FUNDAMENTALS OF NURSING CARE IN PATIENTS UNDERGOING APHERESIS PROCEDURE

 




LEARNING OBJECTIVES

At the end of the course the nurse will be able to:

πŸ”° organize appropriate plan of care with regards to emergencies,     early detection and prevention of immediate& late complications
πŸ”° Perform nursing procedures specific to Apheresis procedure


INTRODUCTION

Apheresis, derived from the Greek words ‘apo’ meaning ‘away’ and ‘pheresis’ – ‘taking’, is the process which involves the removal of whole blood, and then separating and collecting any of the components, whilst returning remaining blood components to the patient/donor. 

In some situations this requires the replacement of a collected component to maintain haemodynamic status. 

Often the term ‘apheresis’ is prefixed by the name of the component being targeted –

πŸ€ Plasmapheresis: collection of plasma 
πŸ€ Plateletpheresis: collection of platelets 
πŸ€ Leukapheresis: collection of white blood cells 
πŸ€ Eythrocytapheresis: collection of red blood cells 


The advent of sophisticated blood cell separators has dramatically changed the applications of apheresis with increasingly specific blood cells being targeted.

Anticoagulated blood is separated either by centrifugation (cells are separated according to size and density) or filtration (cell size) or a combination of both. This technology is now used in both the donor setting for the collection of blood products (apheresis has become an integral component of transfusion medicine) and in therapeutic applications for the treatment of many disease processes - often as supportive therapy alongside conventional therapies such as chemotherapy. 

Automated cell separators are machines used to collect and/or treat blood components in apheresis. The devices have an enclosed extracorporeal circuit through which whole blood travels with the aid of pumps. Whole blood is separated within these machines by centrifugation: blood components have different specific gravities. When exposed to centrifugal force, blood components will separate according to their specific gravities. This method of separation is the most commonly used in apheresis procedures.

Abbreviations


Definitions









Anticoagulation

Anticoagulation of the donor/patient blood whilst in the extracorporeal circuit is necessary to prevent blood from clotting. 

The anticoagulant of choice for most apheresis procedures is citrate (ACD-A). 


ADC-A is administered directly into the patient’s blood as it is drawn into the extracorporeal circuit, and then returned to the donor/patient indirectly where it is rapidly metabolized by the kidney, liver and muscles. 

ACD-A prevents coagulation by lowering the pH of the blood and also binds ionized calcium, essential in the clotting process. The half-life of ACD-A is 20-60 minutes where liver function is normal. A citrate reaction is therefore more likely to occur if the patient has abnormal liver function.

Systemic anticoagulants such as heparin are not used in the donor setting. Heparin does not affect the pH or ionized calcium levels in the blood therefore platelet aggregation is not inhibited making the use of heparin as an anticoagulant not conducive for platelet storage.

Vascular Access


Good vascular access is essential for a successful apheresis procedure. At least one good cubital fossa vein is required to draw whole blood from the donor/patient. A steel 16-17 gauge backeye butterfly needle is used to support rapid flow of whole blood during apheresis procedures.

If good peripheral access is not available, then a large bore central venous catheter should be considered, such as a ‘Vascath’ / ‘Certofix’ (generally 11 – 12 French).

Access through peripheral veins is preferred because it is associated with fewer infections, thrombotic complications, and insertion-related complications (bleeding or pneumothorax) as compared to central lines. When frequent procedures over a prolonged period of time are required, for example in TTP (thrombotic thrombocytopenic purpura) therapy, a double-lumen central venous catheter designed for apheresis or hemodialysis should be inserted. For patients requiring chronic apheresis, an arteriovenous fistula or an apheresis implantable access device may be used.

Apheresis procedures performed at BOC

🍬 Peripheral Blood Stem Cell Collection (PBSC)
🍬 Therapeutic plasmapheresis (TPE / Plasma exchange)
🍬 Therapeutic Leukapheresis
🍬 Plateletpheresis
🍬 Therapeutic Plateletpheresis
🍬 Granulocyte collection
🍬 Therapeutic erythrocytapheresis (Red Cell Exchange)

Peripheral blood stem cell collection

Peripheral blood stem cell collection (PBSC) is the collection of haematopoietic progenitor cells (HPC’s) from the peripheral blood circulation of patients and donors. Often called stem cells, these cells have the capability to self-renew and differentiate into any of the blood cell lines produced in the bone marrow and are used in bone marrow rescue after high dose chemotherapy for the treatment of leukaemia and other cancers. PBSC harvest/collection has in the main replaced the traditional bone marrow procedure.


PBSC collections may be from patients donating cells for their own, future use (autologous collection) or from donors (allogeneic collection). 

The donor may be matched and related to the recipient, as in the case of a sibling donor, or matched and unrelated to the recipient. 

If the sibling is an identical twin of the recipient the collection is referred to as syngeneic. 

All donors are tested & matched for six key Human Leukocyte Antigens (HLA) & their associated molecules with the recipient. 

In either situation the patient/donor receives priming with granulocyte colony stimulating factor injections (G-CSF), a naturally occurring hormone which mobilizes HPC’s (Haematopoietic Progenitor Cells) into the peripheral blood stream. 

Patients may also receive priming with chemotherapy prior to their collection to enhance cell numbers and limit the possibility of tumour contamination within the collected product.

A surface antigen called CD34+ identifies progenitor cells. This enables these cells to be counted when the blood is tested by flow cytometry. 

The number of collected CD34+ cells in the final product determines whether sufficient progenitor cells have been collected for transplant. 

Stem cell factor may also be given to patients who have not mobilized with G-CSF.

