RBC Transfusion in Sickle (bsh 2016(1) & 2016(2))

Intro

 

Goals of Tx in Sickle

Improving oxygen-carrying capacity by correcting anaemia

Preventing or reversing complications of SCD related to vaso-occlusion and haemolysis by decreasing the proportion of HbS in relation to HbA

 

Common steady state haemoglobin levels:

60-90 in HbSS

70-90 in S/B0 Thal

90-120 in S/B+ Thal

90-140 in HbSC

Also document baseline reticulocyte count for comparison in acute illness

 

Avoiding hyperviscosity

 

HbS %

  • Sickling complications are related to HbS %

  • No single target covers all indications but aiming for HbS <30% is general rule

  • Keeping HbS <30% reduces rates of stroke, ACS, priapism, avascular necrosis

 

Hb

  • Post-transfusion Hb should not exceed baseline Hb, esp if HbS% remains >30%

  • Post-transfusion Hb may be set higher in context of chronic transfusion programme as HbS % will be lower and so lower risk of hyperviscosity.

 

Transfusing in Acute Illness

 

General Principles

  • Contact pt’s primary hospital for their baseline Hb, retic count, transfusion history and red cell pheno/geno-type and history of alloantibodies.

  • Patients should carry a card stating their phenotype +/- alloantibodies

  • Aim to prevent need for transfusion with good SCD management – i.e. incentive spirometry, analgesia, hydration.

 

Long term complications of transfusion

 

Alloimmunisation - Hydroxycarbamide reduces transfusion requirements

 

Iron Overload

  • 3 monthly ferritin

  • MRI liver 1-2 yearly if suspected or proven overload

  • Use of automated red cell exchange prevents or even corrects iron overload

 

Transfusion-Transmitted Infection

  • Immunise against Hep B

  • Annual Hep B/C and HIV testing if transfused

 

Top Up vs Exchange Transfusion

 

Indication

  • Top-up preferred for treatment of symptomatic severe anaemia

  • Exchange preferred for immediate or sustained reduction in complications of SCD

 

Hyperviscosity

  • Risk of hyperviscosity at a given Hb is dependent on Hb S% and Hct

  • Hyperviscosity reduces oxygen delivery and exacerbates sickling.

  • Viscosity effect of sickle cells is reduced by presence of normal red cells

  • However simple top-up will also raise Hct, negating the effect of reduced HbS%

 

Iron balance

  • Top-up causes increased in total iron

  • Manual exchange decreases rate of iron loading by 40% compared to top-up

  • Automated exchange can achieve neutral or negative iron balance

 

Alloimmunisation

  • Automated exchange consumes more units than top-up or manual exchange but does not appear to increase risk of alloantibody formation.

 

Venous Access

  • Limits exchange in many patients

  • Indwelling venous catheters an option but high complication rate – inf and thrombosis

 

Resources

  • Exchange has higher resource and financial requirements than top-up

 

Automated exchange

  • Reduces HbS% faster than manual as plasma, platelets and white cells are returned to patient.

  • Takes 2 hours if good IV access

  • More effective and so allows 6-weekly transfusion intervals

  • Limits or eliminates iron loading

  • SE: Dilutional thrombocytopenia, hypocalcaemia, line complications, fluid shifts

 

Manual Exchange

  • Aim to exchange 30% of blood volume and so achieve 30% HbA.

  • Typically remove 4 units, transfuse 3 units and replace remaining vol with saline

    • Usually increases Hb by 10-20g/l

 

Laboratory Aspects

 

Use ABO, extended Rh- and Kell matched blood as a minimum standard

Significant differences in RBC antigen frequencies between Caucasian and African donors contributes to alloimmunisation.

Sensitisation occurs against Rh variants identifiable on molecular genotyping but not by serological methods.

 

Compatibility testing

  • Fully automated systems for ABO typing should be used

  • Antibody screening should always be part of pre-transfusion testing

  • For those not on a regular transfusion programme, antibody screening should be repeated after every transfusion episode.

  • Serology should be performed within 72 hours prior to transfusion if recently transfused.

