College Answer

With respect to plasma exchange therapy:

(a)        What are the physical principles of plasma exchange therapy?

•    Separation of plasma from blood cells by centrifugation or membrane filtration
•    Reinfusion  of  cells  plus  autologous  plasma  or  another  replacement  solution  eg albumin
•    Removes large molecular weight substances

(b)        What substances can plasma exchange effectively remove?

•    Pathogenic auto-antibodies
•    Immune complexes
•     Cryoglobulins
•    Myeloma light chains
•     Endotoxin
•    Cholesterol-containing lipoproteins /triglycerides

(c)        List 5 acute conditions where therapeutic plasma exchange is indicated.

Myasthenic Crisis
•    Goodpasture’s Syndrome with pulmonary haemorrhage
•    Hyperviscosity syndromes o   Cryoglobulinaemia o Paraproteinaemia 
o Waldenstrom’s Macroglobulinaemia 
•    Wegener’s Granulomatosis with pulmonary haemorrhage
•    Guillain-Barre Syndrome/Acute Inflammatory Demyelinating Polyradiculopathy
•    Antiphospholipid Antibody Syndrome
•    HELLP syndrome
•    Multiple sclerosis
•    HIV-related neuropathy
•     SLE
•     Pemphigus
•    Paraneoplastic syndromes
•    Rapidly progressive glomerulonephritis
•    Renal transplant rejection
•    Coagulation inhibitors
•    Auto-immune haemolytic anaemia
•     DIC
•    Overwhelming sepsis syndromes eg meningococcaemia
•    Reye’s syndrome
•    Paraquat poisoning

(d)        List     4     common     complications     of     this     therapy,     excluding     catheter-related complications

•    Hypotension due to excess fluid removal +/ inadequate volume replacement
•    Citrate-induced hypocalcaemia
•    Anaphylactic/transfusion reactions to fresh frozen plasma replacement solution
•    Coagulation  abnormalities  due  to removal  of  clotting  factors  not  replaced  when albumin replacement used.
•    Removal of useful immunoglobulins and complement which can in theory lead to an immunodeficient state.
•    Drug  removal  –  especially  drugs  with  high  protein-binding  and  low  volume  of distribution.  Potentials  in the diseases  in which  therapeutic  plasma  exchange  is used are cyclophosphamide and azathioprine.
•     Hypothermia
•    Pyrogenic reactions

•     Anaemia
•     Thrombocytopenia
•     Hepatitis

•     Vasovagal reactions

Discussion

This college answer is an excellent concise overview of what is expected from the college fellows. Note the extensive lists. The candidates were not expected to generate this many indications or complications; the right number of anything from the college list would have earned marks. One can do little in the discussion of such a well-answered question, except provide references for more detailed reading.

Thus; most of the question can be answered after reading Jeffrey L. Winters' 2012 article fromHematology. Additionally, our very own college examiners have put a whole chapter on this technique into Oh's Manual (Chapter 97, pp. 993).

a) Principles of plasmapheresis

• Plasmapheresis may refer to a variety of procedures, all involving the therapeutic separation of blood into components.
• Separation of blood into cellular and fluid components offers the opportunity to discard or modify those components. 
• This separation is usually accomplished by means of either a centrifuge or by the less frequently used method of porous membrane filtration.
• Unlike dialysis or haemofiltration, there is no size barrier: plasmapheresis removes the whole plasma with molecules of all sizes.
• Some blood components are then reinfused into the patient with or without modification, and the rest may be discarded or stored.
• If plasma is being removed,  volume is replaced with 4% albumin or FFP.

   Characteristics of a disease process which make plasmapheresis an effective option:

1. The disease has to be caused by some circulating factor, i.e. it has to be present in the blood
2. That factor has to have a sufficiently long plasma half-life, such that "turning off" the process of its production will still result in significant amounts of it persisting in the bloodstream.

b) Blood components removed by plasmapheresis

Undesirable blood components:

• Antibodies
• Immune complexes
• Abnormal plasma proteins, eg. myeloma light chains
• Immunoglobulins

• Protein-bound drugs
• Monoclonal antibody drugs, eg. rituximab
• Immune complexes
• Cryoglobulins
• Myeloma light chains
• Bacterial endotoxin
• High molecular weight toxins, eg. animal venom
• Cholesterol-containing lipoproteins /triglycerides
• Abnormal cells (eg. leukaemia blasts, excess RBCs or platelets)

Desirable blood components which you'd rather keep:

• Antithrombin
• Pseudocholinesterases and plasma esterases
• Useful antibodies, including monoclonal biological agents
• Useful medications
• Nutrients, eg. glucose, amino acids, water-soluble vitamins
• Diagnostically interesting antibodies (i.e. for serology)

c) Indications for urgent plasmapheresis

Urgent plasma exchange:

• TTP
• Catastrophic antiphospholipid syndrome
• Hyperviscosity syndrome (eg. myeloma)
• Guillain-Barre syndrome
• Myasthenia gravis
• Acute fulminant hepatitis with encephalopathy
• Amanita phalloides poisoning

Less urgent plasma exchange:

• Erythrodermic cutaneous T-cell lymphoma
• Wegeners granulomatosis
• Goodpasture's syndrome
• Eaton-Lambert syndrome
• Babesiosis
• Autoimmune haemolytic anaemia
• Cryoglobulinaemia
• Dermatomyositis/polymyositis
• Hemolytic uremic syndrome
• Familial hypercholesterolaemia
• Focal segmental glomerulosclerosis
• Paraproteinaemic polyneuropathy
• Antibody-mediated renal transplant rejection
• Fulminant Wilson's disease.

One should note that in their list of indications, the college noted some Grade II, III and IV recommendations, such as:

• HELLP syndrome
• Multiple sclerosis
• HIV-related neuropathy
• Pemphigus
• Coagulation inhibitors
• DIC
• Overwhelming sepsis syndromes eg meningococcaemia
• Reye’s syndrome
• Paraquat poisoning

d) Complications of plasmapheresis

• Due to vascular access
  • all the complications of large CVAD insertion: CLABSI, bleeding, vessel damage, etc etc
• Due to the circuit exposure
  • Low fibrinogen and coagulopathy
  • Haemolysis and thrombocytopenia
  • Hypothermia
  • Complement activation
• Due to anticoagulation
  • Paraesthesia due to hypocalcemia (due to regional citrate anticoagulation)
  • Bleeding complications
  • HITS
• Due to the replacement fluid
  • Urticaria
  • Febrile reaction to blood products
  • Anaphylaxis
• Due to the unavoidable removal of useful blood components
  • Loss of useful drugs
  • Immunosuppression
  • Anaphylaxis
  • Hypothermia
• Due to volume loss
  • Hypotension
  • Vasovagal syncope
  • Nausea and vomiting