Transfusion Reactions

Dr Gaurav Pawar

Transfusion reactions

Transfusion of blood and its product is

ordinarily safe and effective way of correcting hematogical defects but adverse effects do occur during or after transfusion and they are commonly called Blood transfusion reactions.

Non-threatening to fatal

Categories of Transfusion Reactions Reaction -- Immune mediated Acute rapid onset within < 24 hrs Delayed days to weeks Reactions may involve antigen-antibody
interactions

May involve infectious agents

IHTRs occur very soon after the transfusion of immunological incompatible whole blood or red cells to a recipient.Commonly red cells AB e.g anti A , anti B, Anti -kell, anti- Jka, Fyb cause IHTR. IHTR can destroy red cells by both Intravascular and Extravascular hemolysis. Causes- Clerical and Technical

Hemolytic Transfusion Reactions (ImmuneHTR)

Clerical Errors
Inadequate or incorrect labelling of blood bag
Confusion in the identity of patient at time of collection Improper identification of patient blood sample

Wrong blood issued

 Technical Error
Error in blood grouping and cross matching Weak Ab not detected by routine test Incompatibility not detected due to improper method Destruction of recipients by donor Ab Incorrect interpretation of test result The interaction of AB-Ag on a red cell membrane can initiate neuroendocrine responses , complement activation,cytokine effect ,coagulation effects.

Signs and Symptoms

Chills and Fever >1or 2 C , with or without chills Acute renal failure Early signsAnxiety Pain at infusion site Back/chest pain Oozing of blood from intravenous line site Oliguria and anuria Shock Haemoglobinuria, Haematuria

Non immunological-HTR

Bacterial contamination reactions. Circulatory overload. Transfusion haemosiderosis. Complications of massive transfusion. Non immune hemolytic reaction Disease transmission.

Bacterial contamination reaction

Although uncommon,but this type of specific reaction can have a rapid onset and high mortality in recipients. The presence of bacteria in transfused blood may lead either to febrile reactions in the recipient ( due to pyrogens ) or serious manifestations of septic or endotoxic shock. Commonly caused by endotoxin produced by bacteria capable of growing in cold temperatures such as Pseudomonas species, E. coli, Yersinia enterocolitica.

Infection of stored blood is extremely rare.

Skin contaminants are not infrequently present in freshly donated blood but these organisms ( predominantly staphylococci ) do not survive storage at 4 C although they will grow profusely in platelet concentrates stored at 20- 24 c

Healthy donor who are bacteremic at the time of donation. The majority are due to Yersinia enterocolitica, which grows well in red cell components due to its dependence on citrate and Iron.
Gram negative, endotoxin producing contaminants found in dirt, soil and

Clinical manifestation
Rapid recognition is essential

Usually appear rapidly during transfusion or within about 30 minutes after transfusion with dryness, flushing of skin. Fever, Hypotension, Chills, Muscle pain, vomiting, Abdominal cramps, Bloody diarrhoea, Hemoglobinuria, Shock, Renal failure, DIC.

Management

Immediately stop the transfusion.

Therapy of shock, steroids, vassopressors, fluid support, respiratory ventilation and maintenance of renal function.
Broad spectrum IV antibiotics The blood component unit and any associated fluids and transfusion equipment should be sent immediately to blood bank for investigation ie: gram stain and culture. Blood C & S from the recepient.

Circulatory overload

All patient will experience a temporary rise in blood volume and venous pressure following the transfusion of blood or plasma except for those who are actively bleeding. However, young people with normal cardiovascular function will tolerate this changes provided it is not excessive. Pregnant women, patient with severe anaemia, elderly with compromised cardiovascular function will not tolerate the increase in plasma volume and acute pulmonary edema may develop,Acute Renal Failure. Frequently due to transfusion of a unit at too fast rate,multiple transfusion in short duration. Signs of cardiac failure raised JVP, basal crepitations in both lungs, dry cough, breathlessness.

 Management

Prop up the patient

Oxygen therapy

Stop the transfusion immediately.

Intravenous diuretics should be used appropriately. If more rapid volume reduction is needed, therapeutic phlebotomy can be used. Prevention-Packed cell should be used instead of whole blood. Packed cells should be given slowly over 4 hours. Patient at risk, rate should be 100 ml per hour or less are appropriate.

Diuretics should be given at the start of the transfusion and only one or two units of concentrated red cells should be transfused in any 24 hour period.
Blood transfusion should be given during the daytime, Overnight transfusion should be avoided wherever possible.

