Hazards of Transfusion

Muhammad Asif Zeb

Lecturer-Hematology

Khyber medical university

Peshawar

Hazards to the Donor

Hazards to Recipient / Patient

Transfusion risks and adverse reactions

Many of the signs and symptoms of transfusion reactions are Similar

All reactions should be taken seriously

The most commonly encountered reactions are

– Allergic – not life-threatening

– Febrile – respond to treatment

Reactions that cause the most concern are

– Transfusion related acute lung injury (TRALI),

– ABO mismatch,

– TA-GvHD

– Sepsis

Introduction

Introduction

ABO incompatible blood can lead to serious consequences.

Precautions should be taken during:

– Collection of specimen of blood

– Cross matching procedures

– At the time of issue

– At the time infusion of the crossmatched unit of blood

ensure that no error in patient identification is made.

Haemolytic reactions

When transfused red cells are destroyed in the recipient, this is

classified as a haemolytic transfusion reaction.

These reactions are either acute or delayed,

& cell destruction is either intra- or extravascular.

Acute reactions

Reactions that occur shortly after the start of the transfusion are

termed acute.

Although there are many reasons why a recipient could react

immediately – it may be an indication of ABO incompatibility.

Haemolytic reactions

Delayed reactions

Occur due to red cell incompatibility - becomes apparent > 24

hours after transfusion.

Recipient red cell antibodies – too weak for detection during crossmatching or antibody screening

Immune response occurs in the recipient – transfused cells are removed from the circulation.

No reaction occurs immediately after transfusion – reaction is suspected when the Hb fails to increase after transfusion.

Kidd antibodies are sometimes implicated in delayed reactions .

Extravascular haemolytic reactions

Extravascular reactions – antibodies - that do not activate complement – Rh, Duffy or Kell etc.

Incompatible - sensitized red cells – removed from by RE systems of liver or spleen.

Hyperbilirubinaemia is seen

The severity of a haemolytic reaction depends

– Immunoglobulin class of antibody

– Specificity of antibody

– Thermal range of antibody

– Activation of complement

– Titre and strength or potency of antibody responsible and

– Volume of red cells (with the corresponding antigen)

transfused.

Major incompatibility

Serious haemolytic transfusion reactions may occur when a patient receives blood of the incorrect ABO group, usually as a result of misidentification.

patient Such errors mostly occur

– In emergency situations when personnel are under extreme pressure

– During quiet times when there is lack of concentration on the job at hand.

The reactions usually involve antibodies in the recipient that react with antigens on the incoming red cells.

Minor incompatibilities

An adverse reaction seen

– Plasma high titre or haemolysing ABO antibodies – transfused

into a compatible but ABO non-identical group

– Example : donor group O plasma with high titre or haemolysing

anti- A – transfused to group A recipient.

– Donor plasma contains strong, irregular antibodies of

other specificities – in recipient with corresponding

antigen

These adverse reactions are termed minor

incompatibilities – occur rarely

Haemolytic transfusion reaction

Signs and symptoms

– Urticaria/rash

– Pruritus (itching)

– Headache

– Restlessness

– Unexplained bleeding

– Lower back and joint pain

– Tachycardia and chest pain

– Sudden change in blood pressure

CLASSIFICATION

Transfusion reaction

acute delayed

Immunologic Nonimmunologic Immunologic Nonimmunologic

Haemolytic transfusion reaction

Indication when recipient is anaesthetize

Haemoglobinuria

Oliguria and / or anuria

Shock.

ABO hemolytic transfusion reaction

ABO mismatch blood administration

Activation of complement system lead to lysis of RBC,s

C3a, C5a are anaphylotoxin and cause activation and

attraction of Monocytes and neutrophils, endothelial cells,

macrophages, platelets.

Activation leads to release of interleukin and cytokines, e.g

IL 6,8,1, TNFα,

Interleukin 8 (IL-8), which activates neutrophils, and

tumor necrosis factor alpha (TNFα), which activates the

coagulation cascade.

C3a and C5a also activates mast cells and basophiles releasing histamine and serotinin leading to vasodilatation, smooth muscles constriction espicialy bronchial and GIT

Hypotension may be due to vasodilation of blood vessels.

