Apheresis, Plasmapheresis and Plasma Exchange

OVERVIEW

Definitions

• Apheresis is the general technique of extracorporeal blood purification whereby one constituent is removed and the remainder is returned to the patient
• removal may involve centrifugation or filtration
• Cytapheresis is removal of cellular components from the blood
• Plasmapheresis is a subset of apheresis whereby plasma is removed; this is termed ‘plasma exchange’ when host plasma discarded and replaced  by donor plasma or an alternative colloid

RATIONALE FOR APHERESIS

• substance must be present in the intravascular space
• substance must be so large it can’t be removed by haemofiltration or high-flux haemodialysis
• substance must have sufficiently long-half life
  • can be rapidly cleared by apheresis as compared to endogenous clearance
• substance removal by apheresis must be more rapid than renewal
• substance to be removed must be acutely toxic and resistant to conventional therapy
• untreated the disease must be sufficiently serious to warrant treatment, and there must be a reasonable chance of recovery

PLASMAPHERESIS

• extracorporeal blood purification technique designed for removal of large molecular weight substances from plasma
• separation of plasma from blood cells by centrifugation or by membrane filtration
• reinfusion of cells with:
  • ‘cleaned’ autologous plasma, or
  • donor plasma, or another replacement colloid solution (e.g. albumin, FFP or cryoprecipitate)(this is termed plasma exchange)

SUBSTANCES REMOVED BY PLASMAPHERESIS

• immunoglobulins
• immune complexes
• coagulation factors
• cytokines
• endotoxins
• protein-bound substances (e.g. drugs and toxicants)
• albumin
• triglycerides and other lipids
• myeloma light chains
• cryoglobulins
• auto-antibodies

SPECIFIC INDICATIONS

** = indicated with level 1 evidence (A CHIP O)

Hyperviscosity syndromes

• ** hyperleucocytosis with leukostasis (ALL or AML) – start with hydroxyurea + induction chemotherapy
• ** monoclonal gammapathy – ** multiple myeloma (monoclonal immunoglobulins)
• ** sickle cell crisis – removal of sickled RBCs and replacement with functional RBCs

Immunoglobulins

• ** cryoglobulinaemia (cryoglobulins)
• ** paraproteinaemic polyneuropathies (IgG/IgA)
• Waldenstrom macroglobulinaemia (monoclonal immunoglobulins)

Autoantibodies

• ** AIDP (Guillian Barre Syndrome) – no difference compared to treatment with IV IgG
• ** CIDP (Chronic inflammatory demyelinating polyradiculopathy)
• ** Myasthenia gravis – use in myasthaenic crisis (Anti-ACh receptors)
• ** anti-GBM antibody disease (Goodpastures) – start early prior to Cr > 600
• SLE
• systemic vasculitis with pulmonary haemorrhage
• Hemophilia due to anti-FVIII inhibitors
• Anti-phospholipid antibody syndrome (APLS)
• TTP — plasmapheresis is the mainstay of treatment
• autoimmune haemolytic anaemia (e.g. cold agglutinins)

Circulating immune complexes

• immune complex glomerulonephritis
• SLE
• systemic vasculitis

Protein bound substances

• thyroid storm
• Amanita phalloides toxin (mushroom)
• familial hypercholesterolaemia
• paraquat
• digoxin
• envenomation

Others

• HELLP syndrome
• Multiple sclerosis
• HIV neuropathy
• pemphigus
• paraneoplastic syndrome
• renal transplant rejection
• DIC
• overwhelming sepsis syndromes (e.g. meningococcemia)
• Reye’s syndrome

PRACTICAL ASPECTS

Removal

• 1-1.5 plasma volumes (3-4 L) removed in one sitting (efficiency is less at >1.5 plasma volume exchanges)
• usually repeated daily or on alternate days
• removal of substance follows 1st order kinetics
• A single volume plasma exchange (40 mg/kg) will reduce the concentrations of immunoglobulins, complement proteins, fibrinogen, and other coagulation factors by 50-60% if the plasma is not replaced. Most constituents will return to normal levels within 24 to 48hours
• The efficiency of removal of antibody is often less than anticipated because of rapid resynthesis during an immune response

Replacement

• replacement fluid is typically 4% albumin, FFP or cryoprecipitate
• replacement fluid is given concurrently -> maintains haemodynamic stability

ADVERSE EFFECTS

Vascular access

• vascular access complications as for vascaths

Procedural problems

• hypocalcaemia (from citrate toxicity due to citrate anticoagulation in tubing)
• vasovagal, hypovolaemia, hypotension
• mechanical haemolysis
• air embolism

Replacement fluid effects

• transfusion reactions
• coagulopathy (dilutional from replacement of plasma with non-plasma fluid)
• pharmacological changes -> removal of drugs
• hypothermia
• pyrogenic reactions (fever, chills)
• anaemia
• hepatitis
• electrolyte imbalance
• suxamethonium apnea (due to depletion of plasma cholinesterase)
• sepsis
• hypoproteinemia

References and Links

Journal articles

• Lee G, Arepally GM. Anticoagulation techniques in apheresis: from heparin to citrate and beyond. J Clin Apher. 2012;27(3):117-25. PMC3366026.
• Russi G, Marson P. Urgent plasma exchange: how, where and when. Blood Transfus. 2011 Oct;9(4):356-61. PMC3200401.
• Urbaniak SJ, Robinson EA. ABC of transfusion. Therapeutic apheresis. BMJ. 1990 Mar 10;300(6725):662-5. PMC1662442.