Apheresis

Apheresis is a automated machine-assisted procedure in which blood is removed from a patient through an intravenous line. The blood is fed into an apheresis machine where it is centrifuged to separate the blood into parts (Red Blood Cells, Plasma, Platelets, White Blood Cells). Individual components can be harvested and the remainder of the components can be returned back into the patient. Apheresis can be used as a way to donate Red Blood Cells, Platelets, Plasma, Granulocytes, Stem Cells, etc., but also as a therapeutic procedure for many conditions. 

The TerumoBCT Spectra Optia is a common CFC
apheresis machine and a popular choice for therapeutic apheresis. 

There are two main apheresis systems which consists of continuous flow centrifugation (CFC) and intermittent flow centrifugation (IFC). Other lesser used methods involve filtration and adsorption. Intermittent Flow Centrifugation involves a system in which blood is removed from the vein centrifuged/processed within the machine, and unused components are returned back into the patient's circulation. This happens in cycles until the desired volumes have been achieved. Continuous Flow Centrifugation involves a system in which the blood can be removed and returned to the patient simultaneously without waiting for the cycle to complete like with IFC. This typically requires two IV lines (both arms for example) to perform, but newer technology being created allows for CFC to be performed using one IV line. 

IFC is not typically used for therapeutic apheresis purposes. Many instances of IFC apheresis machine use is seen in smaller donation centers or mobile donation centers with apheresis capabilities. IFC is a slower procedure due to the waiting-time in between cycles and it requires a higher extracorporeal volume to run. Extracorporeal refers to a process taking place outside of the body, so the extracorporeal volume in this case is the amount of the blood that the apheresis machine needs to take out of the body at a given time to process it. CFC can be performed quicker and also uses a lower extracorporeal volume (ECV) due to the continuous nature of the process. This is advantageous to children and elderly who may have lowered Total Blood Volumes or may be otherwise negatively impacted by a larger volume of blood being removed from the body at any given time. IFC also typically requires the patient to be exposed to higher levels of anticoagulant solutions over CFC methods. 

The majority of new apheresis technologies on the market are CFC based. Haemonetics makes most of the IFC-based apheresis machines in the market today such as the MCS+,PCS2, and CYMBAL. They've also made S-30 and V-50 machines in the past. Trima Accel, Optia Spectra, Cobe Spectra, Amicus by Fresnius Kabi are some of the more popular and commonly used CFC devices. 

This is the Channel that connects into the centrifuge bowl of a Spectra Optia. During centrifugation parts of the blood are separated by density. Red Blood Cells will be at the bottom of the channel, plasma will be on top. Platelets, Mononuclear Cells, and Granulocytes will have a layer somewhere in the middle. The apheresis machine can monitor the interface and allow the user to select which portions to keep and which portions to remove for collection/removal. There are multiple lines leading from the channel and the user can remove product from different zones of sedimentation allowing for removal of just 

https://www.terumobct.com/Public/306670488.pdf

Typically, it is required to perform some calculations prior to performing an apheresis procedure to ensure the proper amount of blood is removed and returned. Most importantly the Total Blood Volume of a person must be calculated. It is not enough to assume the "average" of 5.0 liters. Typically this calculation involves a patient's height, weight, and sex. Depending on the procedure, it may be necessary to know the patient's hematocrit, plasma volume, pre-transfusion Hemoglobin S percentage, etc. Many of the automated systems will perform a Total Blood Volume or plasma volume calculation right in the software.

Donation Apheresis

• Red Blood Cells -- Apheresis can be used to donate Red Blood Cells. The machine will separate the Red Blood Cells to collect and return plasma, platelets, and white blood cells back to the patient. This donation type is often termed "Power Reds" or "Double Reds" due to the fact that the collection results in a donation of two whole Red Blood Cell units compared to just one during a normal gravity fed whole-blood donation. Patients must meet a strict height and weight minimum to be able to donate with their blood donation center. There is generally a minimum Hemoglobin requirement as well which is usually 13.3g/dL. Patients will generally have less side effects compared to typical whole blood donation, because their plasma is being returned. 

• Plasma --- The process is also known as Plasmapheresis -- Blood plasma can be donated via apheresis as well. The procedure has the ability to collect up to four times the amount of plasma that would be donated during a normal whole blood donation. This is especially important for patients who are type AB. Type AB plasma is compatible with all blood types, which makes it a top choice for emergent situations, such as a trauma, when a patient's blood type may not be yet known. Depending on the patient's blood volume, enough plasma may be collected to process up to four entire units of plasma. Plasmapheresis is the preferred donation method for type AB patients for this reason! Patients can generally donate every 28 days. That's 13 times a year!
  
