APHERESIS THERAPIES

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APHERESIS THERAPIES DR RASHMI SOOD (TRANSFUSION MEDICINE & IMMUNOHEMATOLOGY)

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Guillain Barre Syndrome CIDP Myasthenia Gravis Demyelinating Neuropathy Hemolytic Disease of fetus and New Born Drug Poisonings Acute Hepatic Failure Thrombotic Thrombocytopenic Purpura Possibility of Good Pasture Syndrome Organ Transplant Other RPGN Across ABO Barriers ? Hypercholesterolemia Rheumatoid Arthritis Cryoglobulinemia List is Long and evolving……..…………. Acute Crisis Refractory Case

Evolution –Changing Roles:

Evolution –Changing Roles BLOOD BANKS have evolved from Blood collection centres to full-fledged fully automated departments of Transfusion Medicine and Immunohematology performing multiple specialised roles - including active patient management with various cellular therapies, donor apheresis and patient therapeutic apheresis including plasma exchange .   Glass bottles Plastic Bags Anticoagulant Additives Whole Blood Blood Components Antigens-Antibodies-Immunohematology

APHERESIS:

APHERESIS Word of Greek Derivation meaning ‘’SEPARATION Or TAKING AWAY ” An extracorporeal medical treatment Blood of a donor/ patient is withdrawn from him , separated ex-vivo into some /all of its components - Required component to be collected/removed is taken away and the remainder is returned to the patients circulation

APHERESIS - 2 TYPES:

APHERESIS - 2 TYPES 1 DONOR APHERESIS : G enerates Apheresis components for the patients for numerous indications Includes Platelets- Plateletpheresis – Specify Indications Plasma- Plasmapheresis Red Blood Cells(RBCs )-Erythrocytapheresis Granulocytes - Granulocytapheresis Hematopoietic Progenitor Cells(HPCs) - Stem cell apheresis Multicomponent apheresis : RBCs plus Plasma 2-units RBCs Platelets & RBCs Platelets & Plasma Advantage Reduced Donor Exposure Standardized component Good yield Better dose Safer for donor as well as patients

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2.Therapeutic Apheresis All types- treat diseases by removing substances from the blood causing severe symptoms of disease. What can be removed : Injurious and Noxious Large Molecular weight substances : antibodies-auto and allo , antigen-antibody complexes, toxins , protein bound drugs , myeloma light chains , endotoxins, cryoglobulins , lipids such as cholesterol & TGs & few poisons in the plasma. THERAPEUTIC PLASMA EXCHANGE (TPE ) : Removal of the liquid portion of blood to remove harmful substances and replacement with a replacement solution . Term plasmapheresis is popularly used for TPE, Plasmapheresis  involves no replacement . THERAPEUTIC RED CELL EXCHANGE ---- Involves RBC exchange LDL APHERESIS  - Removal of low density lipoprotein in patients with familial hypercholesterolemia. THERAPEUTIC CYTAPHERESIS : Photopheresis - Collection of circulating Mononuclear cells ,exposing them to

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Photo activating 8-Methoxypsoralen,and then exposure to Ultraviolet A light. (To treat graft-versus-host disease, cutaneous T-cell lymphoma and rejection in heart transplantation .) Leukocytapheresis  - Removal of malignant white blood cells (in patients with leukemia )esp when very high white blood cell counts are causing symptoms. Thrombocytapheresis  - Removal of platelets in cases with symptoms from extreme elevation in platelets (as in cases with myeloproliferative disorders,  essential thrombocythemia  or polycythemia vera) IMMUNOADSORPTION(IAS): A blood purification technique that enables the selective removal of Immunoglobulins from separated plasma through high-affinity adsorbers.

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IMMUNOADSORPTION(IAS) Conti. esp. effective in Autoimmune diseases were TPE failed to be effective. Lack of any Controlled Trials for Immunoadsorption. Devices available in market : Non selective adsorbers : Selesorb: Dextran sulphate column Semi-selective: Prosorba ,Immunosorba:with Staphylococcal protein A-agarose column Selective:Therasorb :with antihuman Ig Adsober column Indian Experience : Evaflux Columns 2A: Pretransplant and Post Transplant Evaflux column 5A: LDL Apheresis.

