Plasmapheresis Yousaf khanRenal Dialysis LecturerIPMS -KMU

Plasmapheresis:• Therapeutic apheresis refers to an extracorporeal procedure in which

blood separator technology is used to remove abnormal blood cells and plasma constituents.

• The terms plasmapheresis, leukapheresis, erythrocytapheresis and thrombocytapheresis describe the specific blood element that is removed.

• In plasmapheresis or therapeutic plasma exchange large quantities of plasma are removed from a patient and replaced with fresh frozen plasma, albumin solution and saline.

Plasmapheresis

Techniques of Plasmapheresis:

• During plasmapheresis, blood (which consists of blood cells and a clear liquid called plasma) is initially taken out of the body through a needle or previously implanted catheter.

• Plasma is then removed from the blood by a cell separator.

• Two procedures are commonly used to separate the plasma from the blood cells, with each method having its own advantages and disadvantages:

Technical considerationsMembrane apheresis:Advantage: • Fast and efficient plasmapheresis• No citrate requirement • Can be adapted for cascade filtration

Disadvantage: • Removal of substance limited by sieving coefficient of membrane• Unable to perform cytapheresis• Requires high blood flows, central venous access• Requires heparin anticoagulation limiting use in bleeding disorders

Technical considerations

Centrifugal devicesAdvantage: • Capable of performing cytapheresis• No heparin requirement • More efficient removal of all plasma components

Disadvantage: • Expensive • Requires citrate anticoagulation• Loss of platelets

Procedure • After plasma separation, the blood cells are returned, while the

plasma, which contains the antibodies, is first treated and then returned to the patient in traditional plasmapheresis.

• In plasma exchange, the removed plasma is discarded and the patient receives replacement donor plasma, albumin, or a combination of albumin and saline (usually 70% albumin and 30% saline).

• Medication to keep the blood from clotting (an anticoagulant) is

given to the patient during the procedure.

• Plasmapheresis is used as a therapy in particular diseases.

• An important use of plasmapheresis is in the therapy of autoimmune disorders, where the rapid removal of disease-causing autoantibodies from the circulation is required in addition to other medical therapy.

• It is important to note that plasma exchange therapy in and of itself is useful to temper the disease process, while simultaneous medical and immunosuppressive therapy is required for long-term management.

• Plasma exchange offers the quickest short-term answer to removing harmful autoantibodies; however, the production of autoantibodies by the immune system must also be suppressed, usually by the use of medications such as prednisone, cyclophosphamide, cyclosporine, mycophenolate or a mixture of these.

• Other uses are the removal of blood proteins where these are overly abundant and cause hyperviscosity syndrome.

Condition for which PE has an established role

Removal of abnormal circulation factor• Antibody ( anti –GBM disease, myasthenia gravis )• Monoclonal protein ( myeloma protein )• Circulating immune complexes ( cryoglobulinemia, SLE)• Alloantibody ( Rh alloimmunization in pregnancy )• Toxic factor

Replenishment of specific plasma factor• TTP (Thrombotic Thrombocytopenic Purpura)

Other effects on immune system:• Improvement in function of reticuloendothelial system• Removal of inflammatory mediators ( cytokines, complement)• Stimulation of lymphocyte clones to enhance cytotoxic therapy

Renal indication Primary renal disease• Goodpasture's syndrome• Recurrent focal and segmental glomerulosclerosis in the transplanted

kidney• IgG nephropathy• Transplantation

Seconday renal disease:• Rhabdomyolysis• Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome• Multiple myeloma in kidney

Vascular access:

• Centrifuge device systems blood flow in the range of 40 -50 ml/mint.• Best approach is the use of a large bore, dual lumen catheter • Intravascular devices available for nondialysis use such as swan Ganz

catheter and triple lumen catheter

Techniques of plasmapheresis ancillary measuresAnticoagulation:• Either heparin or citrate can be used• Heparin requirements are double that for HD due to loss in plasma.• Loading dose is 30-60 u/kg, followed by 1000 u/h infusion.• For citrate anticoagulation citrate is infused continuously as acid citrate

dextrose.• Patients should receive calcium IV or orally.• Problems include hypocalcemia and alkalosis.• Citrate metabolism impaired in liver disease.• FFP contain citrate.

Techniques of plasmapheresis ancillary measures

• Ancillary immunosuppression: • Used to suppress further antibody synthesis during and after PE (e.g.

cyclophosphamide or azathioprine).