  
• Platelets -- Platelets collected via apheresis are typically the most common type of platelet available on a transfusion center Blood Bank's shelf. Some blood centers do still offer pooled platelets collected from several whole blood donations, but they are much less common these days. Apheresis platelet collection is also the preferred method of collection for platelets. Depending on the platelet count and blood volume of a patient, an apheresis procedure can procure up to three entire units of platelets. This is especially important because platelets are in constant need. A unit of platelets is only good for 3-5 days once it reaches a transfusion center Blood Bank. A platelet donor can donate much more often than Red Blood Cells or plasma. It may depend on the blood center, but the American Red Cross for example, allows donation of platelets every 7 days.
  
  
• Granulocytes -- Granulocytes (a type of White Blood Cell) can be donated to those battling severe infection who don't have a functioning immune system to fight the infection by themselves and haven't responded to antimicrobials. This is not a routine donation, and blood centers will generally contact previously known donors (such as frequent apheresis platelet donors) to come in and donate granulocytes. Donors, especially in the United States may be given Granulocyte Colony Stimulating Factor (G-CSF) to stimulate the production of excess granulocytes that can then be harvested in greater numbers during apheresis. 
  
  
• Stem Cells -- The most common form of hematopoietic (blood) stem cell donation today is through apheresis. Donors will typically be asked to receive injections of Filgrastim (Neupogen) for a few days prior to donating. Filgrastim forces tells the bone marrow to make more cells, and in doing such creates a higher concentration of circulating hematopoietic (blood) stem cells in the donor as well. The vast majority of donors have a high enough stem cell count that they only need to donate once after being stimulated with Filgrastim. The recipient requiring a stem cell transplant can then receive the hematopoietic stem cell donation via simple intravenous infusion like any other blood product.

Therapeutic Apheresis 

Erythrocytapheresis -- Apheresis can be used therapeutically in regards to Red Blood Cells as well. Some of the most common indications include:

Red Blood Cell Exchange (RBCX) transfusion -- 

• Sickle Cell Disease ---  patients who consistently have higher Hemoglobin S counts and are prone to sickle cell complications or HAVE such complications as Sickle Crises, Acute Chest, stroke, etc., are the most common population to benefit from Red Blood Cell exchanges. The apheresis process can remove a large portion of the patient's sickled blood and replace it with donor NON-sickled (Hemoglobin S negative) blood. The procedure will not remove 100% of Hemoglobin S positive cells in one procedure. Many patient's who meet the criteria will be set up on a schedule and get regular, usually monthly RBCX transfusions. This procedure can help relieve symptoms from the previously mentioned as well as relieve issues such as iron overload that may be seen in sickle patient's who receive frequent simple transfusions. Using an automated apheresis also allows the clinical team to accurately input values to achieve a target post-transfusion HgbS count as well as hematocrit. 
  
  
• Intracellular Infection -- Patients with severe intracellular parasitic protozoan infections such as Babesia or Malaria with a high parasitic load may benefit from Red Blood Cell exchange therapy to lower the amount of parasite-infected Red Blood Cell within the body. This is usually done in conjunction with other therapies and is not the first line therapy. With Malaria apheresis may be indicated when %parasitemia reaches 30% or greater in patient's without excess complications, and 10% or greater with patient's with infection complications. Babesia infected patients will generally benefit from apheresis if there %parasitemia is 10% or greater who have severe symptoms or are at high risk of complications. This is not commonly performed and typically other methods of treatment will be sought first. 

Reducing Erythrocytes (Red Cell Depletion) --

• Incompatible Hematopoietic Stem Cell Transplant -- Patient's receiving ABO incompatible hematopoietic stem cell transplants may have their allogeneic stem cell collection Red Blood Cell depleted which lowers the amount of incompatible Red Blood Cells that they may come in contact with. This is done to prevent any immediate hemolyzing event upon infusion of the product. 

• Erythrocytosis -- Patients with a erythrocytosis (excess Red Blood Cells in circulation) may benefit from an apheresis procedure designed to lower the amount of the red blood cells in circulation to prevent or alleviate symptoms caused by too many Red Blood Cells in circulation. The removed blood is generally replaced with 4% albumin. Erythrocytosis can be caused by Polycythemia vera, a type of cancer, or by other secondary causes. Erythrocytapheresis (Red Blood Cell apheresis) is more likely to be performed on a patient with Polycythemia vera than a patient with secondary causes of erythrocytosis. Read more about Polycythemia vera
  
  
• Hereditary Hemochromatosis -- Patient's with hereditary hemochromatosis have a genetic predisposition to retain more iron than is actually needed. The iron builds up in the body and can begin to exhibit toxic affects on the body and organs. One way to remove excess iron is by removing portions of the blood at given intervals. Often times, this is done by a simple phlebotomy where blood is drawn into a bag (similar to donating blood) and discarded. Depending on the indications and conditions of the patients apheresis may also be used to achieve this. Some studies have shown it is more effective in reducing the iron storage overload over traditional phlebotomy methods. 
  
