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

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