For autologous collections, a minimum of 2.0 x 106/kg (recipient bodyweight) CD34+ cells are required (Referring physician will notify what the target yield will be). 

Prior to collection the patient will have blood taken for FBE (Full Blood Examination), CD34+, U&E (Urea& Electrolytes), virology.


For allogeneic collections, ideally, 4.0 – 6.0 x 106/kg (recipient bodyweight) CD34+ cells are required.


Approximately 2-3 total blood volumes of blood are processed through the apheresis machine to ensure adequate cell numbers are collected, and the procedure may take from 3-5 hours to complete.

Subsequent collections (at the discretion of the attending physician) are scheduled daily until required cell numbers have been collected.

Allogeneic collections are generally transfused ‘fresh’ to the patient, either on the day of collection, or the following day if a second collection is required. 

Allogeneic collections may be stored up to 72 hours at 4ΒΊ Celsius, allowing for transport to other areas in the country or around the world.

Peripheral blood stem cell transplantation

PBSC transplantation has been used increasingly in the treatment of malignant and nonmalignant haematological disorders and solid tumours.

The aim of PBSC and bone marrow transplantation is:
πŸ„The administration of high dose myelosuppressive chemotherapy to destroy disease with subsequent stem cell rescue
πŸ„ The replacement of diseased bone marrow.

Mobilisation

A variety of methods can be used to increase the number of circulating PBSCs/PBPCs in the peripheral blood by “mobilising” them from the bone marrow into the circulation. 

McLeod (2000) states:
“The rationale for mobilising stem cells is to decrease the number of apheresis procedures required to obtain as many stem and progenitor cells as needed to provide prompt and sustained hematopoietic reconstitution”.

Without mobilisation it takes many donations of lengthy duration to yield sufficient numbers for transplantation. 

Mobilisation methods include Chemotherapy, hematopoietic growth factors and a combination of both.

Chemotherapy

Chemotherapy is used in the autologous transplant setting. 
A variety of chemotherapeutic regimens can mobilise stem cells into the peripheral circulation. 

The type of chemotherapeutic regimen used is dependent on the patient’s disease and medical condition.

Chemotherapy induces a transient myelosuppression in patients with the leukocyte count dropping to below 1.0 x 109 /L 7-14 days post administration. 

This is then followed by a “rebound phase” increasing the leukocyte count to well above baseline levels indicating haematopoietic recovery. 

During this rebound phase, there can be an increase in CD34+ levels up to 20-25 fold of those at baseline. These increased levels can persist for several days during which PBSCs/PBPCs can be collected. 

Currently chemotherapy alone is not used for mobilisation of PBSCs in the autologous setting. All patients receive G-CSF.

Haematopoietic growth factors

Haematopoietic growth factors are glycoproteins, which act on haematopoietic cells by binding to specific cell surface receptors and stimulating proliferation, differentiation and some end-cell functional activation.

Growth factors can be used alone to mobilise stem cells from the bone marrow into the peripheral circulation. 

G-CSF is the most common of these factors and is administered subcutaneously for 4-5 days prior to apheresis and continues until completion of all donations. 

Stem cell factor may also be used in cases where mobilisation do not occur using G-CSF.

This type of mobilisation method is used both in the allogeneic and autologous settings.

Chemotherapy and Growth Factors

A combination of both chemotherapy and growth factors has proven to be a very effective mobilisation method. 

It is currently the most common method of mobilisation in the autologous setting. 

The combination of the two can increase the circulating CD34+ level up to 100-160 times that of baseline.

Factors Affecting Mobilisation

At times it may be difficult to obtain sufficient amounts of PBSCs/PBPCs for transplantation.

Failure to mobilise may be due to a variety of factors, which include:
 
🍧 Mobilisation technique
🍧 Prior treatment- chemotherapy/radiotherapy (i.e.)      melphalan, carboplatin and carmustine (BCNU) administered over long periods of time or in large doses
🍧 Presence of marrow disease or metastases
🍧 Diagnosis
🍧 Patient/Donor age
🍧 Sepsis
🍧 Genetic factors

Advantages

🌸No requirement for general anaesthesia as compared with bone marrow donation
🌸Less invasive procedure
🌸Decreased period of neutropenia and thrombocytopenia post-transplant due to PBSC/PBPC being more mature than bone marrow cells

Disadvantages

🌸 Donor exposure to apheresis related complications
🌸 Specific apheresis donor requirements
🌸Potential and unknown adverse effects from mobilisation growth factors
🌸 Expensive
🌸 Labor intensive
🌸Donor time commitment (may require up to two (2) consecutive donations to obtain a sufficient yield for transplantation)

Cell development diagram



Plateletpheresis- Single Donor Platelets


Platelets can be donated via apheresis from:

🌹 Donor volunteers who may be ABO or HLA (Human Leukocyte Antigen) compatible, or 
🌹 Family members 

Platelets obtained using apheresis is commonly referred to as single donor platelets.  One bag of single donor platelets (SDP’s) is equivalent to one bag of ‘pooled’ platelets prepared from whole blood donations. 

Apheresis platelets contain approximately >240 x 109/unit (or 2.4x1011/unit) of platelets and <1.0 x 106/unit of leucocytes.  

Patients undergoing bone marrow transplantation who require matched apheresis platelets will need to have donor collections scheduled to support them throughout the post-transplant period. 

Indications 

Indications for single donor platelets are generally for patients who have demonstrated refractoriness to random donor platelet concentrates or to prevent or limit refractoriness. 

Refractoriness can be defined as “the failure of two  consecutive transfusions to give a corrected increment of greater than 7.5 x 10 9/l one hour after transfusion in the absence of fever, infection, severe haemorrhage, splenomegaly or disseminated intravascular coagulation”.

