Chapter 14 Apheresis

• Apheresis is a procedure where whole blood is removed, a specific blood constituent is separated, and the remainder is returned to the individual's circulation.
• This automated process can be performed on blood donors or patients.
• Apheresis allows collecting a larger volume of specific components compared to whole blood donation.
• Therapeutic apheresis removes disease-causing or unwanted blood constituents.
• Apheresis harvests stem cells from peripheral blood, avoiding bone marrow extraction.
• Apheresis technology is now commonplace in blood donor centers, hospitals, and acute care settings.

History and Development

• Early apheresis involved Dr. Edwin J. Cohn's method for purifying albumin from pooled human plasma using a dairy centrifuge.
• Cohn's method provided a safer therapeutic agent for wounded soldiers, reducing hepatitis risk.
• In the 1960s, Solomon and Fahey used centrifugation for therapeutic plasmapheresis.
• In 1965, Freireich and Judson developed the first continuous flow apheresis machine.
• In the 1970s, apheresis was used to extract one cellular component.
• In 1978, the primary membrane plasma separator was introduced for therapeutic plasma exchange.
• Apheresis today involves withdrawing blood, separating it into components, collecting one or more components, and returning the rest.
• Apheresis is used for donor component collection or therapeutic purposes.
• The process is named based on what's removed: plasmapheresis (plasma), plateletpheresis (platelets), erythrocytapheresis (red blood cells), leukapheresis (leukocytes).

Table 14-1 Types of Apheresis Procedures and Their Application

• Plasmapheresis removes plasma and can be used on both donors and patients.
• Plateletpheresis removes platelets and is primarily used on donors.
• Leukapheresis removes white blood cells and can be used on both donors and patients.
• Erythrocytapheresis removes red blood cells and can be used on both donors and patients.
• HPC apheresis removes hematopoietic progenitor cells and can be used on both donors and patients.
• Blood component separation is based on specific gravity.
• Heavier red blood cells settle at the bottom, lighter plasma at the top.
• White blood cells and platelets form a buffy coat layer between red blood cells and plasma.
• Apheresis uses a large-bore needle, mixes blood with anticoagulant, transports it to a separation device (centrifuge), separates components, withdraws one component, and returns the rest.

Physiology of Apheresis

• Apheresis differs from routine whole blood collection due to the blood manipulation and reinfusion.
• The human body can be impacted in many ways.

Anticoagulation

• Citrate is the primary anticoagulant, binding calcium ions to inhibit coagulation.
• Citrate is immediately mixed with blood as it leaves the vein to prevent clotting.
• Metabolization of citrate-calcium complex releases calcium back into the bloodstream and activates parathyroid hormone.
• Parathyroid hormone mobilizes calcium from bone which increases intestinal absorption.
• Circulating calcium levels maintain adequate levels.
• A decrease in ionized calcium levels can result in transient hypocalcemia.

Fluid Shifts

• Intravascular volume changes during apheresis due to blood removal into the extracorporeal circuit.
• Donors may experience hypotension if additional fluid is not infused as a result of volume depletion.
• Hypovolemic reactions are uncommon due to regulatory restrictions on extracorporeal volume (10.5 mL/kg).
• Hypotension occurs as a vasovagal reaction.
• Vasovagal reactions increase parasympathetic and decrease sympathetic nervous system output, leading to a slower heart rate and hypotension.
• Younger age and female sex are factors with vasovagal reactions.
• Vasovagal reactions are less frequent in apheresis than whole blood donors.

Cellular Loss

• The procedure intends to remove a specific component which decreases levels of specific cells
• The FDA and AABB regulate the time between procedures depending on components collected.
• Platelet donors typically see a 20% - 29% platelet count decrease.
• The decrease tends to be greater among females.
• No adverse effects have been demonstrated, and platelet counts normalize within days.
• Platelets and RBCs occur in granulocyte collections, a drop in hematocrit of 7% and a 22% fall in platelet counts after a granulocyte donation.
• Varying numbers of RBCs are lost during each donor apheresis procedure, depending on equipment and component collected.
• Collection facilities must ensure the annual red cell loss for apheresis donors is not exceeded, including donation of whole blood, RBCs, other apheresis components, and sample collection.

Methodology

• Apheresis uses automated technology with separation typically by centrifugation.
• Instruments have a control panel, allowing the operator to select the component.
• Optical sensors detect specific interfaces and divert the component to a collection bag.
• Machines use disposable equipment unique to the machine.
• The procedure ranges from 45 to 120 minutes, longer for hematopoietic progenitor cell collection.
• Appropriate instrument is selected based on the goal, each instrument has performance characteristics.
• Some instruments are for donor apheresis only, others for therapeutic.
• Operators manipulate variables to harvest plasma, platelets, WBCs, or RBCs.
• Considered variables include centrifuge speed and diameter, dwell time, solutions added, and patient's cellular content or plasma volume.

