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.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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