Patients should be tested for the presence of HLA antibodies and, if necessary, the exclusion of anti-HPA-1a.  

Those who meet the criteria for immunologic refractoriness to platelets should receive either ABO or HLA matched single donor platelets.

Advantages: 

🍭 Limited donor exposure 
🍭Leukocyte reduced at time of donation via filtration or elutriation reducing febrile non hemolytic transfusion reactions and alloimunisation causing platelet refractoriness.
🍭 Reduces the risk of CMV transmission 
🍭 Low RBC count 

Disadvantages: 

🌷 Limited availability of group A and O at times 
🌷 Labour intensive specific apheresis donor requirements 
🌷 Donor exposure to apheresis related complications 
🌷Family donors:  issues of risk disclosure due to coercion and obligation.

Granulocytes
PMN (Polymorphonuclear Leukocytes (neutrophils/ granulocytes)) concentrates, commonly referred to as granulocyte transfusions are used to treat bacterial, yeast and fungal infections associated with severe neutropenia (<0.5 x10 9/PMN/L) and disorders of neutrophil function. 

The use of granulocyte transfusions has been controversial over the years and “this can be explained in part by the development of more effective antimicrobial agents to treat infections and, possibly, by availability of recombinant haematopoietic growth factors and peripheral blood progenitor transfusions to hasten marrow function, many physicians hold strong negative opinions about the value of GTx – believing it holds little, if any, role in the management of infected neutropenic patients”.

Another limiting factor to the use of granulocyte transfusions was the inadequate number of granulocytes collected to obtain a therapeutic dose and the known possibility of life-threatening pulmonary toxicity, which can occur after transfusion. 

Granulocytes collections from donors may be used for the treatment of severe neutropenia in patients who have a coexisting intractable infection (bacterial, yeast and fungal infections), which has failed to respond to antibiotic therapy.  

Daily transfusions are given until the infection has resolved or the patient’s neutrophil count is stable at >0.5 x 109/L. 

Donors are generally recruited from the patient’s immediate family circle and friends, and are preferably ABO compatible.  

Routine screening for viral serology is performed prior to the collection and all donors are assessed by the nominated Medical Officer / Consultant for eligibility to donate.  

Granulocytes will require irradiation prior to transfusion. 
In order to maximise collection efficiency (CE%), donors receive oral dexamethasone and G-CSF injections prior to donation to increase the numbers of circulating polymorphonuclear neutrophils (PMNs) in the peripheral blood.  

A red cell sedimenting agent (e.g., Dextran 70 or equivilant) is added to the extracorporeal circuit to sediment the donor’s red blood cells (RBC) during the collection and therefore ensures enhanced collection of granulocytes with lower RBC contamination. 

The decision to use granulocyte donations is generally one of urgency.  

Granulocytes are infused daily until there is an improvement in patient’s clinical condition.  

Donations of granulocytes are taken from the patient’s family and friends. 

Generally, two consecutive donations/donor are required.  

Issues Relating to Donation of Granulocytes 

🌲 Donor exposure to apheresis related adverse events 
🌲 Specific apheresis donor requirements 
🌲 Adverse effects from mobilisation medication 
🌲 Labour intensive donor work-up 
🌲 Donor time commitment 
🌲 Issues relating to donor disclosure of risks due to coercion and obligation

Dendritic cells

Dendritic cells may be collected for clinical research trials. If the institution is affiliated with research centers may collect these cells. All trials have their own protocols.

Therapeutic Apheresis 

The aim of apheresis in this setting is the removal of a harmful circulating factor, which is implicated in a disease process and is causing injury to a given organ. 
“Therapeutic apheresis is not curative, but rather, it is an adjunct to conventional therapy in which relief of symptoms and control of pathogenic process may be achieved more quickly”. 
Therapeutic apheresis only affects the intravascular compartment. 

The efficacy of the treatment is related to: 
🌰 The volume of blood processed 
🌰 The rate of resynthesize of the offending factor and 
🌰 The ability of the end organ to repair itself

Therapeutic apheresis can be divided into two areas: 
🌻 Therapeutic Plasma Exchange 
🌻 Therapeutic Cytapheresis 

Plasmapheresis - the collection of plasma without giving replacement fluid.

🌻 Therapeutic Plasma Exchange 

Therapeutic plasma exchange is also known as Plasmapheresis.

During this therapy, small amounts of blood are gradually removed through an inserted needle or central line catheter and circulated through a machine that separates blood into red cells, white cells, platelets, and plasma.

The plasma portion of the blood is removed and replaced by a plasma substitute and then added back to the cells (red cells, white cells, and platelets) and finally returned by intravenous or central venous catheter access. The removed plasma is discarded.

One procedure typically removes 65% to 70% of the disease-causing proteins (antibodies) in the plasma. Typically, several procedures are needed to lead to clinical improvement.

Plasma exchange is a safe procedure with a few possible side effects.

TPE is mostly used for antibody removal from circulation as well as other molecules such as drugs and low-density lipoproteins. Moreover, it can be used to correct deficiencies of a plasma clotting factor when large volumes of plasma infusion would result in severe fluid overload in the patient. 

The volume of blood to be exchanged is based on a kinetic model of an isolated one-compartment intravascular space, which assumes that the component is neither synthesized nor degraded during the procedure and that it remains within the intravascular compartment. 

The time interval between plasma exchanges is generally chosen based on the need to allow the component of interest to re-equilibrate into the intravascular space and the need to minimize the risk of bleeding as a result of dilutional coagulopathy.

