Transfusion reaction - investigation and management from the Haematologist’s perspective

Occurs in the context of pre-existing red cell antibodies in the recipient. The most life-threatening event is in the context of ABO incompatibility where IgM host antibodies result in intravascular haemolysis of transfused cells and can precipitate hypotension, renal failure and DIC. Occurs 1:25000, Fatal 1:600,000

Symptoms:

• Hypotension/Shock
• Loin pain
• Rigors
• Haemoglobinuria
• Dyspnoea
• “Feeling of impending doom”

Differential Diagnosis:

• Bacterial Contamination
• Febrile non-haemolytic transfusion reaction (FNHTR)
• Transfusion related acute lung injury (TRALI)

Management of the patient in this situation includes:

• stopping transfusion and establish new venous access if possible so no additional blood is infused through previous venflon.
• involvement of acute medical/HDU/ITU team,
• fluid resuscitation,
• consideration or inotropic and renal support, and
• management of DIC.
• if bacterial contamination cannot be excluded broad spectrum antibiotics
  should be given.

ABO incompatibility suggests that there has been a transfusion-related error at some step in the process and requires immediate investigation as there may be another patient at risk (eg if switched samples). When this is suspected, the consultant haematologist on call should be informed. Where possible, other transfusions to patients in that area should be suspended until the cause is identified.

Investigations required:

• Check name on unit and patient match
• Repeat XM (pink) and serum sample to blood bank for antibody investigation (yellow), DAT, FBC, Coag screen (?DIC), Biochemistry, LDH, Haptoglobin (yellow), Urine for haemoglobinuria (plain container)
• Immediate ward/laboratory investigations to determine source of error – ensure senior medical and biomedical staff involved.

Reports: SHOT and SABRE

Contamination of blood components prior to transfusion. More frequent with platelets (1:10 000) due to storage at room temperature hence efforts to test for bacteria pre authorisation.

Symptoms:

• Fever
• Rigors
• Hypotension/Shock

Differential Diagnosis:

• AHTR
• FNHTR
• Allergic Transfusion Reaction
• Pre-existing infection in patient

Management:

• Stop transfusion
• Broad spectrum antibiotics
• IV fluids

Investigations required:

• Send implicated component back to Blood bank immediately to send to SNBTS for culture with giving set attached.
• Inform SNBTS medic (day or night) as there may be other implicated components from that donor that may need to be quarantined
• FBC, Coag screen, Biochemistry, Blood cultures
• Recrossmatch if further blood required
• Other investigations as per other causes if not excluded (eg AHTR)

Reports: SHOT and SABRE

Common occurrence during transfusion (up to 1:100 red cells, 1:5 platelets) probably caused by cytokines generated during storage.

Symptoms:

• Fever, occasionally rigor
• Nil else specific

Differential diagnosis:

• Beginning of a more serious reaction therefore need to consider AHTR/Bacterial contamination/TRALI etc

Management:

• Stop transfusion initially, but if temperature rise <2˚C and patient otherwise well give paracetamol and restart transfusion at slower rate (NB The unit will have to be taken down 4 hours after it was first taken out of fridge, irrespective of amount of blood transfused).
• If patient unwell, stop transfusion, recrossmatch and investigate as per AHTR and Bacterial Contamination

Reports: SHOT report if temp ≥2˚C only.

Common occurrence (1:300) and occurs as a result of allergenic substances in plasma of donated component reacting with pre-exisiting IgE antibodies in the recipient.

Symptoms:

• Mild urticaria only

Differential Diagnosis:

• Beginning of a more serious allergic/anaphylactoid reaction

Management:

• Stop transfusion initially but if happy otherwise well, give chlorpheniramine and restart at slower rate.
  

Reports: SHOT only

Symptoms:

• Hypotension/Shock
• Angioedema
• Wheeze/Respiratory distress

Differential Diagnosis:

• Initially may be difficult to differentiate from TRALI though not if true angioedema/bronchospasm

Management:

• Do not restart transfusion until fully investigated
• If transfusion cannot be delayed – D/W senior haematologist

Investigations Required:

• Mast cell tryptase – 3 samples – immediate, 1-3 hours post and 24 hours post (see separate request form (“tryptase” on trak) – yellow topped bottle)
• IgA level - yellow topped bottle to biochemistry (and anti-IgA antibodies if deficient –10ml x clotted)
• Identification of appropriate blood components for future transfusion – Discuss with SNBTS medic.

Report: SHOT and SABRE

NB: If found to be IgA deficient following a reaction will need lifelong IgA deficient blood components – inform patient and blood bank (Special requirements form), and alert on Trakcare.

Interaction between donor neutrophil antibodies/neutrophil priming agents and recipients leucocytes resulting in inflammatory process, increased vascular permeablility and lung damage. Occurs more commonly in patients who are already unwell so can be difficult to diagnose. More common with plasma product components.

