Plasmapheresis

Plasmapheresis is a term used to refer to a broad range of procedures in which extracorporeal separation of blood components results in a filtered plasma product. ^{[1, 2]}

The filtering of plasma from whole blood can be accomplished via centrifugation or the use of semipermeable membranes. ^[3] Centrifugation takes advantage of the different specific gravities inherent to various blood products, such as red blood cells (RBCs), white blood cells (WBCs), platelets, and plasma. ^[4] Membrane plasma separation uses differences in particle size to filter plasma from the cellular components of blood. ^[3]

Traditionally, in the United States, most plasmapheresis has been done with automated centrifuge-based technology. ^[5] In certain instances—in particular, in patients already undergoing hemodialysis—plasmapheresis can be carried out using semipermeable membranes to filter plasma. ^[4]

In therapeutic plasma exchange, using an automated centrifuge, filtered plasma is discarded and RBCs along with replacement colloid (eg, donor plasma or albumin) are returned to the patient.

In membrane plasma filtration, secondary membrane plasma fractionation can selectively remove undesired macromolecules, which then allows return of the processed plasma to the patient instead of donor plasma or albumin. Examples of secondary membrane plasma fractionation include cascade filtration, ^[6] thermofiltration, cryofiltration, ^[7] and low-density lipoprotein pheresis.

Plasmapheresis is currently employed as a therapeutic modality in a wide array of conditions. ^{[2, 8]} Generally, it is used when a substance in the plasma (eg, immunoglobulin) is acutely toxic and can be efficiently removed. Myriad conditions that fall into this category (including neurologic, hematologic, metabolic, dermatologic, rheumatologic, and renal diseases, as well as intoxications) can be treated with plasmapheresis.

The Apheresis Applications Committee of the American Society for Apheresis (ASFA) periodically evaluates potential indications for apheresis and categorizes them from I to IV in the basis of the available medical literature. The following are some of the indications, and their categorization, from the society’s guidelines. ^[2]

Category I indications (disorders for which apheresis is accepted as first-line therapy, either as a primary standalone treatment or in conjunction with other modes of treatment) include the following:

• Guillain-Barre syndrome
• Myasthenia gravis (acute short-term treatment)
• Chronic inflammatory demyelinating polyneuropathy
• Hyperviscosity in hypergammaglobulinemia
• Thrombotic thrombocytopenic purpura
• Goodpasture syndrome (unless it is dialysis-dependent and there is no diffuse alveolar hemorrhage)
• Thrombotic microangiopathy, complement mediated (autoantibody to factor H)
• Wilson disease, ^[9] fulminant

Category II indications (disorders for which apheresis is accepted as second-line therapy, either as a standalone treatment or in conjunction with other modes of treatment) include the following:

• Lambert-Eaton myasthenic syndrome
• Multiple sclerosis (acute central nervous system demyelination disease unresponsive to steroids ^[10] )
• Thyroid storm
• Mushroom poisoning
• Acute disseminated encephalomyelitis
• Autoimmune hemolytic anemia (severe cold agglutinin disease)
• Systemic lupus erythematosus (severe)
• Myeloma cast nephropathy

Category III indications (disorders for which the optimal role of apheresis therapy is not established; decision-making should be individualized) include the following:

• Posttransfusion purpura
• RBC alloimmunization in pregnancy
• Autoimmune hemolytic anemia (severe warm)
• Hypertriglyceridemic pancreatitis ^{[11, 12]}
• Thrombotic microangiopathy, complement mediated (complement factor mutations)
• Stiff person syndrome
• Drug overdose/poisoning
• Immune thrombocytopenia

Category IV indications (disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful; institutional review board [IRB] approval is desirable if apheresis treatment is undertaken in these circumstances) include the following:

• HELLP syndrome (ante partum)
• Hemolytic uremic syndrome (typical diarrhea-associated)
• Multifocal motor neuropathy
• Idiopathic polyarteritis nodosa

There is some evidence that plasmapheresis can be successfully used in patients to alleviate infection-related symptoms associated with antibody-dependent enhancement (ADE) of bacterial disease. ^[13]

It has been suggested that plasmapheresis may be useful in the treatment of COVID-19 by removing cytokines and thus reducing the cytokine response. ^{[14, 15]}

Plasmapheresis is contraindicated in the following patients:

• Patients who cannot tolerate central line placement
• Patients who are in an actively septic state or are hemodynamically unstable - Although plasmapheresis can remove various mediators from the blood and so, in theory, would appear to be potentially useful in treating sepsis, patients in a septic state are often coagulopathic and hemodynamically unstable, which poses significant risks when catheters are inserted and connected to a mechanical circuit; there are some ongoing trials evaluating plasmapheresis in sepsis, but at present, there are no clear data to suggest that the clinical benefits of using plasmapheresis in this setting outweigh the risks associated with its use
• Patients who have allergies to fresh frozen plasma (FFP) or albumin, depending on the type of plasma exchange
• Patients with heparin allergies should not receive heparin as an anticoagulant during plasmapheresis
• Patients with hypocalcemia are at risk for worsening of their condition because citrate is commonly used to prevent clotting and can potentiate hypocalcemia
• Patients taking angiotensin-converting enzyme (ACE) inhibitors are advised to stop taking the medication for at least 24 hours before starting plasmapheresis

Terminology

Although the term plasmapheresis technically refers only to the removal of plasma, it is also widely used to encompass therapeutic plasma exchange in which a replacement product is transfused after removal of the plasma. ^[16]

As distinct from plasmapheresis, cytapheresis is the selective removal of RBCs, WBCs, or platelets and can be accomplished by using identical centrifuge-based equipment. Applications include the following:

• Erythrocytapheresis (selective removal of RBCs) is used in conditions such as sickle cell disease or malarial infection, in which RBCs are selectively removed and replaced with donor erythrocytes
• Leukapheresis (selective removal of WBCs) is used in conditions such as hyperleukocytosis, in which pathologically high number of white cells are present (as, for example, in leukemia); it can also be used to collect peripherally circulating stem cells that can then be infused in an autologous or allogeneic stem cell transplant
• Platelet apheresis (selective removal of platelets) can be used in conditions of thrombocytosis (eg, polycythemia vera)

Complication prevention

Having all the equipment and medications required for the procedure readily available at the start in order to minimize complications is important. Sterile technique is advised in order to reduce the likelihood of infection.

Premedication with acetaminophen, diphenhydramine, and hydrocortisone are often given if the patient is to receive any blood product, including priming the tubing with packed RBCs, in particular if a history exists of prior reaction to blood products. ^[17]