Replacement fluid is usually Albumin 4%, however in certain disease processes Fresh Frozen Plasma (FFP) or Cryosupernatant Plasma is the preferred replacement.  Replacement fluids are given concurrently, with the collection of patient’s plasma into waste bags. This maintains haemodynamic stability.  Patients require constant monitoring for problems associated with large volume fluid shifts and reactions to replacement fluids, as well as the general adverse events associated with apheresis.
  
Often 1-1.5 plasma volumes (usually 3-4L) are removed to ensure that the offending pathogen or toxin is removed.  Calculations are performed to determine the percentage of plasma in a patient’s total blood volume using the patient’s current hematocrit as determined by full blood examination (FBE). The referring physician prescribes the volume of plasma to be removed.
  
Frequency of procedures is determined by the referring physician and would depend on the speed at which the offending substance is renewed in the blood.  

TPE may be required daily, sometimes twice daily, alternate days or even weekly to maintain a patient’s condition.

Long-term maintenance TPE has been effective in treating diseases such as Myasthenia Gravis or chronic, relapsing Thrombotic Thrombocytopenic Purpura (TTP). 

Examples of disease processes in which TPE has shown benefit are: 

🍹 Hyperviscosity Syndrome (Waldenstrom’s Macroglobulinaemia, Multiple Myeloma) 
🍹 Acute Myasthenia Gravis 
🍹 C.I.D.P. (Chronic Inflammatory Demyelinating Polyneuropathy) 
🍹 Goodpasture’s Syndrome 
🍹 Acute Guillian-Barre Syndrome 
🍹 TTP (Thrombotic Thrombocytopenia Purpura) 
🍹 Cryoglobulinaemia 
🍹 Poisons (mushroom) 
🍹 Drugs

Nursing Consideration:

πŸ’¦Prior to the procedure, educate the patient to drink large amount of noncarbonated, nonalcoholic beverages for a couple of days. Also recommend eating a meal prior to the scheduled procedure.

πŸ’¦If intravenous catheters (IVs) are placed, patients’ arms should be propped on pillows, and encourage the patient to squeeze their fist to help promote blood flow. 

πŸ’¦Patients may experience bruising or discomfort where the IVs are placed. If a larger catheter or port is used instead, patients will have free use of their arms during the procedure.

πŸ’¦The procedure typically lasts two to three hours but can be shorter or longer depending on a variety of factors.

πŸ’¦After starting the procedure, patients may experience some mild numbness, tingling, light-headedness, or nausea. 

πŸ’¦An apheresis staff member who specializes in the procedure will be with the patient during the entire treatment. 

πŸ’¦Educate the patients to tell if any side effects or symptoms they feel.

Replacement Fluids

The patient's fluid volume removed by apheresis must be replaced to prevent marked volume depletion. Albumin (5 percent), normal saline, or a combination of albumin and normal saline are the replacement fluids of choice for most conditions.

The optimal choice often varies with the clinical setting. Albumin is used for most conditions; normal saline for hyperviscosity; and some combination of albumin and normal saline if cost is a consideration.

We prefer 5 percent albumin or a crystalloid-colloid (albumin-normal saline) combination as the replacement fluid, rather than normal saline alone. It is generally recommended that plasma only be used as the replacement fluid for conditions in which constituents of plasma are necessary, such as in thrombotic thrombocytopenic purpura (TTP). 

Albumin 25 percent should not be used unless it is diluted to 5 percent concentration by the hospital pharmacy.

Five percent albumin: The advantages of 5 percent albumin are the markedly lowered risks of pathogen transmission and anaphylactic reactions. However, a post-apheresis dilutional coagulopathy due to coagulation factor depletion and a net loss of immunoglobulins can occur.

Albumin-saline combination: When colloid and crystalloid solutions are used in combination, the amount of colloid should not be less than 50 percent of the total infused. An appropriate replacement solution would consist of 1:1 ratio of 5 percent albumin to whole blood and a 2:1 ratio of saline to whole blood for the remainder. For example, if a 3000 mL exchange is performed and 1500 mL of 5 percent albumin is used, 3000 mL of saline solution should be used to replace the other 1500 mL of patient fluid.

Saline: Normal saline alone provides insufficient oncotic pressure and tends to lead to significant edema and/or hypotension. Thus, we prefer 5 percent albumin or an albumin-normal saline combination. However, there may be medically compelling reasons for the use of normal saline in some cases, for example, if albumin is not available or for complications such as allergies occurring with albumin or plasma.

Plasma: Plasma can be provided in the form of Fresh Frozen Plasma (FFP), Plasma Frozen Within 24 hours after phlebotomy, Thawed Plasma, or other products. 

NB: When FFP is used as the replacement fluid the ACD-A (Anticoagulant Citrate Dextrose solution - A) ratio will need to be adjusted to prevent citrate toxicity due to the citrate component of the FFP, i.e. to reduce the amount of ACD-A given. 

Plasma replaces proteins removed by apheresis so that significant depletion of coagulation factors or immunoglobulins does not occur with multiple or consecutive daily procedures. However, other complications are more common with plasma than with albumin.

Cytapheresis

In cytapheresis, the cellular components of blood (eg, RBCs, white blood cells [WBCs], platelets) are separated. This is often done on donated blood so that each component may be given to a different recipient. Cytapheresis also may be done therapeutically to remove excess or defective cellular components.

Therapeutic cytapheresis

Rapid removal of cellular components implicated in a disease process.

Leukocyte Cytapheresis :

Indicated in various forms of leukemia to rapidly remove white blood cells and reduce blood viscosity thereby preventing neurologic and respiratory impairment. 