  

Plasmapheresis -- Therapeutic Plasma Exchange (TPE)  or PLEX (Plasma exchange) is used for many conditions, especially autoimmune conditions and diseases that aim to remove the target autoantibodies from the plasma and replace it with other fluids. In some cases, the replacement fluid maybe FFP/plasma. In other cases, it may be albumin and or a mix of albumin and normal saline (NS). Actual human derived plasma units are generally used only when necessary in order to reduce recipient exposure to donor plasma which always carries inherent risks.  The most common indications for plasma exchange therapy include:

• Thrombotic Thrombocytopenic Purpura (TTP) -- Patient's with TTP often have an autoantibody inhibiting the function of an enzyme known as ADAMTS13. This enzyme helps to ensure von-Willebrand factor/platelet complexes do not grow out of control and form clots within the circulating blood. Patient's with TTP are at an extreme risk of clotting due to this inhibition, but also bleeding because platelets are used up in this process of inhibition as well. Donor FFP units, which should have normal levels of ADAMTS13 and no autoantibodies, are generally used in this instance to replace the patient's plasma. 
  
  
• Myasthenia gravis (MG) --- MG is an autoimmune condition in which autoantibodies (antibodies directed towards part of yourself) attack specific neuromuscular targets such as nicotinic acetylcholine receptor or Muscle-Specific Kinase which can lead to skeletal muscle weakness and fatigue. Patient's with MG can typically get rounds of plasmapheresis which can remove their plasma containing the harmful autoantibodies and replace it with an albumin solution.
  
  
• Goodpasture Syndrome -- Goodpasture Syndrome is another autoimmune disease in which autoantibodies are created towards the "Basement Membrane" of the lungs and/or kidneys. These antibodies can eventually lead to the destruction of lung and kidney tissue which can cause bleeding in the lungs, hemoptysis (coughing up blood), and glomerulonephritis/kidney damage. A plasma exchange with albumin can help remove these autoantibodies from causing damage. 
  
  
• Guillain-Barre syndrome - Patient's with Guillain-Barre syndrome have autoantibodies directed towards the peripheral nervous system (as opposed to the Central Nervous System such as brain or spinal cord) and sometimes the myelin sheath, which protects and insulates nerve cells causing pain and muscle weakness/fatigue. Plasmapheresis is a usable treatment to remove the antibodies from the patient's plasma. 

While these are the most common indications, the list is certainly not exhaustive. Other indications include people with Wilson's Disease, certain stages of ANCA associated vasculitis, patient's receiving an incompatible Blood Type organ, patient's with atypical Hemolytic Uremic Syndrome in the setting of auto-Factor H antibody, patients with plasma hyperviscosity in the presence of hypergammaglobulinemia, and many more.   

Plateletpheresis -- also known as Thrombocytapheresis. Plateletpheresis is generally indicated in patients with demonstrated thrombocytosis (elevated platelet count above 450K) or sometimes referred to thrombocythemia. Severe thrombocytosis is generally a result of a malignant process such as Polycythemia vera, myelofibrosis, leukemia, or essential thrombocythemia. 

Thrombocytosis can result in an increased risk of clotting within the vessels leading to stroke, heart attack, or other organ damage as well as an increased risk of bleeding due to the potential production of abnormal / non-functioning platelets. Apheresis can help remove excess platelets to drastically decrease the risk of a thrombotic (clotting) event. This is typically done in conjunction with a cytoreduction medication therapy (such as hydroxyurea) which can help keep platelet levels from increasing again after the procedure. 

Thrombocytapheresis is generally considered once PLT count levels reach 1,000,000 platelets per microliter. Post-procedure goal is to get the platelets below 400-450,000 per microliter. 

Leukocytapheresis -- also known as Leuko/Leukapheresis or White Cell depletion. This procedure is typically performed on patients who have a malignancy that is causing their White Blood Cell count to elevate to dangerous levels, such as Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia. Hyperleukocytosis (White Blood Cell levels above 100,000 per microliter of blood) is especially dangerous and usually requires more immediate and more unique treatment. 

Counts above 100,000 can lead to Leukostasis, a emergent pathology in which white blood cells begin to "plug" the microvasculature and and in turn decrease the amount of oxygen that is fed to the tissues of the body and can initially lead to dyspnea, hypoxia, headaches, dizziness, confusion,etc., before worsening to outright tissue damage and death. White Blood Cell counts that high also put the patient at an increased risk of Disseminated Intravascular Coagulation (DIC), hypercoagulable/hyperviscous blood which can lead to stroke/heart attack/tissue damage, and tumor lysis syndrome. 

