Plasmapheresis

Both Question 22 from the second paper of 2014 and the near-identical Question 14 from the first paper of 2010 discuss the principles, indications and complications of plasmapheresis. Question 21 from the first paper of 2013 mentions it in the context of TPP (we are invited to explain the difference between plasmafiltration and plasmapheresis). Question 5 from the first paper of 2005 takes a more reflective "critically evaluate" direction.  The college answers to these questions form an excellent concise overview of what is expected from the candidate. Most of the SAQs can be answered after reading Jeffrey L. Winters' 2012 article from Hematology. Additionally, our very own college examiners have put a whole chapter on this technique into Oh's Manual (Chapter 97, pp. 993).

In brief, there are 2 techniques:

Size-based separation using porous filters (less common)

Density-based separation using centrifuges (more common)

In the centrifuge method, blood separates into layers within a rapidly rotating cylinder, with the plasma staying in the centre of the cylinder, and cellular components moving to the periphery. The plasma is discarded and the remaining cells are mixed with a replacement fluid (albumin or FFP) and returned to the patient.

Unlike dialysis, this technique removes the whole plasma, with molecules of all sizes - not just small and middle molecules.

One measures the "dose" of plasma exchange by volume of replacement fluid as compared to the total plasma volume of the patient. If a patient has about 4L of plasma and 4L of replacement fluid is used in the course of plasma exchange, it is said to be a 1 plasma volume exchange.

The rate of removal is incomplete - one cannot remove the entire fluid volume by spinning the cells down to their "dry" weight. Thus, for every 1-1.5 plasma volumes exchanged, about 60-70% of the plasma substances are removed. For every subsequent volume exchanged, the absolute amount of the substances decreases but the proportion remains the same (60-70%). Thus, with increasing doses of plasma exchange, the efficiency diminishes. Generally speaking only 1-1.5 plasma volumes are exchanged in each session.

The process of exchange is non-selective, and removes all plasma contents, good and bad. FFP replaces some of these, but not all.

Undesirable molecules removed by plasma exchange

  • Immunoglobulins
  • Protein-bound drugs
  • Monoclonal antibody drugs, eg. rituximab
  • Immune complexes
  • Cryoglobulins
  • Myeloma light chains
  • Bacterial endotoxin
  • Cholesterol-containing lipoproteins /triglycerides

Desirable molecules removed by plasma exchange, and not replaced with FFP and albumin:

  • Antithrombin
  • Pseudocholinesterases and plasma esterases
  • Useful antibodies (for diagnostic serology)
  • Useful medications

Indications for urgent plasma exchange

Russi and Marson have a 2011 article which presents a table with a few indications for urgent plasma exchange. The gospel list of all indications can be found in the ASFA guidelines statement from 2010. Their list is massive, spanning three pages of their ninety-five page statement. Highlights from this list (those indications which received Grade I recommendation) include the following:

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

Complications of plasma exchange

The question specifically asks about complications unrelated to catheterisation.

  • Paraesthesia due to hypocalcemia (due to regional citrate anticoagulation)
  • Urticaria
  • Low fibrinogen and coagulopathy
  • Hypotension
  • Vasovagal syncope
  • Nausea and vomiting
  • Haemolysis and thrombocytopenia
  • Loss of useful drugs
  • Immunesuppression
  • Anaphylaxis

 

References

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.