Therapeutic plasma exchange

this presentation is mostly on basic TPE

1. Therapeutic plasma exchange in Clinical M edicine Dr.Md.Mizanur R ahman C howdhury Specialist Transfusion medicine United hospital ltd.

2. Therapeutic plasma exchange (TPE, plasmapheresis) is an extracorporeal treatment that can be performed by centrifugation or filtration and is designed for the removal of plasma along with pathogenic substances, such as antibodies, immune complexes, or large molecular weight substances from the plasma . Therapeutic plasma exchange

3. In TPE, using centrifugation, whole blood is pumped into a rapidly rotating separation chamber and component separate into layers based upon their density, plasma layer is removed and discarded and the remaining cellular elements are mixed with a replacement fluid and returned to the patient. In TPE using membrane filtration, secondary membrane plasma fractionation can selectively remove undesired macromolecules, which then allows for return of the processed plasma to the patient instead of donor plasma or albumin. Continue…

4. Advantages Disadvantages Membrane apheresis Fast and efficient plasmapheresis No citrate requirements Can be adapted for cascade filtration Removal of substances 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 Centrifugal devices Capable of performing cytapheresis No heparin requirement More efficient removal of all plasma components Expensive Requires citrate anticoagulation Loss of platelets

5. Advantages Disadvantages Membrane apheresis Fast and efficient plasmapheresis No citrate requirements Can be adapted for cascade filtration Removal of substances 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 Centrifugal devices Capable of performing cytapheresis No heparin requirement More efficient removal of all plasma components Expensive Requires citrate anticoagulation Loss of platelets Comparisons of this methods

6. The MCS+ fills the disposable centrifuge bowl with anticoagulated whole blood . Sterile air is displaced from the bowl into the air bag . During the filling bowl phase, substitution fluid flows into the substitution fluid bag on the weigher . The bowl will fill up and a cellular separation will occur . The plasma begins to overflow from the bowl into the waste. How machine works..

7. When the buffy coat is detected by the Bowl Optic Sensor end of collection algorithm . P acked cells from the bowl and fluid from the temporary substitution fluid bag are mixed and returned to the patient (if substitution is enabled). Continue..

8. T otal Plasma Volume (TPV) to be removed is calculated by obtaining the total blood volume (TBV) multiplied by (100% -Hct %) Total blood volume is between 5.5-7.5% of body mass for most adults and may be estimated as 70ml/kg for males and 65 ml/kg for female . Because TBV increase with muscle mass . Example: Patient Wt:70 kg and Patient Hct40% TBV : 70 kg x 70ml/kg = 4900ml TPV : 4900 ml x (100% -40%) = 2940 ml Plasma volume calculation

9. Kaplan's equation [ 0.065 x weight (kg)] x (1- Hct ) A course of plasma exchange consist of 3-5 exchanges of 1-1.5 volumes each, with an interval of 1-2 days between procedures. Continue..

10. 5% Albumin Most common used replacement fluid Dilute only with Saline GBS , MG, Goodpasture’s Syndrome Combination of saline and albumin FFP (Fresh Frozen Plasma) Used when necessary to replace clotting factors Typically used with TTP patients Cryo poor Plasma Cryoprecipitate has been removed Useful in refractory TTP patients Replacement fluid

11. Advantage Albumin FFP No risk of hepatitis Coagulation factors Stored at room temperature Immunoglobulin's ‘’ beneficial’’ factors complement Allergic reaction are rare No concern about ABO blood group Depletes inflammation Disadvantage Expensive Risk of hepatitis, HIV transmission No coagulation factors Allergic reaction No immunoglobulin's Hemolytic reaction Must be ABO compatible Citrate load

12. Citrate Heparin Anticoagulant

13. Patho -physiological changes in TPE

14. Apheresis procedure require anticoagulation,& citrate has become the anticoagulant of choice. It a nticoagulates by chelating calcium ion and blocking calcium dependent platelet activation and clotting factor activation. 47% of plasma calcium is free and, it is this free (ionized)calcium fraction that participate in coagulation reaction and chelated by endogenous citrate . Calcium regulation