Methods of Centrifugation

• The most commonly used instruments employ intermittent flow centrifugation (IFC) and continuous flow centrifugation (CFC).

Intermittent Flow Centrifugation

• Blood is processed in batches or cycles in IFC.
• Whole blood is drawn with a pump and mixed with anticoagulant as it is pumped into a centrifuge bowl through the inlet port.
• The bowl rotates, separating components by gravity - RBCs pack against the outer rim, followed by WBCs, platelets, and plasma.
• Once separated, the pump reverses and the desired component(s) is pumped into a collection bag.
• The undesired components are pumped into a reinfusion back and returned to the individual as one cycle.
• Six to eight cycles collect a therapeutic dose.
• The IFC procedure can be performed as single needle procedure or double needle procedure.

Continuous Flow Centrifugation

• CFC performs blood withdrawal, processing, and reinfusion simultaneously in a continuous manner.
• Two venipuncture sites are necessary, or a dual-lumen central venous catheter can be used.
• Blood is mixed with anticoagulant, and collected in a designed chamber or belt.
• The chamber separates with centrifugation, diverting and retaining the specific component and the remainder of the blood is reinfused.

Comparison of IFC and CFC

• IFC equipment is smaller and more mobile, lending itself for use on mobile donor collections.
• A single venipuncture may be used with the IFC procedures, whereas two venipunctures are usually required with the CFC procedures.
• Based on AABB Standards, the extracorporeal blood volume for blood donors should not exceed 10.5 mL per kg of body weight, which is usually greater with IFC.
• Improvements in apheresis have allowed IFC and CFC processes to be incorporated into a single platform.
• The Trima uses intermittent flow technology to draw and reinfuse blood to the donor, while the centrifuge operates with continuous flow.
• Concurrent components collection using automated collection.

Membrane Filtration

• Membrane filtration technology also separates blood components.
• Membrane separators are composed of hollow fibers or flat plate membranes with specific pore sizes of plasma.
• As whole blood flows over the fibers, plasma passes through and is collected, returning cellular components.
• Filtration is used in the collection of plasma because the pores can be sized to prevent passage of even small cellular elements.
• Collection of cell-free product; ability to selectively remove specific plasma proteins by varying the pore size.

Component Collection

• A healthy donor undergoes an automated procedure to obtain a blood component for a patient.
• Apheresis donors must meet additional requirements by AABB and FDA.
• Collection of each apheresis blood component carries its own deferral period.
• Apheresis collections can be done more often than possible.
• Red cell loss for each apheresis procedure is monitored to ensure donor's cumulative annual loss doesn't exceed the maximum.
• A qualified physician must be responsible for aspects of the apheresis program with equipment and staff.
• Written, informed consent must be obtained from the donor.
• Apheresis blood component does not provide donor with specific medical benefit, but the procedure may be more comfortable for the donor. In addition, donors typically receive saline infusions which may help reduce donor reactions

Donation Frequency

• 2 Unit RBC Apheresis has a donation frequency of every 16 weeks
• Plasma (frequent) has a donation frequency of every 2 days or no more than twice in 7 days
• Plasma(infrequent) a donation frequency of every 4 weeks or no more than 13 times in a year
• Platelets has a donation frequency of every 2 days or no more than twice in 7 days and no more than 24 times within 12months
• Platelets double or triple the donation frequency is every 7 days
• Granuolcytes has a donation frequency of every 2 days

Red Blood Cells

• RBCs collected by apheresis are typically double units.
• Plasma and platelets are returned, or collected concurrently.
• Apheresis collection can reduce the number of donors needed for recipients because they can can receive from a single donor
• FDA requires the collection facility to follow donor selection criteria
• Volume: 2RBC procedure is greater so donors need stringent hematocrit
• If two units are collected, a donor must wait 16 weeks before another RBC donation.
• Donor reaction compared to whole blood decreased because lost volume is replaced with saline

Plasma

• Plasma Collection = plasmapheresis (Centrifuge blood, plasma is collected, and cellular components are returned. This allows for larger amounts of blood to be collected)
• Used to augment Fresh Frozen Plasma in AB groups. Can be taken from high antibody titer donors. Plasma is collected commercially for further production.
• Infrequent plasmapheresis: Donation occurs once every 4 weeks, same requirements as blood donors.
• Frequent or Serial Donors: More than once ever four weeks, at least 2 days in between procedure and no more than 7 days in a 2 week period
• RBC loss can be no less than 25mL per week, and must by physician must undergo lab tests

