BLOOD TRANSFUSION

REACTIONS

Dr. Madhuvan Gupta

BLOOD TRANSFUSION
REACTIONS
IMMUNOLOGICAL NON-IMMUNOLOGICAL
 Alloimmunization  Volume overload

 Hemolytic transfusion  Due to massive transfusion

reaction Metabolic effects
 Febrile transfusion reaction Hypothermia
 TRALI Dilutional effects
 Allergic reaction Pulmonary
 Transfusion related GVHD microembolism
 Transfusion related  Miscellaneous
immunomodulation Plasticizers
Haemosiderosis
• Infections
ALLOIMMUNIZATION TO
TRANSFUSED ANTIGENS
 RBC Ag – Production of these Abs is
proportional to receipient’s immune response
and immunogenicity of different red cell Ags
 LEUKOCYTE Ag - Alloimmunization to HLA
and other leucocyte Ag
Mainly in multiparous and multitransfused
patients. Use of leukoreduced products
decrease the incidence
ALLOIMMUNIZATION TO
TRANSFUSED ANTIGENS
 PLASMA PROTEINS – Abs developing
against various plasma proteins like
lipoproteins. Incidence very less.
Few anaphlactic reactions atttributed to IgA
Abs in patients who are IgA deficient
HEMOLYTIC TRANSFUSION
REACTIONS
 Accelerated clearance or lysis of transfused
RBCs due to immunological incompatibility
 To be differentiated from autoimmune
hemolysis and nonhemolytic transfusion
reaction
 2 types: Immediate (Intravascular)
Delayed (Extravascular)
IMMEDIATE HTR
 Occur within 24 hours. Mostly during or shortly after
transfusion
 Mostly associated with ABO incompatibility and
occur after RBC transfusion
 Anti A and Anti B are IgM Abs and capable of
binding complement and causing intravascular
destruction of RBCs
 Rare and mostly due to clerical error
 Characterized by hypotension, impaired renal
function and DIC
IMMEDIATE HTR
 Sometimes, Anti A1 occuring naturally in
group A donors of subgroup A2 has been
reported to cause HTR
 Bystander hemolysis: Along with loss of
transfused cells, complement deposition on
autologous RBC causes their destruction.
Mostly this hemolysis mild. But in sickle cell
patients, this bystander hemolysis can be
significant and called sickle cell - HTR
SYNDROME
DIAGNOSIS OF HTR