White blood cell (WBC) levels greater than 100 x 109/l can cause fatal problems associated with an increase in blood viscosity, vascular occlusion, and associated problems with blood flow to vital organs.  

Generally, found in patients with myeloproliferative disorders and acute leukemia, for example, chronic myeloid leukemia (CML), or acute myeloid leukemia (AML).  

The severity of the presenting symptoms varies between individual patients and the types and volume of white cell burden within the bloodstream.   

The role of therapeutic leukapheresis is to initially and rapidly decrease the burden of leukocytosis on the body by 50-60% whilst chemotherapy is commenced.  

Patients are referred by the attending physician, who will determine the frequency and number of procedures to be performed.   

Procedure parameters are tailored to the type of white cell being targeted to ensure the greatest collection efficiency.  

Large volumes of cells may be collected; therefore fluid replacement may be indicated to counter problems associated with hypervolemia. 

Therapeutic leukapheresis is often performed as an acute, emergency procedure and the patient may require intensive nursing in an area such as ICU.  In this situation the procedure is undertaken in ICU. 

Red Cell Cytapheresis:

Used for rapid, isovolemic removal of large quantities of red cells, this may also be abnormal.  
e.g. polycythaemia rubra vera, sickle cell crisis. 

Platelet Cytapheresis used to rapidly lower platelet counts in patients with myeloproliferative disorders and with platelet count >1000 x 10 9/L.  

The main aim is to prevent the development of thrombotic and hemorrhagic complications until conventional therapy can control platelet production.  

It should be noted that in disease processes, which result in thrombocythaemia, the platelets are generally atypical and function poorly and therefore platelet transfusions post apheresis may be indicated (this is rare).   

Apheresis Adverse Events

Although apheresis is a relatively safe procedure it is not without potential complications.  

The rate of adverse events during apheresis is generally greater in therapeutic procedures as compared to donor procedures.  

This is due to the age and co-morbidities of patients in the therapeutic setting as opposed to healthy donors. 

Nursing staff must understand these complications and adverse events in order to try and prevent such incidents occurring. 

The ability of the nurse to detect or pre-empt adverse events and initiate prompt corrective action to minimize the impact to the patient/ donor and/or procedure is essential. 

Many apheresis complications may develop as a result of the procedure itself or alternatively from the patients primary or secondary medical conditions. 

Identifying any preexisting medical conditions and determining the possible impact on the management of the patient during an apheresis procedure, aids in minimizing or preventing any adverse events. 

The following is a list of potential adverse events associated with apheresis. 

πŸ“ Hypocalcemia (citrate toxicity) 

πŸ‡ Most commonly seen in the donor setting 
πŸ‡ Related to the infusion of citrate anticoagulant 
πŸ‡May be mild, moderate or severe (warranting cessation of procedure) 

πŸ“ Vasovagal 

πŸ‡ Common in whole blood donation  
πŸ‡ Also seen with apheresis procedures but with less frequency
πŸ‡ Related to donor anxiety, fear, pain 

πŸ“ Hypovolemia/ Hypervolemia 

πŸ‡ Changes in intravascular volume as a result of fluid shifts 
πŸ‡ Removal of whole blood and retainment of components 
πŸ‡Extracorporeal volume i.e.) >15% of donor’s/patient’s whole blood volume in circuitry at any one time  Fluid overload in patients with cardiac/renal dysfunction 
πŸ‡ Drug related eg: ACE inhibitors should be withheld 24 hours pre-plasma exchange to prevent hypovolemia 

πŸ“ Vascular Access 

πŸ‡ Hematoma 
πŸ‡ Venous sclerosis 
πŸ‡ Thrombosis 
πŸ‡ Infection 
πŸ‡ Nerve, muscle, tendon injury 
πŸ‡ May be more frequent in apheresis procedures as compared with whole blood donations due to the longer indwelling time of the catheter 

πŸ“ Air Embolism
 
πŸ‡ Malfunction with machine circuitry 

πŸ“ Mechanical Haemolysis 

πŸ‡ Potential destruction of Red Blood Cells within machine circuitry as a result of collapsed or kinked tubing and improper harnessing of kit 

πŸ“ Transfusion Reactions 

πŸ‡ Therapeutic setting 
πŸ‡ Associated with blood products used as replacement fluid in plasma exchange i.e. Albumin, FFP 

πŸ“ Coagulopathy
 
πŸ‡ Therapeutic setting 
πŸ‡Altered coagulation status post therapeutic plasma exchange when plasma is exchanged with replacement fluids, which do not have coagulation factors 

πŸ“ Pharmacological Changes 

πŸ‡ Therapeutic setting 
πŸ‡ Removal of large quantities of plasma during plasma exchange may decrease the concentration of certain medications.  

The quantity of medication removed is related to its plasma binding capacity, distribution and clearance of the drug. 

Careful monitoring of the donor/patient before, during and after is essential in providing a safe and effective procedure. 

Astute nursing care and assessment are imperative in the prompt management of reactions, which may occur.

Indications for Apheresis in BOC



Apheresis Machines used in BOC

Spectra Optia

PLASAUTOΞ£

Extracorporeal photo chemotherapy


Extracorporeal photochemotherapy or photopheresis is a type of therapy used to treat autoreactive or neoplastic disorders caused by aberrant clones of T lymphocytes.

It combines aspects of leukapheresis and traditional phototherapy.

“Photopheresis, the process by which peripheral blood is exposed in an extracorporeal flow system to photo-activated 8-methoxypsolaren (8-MOP), is a new treatment for disorders caused by aberrant T Lymphocytes.”    