DIC

may lead to bleeding from different site

Intrinsic pathway of coagulation activation due to Ag Ab comlex

Extrinsic due to Activated complement, as

well as TNFα and IL-1 which cause

increase expression of Tissue factor.

Shock may be a component of DIC

Renal failure

Due to free hb

Thrombus formation

Ag Ab complexes

vasoconstraction

Nonimmune-Mediated Hemolysis Transfusion-associated hemolysis can also occur from several

nonimmune-mediated causes.

Before issue, improper shipping or storage temperatures as

well as incomplete deglycerolization of frozen red cells can

lead to hemolysis.

At the time of transfusion, using a needle with an

inappropriately small bore size or employing a rapid pressure

infuser can cause mechanical hemolysis, which may be seen

with the use of roller pumps as well.

Improper use of blood warmers or the use of microwave ovens

and hot water baths can cause temperature-related hemolysis.

Febrile Nonhemolytic

Transfusion Reactions

Studies found that as few as 0.25 × 109 leukocytes could produce a

temperature elevation in the recipient.

FNHTRs may also be the result of accumulated cytokines in a cellular

blood component.

This mechanism may be particularly relevant in reactions seen after the

transfusion of platelets.

Some FNHTRs are attributable to recipient antibodies, particularly HLA

anti- bodies, that react with antigens on transfused lymphocytes,

granulocytes, or platelets.

Cytokine release in the recipient in response to these antigen-antibody

reactions may con- tribute to the severity of the reaction

Pathogenesis Fibrile non hemolytic transfusion reaction

• ?? Previous Transfusion &/Or Preganancies

• Temprature↑ α No: of Leucocytes Transfused

• ?Reacting - Antibodies to HLA reacting with donor leucocytes

Recipient Abs bind to Donor leucocyte Ags

↓

Fix Complements

↓

Activate recipients Monocytes, Lymphocytes & Endothelial cells

↓

secrete Pyrogens Mainly IL-1

Platelet Transfusion

?? Without prior sensitization

• Due to presence of Pyrogenic Cytokines

IL-1β, IL-6 & TNF-α released from leucocytes during the 5

day platelets storage

Theory supported by

a. Very high levels of Cytokines during storage

b. Reaction associated with the plasma portion

c. Not prevented by bedside filteration

d. No ↑ of Cytokines if pre-storage leucocyte filtered

Signs and symptoms

Chills or rigors and fever are noted after

transfusion.

Allergic Reactions

Most allergic transfusion reactions are

mild, but the spectrum can range from a

simple allergic reaction (urticaria) to

anaphylaxis.

Symptoms generally occur within

seconds or minutes of the start of the

transfusion.

Pathophysiology

Allergic reactions are hypersensitivity reactions to allergens in the component and are less commonly caused by antibodies from an allergic donor.

Preformed IgE antibody in the patient or recipient interacts with the allergen, usually a plasma protein in the component.

Mast cells are activated by the binding of allergen to the IgE bound to the mast cells (type I hypersensitivity).

Activation results in degranulation, with the release of preformed histamine, chemotactic factors, proteases, and proteoglycans.

Secondary mediators, including cytokines and lipid mediators such as arachadonic acid metabolites, leukotrienes, and prostaglandin D2, as well as platelet-activating factor, are generated and released in response to mast cell activation

Signs and symptoms

Simple allergic reactions – cause a diffuse rash (urticaria) &

itchy, swollen red areas on the skin

Immune complexes of antigen–antibody in recipient or the donor - stimulate tissue mast cells to release histamine

it results in

– Vasodilatation

– Raised red marks on the skin

occur during the transfusion or within an hour

Oedema (swelling) of the face, lips or mouth - occasionally

Difficulty in breathing occur sometimes

Transfusion associated acute lung injury

TRALI is caused by anti-HLA or anti-granulocyte antibodies in donor

plasma.

Antibodies formed - sensitization of donors

– With a history of pregnancy - multiparous female

– Previous blood transfusion.

Plasma containing these antibodies may activate complement in vivo

WhenTransfused,cause lung injury in the recipient.

When large volumes of components containing plasma are transfused

-TRALI is more likely

Small volumes of plasma may also cause a reaction.