 Detection of free Hb- Visual inspection and

spectroscopy. False positive results in
nonimmune hemolysis, RBC fragmentation
syndromes, Hbnopathies, burns,
polyagglutination and drawing sample
through improper techniques. False negative
results if test performed late or if sample is
icteric
DIAGNOSIS OF HTR
 DAT which can detect even 10% Ab coated
cells. False negative if Ag positive cells have
been cleared from circulation or titres of Ab
coated RBC is low
 Flow cytometry and Ab elution can detect 1%
of Ab coated RBC
WORK UP IN HTR
 First tier investigation
Posttransfusion serum Hb (qualitative)
Posttransfusion DAT
• Second tier investigation
Pretransfusion and posttransfusion ABO-Rh
Repeat antibody screen
Repeat special antigen typing
Repeat crossmatch
WORK UP IN HTR
 Third tier investigation
Antibody identifications panels
Red blood cell eluate on pre and postreaction
samples
Investigation of transfusion technique and storage
conditions
Enhanced and minor crossmatches
Tests for polyagglutination
Quantitative serum Hb
Bacterial culture and gram stain
Blood coagulation studies
D/D OF HTR
 Delayed serological transfusion reaction
 Autoimmune hemolysis
 Cold haemagglutinin disease
 Nonimmune hemolysis
 Hemolytic anemias
 Hemoglobinopathies
 Drug induced hemolysis
 Microangiopathic hemolytic anemias
 Infection
PATHOPHYSIOLOGY
 Ag- Ab interaction- depends on Ag site
density, class of alloantibody and its ability to
activate complement
 Phagocytosis and inflammatory cell
activation- Interaction of Ig/complement
coated RBC with phagocyte receptors. FcγRI
and FcγRIII present on IgG receptors
mediate phagocytosis by monocytes and
splenic macrophages
PATHOPHYSIOLOGY
 Systemic response mediated by TNF-α, IL-8
and MCP-1 which are proinflammatory,
pyrogenic, causes activation and
degranulation of leukocytes and have
procoagulant properties
DELAYED HTR
 Mild and involve extravascular hemolysis
 2-10 days after transfusion and can be more than 6
weeks later
 Represent secondary or anamnestic response
 Abs to Kidd and Rh
 Involves IL-1ß, IL-6 and TNF-α which cause B cell
growth and differentiation and promote production of
RBC Ab associated with delayed HTR
FEBRILE NHTR
 More common in multitransfused and with
nonleucoreduced RBC’s
 Defined as increase in body temperature of 1ºC
unrelated to hemolysis, sepsis or other known cause
of fever that occurs during or within several hours of
transfusion
 Persists no more than 8-12 hours and self limiting
 Prevented by prestorage leucoreduction, use of
aphaeresis platelets and shorter storage time
ETIOLOGY OF FEBRILE NHTR
 Alloimmunization to Ag on leukocytes and
platelets
 Transfusion of cytokines developed in vitro
like IL-6, IL-1ß and TNF-α which increases
with age of platelet concentrates and
leukocyte concentration in products
 Possibility of bacterial contamination like
Yersinia enterocolitica which proliferate in
RBC at storage temperature
TRALI
 Defined as new acute lung injury occuring
during or within 6 hours after transfusion with
a clear temporal relation to transfusion in
patients with or without risk factor for acute
lung injury other than transfusion
 Associated with altered permeability of
pulmonary capillary bed leading to fluid
accumulation, inadequate oxygen and
decreased cardiac return
PATHOGENESIS OF TRALI
 Leuco- agglutinating antibodies in donor
plasma lead to complement activation which
release oxygen radicals leading to endothelial
damage and capillary leakage
 Priming of neutrophils by LPS and respiratory
burst of proteases causing endothelial injury
ALLERGIC HTR
 Type I immediate hypersensitivity. Called
anaphylaxis if systemic manifestation
 Mediated by recipients IgE or non IgE Ab to
protein or other allergenic soluble substance
in donor plasma resulting in secretion of
histamine from mast cells and basophils
 Whole blood and plasma more likely than
concentrated RBC’s to cause such reactions
 Those with history of atopy are at higher risk
ALLERGIC HTR
 Can be prevented by decreasing plasma
content of transfused blood products by
centrifuging or washing
 In patients with severe anaphylaxis, Abs
reacting with Ig A in donor plasma should be
considered in patients with IgA deficiency. If
plasma transfusion necessary in such
patients, those of IgA deficient donors should
be used
POST TRANSFUSION
PURPURA
 Life threatening thrombocytopenia 5-10 days
after transfusion
 Development of alloantibody Anti HPA-1
usually implicated
 Most patients sensitised by prior pregnancy
or transfusion
 Such Abs can be detected by
immunofluorescence
TRANSFUSION RELATED
GVHD
 Transfer of viable cytotoxic allogenic lymphocytes to
a recipient unable to reject them owing to
immunosuppresion evoke GVHD
 Pathogenesis involves conditioning, donor T- cell
activation and inflammatory effects
 In conditioning, irradiation or chemotherapy causes
host tissue damage and activates host cells to
secrete cytokines creating a primed environment for
donor cells to recognize host differences
TRANSFUSION RELATED
GVHD
 Donor T- cell activation occurs causing
differentiation and proliferation of T cells and
interaction with MHC moiety of APCs which
induces secretion of IL-2 and IFNγ which
mediate GVHD
 Cytokine mediated damage caused by TNFα
and IL-1 responsible for inflammatory
reaction with fibrosis seen in chronic GVHD
 Skin and liver primary organ of involvement
TRANSFUSION RELATED
GVHD
 Diagnosis of GVHD is based on underlying
disease, a transfusion within 4 to 30 days, a
fulminant illness (with rash, liver dysfunction
and diarrhea) and presence of severe
pancytopenia and bone marrow hypoplasia
 Irradiation of blood components using a
minimum dose of 25 Gy is done to prevent
this condition.
PATIENTS AT RISK FOR GVHD
 Neonates
 Genetically immunodeficient
 Immunosuppression by chemotherapy or
irrradiation
 Hematopoietic stem cell transplantation
 Other organ transplant
 Solid tumors
TRANSFUSION RELATED
IMMUNOMODULATION(TRIM)
 Allogenic blood transfusion may be
associated with down regulation of recipient’s
immune response. This raises concern as it
enhances tumor growth and formation of
metastatic lesions and also increases risk of
infection
TRANSFUSION RELATED
IMMUNOMODULATION(TRIM)
Beneficial effects
Improvement of renal allograft survival
Reduction in spontaneous recurrent abortions
Decrease in relapse rate of crohn’s
Apoptive immunotherapy for CML preventing
relapse after BMT
IMMUNE FUNCTION ALTERATION
ASSOCIATED WITH TRIM
 Decreased CD4 count
 Decreased CD4/CD8 T-lymphocyte ratio
 Decreased lymphocyte response to mitogens
 Decreased NK cell function
 Hypergammaglobulinemia
 Decreased cytokine production
 Decreased monocyte phagocytic function
 Suppression of lymphocyte blastogenesis
COMPLICATIONS OF MASSIVE
TRANSFUSION
 Citrate toxicity: causes calcium chelation.
More significant in patients with liver failure,
renal failure or parathyroid dysfunction.
Paraesthesias occur due to hypocalcemia
 Electrolyte disorders: Hyperkalemia occuring
with transfusion of old RBCs(>7 days old).
Can be prevented by saline washing.
Hypokalemia can occur in alkalotic conditions
when citrate is metabolized to bicarbonate
COMPLICATIONS OF MASSIVE
TRANSFUSION
 Hypothermia: Defined as core body
temperature less than 35ºC caused by rapid
infusion of cold products. Can cause cardiac
arrythmias if infused in central lines.Over
warming can also result in hemolysis and can
provoke DIC
 Circulatory overload: Significant in patients
with cardiac insufficiency, renal impairment or
in infants and small children
COMPLICATIONS OF MASSIVE
TRANSFUSION
 Reactions attributed to microaggregate
debris: Consists of platelets, WBC and
strands of fibrin. Can cause cerebral and
renal dysfunction due to occlusion of end
organ capillaries
 Plasticizer toxicity
REFERENCES
 Simon TL,Dzik WH,Snyder EL, et al,eds.
Rossi’s principles of transfusion medicine,3rd
ed. Philadelphia: Lippincott Williams and
Wilkins,2002.
 Mollison PL, Engelfriet CP, Conteras M, eds.
Blood transfusion in clinical medicine, 10th ed.
Malden: Blackwell Science Inc,1997
 Eder AF, Chambers LA. Noninfectious
complications of blood transfusion. Arch
Pathol Lab Med 2007;131:707-718.
REFERENCES
 Galel SA, Malone JM, Viele MK. Transfusion
Medicine.In: Greer JP,Wintrobe’s clinical
hematology.11th ed.USA: Lippincott Williams
and Wilkins,2004:831-882.