Plasmapheresis

Plasmapheresis By Yousaf khan Renal dialysis lecturer IPMS KMU

1. Plasmapheresis Yousaf khan Renal Dialysis Lecturer IPMS -KMU

2. 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.

3. Plasmapheresis

4. 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:

5. Technical considerations Membrane 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

6. Technical considerations Centrifugal devices Advantage: Capable of performing cytapheresis No heparin requirement More efficient removal of all plasma components Disadvantage: Expensive Requires citrate anticoagulation Loss of platelets

7. 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 .

8. 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.

9. 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

10. 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

11. 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

12. Techniques of plasmapheresis ancillary measures Anticoagulation: 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.

13. 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

14. 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

15. 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

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

17. 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

18. Dialysis and Hemoperfusion Criteria for consideration of dialysis or hemoperfusion in poisoning Progressive deterioration despite intensive supportive therapy Severe intoxication with depression of midbrain function leading to hypoventilation hypothermia and hypotension. Development of complication of coma, such as pneumonia or septicemia etc Impairment of normal drug excretory function in the presence of hepatic, cardiac or renal insufficiency Intoxication with agents with metabolic and or delayed effects Intoxication with and extractable drug or poison, which can be removed at a rate exceeding endogenous elimination by liver or kidney

19. 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

20. Technical points Vascular access for hemodialysis or hemoprfusion in poisoning – with out AVF – Percutaneous cannulation of large central vein using dx catheter. Choice of hemodialyzer : high flux, high efficiency dialyzer with high urea clearance and biocompatible membranes used. Choice of a hemoperfusion cartridge The hemoperfusion circuit: same circuit like dx Priming the hmoperfusion circuit setup and priming procedure differ depending on the brand of cartridge used. Heparinization during hemoperfusion (2000-3000 units bolus in arterial line) Duration of hemoperfusion : 3hours

21. 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

22. Complication 1 : Hemodialysis Hypophosphatemia ( P is not present in dx solution) Alkalemia ( standerd dx solution have high HCO3) Disequilibrium syndrome ( pt have high urea and poison dialyzed with high flux dialyzer lead to disequilibrium syndrome. 2 : Hemoperfusion : Mild transient thrombocytopenia and leukopenia can occur but levels usually return to normal with in 24 to 48 hr. Adsorption or activation of coagulation factors has also been observed rarely. 3: Continuous therapy: Fluid and electrolyte imbalances may be potential problem and require frequent monitoring. Prolonged anticoagulation may predispose to bleeding.