BLOOD TRANSFUSION REACTION

Non immunological
By Rusmawati bt. Ismail

Non immunological transfusion reaction

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2. 3. 4. 5.

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

1. 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.

Source of infection.

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 22 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 faeces may rarely grow in the storage condition of blood.

According to CDC , most are caused by blood components contaminated by Yersinia enterocolitica. Since 1987, from 20 cases reported to CDC, 12 are caused by this organism.

Clinical manifestation
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.

Rapid recognition is essential 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.

Prevention
Strict adherence to policies & procedures regarding blood component collection, storage, handling,and preparation is essential to reduce the risk. Visual Inspection of components before release from the transfusion service include any discolouration, visible clots, or hemolysis. Ensure the blood components are infused within standard time limits ( 4 hours ).

Prevention
Blood packs should never be opened for sampling, if any open method of preparation has been used, the unit should be transfused within 24 hours. Blood should always be kept in accurately controlled refrigerators (with alarms), maintained strictly at 2 6 C, the blood should never be removed and taken to the ward or OT until it is recquired.

2. 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 oedema may develop.

Clinical manifestation
Frequently due to transfusion of a unit at too fast rate. Signs of cardiac failure raised JVP, basal crepitations in both lungs, dry cough, breathlessness.

Management
Stop the transfusion immediately. Prop up the patient Oxygen therapy 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.The usual rate of transfusion is about 200 ml per hour. In patient at risk rate of 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.

3. 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.

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.

4. Complication of massive transfusion

1.

Massive transfusion is defined as the replacement of total blood volume within a 24 hour period. This will inevitably lead to : 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 of most 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 calsium 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.

5.Non immune hemolytic reaction

Mechanical heat damage from blood warmer, cold, small gauge needle. Environment hypotonic or hypertonic solution.

6. 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. In HUSM, EIA method is used with 99.9 % sensitivity. HBsAg positive subjects are permanently excluded from donations.

Hepatitis
Hepatitis C All donated blood are tested for anti HCV. Improved screening assays based on multiple recombinant or synthetic antigens including viral core protein are now available. Individuals with a history of jaundice may be accepted as donors 1 year after the illness provided they tested and negative for HBsAg and anti HCV.

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. In HUSM , 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.

Investigation of transfusion reactions.

Investigations of transfusion reaction are necessary for : 1. Diagnosis 2. Selection of appropriate therapy 3. Transfusion management 4. Prevention of future transfusion reaction. Investigations should include correlations of clinical data with laboratory result . Important clinical data : 1. Diagnosis 2. Medical history of pregnancies, transplant, and previous transfusion. 3. Current medication 4. Clinical signs and symptoms of the reaction.

5. Question related to the transfusion: Amount of blood transfused to cause the reaction. How fast , how long ? The use of blood warmer. Any filter used ? Other solutions. Any drugs given at the time of transfusion

Laboratory investigation outline of transfusion reaction.

1. Immediate procedures Clerical checks. Visual inspection of serum and plasma for free hemoglobin ( pre and post transfusion ) Direct anti globulin test. ( post transfusion EDTA sample )

2. As recquired procedures

ABO grouping and RH typing, pre and post transfusion Major compatibility testing , pre and post transfusion Antibody screening test , pre and post transfusion Alloantibody identification Antigen typings Free hemoglobin in first voidedurine post transfusion Unconjugated bilirubin 5 7 hours post transfusion.

3. Extended procedures

Gram stain and bacterial culture of unit

Quantitative serum Hemoglobin.

Serum Haptoglobin , pre and post transfusion

Peripheral blood film. Coagulation and renal output study Urine hemosiderin

References: 1. Modern blood banking and transfusion practice. Denise M. Harmening. 2. Post graduate haematology.

THE END Thank you for your attention.