15. Hypocalcemia most often manifests in perioral and/or peripheral paresthesia. Sever case of hypocalcemia may cause continuous muscle contraction if not corrected tetany , laryngospasm grand mal seizures. Chvostek`s & Trousseau`s sign may be positive. Infusion of Ca to the return line or with replacement fluid may reduce incidence of citrate toxicity. Calcium regulation Calcium regimen Symptom (%) Author No calcium 9.1% Mokrzycki M, kaplan A, Am j Kidney Dis 1994 IV Ca++ gluconate 1% Ca++ added to albumin 2.7% Kankirawatana et al. J Clin Apheresis 2007

16. Potassium decrease (minimal)(0.25meq/L with albumin and up to 0.7meq/L with FFP No change in sodium and glucose Bicarbonate decrease 6meq/L and chloride increase 4meq/L with albumin and this reverses with FFP (more citrate in FFP) Electrolytes

17. One plasma volume exchange: IgG drops to 34% of baseline IgA drops to 39% of baseline IgM drops to 31% of baseline Ranges from 3 days to 5 weeks to full recovery Most non immunoglobulin proteins recover to nearly 100% of baseline within 48 to 72 hours after TPE. Administration of immunosuppressive drugs may effect the contribution of synthesis to the recovery of immunoglobulin after TPE. Normal Immunoglobulins

18. When plasma is exchanged for nonplasma replacement solution, coagulopathy resulting from dilution of coagulation factor is a potential problem. Prothrombin time rise 30% Activated partial thromboplastin time rise 100% Fibrinogen levels may decrease 25% Plate count reduce resulting from adherence to the surfaces of the apheresis circuit are usually modest & level quickly return to base line . These changes revert toward normal within several hours except which recovered to baseline levels after 2 to 3 days. Coagulation status

19. Fibrinogen: Decrease to 25% of pretreatment with single exchange of 1 PV Decrease to 10-30% of pretreatment with consecutive daily 1 PV exchange recover to 100% of pretreatment levels by 2-3 days Prothrombin : Decreased to 30% of baseline Factor VII & factor VIII: Decreased to 45-50% of baseline Factor IX: Decreased to 60% of baseline Factor V, X, XI: Decrease to 38% of baseline Antithrombin: Activity to 40%, Ag to 70%r to 100% of pretreatment levels by 2-3 days Coagulant Proteins

20. Fluid over load may be a problem for patient with cardiac or renal impairment . I n other situations , hypovolemia may be a concern. Hemodynamic changes are more common with intermittent flow centrifugation than with continuous flow procurer. Hemodynamic changes

21. TPE can remove pharmacological the quantity of drug that is removed depends on its volume of distribution(intravascular Vs other),its half life in circulation, and weather it is administered immediately before or during apheresis. Dilutional effect

22. As large volume of donor or patient blood circulate through an apheresis device blood cells are intentionally or incidentally removed. Apheresis only modest decrease in circulating blood cell counts, which are not associated with any immediate toxicity. Small amount of red lost in apheresis circuit which is well tolerated except anemic patient meager production capacity who is undergoing multiple procedures. Although generally well tolerated, large volume leukapheresis for stem cell collections in often result decline in hematocrit and platelet count. Cellular loss

23. Removal of paraproteins ( ie myeloma) is 50% of predicted Some cases can have greater removal than predicted (see last 2 reasons) Due to: Increase in plasma volume (up to 1.5x greater, especially if IgG >40g/L) Some myeloma patients have higher proportion of IgG in intravascular space (56-85%) As remove paraprotein in TPE, plasma volume progressively decreases Paraproteins

24. An early study of 29 patients with multiple myeloma and acute kidney injury included 24 patients on dialysis and an additional 5 with creatinine concentrations higher than 5 mg/ dL . The patients were randomly assigned to one of two groups: 15 patients received plasmapheresis plus standard therapy, and 14 patients received standard therapy alone. Of the 15 patients who received plasmapheresis, 13 patients recovered renal function ( creatinine concentration < 2.5 mg/ dL ), in contrast to only 2 of the 14 receiving standard therapy. 51 However, in a study of 21 patients who were randomly assigned to receive either plasmapheresis plus chemotherapy or chemotherapy alone, Johnson and colleagues 52 reported no difference in patient survival or in recovery of kidney function. The mortality rate at 6 months was 20% in each group, which increased to 60% to 80% at 12 months. In the largest study to date, 97 patients with multiple myeloma and acute kidney injury were randomly assigned to receive either conventional therapy alone or conventional therapy plus five to seven plasma exchanges (5% human serum albumin) of 50 mL per kilogram of body weight for 10 days. The primary endpoint (death, dialysis, or glomerular filtration rate <30 mL/min) occurred in 33 (56.9%) of 58 patients who received plasmapheresis and in 27 (69.2%) of 39 control subjects. 53

