We started with a 74 year old gentleman who was admitted with weight loss, fatigue and change in bowel habit. A mass in the right iliac fossa was palpated and a colonic malignancy was suspected. He had thrombocytosis with microcytic indices and Hb 74g/l consistent with iron deficiency. This was confirmed with a ferritin of 7μg/l. The management of iron deficiency consists of:
- Finding and correcting the cause
- Replacing iron
A colonoscopy was organised and therefore it was suggested that iron was replaced. This can be done in a number of ways:
- Modification of diet – this is unlikely to replace depleted stores but can be useful to maintain adequate stores
- Oral iron supplementation
- Can be bought from health food shops alone or as a multivitamin – doses are generally low
- Can be prescribed at higher doses (there is an increasing evidence base that alternate days 60mg elemental iron (e.g. ferrous sulphate 200mg) is more efficacious and better tolerate than the traditional TDS regime – see references)
- Intravenous iron supplementation
- Red cell transfusion – generally avoided unless the patient is very symptomatic or intervention is required and cannot wait for the effects of iron supplementation
Features can vary from being pale and fatigued to cardiac complications. The history can often help determine the speed of onset – here this was a gradual decline in function so it is likely iron deficiency has been longstanding. Often these patients can tolerate a lower haemoglobin as their body has time to compensate. Unfortunately in this case the patient was prescribed two units of red cells without taking this into account – especially as the patient did not describe chest pains, palpitations or severe breathlessness. The other key point was the patient’s body weight. He was only 48kg and patients with lower body weight should have their prescription altered. As a general guide, transfusing a volume of 4ml/kg will typically give a Hb increment of 1g/dl. The concept that one unit of red cells gives a Hb increment of 1g/dl should only be applied as an approximation for a 70-80 kg patient.
Transfusion-associated circulatory overload (TACO)
Our patient became more short of breath and hypoxic towards the end of the second unit. A CXR revealed some upper lobe diversion and small pleural effusions.
TACO is the most common cause of death associated with transfusion. There were 86 reported to SHOT in the UK in 2016. There were 14 deaths where the transfusion was considered to be contributory, 1 definitely related, 5 probably related and 8 possibly related. This likely represents an under-reporting.
- Acute or worsening respiratory distress within 6 hours of transfusion (some cases may occur up to 12 hours).
- Pulmonary oedema, raised JVP
- Positive fluid balance
- PA pressures above 18mmHg
- No neutropenia
- Raised Hb
Those at risk are:
- Heart disease
- B12/folate deficiency
- Already overloaded/positive fluid balance
- Renal failure
- Co-administration of IV fluids
This may help in the assessment of those at risk (Taken from 2016 SHOT report):
- Stop the transfusion
- Assess the patient: ABCDE
- Give oxygen
- Bloods: FBC, U&E, pro-NT-BNP, repeat group and screen (sometimes the cause of deterioration is not clear initially)
- Intravenous diuretic
Transfusion-associated lung injury (TRALI)
TRALI and TACO can appear similar, but TRALI is very rare. There were no confirmed cases in the UK in 2016. This is usually due to anti-HLA class I and II or anti-HNA antibodies (especially HNA-1a and HNA-3) in donated product against patient WCC and pulmonary epithelium. Results in ARDS picture with tissue damage to lungs and alveolar spaces filled with fluid. It occurs within six hours of transfusion and plasma-containing products are more commonly implicated. May get mild neutropenia and the JVP is not elevated. Blood pressure may go down and there may be fever. It is comfirmed with clinical features and an antibody in the patient’s plasma with concordant antigen on the donated product. Management is supportive and often ventilation is required. Incidence has reduced due to better testing and definitions in addition to using male only plasma in FFP and platelets (men are less likely to have HLA/HNA antibodies than women who are sensitised during pregnancy) or the use of pooled FFP (e.g. Octaplas) where any antibody in donors is dilute due to the number of people that contribute to one unit.
Delayed haemolytic transfusion reaction
Delayed haemolytic transfusion reactions (DHTR) are defined as fever and other symptoms/signs of haemolysis more than 24 hours after transfusion; confirmed by one or more of the following: a fall in Hb or failure of increment, rise in bilirubin, incompatible crossmatch not detectable pre transfusion. It is important to remember that in many transfusion labs a serological (or ‘wet’) crossmatch (i.e. the patients plasma is mixed with the donated red cell) is not performed in all cases. We rely on looking for the ABO group, RhD status, Kell (in some cases) and looking for an antibody. There are over 30 blood group systems and over 300 antigens – it’d be impossible to match for all antigens. Therefore when anyone has a transfusion there is a risk that they will develop an antibody where there has been a mismatch. This is around 2-4%. We look for an antibody by buying three patient’s red cells. These three patients will have a variety of antigens on the red cell surface and assuming our patient’s plasma does not react with any of these red cells we can assume that there is no clinically significant antibody. This is a very robust system but occasionally things can fall through the net. Such as:
- Wrong blood in tube.
- Antibody is at a very low level and not detected by the screening panel but can re-appear when transfused) – the Kidd blood group is well recognised for causing this.
- There is an antibody to an antigen that is not featured on the red cell screening panel (antibody to low frequency antigen) – usually these antibodies are non-significant but can be on occasions
Delayed haemolytic transfusion reactions should be suspected if there is new onset jaundice or the haemoglobin has fallen back to baseline after a transfusion. Investigations should include a full haemolysis screen (FBC, reticulocytes, LDH, haptoglobin, direct/indirect bilirubin, blood film, urine haemosiderin and a direct antiglobulin test). The DAT (or Coomb’s test) looks for any antibody on the patient’s red cells. A repeat antibody screen should be performed and a ten red cell panel to specify any antibody. An eluate (washing any antibody off the patient’s red cells) should also be performed to identify any antibody.
Management of delayed haemolytic transfusion reaction are generally supportive. Folic acid can be administered. Red cells can be given if required but this may need input from a specialist immuno-haematology transfusion laboratory. Once a patient has developed one antibody they are at risk of another. From now on these patients will require a serological cross match and as well as being ABO and RhD compatible any donated blood should also be negative for the implicated antigen. Some labs may try and match for all of the Rh antigens (C, c, E, e) as these are commonly implicated.
In our patient you can see that the blood film showed spherocytes:
You can also see that the repeat screening panel was positive in lines two and three (see that these red cells had Jka antigens on their surface and that the reaction was stronger in two where there was more Jka on the red cell surface (i.e. the red cells in two did not also express Jkb).
A more comprehensive red cell panel is below:
From these anti-Jka is the most likely culprit and our patient did not express Jka on his red cells. These are pretty advanced transfusion knowledge and would not be expected for most people (just for fun for the transfusion bods!). Our patient probably was sensitised from his transfusion years ago and the antibody was too weak to show on the panel but reared its head once transfused (both units were Jka+).
Important points from this case:
- Use blood transfusion appropriately – could our patient have managed with iron replacement? IV iron would be appropriate as oral iron not good pre colonoscopy
- If blood is required then transfuse one then review
- Assess patients for risk of TACO pretransfusion – especially important if low body weight – our patient’s post transfusion Hb was >105g/l
- Patients should be made aware of risks of transfusion
- Be aware of delayed haemolysis – especially if the haemoglobin is back to baseline quickly
- Both of these complications should be reported to SHOT
- Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women
- Serious Hazards of Transfusion report 2016
- NICE blood transfusion guidance
- Summary of NICE guidance
- BSH guidance – administration of blood components
- BSH guidance – investigation and management of acute transfusion reactions