Symptoms:

• Shortness of breath – within 6 hours, usually within 2.
• Fever
• Unwell
• Fall in pO2

Differential Diagnosis:

• TACO
• Allergic reaction

Clinical Investigations and Management:

• CXR – “suggestive of pulmonary oedema” in the context of normal heart, and low pulmonary wedge pressure and normal echo (in contrast to TACO)
• Should be treated with fluid resuscitation and tends to worsen with diuretics
• Management largely supportive

Laboratory Investigations:

• D/W SNBTS medic
• Recipient testing of HLA type (2 x EDTA, 10ml x clotted)
• Donor testing for Anti-granulocyte or anti-HLA antibodies
• Donor/recipient crossmatch
• N.B. All blood products administered in preceding 6 hours are should be considered potentially responsible.

Report: SHOT and SABRE

Characteristically occurs in older age group with cardiac compromise, but can happen in any age group, particularly if transfusing large volumes.

Symptoms:

• Shortness of breath and signs of pulmonary oedema within 6 hours of transfusion
  

Differential Diagnosis:

• TRALI

Management:

• Stop transfusion and treat as cardiac failure

Laboratory Investigations:

• Nil specific if diagnosis clear, otherwise investigate as per other potential causes
• Review need for education re transfusion rates/volumes

Report: SHOT and SABRE

Symptoms and signs of haemolysis >24 hours after transfusion, occurring as a result of alloimmunisation – caused by interaction between donor red cells and pre-existing recipient IgG antibodies.

Management:

• No specific management of the patient is required unless there has been a massive transfusion, but they may need further transfusion (as they will have haemolysed the recently transfused blood) and appropriate investigation is required prior to issuing further blood

Laboratory Investigations: – to confirm alloimmunisation + haemolysis

• FBC, Film, DAT (on pre-transfusion sample if still available and post transfusion sample), Bilirubin, LDH, Haptoglobin
• Identification of antibody responsible
• NB Needs serum sample for weak relevant antibodies eg Jka
• Review pre-transfusion crossmatch – could it have been detected?

Report: SHOT only unless harm caused or laboratory error.

NB: If haemolysis occurs 4-10 days after transfusion in a patient with sickle cell disease, this can be associated with rapid bystander haemolysis and hyperhaemolysis syndrome. This can be life threatening and should be discussed with the haematology consultant immediately it is suspected.

Acute episode of profound thrombocytopenia approximately 7 days post transfusion in the context of alloimmunisation and anti HPA (often HPA-1a) antibodies. Occurs more frequently in females who have been previously alloimmunised through pregnancy. Rare-approximately 1:500 000. The secondary immune response generated by the transfusion and pre-existing alloantibodies causes an ill-understood bystander destruction of the recipient’s own platelets, usually dropping them into single figures. Haemorrhage is common and can be severe. This usually persists for about 3 weeks.

Differential diagnosis:

• Other non-transfusion related causes of profound thrombocytopenia

Management:

• No randomised trials but IVIGS commonly used with 85% response
• No evidence that antigen negative platelets do any better – so random platelets if patient bleeding in the acute setting
• For future transfusion episodes it is suggested that antigen-negative platelets are used to prevent the re-stimulation.

Investigation:

• Patient HPA typing and anti-HPA antibody investigation (2 x Pink EDTA to H&I lab SNBTS)
• Platelet crossmatch/MAIPA – Discuss case and sample requirements with SNBTS

Report: SHOT and SABRE

NB: There is no value in routinely testing for HLA, HPA or HNA in the setting of ATR; these tests should be restricted to patients with evidence of refractoriness.

Rare yet highly fatal reaction due to engraftment of donor lymphocytes in an immuno-incompetent host. Although the incidence has dramatically reduced following leucodepletion, the high fatality rate, and limited treatment options mean that preventing the possibility (by using irradiated products where indicated) is essential.

Symptoms:

• Occurs 1-6 weeks post transfusion (median start 8-10 days)
• Fever, rash (marked), liver dysfunction, diarrhoea, pancytopenia
• Death within 3 weeks in the vast majority of cases

Management:

• Predominantly supportive

Investigation:

• Clinical diagnosis + classical biopsy findings
• Donor and patient HLA type (2 x EDTA tubes and 10ml x clotted).
• Determine the root cause of the patient receiving the incorrect blood component and implement changes to prevent it happening again

Report: SHOT and SABRE

for detailed guidance and references see Appendix 2 on the BSH website

* Standard investigations: full blood count, renal and liver function tests, and assessment of urine for haemoglobinuria
Abbreviations: DAT - direct antiglobulin test; Ig - immunoglobulin; LDH - lactate dehydrogenase

• Guideline on the investigation and management of acute transfusion reactions (BSH, 2023)
• Guidelines for pretransfusion compatibility testing in transfusion laboratories (BCSH, 2012)
• NHSGGC Clinical Transfusion policy