25. Removal of circulating pathologic factors Auto Antibodies GBS Alloantibody antibody mediated transplant rejection Immune complexes SLE Cryoglobulin Cryoglobulinemia Myeloma protein Multiple Myeloma Prothorombotic factors Hemolytic uremic syndrome /thrombotic thrombocytopenic purpura lipoproteins familial hyper cholesterolemia Protein bound toxin or drugs barbiturate poisoning Possible mechanisms of action of plasmapheresis

26. Effects on the immune system Removal of complement products Lupus nephritis Effect on immune regulation Transplantation Improvement in reticuloendothelial function Cryoglobulinemia Replacement of deficient plasma factors Antithrombotic or fibrinolytic factor HUS/TTP Effects on the immune system

27. Indications

28. The American Society for Apheresis evaluates potential indications for apheresis and categorizes them from I to IV. Category I (disorders for which apheresis is accepted as first-line therapy) Category II (disorders for which apheresis is accepted as second-line therapy) Category III (optimum role of apheresis therapy is not established; decision-making should be individualized) Category IV (disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful) Indication

29. Hematological disorder

30. DISEASE ASFA/AABB Category ABO-incompatible marrow transplant II Aplastic Anaemia III Autoimmune haemolytic anaemia III Coagulation factor inhibitor II cryoglobulinaemia II HELLP syndrome NR Hemolytic uremic syndrome III Hyper viscocity symdrome /multiple myeloma II Immmune thrombocytopenic purpura II Platelet alloimmunization III Post tyransfusion purpura I Pure red cell aplesia III Red cell alloimmunization III Thrmbotic thmbocytopenic purpura I

31. Neurologic disorders

32. DISEASE ASFA/AABB Category Guillain-Barre syndrome I Chronic inflammatory demyelinating polyneuropathy I Polyneuropathy with IgG/Ig A monoclonal protein I Polyneuropathy with IgM monoclonal protein II Myasthenia gravis I Stiff person syndrom III Lambertr – eaton myasthenic syndrom II Paraneoplastic neurologic syndromes III Polymyositis or dermatomyositis III Multple sclorosis IV Idiopathic inflammatory demyelinating disease III Refsum`s disease II Sydenham`s chorea II PANDAS(Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection) II

33. Renal disorder

34. DISEASE ASFA/AABB Category Glomerular basement membrane antibody disease I Other rapidly progressive glomerulonephritis II Hemolytic uremic syndrome III Recurrent focal and segmental glomerulonephritis III Lupus nephritis IV

35. Rheumatic disease

36. DISEASE ASFA/AABB Category Systemic vasculitis III Scleroderma/ progrresive systemic disease III Systemic lupus erythrometosus NR Antiphopholipid antibody syndrome NR Rhematoid arthritis IV

37. Metabolic disorder Solid organ transplant

38. DISEASE ASFA/AABB Category Acute hepatic failure III Overdose /poisoning III Presensitizatin of donor organ III Transplantation across ABO barrier III Heart transplant rejection III Renal transplant rejection IV

39. The rate of adverse event during therapeutic apheresis is 4% to 5%,with the risk being slightly higher during the first procedure. Citrate-induced hypocalcemia, Metabolic alkalosis Vasovagal reactions Problems related to vascular access Hematoma, venous sclerosis thrombosis Complications

40. 4. Allergic Reaction 5. Anaphylactic reaction to plasma 6. Drug interactions 7. Hemolysis 8. Air embolism Hypotension Infections Coagulation abnormalities Transfusion related acute lung injury Hypothermia Pyrogenic reaction Continue..

41. Plasmapheresis is contraindicated in the following patients : Patients who cannot tolerate central line placement Patients who are actively septic or are hemodynamically unstable Patients who have allergies to fresh frozen plasma or albumin depending on the type of plasma exchange Patients with heparin allergies should not receive heparin as an anticoagulant during plasmapheresis. Contraindications

42. Patients with hypocalcemia are at risk for worsening of their condition because citrate is commonly used to prevent clotting and can potentiate hypocalcemia Patients taking angiotensin-converting enzyme ( ACE) inhibitors are advised to stop taking the medication for at least 24 hours before starting plasmapheresis Contraindications cont.…..

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