Transfusion associated acute lung injury

Signs and symptoms

Dyspnoea

Hypotension

Fever and rigors soon after the onset of reaction

Pulmonary oedema

Hypovolaemia

Hypotension

This is quickly followed by severe hypoxia – with frothy fluid in the trachea

Sepsis – bacterial contamination of

products transfused

Blood is an ideal medium for growth of harmful bacteria.

It is important to:

– Clean the venepuncture site thoroughly prior to donation

– Maintain the cold chain for storage & transportation of

blood components

Platelet concentrate is at the greatest risk of bacterial

contamination – stored at the higher temperature of

22°C ± 2°C.

Reasons of Bacterial Contamination of blood

donation

• Introduction of micro-organisms – time of donation

– Inadequately cleaned venepuncture site

– Contamination of needle

• Introduction of micro-organisms – component preparation and storage

– Faulty equipment or blood bags

– Introduction of air into the container of blood

• Storage and transportation of blood – at high temperatures

• Bacteraemia in an apparently healthy donor

– Endotoxin-producing Gram-negative bacilli – Yersinia

enterocolitica - present as subclinical infection in donor

– Endotoxins may lead to extremely severe reactions & death of

recipient.

Bacterial contamination of a unit of stored blood may be obvious, with a dark brown or purple appearance.

Heavily infected blood may look normal.

Cloudiness may be a sign of contamination in a unit of platelet concentrate.

Some transfusion services have the facility to screen all platelet concentrates and discard contaminated PC

Signs and symptoms

When infected blood is transfused, symptoms usually appear

within 30 minutes.

These are

– Chills

– Headache

– Vomiting

– Muscular pain

– Diarrhoea

– High fever

– Hypotension (low blood pressure)

– Shock.

There is marked erythema (redness) of the skin – in contrast to the pale, cold skin of haematogenic shock (through blood loss).

Delayed Hemolytic Transfusion Reaction (DHTR)

Mechanism

– Antibodies that exist in low titers prior to the transfusion

– Typically to the Kidd, Duffy or Kell system

– Upon re-exposure, titer increases from memory B-cells

– Resulting Extra vascular red cell distruction

– Usually occur 5-10 days after Tx

Delayed HTRs are defined as fever and other symptoms / signs of haemolysis more than 24 hours after transfusion; confirmed by one or more of: a fall in Hb or failure of increment, rise in bilirubin, positive DAT and positive cross-match not detectable pre-transfusion.

Pathophysiology A patient may make an antibody to a red cell antigen he or

she lacks after transfusion, transplantation, or, as seen in hemolytic dis- ease of the fetus and newborn, after pregnancy.

Red cell antibodies may cause a delayed transfusion reaction if the patient subsequently receives a unit of blood that expresses the corresponding red cell antigen.

Primary alloimmunization may occur any- where from days to months after transfusion of antigen-positive red cells depending on the immunogenicity and dose of the antigen.

D-negative blood is usually transfused to D-negative patients, so

although anti-D is capable of causing DHTRs, the frequency

attributable to anti-D is relatively low.

Newly formed alloantibodies are routinely detected during

pretransfusion screening.

Recently transfused or pregnant patients must have samples

drawn for compatibility testing within 3 days of the scheduled

transfusion to ensure identification of any potential new

alloantibodies

Transfusion-Associated Graft-vs-Host

Disease Presentation

The clinical manifestations of transfusion- associated GVHD

(TA-GVHD) typically begin 8 to 10 days after transfusion.

Symptoms can occur as early as 3 days and as late as 30 days

after transfusion.

Signs and symptoms include a maculopapular rash, fever,

enterocolitis with watery diarrhea, elevated liver function tests,

and pancytopenia.

The rash begins on the trunk and progresses to involve the

extremities. In severe cases, bullae may develop

Pathophysiology

Commonly in severely immunocompromised

patient

Donor lymphocytes engrafted in recipient &

multiply

Engrafted lymphocytes react with host tissues

AIDS patients – HIV infects even donor

lymphocytes

Fresh blood – lymphocytes are more active and

hence chance of engraftment is more

Implicated blood products Reported after transfusion of non irradiated

• whole blood

• packed red cells

• platelets

• granulocytes

• fresh, non‐frozen plasma

No report of TAGvHD after

• frozen, deglycerolized red cells,

• fresh frozen plasma,

• cryoprecipitate.