Tumor Lysis Syndrome occurs when a large amount of cells begin to die at the same time (such as when starting chemotherapy for leukemias). The dying cells release their contents into the blood and overwhelm the kidney and the body. This causes things like uric acid, potassium, and phosphate to drastically rise within the blood. Leukocytapheresis can be used effectively to deplete the body of excessive white blood cells, lessening the risk of DIC and leukostasis. It can also be used to drastically lower the amount of circulating leukemic White Blood Cells in circulation prior to giving chemotherapy in order to minimize the Tumor Lysis Syndrome risk. 

Hematopoietic Stem Cell -- As mentioned above, apheresis can collect hematopoietic stem cells for infusion into a recipient in need. It can also be used autologously. For example, in patients with lymphomas and multiple myeloma it is common to perform an autologous hematopoietic stem cell transplant. The hematopoietic stem cells are harvested from the patient via apheresis. They are then usually given drugs and or chemo to kill off the cells in the bone marrow so it can no longer produce cells (including the cancerous ones). They are then given their hematopoietic stem cells back in the form of a transfusion so the cells can repopulate and repair/regrow the bone marrow. 

Apheresis indications are typically based off of known and well established guidelines. The third page and on from this PDF has more specific information regarding apheresis guidelines. 

APHERESIS COMPLICATIONS

 As with any medical procedure, there can be complications associated with apheresis. Some possible complications of apheresis include:

Bleeding: The procedure involves the insertion of a needle into a blood vessel, which can cause bleeding. In some cases, bleeding can be severe and require medical attention.

Low blood pressure: Apheresis can cause hypotension or low blood pressure, which can lead to dizziness, lightheadedness, or fainting. 

One of the primary reasons is that during apheresis, blood is removed from the body and processed outside of the body, which can lead to a decrease in blood volume. When there is less blood circulating in the body, it can cause a drop in blood pressure.

In addition to the decrease in blood volume, other factors that can contribute to hypotension during apheresis include:

• Anticoagulants: Apheresis often involves the use of anticoagulants to prevent blood from clotting during the procedure. These medications can sometimes cause a drop in blood pressure.
  
  
• Vasodilation: Apheresis can cause the blood vessels in the body to dilate or expand, which can decrease resistance to blood flow and lead to a drop in blood pressure.
  
  
• Reflex response: Some people may experience a reflex response to the removal of blood, which can cause the blood vessels to constrict and increase the heart rate. This can lead to an initial increase in blood pressure, followed by a drop in blood pressure as the body tries to compensate.

Infection: There is a risk of infection associated with any procedure that involves the insertion of a needle into the body.

Allergic reactions / Transfusion Reactions: Some people may be allergic to the anticoagulant used during apheresis or to the blood products being transfused back into their body.

Electrolyte imbalances:  Apheresis can cause electrolyte imbalances by removing or adding certain blood components that contain electrolytes. Electrolytes are minerals in the body that have an electric charge and are essential for the proper functioning of various bodily processes. During apheresis, different blood components are removed or added back to the body, which can lead to changes in the levels of electrolytes in the blood.

For example, plasma, which is a component of blood that contains electrolytes such as sodium, potassium, and calcium, may be removed during apheresis. This can cause a decrease in the levels of these electrolytes in the blood. On the other hand, if a person receives a transfusion of blood components such as albumin or red blood cells, this can lead to an increase in the levels of electrolytes in the blood.

In addition to changes in blood components, apheresis can also affect electrolyte balance by removing fluids from the body. This can lead to dehydration, which can cause electrolyte imbalances such as a decrease in sodium levels (hyponatremia).

Furthermore, the anticoagulants used during apheresis can also affect electrolyte balance. For example, citrate, which is commonly used as an anticoagulant during apheresis, can bind to calcium in the blood, leading to a decrease in the levels of ionized calcium. This can lead to a condition called hypocalcemia, which can cause muscle cramps, seizures, and other complications.

Blood clots: Apheresis can increase the risk of blood clots, particularly in people with underlying medical conditions such as cancer, diabetes, or cardiovascular disease.

Nerve damage: Apheresis involves the insertion of a needle or catheter, which can sometimes damage nerves and cause numbness, tingling, or weakness.

Fluid overload: In rare cases, apheresis can cause too much fluid to be returned to the body, leading to swelling or other complications.

Adverse reactions to medications: Some medications used during apheresis can cause side effects such as nausea, vomiting, or allergic reactions.

Hypocalcemia: Apheresis can cause a decrease in calcium levels in the blood, which can lead to muscle cramps, seizures, or other complications.