Complication of massive transfusion

Massive transfusion is defined as the replacement of total blood volume within a 24 hour period.

This will inevitably lead to1. Dilution of platelets. Blood effectively has no functional platelets after 48 hours storage, after 8 to 10 units of blood transfusion, thrombocytopenia will usually seen. Bleeding due to a slightly low platelet is uncommon, therefore routine administration of platelet after certain amount of blood transfusion is unnecessary.

Regular monitoring of platelet count is more important.

Platelet transfusion may be recquired if platelet count <100 x 10 9 /L with continous bleeding or surgical intervention.

2. Dilution of coagulation factors -Stored Whole blood < 14 days has adequate levels atmost coagulation factors for haemostasis. If stored blood of more than 14 days, or plasma reduced blood or red cells in optimal additive solution is used, replacement of coagulation factors with FFP is necessary 3.Hypothermia -( defined as core body temperature less than 35 c ) is associated with large volumes of cold fluid transfusion. This may results in cardiac irregularities in particular VF. Therefore the use of blood warmer is important. 4.Excess citrate can act on the patients plasma free ionized calcium and results in hypocalcaemia ( transient )Citrate toxicity occur with extremely rapid transfusion ( one unit every 5 minute ), in premature infant having ET with blood stored in citrate for longer than 5 days. 5.Hyperkalemia-Can be caused by intracellular loss of potassium from RBC during storage or infusion of intracellular potassium depleted RBC blood components such as washed RBC or frozen washed RBC .

 The most important consideration in

massive blood transfusion is to replace blood loss quickly and adequately. Too little blood , too late has more serious consequences than massive blood transfusion itself.

Lab Investigations

Check identity of patient ,donor blood

Compare the color of plasma of patients pre and post-transfusion blood specimen1) Pink red discoloration in post transfusion sample indicates the presence of free Hb due to destruction 11) Yellow to brown discoloration after 4 to 10 hrs after transfusion indicates bilirubin.

Check the color of bag - 1) Greenish-Purple color and clots in bag may be due to bacterial contamination 11) Change in color both in bag and tubing of bag may be due to hemolysed blood

Repeat ABO, RH(D),testing in pre and post transfusion both from bag and tubes Perform DCT test on patients blood --- 1) If DCT is negative, then red cells not coated with IgG Ab and their is no incompatibility. 11) If Ab coated donor incompatible cells are not immediately destroyed, the DCT on the post -reaction blood sample will be positive 111) If the patients blood sample is drawn several hrs later then the Ab coated donor cells destroyed ,so DCT will be negative. Bacteriological smear and culture of donors blood is done to rule out bacterial contamination.

It is often described as increase of 1c or more temperature,above the patients base line during or within 24 hrs of transfusion without any other medical explanation. These are self limiting and are usually seen in multi-transfused patients or multiparous women who have an Ab directed against donor leucocytes.Such Ag-Ab reaction can activate compliment and cytokines production,so releasing endogenous pyrogens.
Symptoms and signsChills with fever Shaking Hypotension Cyanosis Tachycardia Leukopenia Cough Raises temperature >1C (fever)

Febrile Nonhemolytic Transfusion Reactions(FNHTR)

 Management

- Antipyretics are used to treat fever or are given as a preventive measure Aspirin not used because of its effect on platelet function Leukocyte reduced units should also be given Antihistamines i.m e.g chlorpheniramine Routine use of prophylactic antipyretics is not recommended because they mask symptoms of acute hemolysis.

Allergic Transfusion Reactions

These are attributed to foreign protein (allergens ) in donor plasma that react with IgE in the patient attach to mast cell and basophil. A mild transfusion reaction causes: Urticarial Reaction: hives, itching,rarely laryngeal edema

Erythema: redness of the skin

Dyspnea: shortness of breath The patient should be treated with an antihistamine to ease discomfort.

Transfusing saline wash RBC may help patients with frequent severe allergic reactions.
Corticosteroids are indicated only in severe repetitive cases.

Anaphylactic Reactions
Anaphylactic and anaphylactoid reactions are due to immediate hypersensitivity of immune system.

May begin after infusion of only a few ml of plasma or plasma containing

blood producsts

Symptoms may involve one or several systems Respiratory tract (cough ,bronchospasm, dyspnea)
Gastrointestinal tract nausea,vomiting, diarrhoea Circulatory system-arrhythmia,hypotension,syncope Skin-flushing ,urticaria Good transfusion practice calls for close observation during
the first quarter hour of infusion and less intensive afterwards but nonetheless continuing surveillance is kept.