Platelets

• Platelets from apheresis are the same a six to eight, from one whole blood donation (this decreases donor exposure
• During this, platelets/ some plasma is removed with the collection bag
• Routinely takes 45 -90 minutes and other components may be collected.
• Donor Criteria: Must be same as blood donors + 2 more requirements. (Prior to collection, samples must be taken to take platelet count, >150,000 to be donated. Count must be taken again if 4 weeks have passed
• Platelet medication use will interfere with results
• 48 Hours: Aspirin
• 14 days: Clopidogrel
• Interval: 2 Days in between, with 2 procedures per 7 days. If double/Triple collection, must be 7 days instead and exception may be made

Granulocytes

• Limited Benefit to patient population (Pts that undergoes aggressive chemo may develop neutropenia during therapy, infection becomes life threatening.)
• Shown benefit if: Severe Neutropenia, Unresponsive infection, Bone Marrow w/ Myeloid Hypoplasia
• Also shown results in in treatment of Neutropenic neonates
• Collected by apheresis provides a higher yield product
• Donor Needs: Communication, Advance Planning, Pre-Screening by Physician and blood bank
• Must be tested before, Therapeutic is 1 * 10/ 10 per day

Therapeutic Procedures

• The substance can be more effectively removed
• The Rationale is that a Pathologic Substance exists in blood (That contributes to symptoms)
• Aphoresis is like a smaller more effective extraction of blood with return of cellular parts
• Cytapheresis: Can selectivity be used with RBC / WBC/ Platelets
• Plamspheresis (USE when patho is in Circulation)
• Therapeutic apheresis has placed blood banks and transfu- sion services in the position of providing direct medical care for a patient. (Delineate blood bank, who test /access, monitoring and documentation is need, also requires risks benefits to be mentioned

Advanced Concepts

• Numerous Studies (RCT'S, have supplied clinican w/ data for realistically evaluating aphoresis and the treatment of disorders (American Soc: Defined categories depicting effectiveness in treating various clinical disorder)

Category Types

• Standard and Acceptable : As primary/ adjunct, with randomize based trail
• II - Supporting/ Second Line: Rather than First
• III: No Clear Indication: Insufficiency
• IV: Has been show to Lack is harmful and clinical research under protocol

Vascular Access

• Is Mandatory with higher volumes blood, and longer access from peripheral veins. 2 Site Venous ( Removal / return w/ gauge)

Physiological Consideration

• Patient Extracorporeal Volume Should be at the less than 15 % of the total to to minimize Hypovolemia (TBV based on height and weight/ Plasmapheresis is performed (This ensures Appropriate fluids are maintained)
• Important points: Lower hematocrit is higher IV. Atenion (Pay attention to all schedule Meds, Plamspheresis remove drugs, such as vascular drugs (most sensitive) / Half Life/Timing/Amount/Duration - number / Procedure various with a range from various to single to all depends on case level

Physcial Side effects

• Blood warmer circuit is used to prevent hypothermia ( due to increase rapid infusion)
• Replacement Plasma *
• The most common TA
• The removal and retention of plasma w return with cellular components to patient (Most Common) Removal of Antibody/Toxins
• Also to replace what what might be missing and deficient

Additional Information

• Large Plasma level Volume with Physio Fluids to maintain Intrava Compartment (0%- Most Efficient)
• 1 volume exchange removes the patitent, approx. removes 3 Liters. (But will do so only what is needed) Synthesis + Catabolism of plasma. (Disorders Cryoglob / HyperVisc Syndromes), IGM TPE is the tool of choice. IGG requires a series

Plateletpheresis (therapeutic)

• Used to treat: Abnormally elevated platelet 500K / Myeproliferative- 1Mil ( RISK
• Reduce Rate Via Med (APHERESIS- acute, until med takes effect) and usually reduce to 600K
• Leukophesis ( Hyperleukocytes > 1k)
• AML>ALL
• Single : WBA 30 / 60 however to prevent (L) 1 Fluid removed

Erythrocytophereiss/Cell Exchange

• Large # of RBC/ Plasma Plaletes W Allogeneic Doner RBC. Sickle cell Disease
• Goal is to less than 30 %, usually accomplish in 1 procedure/ Donor to Fresh Leukocyte, Phenotype 26,35

Fluid Replacement

TA and EC Are primed with Normal Saline ( Bolus), the majority of patients will use during cytaphersis procedures and fluid balance issues can resolved (Plasma retains, needs to balanced

• Fluid balance should happen in IV w/ Oncotoic 5% human Sersum Alb, use this to replace remove ⅓ of saline
• The FFP has a optimal replacement, the
• TTP
• Used during TPE on patients with preexisting coagulopathy( server )