R.L.Edelson

Clinical Applications:

🍧GvHD (Graft-vs.-Host-Disease After Allogenic Bone       Marrow Transplantation) – Chronic & Acute
🍧CTCL (Cutanous T-Cell Lymphoma)
🍧Mycosis Fungoides
🍧Sézary Syndrome
🍧SOT Rejection (Heart, Lung, Kidney, Liver)
🍧Lupus Erythematosus
🍧Rheumatoid Arthritis
🍧PSS (Progressive Systemic Sclerosis)
🍧Atopic Dermatitis
🍧Pemphigus Vulgaris
🍧Crohn’s Disease
🍧Colitis Ulcerosa
🍧IBD (Inflammatory Bowel Disease)
🍧Type 1 Diabetes
🍧Epidermolysis Bullosa Acquisita
🍧Erosive Oral Lichen Planus
🍧Other Autoimmune Diseases


The Principle of UVA PIT Photo Immune Therapy (Photopheresis)


Photopheresis (also known as extracorporeal photopheresis or ECP) is a therapy where the patient’s blood is collected to harvest the white blood cells with an apheresis system. 

The collected white blood cells (buffy coat) are treated with a photosensitizer / photoactivator and subsequently are being irradiated with UVA light. 

This photoactivation has fundamental influence to the cell process and leads to an alteration and activation of the patient’s own immune system.

The Photo Immune Therapy is usually done by three principal phases:

πŸ‚The collection phase where lymphocytes and mononuclear cells are collected, preferably highly concentrated with low haematocrit

πŸ‚The irradiation phase in which the buffy coat is being irradiated with UVA light (2 J/cm²) under the presence of a photoactivator    (8-MOP = 8 Methoxypsoralene)

πŸ‚The reinfusion phase where the treated cells are reinfused into the patient



Contra indications

πŸ‡Patients exhibiting idiosyncratic or hypersensitivity reactions to methoxsalen, other psoralen compounds, or any of the excipients.

πŸ‡ Possessing a specific history of a light-sensitive disease state, including lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum, and albinism.

πŸ‡Patients with aphakia because of significantly increased risk of retinal damage

πŸ‡Patients that have contraindications to the photopheresis procedure.

πŸ‡   Pregnancy and lactation

Patient Education

Teach the patient regarding the following:

🍸  The patient before every treatment needs to stay away  from fatty food. When there is a high lipid concentration  in the blood, the cell separation duration (apheresis) can    be affected negatively. 

   πŸΈ After Methoxsalen treatment, patients must use full-protected sunglasses (UVA / UVB protected) for the first 24 hours against the UVA they will receive, either directly or indirectly from the window glass, and cover their skin (wearing trousers and long sleeved clothing, hats) or sun cream (SPF 15 or more).

   πŸΈ In order to reduce process-related toxicity, the patient should always be questioned in terms of the use of photo allergic drugs, and contact the primary physician for drug replacement, if possible. 

   πŸΈ  The patient should be informed not to be exposed to the sun as much as possible, and not to take of the sunglasses for 24 hours after the procedure.

RBC EXCHANGE

 What is Red Cell Exchange?

Red blood cell exchange apheresis, also known as therapeutic erythrocytapheresis, is a nonsurgical therapy that removes and replaces a patient's red blood cells.

Red blood cell exchange apheresis involves removing blood through a needle or catheter and circulating it through a machine where the blood is separated into red cells, white cells, platelets and plasma. 

The red cells, which are responsible for carrying oxygen to all parts of the body, are discarded and replaced with red blood cells provided by a blood donor. 

The donor red blood cells circulate back to the patient with the other blood components (white cells, platelets and plasma) through a return needle.

 Indications:                                


πŸ’¦ Sickle cell disease

πŸ’¦ Malaria

πŸ’¦ Polycythaemia

πŸ’¦ After ABO incompatible bone marrow transplant

Although red cell exchange may help with symptoms, it will not cure the condition as it does not switch off the production of  red cells. It is likely that this procedure will form only one part of the treatment.

How is a Red Cell Exchange procedure done?

During the exchange procedure blood is withdrawn from the patient by placing a venous access device (catheter, port) into the patient's vein. 

The device is connected to a machine, which contains a centrifuge that draws the blood from the patient and then separates it into red blood cells, white blood cells, platelets and plasma, the liquid portion of blood. 

The healthy components of the blood are returned to the patient, while the unhealthy components are discarded. 

A calculated number of units of healthy red blood cells are infused while the diseased (sickled) red blood cells are removed.

How long does it take?

The length of the procedure varies from patient to patient, and depends on the amount of abnormal red blood cells that need to be exchanged. A normal RBC exchange transfusion lasts about 1 to 2 hours.

Preparation before treatment

🌼Some drugs are affected by the red cell exchange. Complete drug reconciliation form and the physician will instruct the patient if any need to miss or delay taking a dose until after the procedure.

🌼 It is important to have something to eat and drink before the procedure and the patient can eat and drink normally during and after a red cell exchange.

During RBC Exchange

If intravenous catheters (IVs) are placed, patients’ arms will be propped on pillows, and they will be asked to squeeze their fist to help promote blood flow. 

Patients may experience bruising or discomfort where the IVs are placed. If a larger catheter or port is used instead, patients will have free use of their arms during the procedure.

The procedure typically lasts two to three hours but can be shorter or longer depending on a variety of factors.

After starting the procedure, patients may experience some mild numbness, tingling, light-headedness, or nausea. An apheresis staff member who specializes in the procedure will be with the patient during the entire treatment. Patients should tell their nurse of any side effects or symptoms they feel.

