Red Cell Exchange In Sickle Cell Disease Dr. M Joshua Daniel M.D., Consultant Transfusion Medicine MIOT Hospitals Chennai

Definition Red Cell Exchange(RCE): “A therapeutic procedure in which blood of the patient is passed through a medical device(cell separator) which separates RBCs from other components of blood, the patient RBCs are removed and replaced with donor RBCs alone; plus colloid/crystalloid solution

Rationale for transfusion in sickle cell disease Correction of anaemia : Increases O2 carrying capacity Decreases the proportion of Hb S: Reduced sickling/ hemolysis Reduced blood viscosity : if RBC exchange Suppressed erythropoiesis (HbS synthesis)

Indications for RBC exchange in SCD SCD-related complications ASFA indication category Acute RCE Non acute or chronic RCE Acute stoke I Acute chest syndrome, severe II Multiorgan failure III Severe intrahepatic cholestasis Priapism Stoke prophylaxis with prevention of iron overload Vaso- occlusive pain Presurgery Pulmonary hypertension III* End-stage renal disease

Red cell exchange Vs Simple Transfusions SIMPLE TOP UP TRANSFUSIONS Euvolemic procedure Not so limits development of iron overload - Controls HbS and hematocrit Reduces risk associated with increased viscosity Expert man power, technological back up and instruments needed more red cell exposure Comparatively less Comparatively expensive Not expensive

Selection of PRBC PRBCs should be selected less than 2 weeks old (older blood may be given if the presence of red cell antibodies makes the provision of blood difficult) Extended Rh and Kell typed and matched Phenotyped +/- genotyped if needed Prophylactic match if presence of multiple alloantibodies HbS negative, leuko-reduced, not irradiation unless other indication

Instruments used in Automated Red cell exchange

Procedural guidelines These instruments calculate the volume of blood to be removed to achieve the target Hct, the volume of replacement fluid/ volume of packed RBC to achieve the desired post-exchange target Hct level and fraction cell remaining(FCR) ECV is depends on both the type of instrument used. ECV of each instrument is fixed (Generally ECV is 15% of the total blood volume ) PRBC priming is done in children, patients with anaemia and hemodynamic ally unstable patients.

Procedural guidelines Generally 1.5 volume RCE reduces the FCR to 30% of the original. Most of the procedure aim for a post-exchange Hct at 30% and FCR at 30%. In chronic erythrocytapheresis post-exchange Hct is kept under 27% to prevent iron overload Isovolemic hemodilution is performed (RBC depletion with 0.9% NaCl replacement followed by standard RCE).

FCR = % of patient’s pre-procedure RBC remaining at end of exchange

Data required •Sex, height, weight •Patient HCT, average replacement fluid HCT & desired HCT •Fluid balance PRBC : AC ratio 15:1 RCV = TBV x hct Est. TBV M: 70cc/kg F: 65cc/kg Infant: 80cc/kg hild: 70cc/kg 1 .5- Volume exchange reduces the FCR to 30% 2 -Volume exchange reduces the FCR to 15- 20%

Access Options • Peripheral access - 18 gauge dialysis-type steel needles - 18 to 20 gauge angiocaths • AV fistula and grafts • Central venous catheters - Tunneled and Nontunneled • Ports (indicated for power injection) - Single and bilateral - Dual lumen

Potential adverse effects Procedure related : Citrate toxicity (most commonly tingling around lips/fingers) , headache, light-headedness, fainting, BP changes, vagal symptoms, nausea, vomiting, chills, fever, malaise, weakness Thrombocytopenia: Vascular access related: Thrombosis Bleeding, infection, pain Transfusion related: Usual risks associated with labile products including potentially fatal ones like acute hemolytic reaction, TRALI, major allergic reaction, bacterial contamination Most common remain fever and minor allergic reaction

Potential adverse effects Cont.... Alloimmunization : Risk of delayed hemolytic transfusion reaction ; Risk of hyperhemolysis (of particular concern in SCD population and due to very high cumulative exposure to foreign antigens ) Iron overload: possible if cumulative gain of RBC Transmission of infectious agents: extremely low risk currently but new pathogen can appear Anti-hypertensive medications and diuretics may need to be withheld

Conclusion Automated red cell exchange offers many advantages over simple transfusion or manual partial exchange in sickle cell disease patients It is very effective to treat/prevent certain complications of sickle cell disease However, patients are exposed to multiple RBC units when compared to simple transfusions, with the risks that this holds The growth in red cell exchange in recent years is putting an increasing burden to recruit and phenotype donors,

RCE Our experience @MIOT More than 100 RCE since 2013: Optia- Terumo BCT Most commonly for AVN – Hip for Hip replacement Average pre RCE HBS- 73 to 85% Around 30% presented with HBS and anaemia 98% of the cases the RCF was brought to less than 30% in single procedure Most common complications- citrate toxicity, alloimmunisation, catheter related, utricaria. One patient presented with Delayed Hyper-hemolysis syndrome

Take home message The choice of transfusion method, simple or exchange, should be based on clinical judgement of individual cases, taking in account the indication for transfusion and the need to avoid hyperviscosity and minimise alloimmunisation, maintenance of iron balance and venous access issues. Centres not affordable to fully automated exchanges can adopt and practice isovolumic manual exchange

Normal RBC transfusions are recommended for anaemia when haemoglobin is <9g/dL / patients / uncomplicated pain crises.  RCE, however, should considered to treat / prevent complications in patients with SCD, Acute stroke management and prophylaxis Severe acute chest syndrome, Severe sickle cell hepatopathy, Multiorgan failure Iron overload Hyperviscosity (latest AABB recommendations)

Question-1 Which among the following is category-1 indication of Red cell exchange in SCD? Acute Stroke Acute severe chest syndrome Multi organ failure Priapism

Question-2 Simple top up transfusions are recommended when the base line haemoglobin concentration is less than……..? (According to latest AABB recommendations) 8 gms% 9 gms% 10gms% 7 gms%