Joint United Kingdom (UK) Blood Transfusion and Tissue PDF Generated JPAC Transplantation Services Professional Advisory Committee 01/10/2021 14:55

Transfusion Handbook

11: Therapeutic apheresis

http://www.transfusionguidelines.org/transfusion-handbook/11-therapeutic-apheresis

11: Therapeutic apheresis

Essentials

Therapeutic plasma exchange (TPE) using an automated cell separator removes harmful large molecules, such as antibodies, from the circulation. Human albumin (± saline) is the usual replacement fluid. Solvent detergent treated fresh frozen plasma should be used for TPE in thrombotic thrombocytopenic purpura. TPE is only indicated for conditions where there is good evidence it is effective and the benefits outweigh the risks. Therapeutic erythrocytapheresis (replacement of abnormal red cells) is mainly used to treat or prevent complications of sickle cell disease. Less commonly used therapeutic apheresis procedures include leucapheresis and plateletpheresis to reduce dangerously high white cell or platelet counts, extracorporeal photopheresis to inactivate T-lymphocytes and column immunoadsorption to remove specific antibodies.

11.1: Therapeutic plasma exchange (TPE)

TPE removes large-molecular-weight substances such as harmful antibodies from the plasma. It is usually carried out using an automated blood cell separator to ensure fluid balance and maintain a normal plasma volume. This may require the insertion of a femoral or jugular line to allow adequate blood flow. Typically, 30–40 mL/kg of plasma (1–1.5 plasma volumes) are removed at each procedure and replaced with isotonic 4.5 or 5.0% human albumin solution (some services substitute 25–50% of replacement volume with 0.9% saline). Exchange with fresh frozen plasma (FFP) is reserved for the replacement of ADAMTS13 in thrombotic thrombocytopenic purpura (see below) or to replace clotting factors. A one plasma volume exchange removes about 66% of an intravascular constituent and a two plasma volume exchange approximately 85%. TPE is normally combined with disease modifying treatment, such as immunosuppressive drugs, for the underlying condition.

11.1.1: Indications for therapeutic plasma exchange

TPE should only be carried out in conditions where there is good evidence of its effectiveness. The American Society for Apheresis (ASFA – http://www.apheresis.org) produces regularly updated evidence- based guidelines (last updated in 2010). Table 11.1 shows the 2010 category I ASFA indications for TPE (recommended as first-line therapy). Category II indications (TPE is an established second-line therapy) are

page 1 of 5 Transfusion Handbook / 11: Therapeutic apheresis shown in Table 11.2. The evidence base is constantly developing and the decision to implement a course of TPE will usually involve discussion with a transfusion medicine specialist or other expert from the team providing the therapy.

Table 11.1 ASFA Category I indications for therapeutic plasma exchange (first-line therapy based on strong research evidence)

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Speciality Condition

Neurology Acute Guillain–Barré syndrome

Chronic inflammatory demyelinating polyneuropathy

Myasthenia gravis

Polyneuropathy associated with paraproteinaemias

PANDASa

Haematology Thrombotic thrombocytopenic purpura

Atypical haemolytic uraemic syndrome (autoantibody to factor H)

Hyperviscosity syndromes (paraproteinaemias)

Severe/symptomatic cryoglobulinaemia

Renal Goodpasture’s syndrome (anti-glomerular basement membrane antibodies)

Antineutrophil cytoplasmic antibody (ANCA)-associated rapidly progressive glomerulonephritis

Recurrent focal segmental glomerular sclerosis

Antibody-mediated renal transplant rejection

Metabolic Familial hypercholesterolaemia (homozygous)

Fulminant Wilson’s disease

a Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection.

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Table 11.2 ASFA Category II indications for therapeutic plasma exchange (established second-line therapy)

Speciality Condition

Neurology Lambert–Eaton myasthenic syndrome

Acute exacerbation of multiple sclerosis

Chronic focal encephalitis

Neuromyelitis optica

Haematology ABO-incompatible haemopoietic stem cell transplantation

Pure red cell aplasia

Life-threatening cold agglutinin disease

Atypical haemolytic uraemic syndrome (complement factor gene mutations)

Myeloma with cast nephropathy

Red cell alloimmunisation in pregnancy

Immunological Catastrophic antiphospholipid syndrome

Cerebral systemic lupus erythematosus (SLE)

Metabolic Refsum’s disease

11.1.2: Risks associated with therapeutic plasma exchange

Plasma exchange with albumin or saline causes a transient fall in blood-clotting factors and mild prolongation of prothrombin and activated partial thromboplastin times recovering in 4 to 24 hours. Clinically

page 4 of 5 Transfusion Handbook / 11: Therapeutic apheresis significant bleeding is rare but a coagulation screen should be undertaken before surgery or organ biopsy is performed. Other risks include haematomas at venepuncture/line insertion sites, vasovagal episodes with fainting, fluid overload or under-replacement, and allergic or anaphylactic reactions due to plasma infusion.

11.1.3: Thrombotic thrombocytopenic purpura (TTP)

This rare condition is a medical emergency with a mortality of 90% if untreated. It is caused by an acquired (autoimmune) or congenital deficiency of von Willebrand factor cleaving protein (ADAMTS13). TPE, using FFP to replace ADAMTS13, is the treatment of choice and should be started as soon as possible after the diagnosis is suspected, ideally within 4–8 hours. The 2012 British Committee for Standards in Haematology (BCSH) Guidelines on the Diagnosis and Management of Thrombocytopenic Purpura and other Thrombotic Microangiopathies (http://www.bcshguidelines.com) recommend solvent detergent treated FFP (SD-FFP) as the replacement fluid. TPE is more effective than FFP transfusion alone. Platelet transfusions are contraindicated in TTP unless there is life-threatening haemorrhage. Thromboprophylaxis with low molecular weight heparin is recommended once the platelet count is >50×109/L. Daily TPE is continued until the platelet count has been >150×109/L for 2 days.

11.2: Therapeutic erythrocytapheresis

Abnormal red cells are removed and replaced by normal red cell components using an automated cell separator. The most common indication is sickle cell disease (see Chapter 8). Side effects from rapid infusion of red cells in citrate anticoagulant include perioral tingling and paraesthesia due to low ionised calcium level.

11.3: Therapeutic leucapheresis

Very high white cell counts in patients with leukaemia can cause life-threatening leucostasis. Removal of white cells by automated apheresis may improve the clinical symptoms until chemotherapy takes effect.

11.4: Therapeutic plateletpheresis

This is occasionally used in patients with myeloproliferative disorders and symptomatic thrombocytosis until chemotherapy and/or antiplatelet drug therapy takes effect.

11.5: Therapeutic extracorporeal photopheresis

T-lymphocytes separated from the patient’s blood are treated with a photosensitising agent, exposed to ultraviolet radiation to inactivate them and then reinfused. Possible indications include graft-versus-host disease after allogeneic haemopoietic stem cell transplantation and cutaneous T-cell lymphoma.

11.6: Column immunoadsorption

Plasma is removed by apheresis, passed through an adsorption medium to remove harmful antibodies and reinfused to the patient. Indications include removal of high-titre ABO antibodies before ABO-incompatible renal transplantation.

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