After RBC Exchange

After the procedure is completed, patients may feel tired for the rest of the day. Recommend drinking plenty of liquids after the procedure. Also recommend that patients have a family member or friend give them a ride home.

LEUKOCYTE APHERESIS


Otherwise known as Leukocytapheresis or Leukapheresis.

Leukapheresis is a process to remove extra white blood cells from the blood.

- a specialized apheresis procedure where donor blood is circulated through an apheresis machine – at AllCells, the Spectra Optia Apheresis System is used – that separates donor mononuclear white blood cells out for collection while returning the other blood components back to the donor’s circulation.

Because granulocytes can affect PBMC (peripheral blood mononuclear cells) viability, leukapheresis protocols are optimized to reduce the quantity of granulocytes  in the collection process.

VENOUS ACCESS: 

In some cases, leukocytapheresis can be done using needles that are placed in each arm. Blood is removed from one arm, the white blood cells are removed, and the rest of the blood is returned to the patient through the other arm. In patients with small or fragile arm veins, the placement of a central venous catheter may be necessary. 

DURATION: 

The length of the procedure depends on how many white
blood cells need to be removed. A typical procedure takes
2-3 hours.

RISKS AND SIDE EFFECTS: 

This is a safe procedure but side effects can occur. Common side effects include fatigue, nausea, dizziness, feeling cold, tingling around the mouth, tingling fingers, and decreased blood pressure. 

Serious side effects like seizures or abnormal heart beat are very rare. 

DISEASES FOR WHICH THE PROCEDURE IS USED: 


This procedure is used for blood disorders with very high
numbers of white blood cells, including acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML). 

OTHER CONSIDERATIONS: 

This procedure may decrease the number of blood platelets
and red cells (anemia). For those patients who already have a decreased number of platelets or red cells, the consultant will
want to carefully monitor the blood counts (CBC) while the patient is receiving treatment; therefore, further lab tests may be needed. 

If needed, the consultant may recommend a transfusion of blood during or soon after the procedure to protect the patient health.

ERYTHROCYTE DEPLETION

Also known as Erythrocytapheresis or red blood cell exchange.

It is a procedure used to remove the red blood cells and replace them with red blood cells from a donor. 

The process of depletion is when a single cell type, such as red blood cells (erythrocytes), is removed from a biological sample.

For example, human peripheral blood mononuclear cells (PBMCs) are often used for studying immunological functions like cellular surface marker expression and cytokine production. The removal of RBCs from PBMCs qualifies as RBC depletion.

As a critical part of sample preparation, RBC depletion is intended to clean up red blood cell contamination in biological samples, such as in bone marrow or dissociated tissue samples. The presence of high quantities of RBCs can create background interference in assays and reduce the accuracy of downstream analysis. For some applications (including simple and fast removal of residual RBCs), RBC depletion may be required for full functionality.

After RBC depletion, a cell sample is ready to be separated into specific cell subsets or otherwise undergo further processing.

Procedure:

🍁 Proper venous access to be done

🍁 During this procedure, blood is removed and sent through tubing that is connected to an apheresis machine. 

🍁 This machine spins blood and separates out red blood cells. 

🍁 Only a small portion of the blood is taken through the machine at any one time. 

🍁 After red blood cells are removed, the remaining blood and the donor red blood cells are returned to the body.

Side effects:

Side effects may include:

🍷 Dizziness or feeling light-headed
🍷 Nausea
🍷 Fever
🍷 Rash
🍷 Itching
🍷 Shortness of breath
🍷 Chest or back pain

Patient Education:

The patient to be educated on the following:

πŸ„ The patient may feel tired after the procedure and should limit the activities for the next 12 hours after the procedure.

πŸ„ Patient arms may feel sore from being in one position during the
procedure. 

πŸ„Instruct to drink plenty of non-caffeinated fluids to stay hydrated.

πŸ„ Keep bandages dry and in place for 4 hours after the procedure.

πŸ„ Do not lift anything heavy or exercise for 24 hours after
the procedure.
πŸ„ Advice the patient if get dizzy, lie down and put legs up.
πŸ„ If there is any redness or have pain where the IV was in the arm, contact the Apheresis Department.

PLASMA APHERESIS

The terms plasmapheresis (PP) and plasma exchange (PE) are often used interchangeably, but when properly used, denote different procedures.  

Plasmapheresis refers to a procedure in which the plasma is separated from the blood either by centrifugation or membrane filtration.  

Once separated the plasma can be manipulated in a variety of ways.  

Plasma exchange refers to discarding the plasma totally and substituting a replacement fluid.  

In this assessment PP/PE will be used to describe the combined procedure. 

PLASMAPHERESIS:


πŸ‘‰Extracorporeal blood purification technique designed for removal of large molecular weight substances from plasma.

πŸ‘‰ Separation of plasma from blood cells by centrifugation or by membrane filtration

πŸ‘‰ Reinfusion of cells with:

  πŸŒΏ‘cleaned’ autologous plasma, or
  πŸŒΏdonor plasma, or another replacement colloid solution 
    (e.g. albumin, FFP or cryoprecipitate)(this is termed plasma     exchange)

SUBSTANCES REMOVED BY PLASMAPHERESIS

πŸ’§ Immunoglobulins
πŸ’§ Immune complexes
πŸ’§ Coagulation factors
πŸ’§ Cytokines
πŸ’§ Endotoxins
πŸ’§ Protein-bound substances (e.g. drugs and toxicants)
πŸ’§ Albumin
πŸ’§ Triglycerides and other lipids
πŸ’§ Myeloma light chains
πŸ’§ Cryoglobulins
πŸ’§ Auto-antibodies

COMPLICATIONS:

πŸ’¦ Vascular access:

πŸ’§ Haematoma
πŸ’§ Pnemothorax
πŸ’§ Catheter infections

πŸ’¦ Replacement fluids:

πŸ’§ Anaphylactic reactions
πŸ’§ Hypocalaemia
πŸ’§ Hypokalemia

πŸ’¦ Other modalities:

πŸ’§ Hypotension
πŸ’§ Dyspnoea
πŸ’§ Thrombocytopenia
πŸ’§ Removal of erythropoietin and drugs bound to plasmaprotein
 
LIPID APHERESIS

When the blood fat is high, and the medicine have not shown a result or have not been taken regularly, this apheresis is done to decrease the fat level in the blood.

