Question 22

In relation to therapeutic plasmapheresis:

a) Describe the principles involved.

b) What are the prerequisites for plasmapheresis to be effective?

c) Give six indications for its use.

d) List three types of potential complications or adverse effects associated with this
therapy, and give one example of each.

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College Answer

Extracorporeal blood purification process to-

  •  remove large molecular weight components of the plasma including antibodies, immune complexes, cryoglobulins, myeloma light chains as examples.
  • Removal is by centrifugation of blood into components. Non plasma components are returned to patient, plasma is discarded.
  • volume removed is replaced by colloid solutions such as plasma products (FFP), or albumin solutions. In some conditions whereby coagulation or immune factors are deficient then FFP replacement provides an additional therapeutic benefit.

To justify therapeutic plasmaphoresis the substances removed should
A) have a sufficiently long T1/2 such that this process results in more rapid removal than other
endogenous clearance (e.g. suppression of macromolecule production),
B) Be key ‘toxic’ factor in the pathogenesis of the disease

Immunoproliferative diseases with monoclonal immunoglobulins
 Hyperviscosity syndrome
 Cryoglobulinaemia
 Renal failure in multiple myeloma
 Autoimmune diseases due to autoantibodies or immune complexes
 Goodpasture’s syndrome
 Myasthenia gravis
 Guillain–Barre´ syndrome
 Chronic inflammatory demyelinating polyneuropathy (CIDP)
 Stiff-man syndrome
 Systemic lupus erythematosus
 Fulminant antiphospholipid syndrome
 Thrombotic thrombocytopenic purpura
 Haemolytic uraemic syndrome
 Rapidly progressive glomerulonephritis
 Coagulation inhibitors
 Autoimmune haemolytic anaemia
 Pemphigus
 Paraneoplastic syndromes
Conditions in which replacement of plasma may be beneficial _ removal of toxins
 Disseminated intravascular coagulation
 Overwhelming sepsis syndromes (e.g. meningococcaemia)
Conditions in which the mechanisms are unknown
 Reye’s syndrome
Removal of protein-bound or large molecular weight toxins
 Paraquat poisoning
 ?Envenomation


a. Complications related to vascular access

i. Catheter-related sepsis

b. Complications related to extracorporeal circuits

i. Hypotension/loss of blood/thrombocytopenia

c. Complications related to exchange fluid

i. More common with FFP (vs Albumin)

ii. Transfusion reactions

iii. Allergic reactions

d. Complications related to anticoagulation

i. Citrate (hypocalcaemia)
ii. Heparin (bleeding, thrombocytopenia)


Though worded slightly differently, this question is nearly identical to Question 14 from the second paper of 2010. That time, the college did not ask for the pre-requisites for effectiveness, just a list of potentially removable substances.

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.

b) 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.

c) Indications for urgent plasmapheresis 

The full list can be seen in this guidelines statement: Zbigniew et al, 2010

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
    • Loss of useful blood proteins (albumin, globulins)
  • Due to volume loss
    • Hypotension
    • Vasovagal syncope
    • Nausea and vomiting


McLeod, Bruce C. "Therapeutic apheresis: use of human serum albumin, fresh frozen plasma and cryosupernatant plasma in therapeutic plasma exchange."Best Practice & Research Clinical Haematology 19.1 (2006): 157-167.

Reimann, P. M., and P. D. Mason. "Plasmapheresis: technique and complications." Intensive care medicine 16.1 (1990): 3-10.

Winters, Jeffrey L. "Plasma exchange: concepts, mechanisms, and an overview of the American Society for Apheresis guidelines." ASH Education Program Book 2012.1 (2012): 7-12.

Oh's Manual: Chapter 97 (pp. 993)  Therapeutic  plasma  exchange  and  intravenous  immunoglobulin  therapy  by Ian  Kerridge,  David  Collins  and  James  P  Isbister.

Szczepiorkowski, Zbigniew M., et al. "Guidelines on the use of therapeutic apheresis in clinical practice—Evidence‐based approach from the apheresis applications committee of the American Society for Apheresis." Journal of clinical apheresis 25.3 (2010): 83-177.

Russi, Gianpaolo, and Piero Marson. "Urgent plasma exchange: how, where and when." Blood Transfusion 9.4 (2011): 356.

Weinstein, Robert. "Basic principles of therapeutic blood exchange." Apheresis: principles and practice (2003): 295-320.