  •  

Extended phenotype/genotype

  • C, c, E, e, K, k, JKa, JKb, Fya, Fyb, S, s

  • Should be performed on all patients at baseline

  • If S-, s- then perform U typing

  • Offer RBC genotyping (Free with NHSBT in 2016/17 but no longer)

 

Blood product Selection

  • Matched for full Rh and K antigens as a minimum

  • R0 wherever possible for R0 patients. rr can be used if R0 unavailable in emergency

  • Match for historical antibodies as may not be identified on current serology.

  • As of 2023, it is no longer recommended to select ‘fresh blood’ for any patient >1 year old. This change has been circulated by NHSBT. Formal addendums to the BSH guidelines will follow. (This replaces the original recommendation: Red cells should be <10 days old for top-up, <7 days for exchange).

 

Haemolytic Transfusion reactions

 

Classical Delayed Haemolytic Transfusion Reaction (DHTR)

  • Anamnestic immune responses in alloimmunised patients

  • Occur in 5-10% of transfused patients

  • Fever + Jaundice + Anaemia 7-10 days after transfusion +/- sickling pain

  • There is clear lab evidence of haemolysis with a fall in HbA %

  • Alloantibody often identified

 

Hyperhaemolysis

  • Sub-type of DHTR - some debate over whether it is truly its own entity.

  • Severe sickle pain + fever + haemoglobinuria

  • Destruction of both donor and patient red cells

  • Post-transfusion Hb lower than pre-transfusion

  • HbS and HbA detectable in urine by HPLC

  • DAT often negative and alloantibody not identifiable

  • Further transfusion worsens haemolysis but should not be withheld in life-threatening anaemia. Transfuse with IVIg + IV Methylprednisolone.

  • Rituximab may have a role.

 

AIHA

  • Auto Anti-e is most common

  • 5-10% of transfused SCD patients

  • More common in multiply alloimmunised patients and molecular Rh typing is starting to show that many supposed autoantibodies are actually Rh alloantibodies against Rh alleles not detectable by serology.

 

Intro to Indications for transfusion

 

2 main goals

  • Correction of anaemia

  • And/or reduction of HbS in proportion to HbA

The low steady state Hb in SCD is the result of the low oxygen affinity of HbS and therefore not a reason to transfuse on its own.

 

Emergency Transfusion with the primary aim of correcting acute anaemia

 

Acute anaemia in SCD = Fall in Hb >20g/l below steady state value.

Causes include:

  • Decreased production, sequestration and increased destruction.

  • Assessment: History of recent transfusion, haemodynamic status, liver and spleen size. FBC and reticulocytes.

 

Aplastic Crisis

  • Acute anaemia + reticulocytopenia. Hb often falls by >40g/l from baseline

  • Usually due to Parvovirus B19

  • Spontaneous recovery after 7-10 days of aplasia

  • Simple transfusion usually sufficient

 

Acute splenic sequestration

  • Acute anaemia + reticulocytosis + sudden splenic enlargement

  • Commonest <1 y.o. (later in HbSC)

  • Life-threatening in severe cases

  • Small volume simple transfusion up to steady state Hb

  • Risk of hyperviscosity when red cells return to circulation

  • High risk of recurrence —> splenectomy if 2 or more episodes

 

Acute hepatic sequestration

  • Acute anaemia + reticulocytosis + sudden liver enlargement

  • Small volume simple transfusion up to steady state Hb

  • Risk of hyperviscosity when red cells return to circulation

 

Increased haemolysis during painful crisis

  • Hb often drops during painful crisis

  • Usually recovers spontaneously

  • Simple transfusion not usually indicated unless drop of >20g/l or Hb <50g/l

 

Other causes of exacerbation of anaemia

  • HU therapy – severe anaemia is usually due to intercurrent illness, not myelosuppression from the drug. Stop drug temporarily and restart when Hb recovers.

  • Sickle cell nephropathy – slow Hb decline which may become symptomatic.

 

Emergency Transfusion with the primary aim of reducing HbS in relation to HbA

 

Acute Chest Syndrome (ACS)

  • Simple transfusion aiming for target Hb 100-110 g/l prevents progression to respiratory failure in mild ACS if given early.

  • Consider exchange if PaO2 <9.0 kPA on room air or other signs of deterioration.

