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Apheresis Procedures 1 Definition From greek „Apheresis“, i.e. „separation“ of plasma through membran filter or centrifuge 16.02.04 Dr. M. Susca 2/34 Overview Plasmapheresis Preparative Plasmapheresis Conserved Plasma Plasma Fractions Therapeutic Plasmapheresis Blood cells non- selective semi- selective selective Plasma Protein Concentrate Coagulation Factors Leucocyte Concentrates Therapeutic Plasma Exchange Cascade Filtration Enzym Adsorption (Bioreaction) Fresh- frozen- Plasma (FFP) Human Albumine Erythrocyte Concentrate Activated Charcoal Adsorption Cryo Filtration Immuno Adsorption Thrombocyte Concentrate Ion Exchange Adsorption Immuno Adsorption Protein A Phenylalanin LDL- Apheresis Tryptophan Heparin Prezipitation Dextransulfat Adsorption Immuno Adsorption Thermo Filtration (?) 16.02.04 Dr. M. Susca 3/34 Plasmapheresis Preparat ive Plasmapheresis 16.02.04 Therapeut ic Plasmapheresis Blood Cells selekt ive Plasma Fract ions semi- selekt ive Conserved Plasma non- selekt ive Dr. M. Susca 4/34 Therapeut ic Plasmapheresis non- selekt ive Ion Exchange Adsorpt ion Activated charcoal Adsorpt ion Plasma Exchange semi- selekt ive selektive Cascade Filtration Enzym Adsorpt ion (Bioreaction) Cryo-Filtration Immuno- Adsorpt ion Immuno- Adsorpt ion Phenylalanin Tryptophan Protein A LDL- Apheresis Heparin Prezipit at ion Dext ransulf at Adsorpt ion Immuno- Adsorpt ion Thermo- Filt rat ion (?) 16.02.04 Dr. M. Susca 5/34 Cryo-Filtration Cascade FiltrationDextransulfat Adsorption Therapeutic Heparin Precipitation Immuno-Adsorption Plasma Exchange 16.02.04 Dr. M. Susca 6/34 Membrane Plasma Separation Centrifuge Plasma Separation Application Therapeutic Plasma Pheresis Preparative Plasma Pheresis Anticoagulation Kont. Heparinisation Citrate with Heparin Initialbolus Side Effects Filter Clotting, mech. Thrombocytopenia, Hemolysis mech. Hemolysis 16.02.04 Dr. M. Susca 7/34 Membrane Filter Separation Filtration Rate <1/3 of Blood Flow Rate Hemocompatibility TMP <100 mmHg Sterilisation: ETO Steam Gamma Secundary Membrane Pore Size 0.2-0.6 µm Sueface 0.13-0.6 m² Material: Polypropylen Polysulfon Cellulosediacetat Cut-off 3 BiDa Sieving Coefficient >0.8 16.02.04 Dr. M. Susca 8/34 Thrombocytes 2-3.5 µm Albumine 69 kDa IgG 150 kDa IgA 160 kDa IgM 900 kDa Fibrinogen 340 kDa LDL 2000-4500 kDa 0.02 µm 16.02.04 Membrane Pores 0.2-0.6 µm Dr. M. Susca 9/34 Sieving Coefficient Concentration ratio of a certain component in separated plasma to the Concentration in plasma before seperation Plasma Component Total Protein Albumine IgG IgA IgM Fibrinogen Cholesterol 16.02.04 Sieving Coefficient 0.9 0.95 0.9 0.85 0.8 0.95 0.8 Dr. M. Susca 10/34 optimal plasma separation 1. plasma/blood flow 1/3 2. low TMP 3. high blood flow 16.02.04 Dr. M. Susca 11/34 TPE - Therapeutic Plasma Exchange Heater PV PPL BLD SAC Heparin V V Plasma Filter SAD PA Advantages Disadvantages rel. simple technic bride spectrum of indication rel. low costs non- selective substitution complications no chronic application 16.02.04 Pl. S Balance Dr. M. Susca 12/34 Blood Access Vessel Access periferal vein V. jugularis interna V. subclavia arterio-venous fistula central-venous access V. cubitalis V. femoralis Cimino Fistula 16.02.04 Dr. M. Susca 13/34 Anticoagulation initial Heparin Citrate 16.02.04 continuous 40-60 IU/kg BW 1000-3000 IU Heparin 10-20 IU/kg/h 1:15-1:25 ACD/Blood Dr. M. Susca 14/34 Coagulation Cascade Defect Injury X Tissue Endothel Endogen System XII XI XIIa XIa Exogen System IX IXa Tissue Factor (III) + Ca2+ (IV) + VII VIII Ca2+ (IV) TF3 TF3 + Xa + V + Ca2+ (IV) Thrombocytes XIII Citrate Thrombin Heparin Prothrombin (II) AT III Fibrin Monmers Fibrinogen (I) XIIIa Fibrin 16.02.04 Dr. M. Susca 15/34 Substitution Clinical Requirement •isovolemic, isotonic, isooncotic •allergen and pyrogen free, sterile •containing coagulation factors and immunoglobulins 16.02.04 Dr. M. Susca 16/34 Substitution Remarcs 1. Plasma Expander Dextrane, Hydroxyethylstarch (HES), Gelatine Preparation. Short Half Life Time 2. Conserved Plasma Protein 3. Fresh Frozen Plasma (FFP) 4. Human Albumine Solution Contain E’lytes, Albumine, Globulins. Expensive, Incompatibility Reactions 16.02.04 AB0-Compatibility, Indikation for TTP und Goodpasture-Syndrom, Allergic Reactions, Viral Infections, Hypocalcemia Albumine + Hemofiltration