Plasma Exchange Chan King Chung

History Begins in the 1970s Initially to treat anti-GBM disease Blood cell separators Initially to treat anti-GBM disease Lowering circulating antibody Widespread use in different condition Some indication replaced by other method Selective extraction for hypercholesterolemia IVIg for immunotherapy

Indications Removal of ‘evil’ humoral substances Antibodies Goodpasture’s Syndrome (Anti-GBM) Wegener Granulomatosis (ANCA) Myasthensia Gravis (Anti-AChR) Toxins Triglycerides Paraproteins Thyroxin Acetylsalicylate Cytokines Sepsis Uncertain Thrombotic Thrombocytopenic Purpura Haemolytic Uraemic Syndrome Guillain-Barre´ syndrome Miller Fisher syndrome Liver failure

Physiology of Body Fluid ECF (27%) 19L Plasma (4 - 5%) 3L Interstitial (12%) 8L RBC (2 – 3.5%) Non-water mass ICF (33%) 23L (40%)

Dosage Blood volume 7% of BW Plasma volume ~4% of BW (40mL/kg) Residual plasma volume = e-(volume removed) Change of 1 plasma volume = 37% remain

Dosage Usual 1-1.3x plasma volume per session Volume = (1- Hct) x 70mL x BW x 1 or 1.3 ~2 to 3L in most case

Dosage Frequency of Plasma Exchange depends on Distribution of substance Rate of production ~5 plasma volume in 7 to 10 days will remove ~90% of the plasma substance

Techniques of Plasma Exchange Access: large vein ± dialysis catheter Anticoagulation Cell Separator Centrifugation Membrane plasma filtration Replacement Fresh frozen plasma Albumin Colloid / Crystalloid

Anticoagulation Heparin Citrate 2000 to 5000 units bolus then 500 to 2000 units/hour Citrate

Cell Separator Centrifugation 600mL in 37 mins                         

Cell Separator                                  Membrane filtration

Performance of Prisma TPE

Replacement Post-filter FFP Contain all component Replacement of specific factor (TTP / Liver failure) Risk of transfusion Citrate Toxicity ? Giving back the ‘Evil’ humoral

Composition of Plasma Water Electrolytes Proteins Na, Cl, Ca, K, PO4, Mg Osmotic pressure of 5526 mmHg Between ECF and ICF Proteins Albumin, Globulins, Complements, Transport Protein, etc. Oncotic pressure of 25 mmHg Distribution between plasma & interstitial fluid

Replacement Albumin Expensive Risk of hypokalemia and hypocalcaemia Risk of bleeding Risk of Prion diseases Mixing electrolyte with 5% albumin solution before use (in paediatrics)

Albumin Replacement e- ECF (27%) 19L Plasma (4 - 5%) 3L Interstitial RBC (2 – 3.5%) Non-water mass ICF (33%) 23L (40%) e-

Replacement Colloids HES / Gelofusin Cheaper compare with Albumin Safer Problem with oncotic pressure Slowly loosing oncotic pressure -> hypovolaemia Pulmonary edema Problem with electrolyte / bleeding

Colloid Replacement ECF (27%) 19L Plasma (4 - 5%) 3L Interstitial RBC (2 – 3.5%) Non-water mass ICF (33%) 23L (40%) H20

Colloid Replacement Risk of hypovolaemia balanced by Higher volume of replacement Close monitoring Risk of pulmonary edema is low Normal oncotic pressure is ~25mmHg Theoretical risk of pulmonary edema when oncotic pressure is <10mmHg

Colloid Replacement Studies using HES (t1/2: 8hr) instead of albumin had demonstrated the safety of colloid Journal of Clinical Apheresis. 12(3):146-53, 1997 Less data is available for using gelatin (e.g. gelofusine t1/2: 2hr) Usually when Albumin > 30g/L

Replacement Crystalloid Crystalloid-only replacement is not used Half crystalloid, half albumin regime is commonly used for saving money ~1/3 of crystalloid stay in intravascular space Bolus of crystalloid may be given for hypotension

Typical Replacement Full volume gelatin Half gelatin then half albumin Resulting Alb level 25g/dL Half gelatin then half FFP Full volume FFP For TTP

Electrolyte Replacement Hypokalemia might occur 3L plasma only contain 10-15 mmol K Large reserve inside the cells Hypocalcaemia 3L plasma contain 6–7 mmol Ca ~10ml 10%CaCl2 Especially if Total Albumin replacement (Ca++ 0.5-0.75mmol/L) Cannot clear citrate (as anticoagulation / FFP / Albumin)

Setup 3L Session (3hr) Anticoagulation (ACDA 240mL/hr) Replacement Blood (120-150 mL/min) Plasma (1L/hr)

Adverse Reaction Hypotension Hypovolaemia Hypocalcaemia Allergic reaction ACEI Membrane activation Prekallikrine activator in SPPF

Adverse Reaction Bleeding tendency Immunosuppression Lowered coagulation factors in underlying bleeding disease (TTP) Immunosuppression Lost of immunoglobulins, complements

Modification of Plasma Exchange Coupled Plasma Filtration Adsorption Plasma Filter Charcoal

How are we going to do ? By Haematology as much as possible Prisma TPE AK10

Prisma TPE More correct monitoring of volume Automatically stop removal pump when the replacement is empty Safer Unfamiliar Higher cost

Prisma TPE Setting Haematocrit Blood flow rate Replacement bottle volume Replacement volume Replacement rate Net patient plasma removal rate ** Net plasma removal volume **

Prisma TPE 3L Session (3hr) Anticoagulation (ACDA 240mL/hr) Replacement (1L/hr) Blood (120-150 mL/min) Plasma [1L/hr]+[0mL/hr]

? Fluid Gain 240mL/hr for 3 hours 720mL over 3 hours A small volume only. Can be handled by kidney Useful to counter act hypotension In theory, may set 80mL/hr net loss, as only 1/3 is in intravascular space

AK10 Cheaper and more familiar Same setup as CVVH Only 1 replacement pump and 1 filtrate pump Volume state less accurate than Prisma Risk of hypovolaemia if the replacement pump stopped