  • Exchange recommended if

    • Severe ACS

    • Failure to respond to simple transfusion

    • Patients with Hb >90g/l (little leeway for simple Tx)

 

Acute Ischaemic Stroke

  • Aim for HbS <30%

  • Simple or exchange but must be performed urgently at time of stroke

  • Avoid hypovolaemia and aim Hb of 100g/l

 

Acute multi-organ failure

  • Complicates severe painful crises

  • More common in mild SCD where steady state Hb is higher

  • Exchange transfusion required

 

Mesenteric (‘Girdle’) Syndrome

  • Rare, severe sequestration in mesenteric vascular bed, liver and lungs

  • Mimics peritonitis and ileus. Often progresses to include ACS.

  • Exchange transfusion required

 

Severe Sepsis

  • Aggravates sickling. Simple or exchange transfusion may be beneficial

 

Acute intrahepatic cholestasis

  • Extreme conjugated hyperbilirubinaemia. Mechanism poorly understood

  • High mortality from liver failure and bleeding

  • No established treatment but exchange transfusion should be tried.

 

Acute priapism

  • Priority treatment is penile aspiration/irrigation followed by intracavernosal injection of sympathomimetic drugs.

  • Simple/exchange transfusion may aid peri-op optimization is surgery required.

 

Chronic Transfusion

 

Primary Stroke prevention in children (2-16 y.o.)

  • STOP and STOP2 trials - Transfusion to maintain HbS <30% in children with SS or S/B-thal with average Transcranial Doppler Ultrasonography (TCD) velocities >200cm/s in the internal carotid or middle cerebral artery reduces risk of first stroke by 92%

  • TWiTCH trial – Switching to HU after at least one year of transfusion is non-inferior to continuing with chronic transfusion provided no severe cerebral vasculopathy on MRA.

Secondary prevention of silent cerebral infarction in children

  • In children identified as having silent cerebral infarcts, discuss risks and benefits of chronic transfusion with parents. MRA may help risk stratify patients

 

Secondary prevention of overt stroke in children

  • Maintain HbS <30% long-term

  • SWiTCH trial – compared transfusion + chelation vs HU + phlebotomy. Trial stopped early due to clear superiority of transfusion + chelation.

 

Primary Stroke Prevention in Adults

  • No evidence to guide practice

  • What to do when turn 17 if had been on chronic transfusion? Discuss with patient

 

Secondary Stroke Prevention in Adults

  • Investigate as per any other patient – AF, carotid artery disease etc

  • Maintain Hb <30% long-term if stroke attributed to SCD

 

Recurrent ACS

  • HU is 1st line

  • Consider chronic transfusion if HU fails or contraindicated

 

Frequent painful crises

  • Hospital admission ≥3 x per year due to crises is ass. with increased risk of early death

  • HU therapy is 1st line

  • Chronic transfusion if HU fails or contraindicated.

  • Chronic transfusion reduces hospital admissions from 2 to 0.2 per patient per year

 

Other possible indications

  • Based on case-by-case discussion with patient

  • Priapism, avascular necrosis, sickle retinopathy lack evidence but may be appropriate

  • Could be considered in ESRF, pre and post kidney transplant

 

Preoperative Transfusion

(N.B. See also 2021 guideline from Association of Anaesthetists for peri-op management in SCD)

 

Anaesthesia and surgery increase sickle-related complications

Optimise oxygenation, warmth and hydration peri-operatively

Should be performed in centres with specialist haemoglobinopathy support.

 

Role of routine preoperative transfusion

  • TAPS 2013 study – small numbers, but ACS occurred post-op in 27% of untransfused compared to 3% of transfused patients undergoing low to medium risk surgery.

 

Optimal preoperative transfusion regimen

  • No good evidence to guide practice

  • Suggest simple transfusion if Hb <90g/l to achieve Hb of 100g/l prior to low to medium risk surgery.

  • Exchange considered if high-risk surgery, severe SCD or other significant co-morbidities.

 

Emergency Surgery

  • No good evidence

  • Do not delay emergency surgery for transfusion, rather perform intra-op or post-op

 

Transfusion in Pregnancy

 

Maternal complications in SCD

  • Sickle problems, pre-eclampsia, pre-term labour and increased rate of c-section.

 

Fetal complications in SCD

  • Intra-uterine growth restriction, prematurity and increased risk of fetal loss

 

Conflicting evidence on prophylactic transfusion

 

Recommend prophylactic transfusion if:

  • History of previous severe SCD complications

  • Repeated SCD complications during pregnancy

  • If other serious co-morbidities present