Kid (Jk)

Susan, 2003; Jeffery, 2005; George, 2006

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CHRONIC REACTION IN TRANSFUSION…

• Alloimmunization of HLA and leucocyte-associated antigens

occur in granulocyte transfusion  20% to 70%
• Platelet alloimmunization can occur in patients who received
repeat platelet transfusion and developed antibodies to
human leucocyte antigens (HLA) atau human platelet antigens
(HPA)  risk of refracter platelet transfusion

Susan, 2003; Jeffery, 2005; George, 2006

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Naomi, 2015
CHRONIC REACTION IN TRANSFUSION…
3. Transfusion associated Graft Versus-Host Disease (Ta-GVHD)
• An extremely rare adverse event
• Develops 5 – 10 days after transfusion
• T-lymphocyte from immunocompetent donor transfuse to
immunocompromised recipient  proliferation of T-cell can
cause rejection of donor
• Incidence 0.002-0.005%
• Manifest as fever, erythema and maculopapula, liver
problem, nausea, bloody diarrhea, leucopenia and
pancytopenia
Shivdasani, 1993; Susan, 2003; Jeffery, 2005

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CHRONIC REACTION IN TRANSFUSION…
• Full marrow aplasia, usually develops within 21 days of
transfusion
• Therapy are corticosteroid, cyclosporin and anti thymocyte
globulin
• Prevented by irradiating cellular blood components
• Leucocyte reduction is not sufficient for prevention

Meghan, 2016

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CHRONIC REACTION IN TRANSFUSION…
4. Transfusion-related Immunomodulation (TRIM)
• Allogenic blood transfusion: RBCs, immune cell, cytokin  as
antigen for recipient can cause modulation of immune system

to increase possibility of transfusion-related

immunomodulation
• Cancer relapse and infection risk after blood transfusion

Susan 2003; Murugan,2005; George 2007

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CHRONIC REACTION IN TRANSFUSION…
• The exact mechanism of immunomodulation is unclear
• The two-hit theory:
1. the patient’s underlying inflammatory condition
primes patient’s immune system or endothelium
2. allogeneic blood transfusion triggers a full-scale
inflammatory activation

Josee, 2011

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CHRONIC REACTION IN TRANSFUSION…
5. Post-Transfusion Purpura (PTP)
• A rare reaction defined as thrombocytopenia
• Develops 5 – 12 days after RBC or platelet transfusion
• Alloantibodies to platelet antigen  HPA-1a antigen in the
platelet glycoprotein receptor

Platelet transfusion can make the severe thrombocytopenia

As a secondary response

Susan, 2003; Jeffery, 2005

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CHRONIC REACTION IN TRANSFUSION…
• Risk factors are platelet transfusions and multiple
transfusions
• Therapy : corticosteroid, IVIg and plasmapheresis  to
prevent platelet degradation
Susan, 2003; Jeffery, 2005

The mechanism of destruction of patient’s own antigen-negative

platelets remains unclear
Meghan, 2016

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CHRONIC REACTION IN TRANSFUSION…
6. Iron Overload
• Anemia chronic need RBCs transfusion long life
• A unit of PRC  200 – 250 mg Fe
• 20 gram Fe make manifest as hyperpigmentation,
developmental delay, cardiac and liver problem
• Prevention with erythropoietin
• Therapy of iron overload : chelating agent

Lawrence, 2003; Susan, 2003; Jeffery, 2005

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 1 unit PRC  200 – 250 mg Fe

Iron overload  + 20 transfusion

WB : 0.47 mg Fe/mL
“Pure”RBCs : 1.08 mg Fe/mL
Porter JB. Br J Hematol. 2001;115:239-52
 INEFFECTIVE
ERYTHROPOIESIS

 IRON
ABSORPTION ANEMIA
BLOOD
TRANSFUSION

IRON OVERLOAD
Repeated blood transfusion  iron overload

Harmatz P et al. Blood 2000;96:76–79

 REPORTING of SERIOUS HAZARDS of TRANSFUSION
(SHOT)

• Suspected or confirmed transfusion transmitted infection

(bacterial, viral, etc)
• All instances where blood intended for one patient is given to
another
• Immediate and delayed haemolysis
• Post-transfusion purpura
• Transfusion associated graft versus host disease
• Transfusion related acute lung injury
 Conclusions

• Delayed/chronic reaction in transfusion occur > 24 hours

• Immunologic and non immunologic reaction
• Initial symptoms of delayed hemolytic transfusion reaction
are complex
• Alloimmunization caused by repeat transfusions
• Transfusion associated Graft Versus-Host Disease related to
T lymphocyte from immunocompetent donor to
immunocompromised recipient

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 Conclusions

• Antigen for recipient can cause modulation of immune

system
• Platelet transfusion can make a secondary response and
cause refracter platelet transfusion
• Chronic anemia need repeated transfusion of RBCs and leads
iron overload
• Chronic reaction in transfusion need the good management

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THANK YOU
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