Causesgenerally caused in patients who Anaphylactic and Anaphylactoid reactions are

are congenitally IgA deficient and have developed anti- IgA deficient Ab by sensitization from tranfusion or pregnancy. IgA is most common immune deficiency 1 in 700-800 persons .

ManagementStop transfusion .keep i.v line open with normal saline Inject epinephrine (adrenaline) S.C /I.M usually about 0.5 ml 1:1000 sol Inject antihistamines If hypoxia develops give oxygen by catheter or nasal mask For RBC transfusion this can be done by using saline washed or frozen thawed RBCs If plasma needed it should be from a known IgA deficient donor.

TRALI(Transfusionrelated acute lung injury)

Also known as non-cardiogenic pulmonary edema, this unusual life threatening complication is associated with altered permeability of the pulmonary capillary bed from activation of compliment ,histamine mediated events ,PGs ,which leads to fluids accumulation, inadequate oxygenation and reduced cardiac return.

Reaction of anti-leukocyte antibodies in donor or patient plasma that react with leukocyte in pulmonary microvasculature ,leading to leukocyte emboli aggregating in the lung capillaries.
Other cause cytokines in the donor units

Manifestations
1 in 5,000 transfusions Symptoms occur within 2 hours and may end in 2-4 days if treated (Average = 6 hrs) Acute onset of Respiratory distress, dyspnea ,cyanosis, fever,chill,X-Ray will show b/l pulmonary infiltrates but no left lung failure signs. Potentially fatal hypoxia may occur and persist for 24-28 hrs

Treatment The cornerstone of therapy is effective supportive care for

respiratory insufficiency . Oxygen therapy and ventilatory assistance i.e intubation

II.V steroids are used imparically but no improvement seen till now
If TRALI caused by patients anti-leukocytes Ab the leukocyte-poor components should be used.

TRALI case

Before

After

Delayed Hemolytic Transfusion Reactions

DHTRs occur at least 24 hrs after transfusion Mediated by IgG antibodies,the initial level of AB in the recipient is low but the transfusion provokes an anamnestic response. Patient previously exposed to RBC antigen and has low antibody titer until exposed again,so resulting in haemolysis

Rh, Kidd, Duffy, and Kell ,anti-Fy, anti Jk

Clinical Features13 days after transfusion. Maximum rate of destruction is 4-

Jaundice occurs 5-7 days afterwards Haemoglobinuria is not uncommon and is seen with antibodies of
different specificities

DHTR s may result occasionally be followed by renal failure

Lab features


A fall in haemoglobin not attributed to any other cause Appearance of new Alloantibody Sphrerocytes in peripheral blood smear may be the only indicator Positive DAT test ,becomes positive after a few days after transfusion and remains so until incompatible cells been eliminated The Ab responsible for this reaction can be detected by preparing an eluate from the patients red cells The Ab is detected 4-7 days after transfusion and peaks after 10-15 days .

Graft-versus-Host Disease (Transfusion Related)

Rare but fatal condition that has a 90% mortality rate Symptoms appear after about 12 days May be caused by donor lymphocytes transfused into an immunocompromised recipient, patients on chemotherapy ,irradiation Pancytopenia occurs as a result of the immunologic response Pathogenesis of GVHD ,the donor lymphocytes engraft and multiply in the recipients .The engrafted cells react with the host tissues to cause the clinical manifestations ,the donor lymphocytes are not destroyed as the host is immunocompromised.

Clinical features- fever , diffuse erythematous rash, diarrhoea ,bone marrow suppression, infection

Prevention can be done by use of irradiated blood and blood components .A radiation dose of 1500-5000 rad for 10 min renders 85-95% of lymphocytes incapable of replication.

Post transfusion Purpura

About 5-10 days after being transfused with platelets, the platelet count drops <10,000/L Usually occurs in multiparous women who do not have the antigen Alloantibody directed against a high-incidence platelet antigen (P1A1) Thrombocytopenia is severe but self limiting Cerebral hemorrhage is a major concern Possibly treat with corticosteroids or intravenous immunoglobulin therapy (IVIG) Plasmapheresis is suggested

Transfusion haemosiderosis
A complication of repeated long term blood transfusion. Most commonly seen in thalassaemic patient. Each unit of blood has about 200 mg of iron, while the daily excretion rate is about 1 mg. The body has no way of excreting the excess unless the patient is bleeding. Assessment of storage iron levels such as ferritin levels should be done. The use of Iron chelating agent, Desferrioxamine does not completely overcome the Iron load, but has delayed the onset of problems due to haemosiderosis. Desferrioxamine is usually prescribed in daily dose of 2040 mg/kg b.wt.S.C in 8 to 12 hrs,usually over night by portable infusion pump. Transfusion of neocytes or young red cells is the other alternative. However, it is expensive, time consuming, and the result are not as favourable as expected.