• Replacement fluids:• Replacement by colloidal agent is essential to maintain hemodynamic

stability.• Albumin generally in the form of an isonatric 5% solution or to plasma

in the form of FFP

Choice of Replacement solution• Albumin• Advantage:• No risk of hepatitis• Stored at room temperature• Allergic reaction are rare• No concern about ABO blood

group• Depletes inflammation

mediators

• Disadvantage:• Expensive• No coagulation factors• No immunoglobulin's

• Fresh Frozen Plasma• Advantage:• Coagulation factors• Immunoglobulin's ‘’ beneficial’’

factors complement

• Disadvantage:• Risk of hepatitis, HIV transmission• Allergic reaction• Hemolytic reaction• Must be thawed • Must be ABO compatible • Citrate load

Complication of plasmapeheresis

Related to vascular access:• Hematoma • Pneumothorax• Retroperitoneal bleed

Related to the procedure• Hypotension form externalization of blood in the extracorporeal

circuit.• Hypotension due to decrease intravascular oncotic pressure.• Bleeding from reduction in plasma levels of coagulation factors• Edema formation due to decrease intravascular oncotic pressure• Loss of cellular elements ( platelets )• Hypersensitivity reactions

Complication of plasmapeheresisRelated to anticoagulation:• Bleeding, especially with heparin• Hypocalcemic symptoms ( with citrate)• Arrhythmias• Hypotension• Numbness and tingling of extremities• Metabolic alkalosis from citrate

Hemodialysis and hemoperfusion in the treatment of poisoning • Hemodialysis and hemoperfusion common• Treatment should be applied selectively in the context of

comprehensive management strategy • Cardiorespiratory support, early gastric lavage and

administration of multiple dose activated charcoal or specific antidots

Dialysis and Hemoperfusion

Criteria for consideration of dialysis or hemoperfusion in poisoning1. Progressive deterioration despite intensive supportive therapy2. Severe intoxication with depression of midbrain function leading

to hypoventilation hypothermia and hypotension.3. Development of complication of coma, such as pneumonia or

septicemia etc4. Impairment of normal drug excretory function in the presence of

hepatic, cardiac or renal insufficiency5. Intoxication with agents with metabolic and or delayed effects 6. Intoxication with and extractable drug or poison, which can be

removed at a rate exceeding endogenous elimination by liver or kidney

CHOICE OF THERAPY

DRUG SERUM CONCETRATION METHOD OF CHOICE

Phenobarbital 100 mg/L HP, HD

Glutethimide 40 HP

Methaqualone 40 HP

Salicylated 800 HD

Theophylline 40 HD

Paraquat 0.1 HP> HD

Methanol 500 HD

Technical points

1. Vascular access for hemodialysis or hemoprfusion in poisoning – with out AVF – Percutaneous cannulation of large central vein using dx catheter.

2. Choice of hemodialyzer: high flux, high efficiency dialyzer with high urea clearance and biocompatible membranes used.

3. Choice of a hemoperfusion cartridge4. The hemoperfusion circuit: same circuit like dx5. Priming the hmoperfusion circuit setup and priming procedure

differ depending on the brand of cartridge used.6. Heparinization during hemoperfusion (2000-3000 units bolus in

arterial line)7. Duration of hemoperfusion: 3hours

Some available hemoperfusion device

Manufacturer device Sorbent type Polymer coating

Asahi Hemosorba Bead charcoal Poly-HEMA

Clark Biocompatible system

charcoal Heparinized polymer

Gambro Adsorba Norit Cellulose acetate

Braun Haemoresin XAD-4 none

Smith and Nephew

Hemocol or Haemocol

Sucliffe speakman charcoal

Acrylic hydrogel

Complication1: Hemodialysisa. Hypophosphatemia ( P is not present in dx solution)b. Alkalemia ( standerd dx solution have high HCO3)c. Disequilibrium syndrome ( pt have high urea and poison dialyzed with

high flux dialyzer lead to disequilibrium syndrome.

2: Hemoperfusion:d. Mild transient thrombocytopenia and leukopenia can occur but levels

usually return to normal with in 24 to 48 hr.e. Adsorption or activation of coagulation factors has also been observed

rarely.

3: Continuous therapy: f. Fluid and electrolyte imbalances may be potential problem and require

frequent monitoring.g. Prolonged anticoagulation may predispose to bleeding.