Plasmapheresis

Plasmapheresis Machine

What is Plasmapheresis?

The word ‘plasmapheresis’ (meaning the withdrawal of plasma) was coined by Abel in 1914 to describe a process by which whole blood is withdrawn from the body and separated into its constitutive parts, the cells being returned to the body while the plasma is retained.

Plasmapheresis is a procedure in which whole blood is taken from a person and separated into plasma and blood cells; the plasma is removed and replaced with another solution, such as saline solution, albumin, or specially prepared donor plasma; and the reconstituted solution is then returned to the patient. Plasmapheresis is used in the treatment of many different conditions, including autoimmune disorders. When the plasma is removed, it takes with it the antibodies that have been developed against self-tissue in an attempt to reduce the attack on the patient’s own body. Plasmapheresis carries with it the same risks as any intravenous procedure but is otherwise generally safe.

In other words, plasmapheresis is a process that filters the blood and removes harmful antibodies. It is a procedure done similarly to dialysis; however, it specifically removes antibodies from the plasma portion of the blood. Antibodies are part of the body’s natural defense system which help destroy things that are not a natural part of our own bodies, like germs or bacteria.

Pheresis, or apheresis, describes any process that removes the blood, filters and retains elements of it, then returns the blood to the body. Platelets, red blood cells, white blood cells, or plasma may be separated.

The procedure is performed using a machine that removes small amounts of blood at a time.

Plasmapheresis

Plasmapheresis Machine

There are two ways to separate the components of blood:

  • Centrifugation. This process spins the blood, which divides it according to the density of the parts.
  • Filtration. This involves passing the blood through a filter to separate plasma.

During plasma exchange, the machine will dispose of unhealthy plasma and replace it with healthy plasma from a donor. Unhealthy plasma can also be replaced with saline, albumin, or a combination of the two.

Technical Considerations:

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.

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 a 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, essential thrombocythemia and polycythemia vera)

Indications of Plasmapheresis:

Plasmapheresis is currently used as a therapeutic modality in a wide array of conditions. Generally, it is used when a substance in the plasma, such as 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.

Therapeutic plasmapheresis is a process by which constituents of plasma that are supposed to cause or aggravate disorders are selectively removed. The remaining components of blood are then mixed with a plasma substitute or an inert replacement and given back to the patient. Blood components that are removed may include immune complexes, lipids, antibodies, toxins, mediators of complement activation or inflammation. Molecules, that are supposed to be potentially harmful, are also removed.

This procedure is used for treating many autoimmune diseases with different success rates. Typically, the process is used to rapidly lessen immune complexes or circulating antibodies during autoimmune conditions. The method is frequently used along with other immunosuppressive therapies that help to enhance its beneficial effects or make them more long-lasting.

The Apheresis Applications Committee of the American Society for Apheresis 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.

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

  • Guillain-Barre syndrome.
  • Myasthenia gravis.
  • Chronic inflammatory demyelinating polyneuropathy.
  • Hyperviscosity in monoclonal gammopathies.
  • Thrombotic thrombocytopenic purpura.
  • Goodpasture syndrome (unless it is dialysis-dependent and there is no diffuse alveolar hemorrhage).
  • Hemolytic uremic syndrome (atypical, due to autoantibody to factor H).
  • Wilson disease, fulminant.

Thrombotic Thrombocytopenic Purpura

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

  • Lambert-Eaton myasthenic syndrome.
  • Multiple sclerosis (acute central nervous system demyelination disease unresponsive to steroids).
  • RBC alloimmunization in pregnancy.
  • Mushroom poisoning.
  • Acute disseminated encephalomyelitis.
  • Hemolytic uremic syndrome (atypical, due to complement factor mutations).
  • Autoimmune hemolytic anemia (life-threatening cold agglutinin disease).
  • Systemic lupus erythematosus (severe).
  • Myeloma cast nephropathy.

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

  • Post-transfusion purpura.
  • Autoimmune hemolytic anemia (warm autoimmune hemolytic anemia).
  • Hypertriglyceridemic pancreatitis.
  • Thyroid storm.

Category IV (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) are as follows:

  • Stiff person syndrome.
  • Hemolytic uremic syndrome (typical diarrhea-associated).
  • Systemic lupus erythematosus (nephritis).
  • Immune thrombocytopenia.

Benefits of Plasmapheresis:

A plasma exchange can help to alleviate symptoms of the conditions above by removing harmful substances from the blood.

If a person has an autoimmune condition, plasma exchange may also prevent the body from producing more harmful antibodies.

The procedure is usually one element of a treatment plan, which may include chemotherapy. Repeated plasma exchanges may be necessary.

