Blood Transfusion – Part 1

Authors: Derek Obiri, Charlotte Davies / Editor: Swagat Mishra / Codes: HC9, SLO3 / Published: 12/12/2023

We transfuse lots of blood in the emergency department (ED), and before we can even consider the science behind massive transfusions, we should consider the basics of transfusion. Transfusion may seem simple, but here are few reminders and updates on the basics of transfusion starting with the transfusion ten commandments – for many of us medical school was our last training! We’ve written some linked SBAs, so keep an eye out for these being published in the next few weeks (members only).

Safe blood is provided by unpaid volunteers. 17 to 65 year olds can enrol as first-time blood donors and there is no upper age limit for regular donors (subject to an annual health check). A medical questionnaire covering health, lifestyle, travel history, medical history and medication is completed before each donation. The minimum mandatory infection screen on all donations is for hepatitis B and C, HIV, HTLV and syphilis, and extra tests are performed as required. Donations are routinely ABO and RhD typed and screened for clinically important blood group antibodies.

Although we commonly think of blood as packed red cells, blood products include:

• Red cells
• Platelets
• Fresh frozen plasma
• Cryoprecipitate (or plasma derivatives manufactured from)
• Albumin
• Coagulation factors (including Octaplex)
• Immunoglobulins (including Anti-D)

1. Transfusion should only be used when benefits outweigh the risks and there are no appropriate alternatives.

The biggest benefit of blood transfusion is increased oxygen carrying potential, which is important for life. Alternatives to transfusion do exist depending on the clinical circumstance and these may include ferrinjet injections (can’t be used in the first trimester of pregnancy).

The risks of blood transfusion can be broadly split into three groups:

• Blood group reactions
• Non-infective hazards
• Infective hazards

Blood Group Reactions

ABO mismatch transfusion is listed as a “never event” and your department will have a document somewhere detailing what they do to minimize the risk of it happening.

There are more than 300 human blood groups but only a minority cause clinically significant transfusion reactions. The two most important in clinical practice are the ABO and Rh systems.

Blood group antigens: Blood group antigens are molecules present on the surface of red blood cells. Some, such as the ABO groups, are also present on platelets and other tissues of the body.

Blood group antibodies: These are usually produced when an individual is exposed to blood of a different group by transfusion or pregnancy (‘alloantibodies’). This is a particular problem in patients who require repeated transfusions, for conditions such as thalassaemia or sickle cell disease, and can cause difficulties in providing fully compatible blood if the patient is immunised to several different groups.

ABO-incompatible red cell transfusion (i.e. wrong blood group) is often fatal and its prevention is the most important step in clinical transfusion practice. Antibody incompatible transfusion can cause reactions that are serious. Alloantibodies produced by exposure to blood of a different group by transfusion or pregnancy can cause transfusion reactions, haemolytic disease of the foetus and new-born (HDFN) or problems in selecting blood for regularly transfused patients.

Because transfusion of the wrong ABO blood group, and the wrong Rhesus status can cause reactions, the laboratory will perform different types of compatibility procedures using a transfusion EDTA sample. Sometimes, there may not be enough blood in the tube to complete all the required tests, so the lab will ask for more blood to be sent to them. Once they have their blood they analyse it carefully:

• Group and screen: to determine the ABO and RhD groups and the plasma is screened for the presence of red cell alloantibodies capable of causing transfusion reactions. This takes about 35 minutes to complete, if no additional screening is required.
• Compatibility (crossmatch) testing: the final step in providing safe blood is to carry out a serological crossmatch between the patient’s plasma and a sample of red cells from the units of blood selected for transfusion. This is performed by the IAT method at 37°C, looking for evidence of a reaction that would indicate incompatibility. This takes a variable amount of time depending on the presence of reactions.

The majority of this work used to be done manually, by a biomedical scientist, however lots of blood is now electronically issued. This is sometimes known as electronic cross-matching.  Most hospitals now issue the majority of blood by this safe and rapid technique. It relies on the fact that if the patient’s ABO and RhD groups are reliably established, and with a sensitive antibody screen being negative, the possibility of issuing incompatible blood is negligible. The laboratory computer can identify all compatible units in the blood bank inventory without the need for further testing. Electronic Issue (EI) is not used in some specific circumstances, such as a patient history of having antibodies or a blood grouping discrepancy.

When needing blood for planned procedures, there is a small risk that the patient may develop new blood group alloantibodies between the time of initial testing and the date of operation, especially if they have recently been transfused or become pregnant. This means that testing should be performed on samples collected no more than 3 days in advance of the transfusion, when a patient has been transfused or become pregnant within the preceding 3 months. An extension to 7 days may be considered for regularly/frequently transfused patients with no alloantibodies and pregnant women with no significant alloantibodies who need to have blood standing by for a potential obstetric emergency such as placenta praevia.

