Therapeutic plasma exchange (TPE) is a procedure in which the plasma is isolated, then discarded and replaced with a substitution fluid such as albumin. Plasma exchange (PE) is a nonspecific therapy, since the entire plasma is discarded. PE has been used in a wide variety of acute and chronic conditions, as well as in the setting of solid organ transplantation.
The terms therapeutic apheresis, plasmapheresis, and therapeutic plasma exchange are often used interchangeably but technically denote different procedures. The American Society for Apheresis (ASFA) definitions for these procedures are as follows:
Apheresis: A procedure in which blood of the patient or donor is passed through a medical device which separates out one or more components of blood and returns remainder with or without extracorporeal treatment or replacement of the separated component.
Plasmapheresis: A procedure in which blood of a patient or the donor is passed through a medical device which separates out plasma from the other components of blood and the plasma is removed (i.e., less than 15% of total plasma volume) without the use of replacement solution.
Therapeutic Plasma exchange: A therapeutic procedure in which blood of the patient is passed through a medical device which separates out plasma from other components of blood, the plasma is removed and replaced with a replacement solution such as colloid solution (e.g., albumin and/ or plasma) or a combination of crystalloid/colloid solution.
This policy addresses TPE and PP as therapeutic apheresis procedures, and does not differentiate between the two for medical policy coverage. The rationale for PE is based on the fact that circulating substances, such as toxins or autoantibodies, can accumulate in the plasma. Also, it is hypothesized that removal of these factors can be therapeutic in certain situations. PE is essentially a symptomatic therapy, since it does not remove the source of the pathogenic factors. Therefore the success of PE will depend on whether the pathogenic substances are accessible through the circulation and whether their rate of production and transfer to the plasma component can be adequately addressed by PE. For example, PE can rapidly reduce levels of serum autoantibodies; however, through a feedback mechanism, this rapid reduction may lead to a rebound overproduction of the same antibodies. This rebound production of antibodies is thought to render the replicating pathogenic clone of lymphocytes more vulnerable to cytotoxic drugs; therefore, PE is sometimes used in conjunction with cyclophosphamide.
Applications of PE can be broadly subdivided into two general categories: 1) acute self-limited diseases, in which PE is used to acutely lower the circulating pathogenic substance; and 2) chronic diseases, in which there is ongoing production of pathogenic autoantibodies. Because PE does not address underlying pathology, and, due to the phenomenon of rebound antibody production, its use in chronic diseases has been more controversial than in acute self-limited diseases.
In addition, plasmapheresis has been used in the setting of solid organ transplantation. It has been used as a technique to desensitize high-risk patients prior to transplant and also as a treatment of antibody-mediated rejection reaction (AMR) occurring after transplant. Prior to transplant, plasmapheresis has been most commonly used to desensitize patients receiving an ABO mismatched kidney, often in combination with a splenectomy. As a treatment of AMR, plasmapheresis is often used in combination with intravenous immunoglobulin (IVIg) or anti-CD20 therapy (i.e., Rituxan).
The use of PE in patients with acute, life-threatening complications of chronic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE), may need to be considered on an individual basis. An example of such a situation would be the development of a severe vasculitis, in which it is hoped that the use of PE can acutely lower the level of serum autoantibodies until an alternate long-term treatment strategy can be implemented. However, in these situations, the treatment goals and duration of treatment with PE need to be clearly established prior to its initiation; without such treatment goals, the use of an acute short-term course of PE may insidiously evolve to a chronic use of PE with uncertain benefit.
Diagnostic Criteria for CIDP
The following criteria are adapted from the Task Force Report of the Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force found in Neurology (1991) 41:617-18. The report included mandatory, supportive, and exclusionary diagnostic criteria. Only the mandatory criteria are excerpted here. The criteria are based on a combination of clinical observations, physiologic studies, pathologic features (i.e., nerve biopsy), and studies of the cerebrospinal fluid (CSF).
I. Clinical criteria include the following mandatory requirements:
- Progressive or relapsing motor and sensory (rarely only motor or sensory) dysfunction of more than one limb of a peripheral nerve nature, developing over at least two months;
- Areflexia (absence of reflexes) which will usually involve all four limbs.
II. Physiologic Studies include: Mandatory - Nerve conduction studies including studies of proximal nerve segments in which the predominant process is demyelination. Must have three of four of the following:
1. Reduction in conduction velocity (CV) in two or more motor nerves:
- <80% of lower limit of normal (LLN) is amplitude >80% of LLN
- <70% of LLN is amplitude <80% of LLN.
2. Partial conduction block or abnormal temporal dispersion in one or more motor nerves: either peroneal nerve between ankle and below fibular head, median nerve between wrist and elbow, or ulnar nerve between wrist and below elbow.
Criteria suggestive of partial conduction block: <15% change in duration between proximal and distal sites and >20% drop in negative peak (p) area or peak to peak (p-p) amplitude between proximal and distal sites.
Criteria for abnormal temporal dispersion and possible conduction block:
- >15% change in duration between proximal and distal sites; and
- >20% drop in p area or p-p amplitude between proximal and distal sites; and
- >20% drop in p or p-p amplitude between proximal and distal sites.
These criteria are only suggestive of partial conduction block as they are derived from studies of normal individuals. Additional studies, such as stimulation across short segments or recording of individual motor unit potentials, are required for confirmation.
3. Prolonged distal latencies in two or more nerves:
- >125% of upper limit of normal (ULN) if amplitude >80% of lower limit of normal (LLN)
- >150% of ULN if amplitude <80% of LLN.
4. Absent F waves or prolonged minimum:
- >120% of ULN if amplitude >80% of LLN
- >150% of ULN if amplitude <80% of LLN.
III. Pathologic features are tested using the following mandatory study: Nerve biopsy showing unequivocal evidence of demyelination and remyelination and demyelination by either electron microscopy (>5 fibers) or teased fiber studies >12% of 50 fibers, minimum of four internodes each, demonstrating demyelination/remyelination.
IV. Cerebrospinal fluid (CSF) studies include the following mandatory tests:
- Cell count <10/mm-3 if human immunodeficiency virus (HIV)-seronegative or <50/mm-3 if HIV seropositive, and
- Negative Venereal Disease Research Laboratory (VDRL).