Plasmapheresis Procedure:

A medical professional will perform plasmapheresis, usually in a hospital but sometimes in a private clinic.

Premedication with acetaminophen, diphenhydramine, and hydrocortisone are often given.

A local anesthetic will numb the affected area, and the procedure should not cause pain.

The doctor will then insert a small tube into a vein in the arm or the groin. The tube will bring blood to the machine, which will collect it, treat it, and return it to the body.

Plasma exchange takes between 2 and 4 hours. A person will need to remain as still as possible to help the blood to flow smoothly. It may help to watch television or read as a distraction.





A medical professional will be present and check for side effects throughout the process.

After the plasma exchange is complete, the machine will be disconnected, and new blood tests will be performed.

Plasmapheresis

Complications of Plasmapheresis:

Patients can experience symptoms of hypocalcemia and or hypomagnesemia during and after the procedure and can be treated with replacement calcium and magnesium, respectively.

Patients frequently become hypothermic during the procedure, in which case they should be warmed appropriately.

Patients can experience transfusion-related reactions, in particular with FFP, and should be treated with diphenhydramine, hydrocortisone, and/or epinephrine depending on the severity of the reaction. These reactions can occur during and after the transfusion.

Patients can experience hypotension as a result of rapid fluid shifts, and proper precautions should be taken to minimize complications such as unintended falls.

Patients can become thrombocytopenic and hypofibrinogenemic after plasmapheresis (especially if albumin is being used as a replacement product) and should be monitored for signs of bleeding.

Patients may also be at further risk for developing hypotension if they have a history of taking angiotensin-converting enzyme (ACE) inhibitors, in particular, while undergoing column-based plasmapheresis. The suspected mechanism is related to increased bradykinin levels caused by the use of ACE inhibitors. This accumulation of kinins leads to hypotension, flushing, and gastrointestinal symptoms. Patients are therefore advised to stop all ACE inhibitors at least 24 hours before starting plasmapheresis.

Contraindications of Plasmapheresis:

Plasmapheresis is contraindicated in the following patients:

  • Patients who cannot tolerate central line placement.
  • Patients who are actively septic or are hemodynamically unstable.
  • Patients who have allergies to fresh frozen plasma 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.

Plasmapheresis VS Plasma Exchange:

Definitions

  • Apheresis is the general technique of extracorporeal blood purification whereby one constituent is removed and the remainder is returned to the patient.
  • Removal may involve centrifugation or filtration.
  • Cytapheresis is the removal of cellular components from the blood.
  • Plasmapheresis is a subset of apheresis whereby plasma is removed; this is termed ‘plasma exchange’ when host plasma discarded and replaced by donor plasma or an alternative colloid.




Plasmapheresis Cost:

The cost of Plasmapheresis is quite high. Per session of this method can cost anywhere between five thousand and ten thousand dollars in the United States. In some cases, this process may be required to be carried out repeatedly. It will help if you have a medical insurance to take care of the costs.

References:

Elliot Stieglitz, MD; Emmanuel C Besa, MD. Plasmapheresis: Background, Indications, Contraindications https://emedicine.medscape.com/article/1895577-overview

Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. J Clin Apher. 2016 Jun. 31 (3):149-62.

Claire Sissons. Plasmapheresis: Side effects and how it works – Last reviewed Tue 10 April 2018. https://www.medicalnewstoday.com/articles/321451.php

McLeod BC, Sniecinski I, Ciavarella D, Owen H, Price TH, Randels MJ, et al. Frequency of immediate adverse effects associated with therapeutic apheresis. Transfusion. 1999 Mar. 39(3):282-8.

Mokrzycki MH, Kaplan AA. Therapeutic plasma exchange: complications and management. Am J Kidney Dis. 1994 Jun. 23(6):817-27.

Brian Weinshenker, M.D. a Mayo Clinic neurologist, describes the process of plasma exchange in the treatment of multiple sclerosis or neuromyelitis optica at Mayo Clinic.

Chris Nickson. Apheresis, Plasmapheresis and Plasma Exchange https://litfl.com/apheresis-plasmapheresis-and-plasma-exchange/

Summary
Plasmapheresis
Article Name
Plasmapheresis
Description
Plasmapheresis is a process that filters the blood and removes harmful antibodies. It is a procedure done similarly to dialysis.
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askhematologist.com
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15 comments

  • I didn’t know that plasmapheresis might include therapeutic plasma exchange processes like leukapheresis and platelet apheresis. I wonder if leukapheresis is the type of plasmapheresis that my brother needs. My mom says they think he might have leukemia, so she’s taking him to a doctor soon.