Lipid apheresis is used to treat patients with severe hyperlipidemia by reducing low-density lipoprotein cholesterol (LDL-C).

It functions by first separating plasma from blood cells with a cell separator and then using either the adsorption of apolipoprotein B by affinity columns containing anti-apolipoprotein B antibodies or dextran sulphate, or their precipitation at low pH by heparin.

Lipid apheresis allows patients to attain lower levels of low-density lipoprotein (LDL), which are usually not attainable with traditional drug therapy alone, while leaving high-density lipoprotein (HDL) levels generally unaffected. 

INDICATIONS:

People who have high LDL levels who can't take medication can benefit from LDL apheresis.

🌷 A condition called familial hypercholesterolemia
🌷An LDL level greater than 200 mg/dL with coronary artery disease
🌷An LDL level greater than 300 mg/dL with or without known heart disease.

What is Familial Hypercholesterolemia (FH)?

Familial Hypercholesterolemia is a rare genetic disorder characterized by high levels of LDL, or bad cholesterol. If untreated, 50 percent of FH patients can experience cardiac and vascular illness by the age of 55, or potentially much younger for more severe cases.
Benefits:

Studies have shown that LDL apheresis can lower LDL cholesterol approximately 70 to 83 percent after a single treatment. 

The liver will continue to produce LDL following treatment, but it will take approximately two weeks to return to baseline levels. 

To maintain lowest possible LDL levels over time, patients will typically require treatment every two weeks. 

Continuing a heart healthy diet and any cholesterol lowering medications can help increase the time in between treatments.

Potential side effects:

πŸ‡ Hypotension
πŸ‡ Nausea
πŸ‡ Flushing 
πŸ‡ Light-headedness  
πŸ‡ Discomfort at the needle site

LYMPHOCYTE COLLECTION

This collection process is very similar to the collection of stem cells. Lymphocytes are collected from donors who have previously donated stem cells to further support the patient in their treatment by helping to introduce a beneficial graft versus disease effect.

Why are lymphocytes needed?

The stem cells or bone marrow previously donated are as a transplant and start to make new blood cells 2-4 weeks later.  Following the transplant, it is expected that the blood cells made from the donor stem cells will replace the patient’s cells.  

However, there is no guarantee that this transplant will be successful in curing the disease. Tests allow to see at a very early stage if there are signs of disease coming back or signs of the patients own cells reappearing. This does not necessarily mean that the disease is back it does increase the risk of that possibility.

Lymphocyte transfusion

Success of the transplant is partly due to the new transplanted cells destroying any remaining cells from the patient’s disease. This is called graft versus disease effect driven by particular white cells known as lymphocytes.

Lymphocytes are present in large numbers in the blood of healthy people. An infusion of lymphocytes given months or sometimes years after a stem cell transplant can boost the patients immunity and help in getting rid of any remaining diseased cells.

Pre collection assessments:

Physical fitness: Ensure the person is physically fit for the collection process by undergoing medical examination and some blood tests.

Procedure:

Lymphocytes are collected on a machine called a cell separator. 

This machine separates blood into its various parts: white blood cells, red blood cells, platelets and the fluid part of the blood – plasma. 

The lymphocytes are within the white blood cell layer of the blood and the machine allows us to collect the lymphocytes and return the rest of the blood back to the person.

To do this a needle will usually be put into a large vein in each arm. The machine will then draw blood from one arm, take off the lymphocytes and return the rest of the ‘processed’ blood to the body through the needle in the other arm. This is a continuous process and so there is only a small amount of blood (about a cup full) out of the body at any one time.

Collecting lymphocytes usually takes 4 hours. Collects approximately 150/250mls of lymphocyte fluid during the collection. When the procedure is finished, the lymphocytes are transported to the storage area for processing and store until needed.

Side effects:

Generally, there are very few side effects with lymphocyte collection and the minor ones that are possible can be treated simply and quickly. Potential side effects are tingling in your lips, nose or fingers or feeling light-headed or faint. 
The patient can eat and drink normally during the procedure. Some people can feel quite tired for 24 hours afterward.

IMMUNO ADSORPTION

Immunoadsorption (IAS) is a blood-purification technique that enables the selective removal of immunoglobulins (Ig) from separated plasma through high-affinity adsorbers. 

IAS (Immunoadsorption) is currently used for treatment of a large variety of antibody-mediated or immunological diseases (e.g., humoral transplant rejection, lupus nephritis, multiple sclerosis)

The principle of Immunoadsorption:


Indications:

Possible complications:

🌸 Allergic reaction to the filter or adsorption column

🌸Dizziness, Nausea, feeling cold or tingling sensation numbness in fingers and lips

🌸 Hypotension

🌸 Increased risk of infection


References:




4. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue

5. Immunoadsorption Versus Therapeutic Plasma Exchange. Will Fibrinogen Make the Difference;  DOI: 10.1159/000369378




















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