Alloimmunization-Blood transfusion exposes a patient to several foreign antigens.If the recipient does not possess these Ag ,antibodies will be formed against them.
Immunomodulation- Transfusion of blood is associated with changes in immune function. The effect is apparent with multitranfused patients.There is decreased lymphocyte responsiveness to phytohaemagglutinatinin and in mixed lymphocyte culture with pooled mormal lymphocytes as stimulator cells.

Disease transmission

Hepatitis
Syphilis Malaria Cytomegalovirus

Human immunodeficiency virus

Human T cell leukaemia viruses. Donor selection criteria and subsequent screening of all donations are designed to prevent disease transmission, but these do not completely eliminate the hazards.

Hepatitis

Hepatitis
A is rarely transmitted by transfusion. Any donor who has been in close contact with Hepatitis A patient or develops hepatitis A is deffered for 12 months.

Hepatitis B is a frequent sequel to blood transfusion. Currently all

blood donations are tested for HBsAg by very sensitive third generation techniques ( eg; ELISA ), able to detect at least 0.5 iu of HBsAg per ml of serum. EIA method is used with 99.9 % sensitivity. HBsAg positive subjects are permanently excluded from donations.

Syphilis

The organism is more likely to be transmitted in platelet concentrate due to their room temperature storage and short shelf life. Treponema pallidum does not survive well at 4 c and red cell preparation are likely to be non infective after 4 days refrigeration. Passive transmission of the antibody to the recepient may cause diagnostic confusion. Any donations with positive result is discarded, any subjects with positive tests are permanently deferred, even after effective therapy.

Malaria

Malarial parasites remain viable in blood stored at 4 C and easily transmitted by blood transfusion.
In some endemic areas, all recipients are treated with antimalarial drugs. Donors who come from endemic area or have had an attack of malaria can be accepted, their plasma can be used for fractionation but red cells must be discarded. BFMP should be tested for certain group of donors ie : army, donors from endemic area

Cytomegalovirus

Post transfusion CMV infection is not uncommon. The infection is characterised by fever spleenomegaly, and atypical lymphoid cells in the peripheral blood. Due to its benign course, screening for past infection among donors are not necessary.

However, there are patient at risk of developing fatal pneumonitis or disseminated CMV infection : prem baby < 1500g, BM or and other organ transplant recipient, pregnant women ( risk to fetus ).

For them, anti CMV free blood & components should be provided.
In UK, incidence of CMV antibodies in adult population is 50 to 60 %.

As an alternative, since CMV is cell associated, leukodepleted blood may be used.

Human immunodeficiency virus

HIV can be transmitted both in cellular and plasma components. The majority of recipient of blood or blood products who have been infected in the past were transfused before 1985 with unheated, non pasteurized pooled plasma products, Factor VIII and IX. HIV is heat labile, therefore prolonged heat treatment of Factor VIII for heomophiliacs is effective.

Human immunodeficiency virus

Routine screening of all donated blood started in October 1985 in UK. This in combination with donor education, and self deferral has reduced the risk of HIV transmission through contaminated blood. There were 2 documented cases in the UK since screening program introduced. With screening programe, HIV transmission still occur through donations given in the window period of infectivity. With current antibody screening technique, the estimated window period is about 3 weeks. PCR for HIV RNA is able to reduce the window period to approximately 1 week.

Human T- cell leukaemia viruses.

HTLV 1 and II are related retroviruses.

HTLV 1 is endemic in the caribbean, parts of Africa and in Japan, 3 6 % of the population are seropositive.
HTLV 1 is associated with tropical spastic paraparesis and adult T cell leukaemia.

Importance of HTLV II is not clear.

Both HTLV 1 and II are cell associated and not transmitted in plasma. Currently available test include ELISA and gelatin particle assay, but confirmation of positive result are difficult due to cross reactivity with other retroviruses.

THE END
Thank you for your attention.