    • Hi Sarah,

      Thank you for your comment.

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

      Regarding your Mother’s blood problem, you can send me her most recent FBC image by email to have a look and advice.

      Kind regards,

  • Nedhal

    I read that plasmapheresis is a treatment protocol for patients with PGNMID condition. How good it is?

    • Hi Nedhal,
      Thank you for your comment.
      It would be better to discuss with a Nephrologist if plasmapheresis has an effective role here or not? However, since the pathogenesis of PGNMID involves a clonal proliferation of B-cells, treating patients with rituximab or bortezomib along with steroids can lead to the improvement of proteinuria and renal function.
      BW,

  • Edidya

    Thank u very much

  • Elisabeth Frankish

    Hello,
    My friend is suffering very terribly from akathisia, following 12 months of 37 prescriptions of many different psychoactive drugs. I think that she is literally poisoned by them due to polymorphisms in her CYP450 genes, meaning that her body can’t fully metabolise and excrete them.
    She has asked me to be her advocate and together we have asked her doctor to arrange for a test of her CYP450 genes and a test for the presence of psychoactive metabolites of the pharmaceuticals prescribed to her, in her blood. If the doctor agrees to do the tests, and if metabolites are found, showing that she is literally poisoned, could she then justifiably be treated by plasmapharesis to remove the metabolites, to give her relief from torturous suffering and save her life.
    She lives in Oregon, USA.
    I would be grateful for your thoughts,
    Thank you,

    • Hi Elisabeth,
      Contrary to the literature about drug removal during hemodialysis, data regarding drug removal during plasmapheresis are sparse. Over the last 40 years, approximately 70 publications—mostly case reports of overdoses—have described the effects of plasmapheresis on pharmaceutical agents.
      BW,

  • Mansi

    Hi. My name is Mansi. My father is a chronic liver cirrhosis patient since 7-8 years and has developed alot of jaundice in past 20 days. No medicine was giving good results to control rising bilurubin so To control his bilirubin level doctors suggested plasma exchange process as his T- cells were very low too. I wanted to ask if this process is safe and beneficial or not. Thankyou.

  • Ana Malinsky

    There are a lot of new gene therapies on the horizon for diseases like Duchenne muscular dystrophy that use a viral vector for delivery. One of the most common vectors used is AAV (adeno-associated virus) that is harmless to people, however many people have been exposed to it and have antibodies to it. As of right now the pharmaceutical companies are saying that AAV based gene therapy can be given only once and only to people who don’t have antibodies to the vector already from previous natural exposure. Isn’t plasmapheresis the solution for this? What am I missing?
    Thank you!

    • Hi Ana,
      Thank you for your comment.
      Plasmapheresis is a procedure that filters and purifies the blood by removing harmful antibodies located in the plasma, thereby preventing them from attacking the body e.g. in autoimmune diseases. Theoretically, your assumption is logic regarding the removal of AAV antibodies from the body via plasmapheresis prior to gene therapy but it is very unlikely that the procedure would remove 100% of antibodies in the plasma. In some autoimmune diseases, one round of plasmapheresis is estimated to remove 60-70% of the disease-causing autoantibodies in the plasma.
      BW,

  • Can you do Plasmapheresis and pulse Steroid together? Will it remove steroids too? Should you wait to do plasmapheresis after 3 days of pulse in very sick CNS lupus/Sjogren patient?

  • Chelsea Benson

    My daughter has autoimmune encephalitis seronegative . We have tried rituximab and Actemra. the progress has been slow do you think plasmapheresis could be beneficial?

    • Hi Chelsea,
      Thanks for your comment.
      I’ll refer you to this article hoping it could help to answer your query:
      Therapeutic plasma exchange as a life-saving therapy in a suspected case of autoimmune encephalitis: A case report from a tertiary health-care center
      Abstract:
      In half of the suspected autoimmune encephalitis (AIE) patients, no antibodies are identified despite extensive investigation. Therapeutic plasma exchange (TPE) is a potential first-line therapy for various subtypes of AIE. Here, we present a case of autoantibody-negative-suspected AIE, managed successfully with TPE after patient showed no response to steroids. A total of 5 sessions of TPE was done. One standard TPE procedure session was 1.2–1.5 plasma volume exchanges using 5% albumin as a replacement fluid. After five sessions, patient’s clinical condition improved significantly, and a repeated magnetic resonance imaging after 5th cycle of TPE revealed a reduction in the areas of signal alteration. This was suggestive of regression of disease. Patient was discharged on 10th day of hospital admission. With early suspicion even in the absence of detectable autoantibodies, TPE plays an important role in the management of encephalitis.
      BW,

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