Haemovigilance is the name given to systematic surveillance of adverse reactions and adverse events related to transfusion’ with the aim of improving transfusion safety. Haemovigilance can identify transfusion hazards and demonstrate the effectiveness of interventions. SHOT (Serious hazards of transfusion) is a national organisation that invites voluntary reporting of serious adverse transfusion reactions, errors and events as well as near-miss incidents. Transfusion reactions and adverse events are investigated by the clinical team and hospital transfusion team (HTT) and reviewed by the hospital transfusion committee (HTC). Under the Blood Safety and Quality Regulations 2005 (BSQR) there is a legal requirement to report serious adverse reactions and events to the Medicines and Healthcare Products Regulatory Agency (MHRA). The MHRA also inspects blood establishments (transfusion centres) and hospital transfusion laboratories to ensure their processes and quality standards comply with the BSQR. SHOT and MHRA work closely together and have a joint reporting system through the SABRE IT system.

Severe and Life Threatening Non Infective Hazards

TRALI is caused by antibodies in the donor blood reacting with the patient’s neutrophils, monocytes or pulmonary endothelium. Inflammatory cells are sequestered in the lungs, causing leakage of plasma into the alveolar spaces (non-cardiogenic pulmonary oedema).

Most cases present within 2 hours of transfusion (maximum 6 hours) with severe breathlessness and cough productive of frothy pink sputum. It is often associated with hypotension (due to loss of plasma volume), fever and rigors and transient peripheral blood neutropenia or monocytopenia. The Chest X-ray shows bilateral nodular shadowing in the lung fields with normal heart size. Treatment is supportive, with high-concentration oxygen therapy and ventilatory support if required. Suspected TRALI should be reported to the transfusion laboratory as well as the Haematology On-Call, who will guide further reports. TACO is defined as acute or worsening pulmonary oedema within 6 hours of transfusion. Typical features include acute respiratory distress, tachycardia, raised blood pressure and evidence of positive fluid balance. It may now be the most common cause of transfusion-related death in developed countries.
At risk patients:

• Elderly with predisposing medical conditions include heart failure, renal impairment, low albumin concentration and fluid overload
• Small patients, such as the frail elderly and children
• Poor pre-transfusion clinical assessment and inadequate monitoring during transfusion

The treatment of TACO involves stopping the transfusion and administering oxygen and diuretic therapy with careful monitoring and critical care support if required. 

Less Severe

Less Severe Non Infective Reactions

Mild allergy: Symptoms are confined to itching (pruritus) and/or skin rash (‘nettle rash’ or hives) with no change in vital signs. They are most common in patients receiving plasma-rich components such as FFP or platelets. Symptoms often improve if the transfusion is slowed and an antihistamine (e.g. chlorpheniramine) is administered orally or intravenously. The patient must be monitored closely for development of a more severe reaction, in which case the transfusion must be stopped, and the laboratory informed.

Febrile Non-haemolytic transfusion reactions (FNHTRs) may be mild or moderate or severe. They manifest as fever, sometimes accompanied by shivering, muscle pain and nausea. They can occur up to 2 hours after completion of the transfusion and are more common in multi-transfused patients receiving red cells.

Mild FNHTRs      (pyrexia >38°C, but <2°C rise from baseline)

Treat by:

• Slowing (or temporarily stopping) the transfusion.
• Giving an anti-pyretic, such as paracetamol
• Monitor closely

Moderate FNHTRs (pyrexia >2°C above baseline or >39°C or rigors and/or myalgia)

Treat by:

• Stopping the transfusion
• If the symptoms worsen, or do not quickly resolve, consider the possibility of a haemolytic or bacterial reaction.
• In most cases it is prudent to resume transfusion with a different blood unit. Return implicated red cell unit to the Blood Transfusion Laboratory for investigation.

Infective Hazards

• Viral infections: Hepatitis A,B,C and E, HIV, CMV, HTLVI &II, Parvovirus B19, WNV
• Bacterial infections: Syphilis, Other bacterial contaminants (Staph aureus, Klebsiella, E coli, Pseudomonas)
• Protozoal infections: Malaria, Chagas disease
• Variant Creutzfeldt–Jakob disease (vCJD)

The next 9 commandments coming in part 2. You can read it here.

References

1. Blood donation. NHS Blood and Transplant.
2. Never events. Guidance. NHS England, 2020. Updated in 2021.
3. The Blood Safety and Quality Regulations 2005 NO 50. legislation.gov.uk
4. Blood: authorisations and safety reporting. Guidance. Gov.UK. 2014. Updated 2021.
5. Soutar R, McSporran W, Tomlinson T, Booth C, Grey S. Guideline on the investigation and management of acute transfusion reactions. Br J Haematol. 2023; 201(5): 832–844. https://doi.org/10.1111/bjh.18789