Solutions with Lactate or Bicarbonate, Low Rate of Side Effects Dr. M. Susca 17/34 Hemofiltration Solution Na+ mmol/l K+ mmol/l Ca2+ mmol/l Mg2+ mmol/l Clmmol/l Lactate mmol/l Glucose g/l Osmol. mmol/l 135-150 0-4 1.6-2.0 0.50-0.75 100-113 35-45 0-2.0 285-312 Na+ mmol/l K+ mmol/l Ca2+ mmol/l Mg2+ mmol/l Clmmol/l Bicarbon. mmol/l Glucose g/l Osmol. mmol/l 140 0-4 1.5 0.5 109-113 35 1.0 290-300 16.02.04 Dr. M. Susca 18/34 Human Albumine Electrolyte Solution 3% 3.5% 4% 4.5% 5% 5.5% 6% Solution Solution Solution Solution Solution Solution Solution HF-Solution (ml) 850 825 800 775 750 725 700 Human Albumine 20% (ml) 150 175 200 225 250 275 300 16.02.04 Dr. M. Susca 19/34 Albumine Solution HF Solution Albumine i.g. 2 Liters 4%-Solution = 400 ml Albumine 20% + 1600 ml HF Solution 16.02.04 Dr. M. Susca 20/34 Exchange Volume Plasma Volume ½ - 2 PV Ratio 1:1 Therapy Time 1 – 3 h acute: 1x day for 3 days lang, then every 2 days Frequency chronic: 1-4 monthly 16.02.04 Dr. M. Susca 21/34 16.02.04 Dr. M. Susca 22/34 Dilution Kinetics 0 10 20 Reduct ion % 30 40 50 60 70 80 90 100 PV Reduction % 16.02.04 0 0 1/3 2/3 28 49 1 1 1/3 1 2/3 74 81 63 Dr. M. Susca 2 86 23/34 Intracellular Space = 40% Extracellular Space = 20% Interstitial Space = 16% Intravascular Space = 4% 16.02.04 Dr. M. Susca 24/34 Distribution Volume Plasma Component Molekular Weight Dalton Intrav. Distribution Half Life Time % Days Normal value g/l Albumine 69 000 40 19 35-50 IgG 150 000 50 20-23 8-18 IgA 160 000 50 5-6 0.9-4.5 IgM 900 000 80 5-6 0.6-2.8 16.02.04 Dr. M. Susca 25/34 Complications technical medical Access Problems Hypotension Plasma Filter Clotting Allergy Blood Leak Fever Hemolysis Hypocalcemia Arrhythmia Edema 16.02.04 Dr. M. Susca 26/34 Indications Dessease ThromboticThrombocytopenic Purpura (TTP) Hyperviscosity Syndrome Cryoglobulinemia Goodpasture Syndrome Myasthenia gravis Guillain-BarréSyndrome Systemic Lupus Erythematodes (SLE) 16.02.04 thrombocytopenia, hemolytic anemie, neurologic symptoms. Substitution of FFP is therapeutic desired. High blood viscosity i.g. in plasmocytoma, M. Waldenström. Neurologic and hematologic disturbances, organ damage. Immunglobulin complexis which precipitate in coldness. Skin bleeding closed to fingers and toes, articulation pain, glomerulonephritis. Rapid progressive glomerulonephritis and lungs bleeding. Prognostic important early indication to plasmapheresis in combination with Immunsuppressive therapy. IgG-Autoantibodies against Acetylcholin rezeptors of skeletal muscles. Neuro-muscular symptoms. Myasthenic crises with respiratory paralysis. Acute inflammatory attack of myelin sheat in peripheral nerves and spinal ganglions through IgG-Antibodies and immuno-complexes. Ascending paralysis of extremities and trunk up to respiratory paralysis. Autoimmuno desease of skin and vessels with deposition of immuno-complexes composed by DNA and DNA-Antibodies. Dr. M. Susca 27/34 Remind 1. Plasmapheresis is often a symptomatic therapy 2. Plasmapheresis can cause a „ReboundEffect“ by resynthesis and redistribution of pathogens 3. Therefore plasmapheresis is regulary accompanied by an immunosuppressive or cytostatic therapy 16.02.04 Dr. M. Susca 28/34 Cascade Filtration Heater PV PPL BLD Heparin V V 16.02.04 Cascade Filter SAC Plasma Filter SAD PA Advantages Disadvantages not too expensive bride spectrum of indication semi-selective complex mechanism Dr. M. Susca 29/34 Cascade Filtration (Dead–End-Procedure) Heater PV PPL BLD Heparin V V Cascade Filter SAC Plasma Filter SAD PA Retinate Pump Retinate Bag 16.02.04 Dr. M. Susca 30/34 Cascade Filtration (Recirculation-Procedure) Heater PV PPL BLD Heparin V V Cascade Filter SAC Plasma Filter SAD PA Recirculation Pump 16.02.04 Dr. M. Susca 31/34 Thermofiltration PV PPL BLD SAC V Cascade Filter Heparin V Plasma Filter SAD Heater PA Retinate Pump Retinate Bag 16.02.04 Dr. M. Susca 32/34 PAP – Plasmaadsorption „single column“ Heater PV PPL BLD Heparin V V PA Particle Filter 16.02.04 Advantages Disadvantages selective chronic application expensive complex mechanism Dr. M. Susca Plasma Adsorber SAC Plasma Filter SAD 33/34 PAP – Plasmaadsorption „double column“ Heater PV PPL Regeneration Solution BLD SAC Heparin V V 16.02.04 Plasma Filter SAD PA Plasma Adsorber Advantages Disadvantages selective chronic application expensive complex mechanism Dr. M. Susca Particle Filter 34/34