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    Patient Parameters to be monitored : 1. Metabolic Functions 2.Acid-Base Balance 3.Respiratory Function(esp intubated patients with FFP exchange) 4.Cardiocirculatory function(removal of drugs during the procedure)Heart rate,Rhythmn ,BP monitored 5. signs of Transfusion Reactions 6. signs of circulatory overload Reference source: To evaluate the appropriateness of therapeutic apheresis : Guidelines of the American Society for Apheresis(ASFA): Drawn up in 2007 and revised and updated from time to time(every 3 years) Using the criteria of Evidence based medicine . Clinical Trials continue to clarify the appropriate use of Therapeutic Plasmapheresis(TPE) in various diseases. Especially Important is Evaluation of scientific literature to the clinical use of therapeutic apheresis to the pathologies in category III which in particular clinical situations can have a strong grade of recommendation for TPE as provided by series of clinical case results as well as summary fact sheets.

Rational for Use of TPE(Few Examples):

Rational for Use of TPE(Few Examples) GULLIAN BARRE SYNDROME Evidence suggests : Improvement in Clincal Grade Shortening of Recovery Time Documented Imp.in mildly affected pat.as well Circulating Myelin Antibodies Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Evidence suggests: TPE especially useful in patients not responding to or not tolerating steroids. Comparable to IVIG Removal of antibodies to myelin protein antigen Peripheral Neuropathy & Monoclonal Gammopathy Commonly done in patients with IgM paraproteins. Myelin associated monoclonal glycoprotein

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Myasthenia Gravis Esp useful for rapid symptomatic improvementesp those with breathing, swallowing ,walking compromise. Useful for those intolerant or unresponsive to other therapies. Useful for in patients who are negative for antibody . Useful to optimize muscle function before thymectomy or other surgery. Comparison with IVIG: Median response time significantly shorter with TPE(p=0.14) Antibody to Acetylcholine receptor ,or antibody to muscle specific kinase on the motor end plate of muscle cells Hyperviscosity Syndrome 1)Serum Viscosity > 3 centipoise greater than water esp with neurological signs 2) Cellular causes of Hyperviscosity(Hyperleucocytosis;Thrombocytosis) IgM paraproteins(WM) ; Multiple Myeloma Single session reduces plasma viscosity by 20-30% Rapid recovery of Renal Functions

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Hemolytic Disease of Foetus and New Born 1.To slow foetal hemolysis 2.Esp useful when IUT is not feasible before 18 weeks of gestation Sensitized D Neg mothers carrying D positive foetus . Allogenic Solid Organ Transplant across ABO barrier Pretransplant TPE of recipient-To avoid delayed engraftment Post Transplant – To correct engraftment and prevent rejection removes Isoagglutinins Allogenic Hematopoietic Stem Cell Tx across major ABO barrier PreTransplantTPE in Recipient-Hemolytic Transfusion Reaction can be avoided Post TransplantT PE in recipient- For Cell Engraftment delay correction Thrombotic Thrombocytopenic Purpura Urgent daily TPE improves survival drastically Deficiency of metalloproteinase ADAMTS13 or Presence of autoantibody inhibitor of the enzyme ADAMTS13 Acute Fulminating Hepatitis Rapid removal of aromatic aminoacids,ammoniac endotoxins,mercaptans,activated coagulation factors,FDPs,TPA,phenols.

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Idiopathic Thrombocytopenic Purpura(ITP) An option for chronic ITP refractory to more standard therapies Protein A silica column Immunoadsorption Pure Red Cell Aplasia & Aplastic Anemia Not a primary therapy-Can be offered to patients who failed to improve from conventional tt ,esp those found to have serum inhibitory factors HELLP Syndrome Patients unresponsive to steroids,supportive therapy like anti hypertensives,fluids,blood &Components,antibiotics Early initiation is life saving Antiphospholipid Syndrome Urgently used to remove pathogenic autoantibodies and procoagulant factors Antiphospholipid antibodies,like Anticardiolipin Antibody,Anti Beta2group1antibody,Lupus anticoagulant Poisoning by Heavy Metals,Amanita Phalloides,herbal products Drug should bind strongly to plasma proteins Removal of drug

Plasma Exchange-ASFA:

Plasma Exchange-ASFA Urgent Plasma Exchange – Emergency Thrombotic Thrombocytopenic Purpura Catastrophic Antiphospholipid Syndrome Acute pancreatitis c Triglyceridemia Intoxication by drugs or poisons Hyperviscosity syndromes Acute fulminating hepatitis Acute Inflammatory Demyelinating Polyneuropathy Myasthenia Gravis ASFA Indication Categories Category I: Standard first line Therapy Category II: Second -line therapy Category III: Uncertainty of effects of tt due to inadequate data CategoryIV: Negative data from controlled trails or ancedotal reports Available Machines: Amicus ; ALYX;COM-TEC;Spectra;Optia;MCS+ etc.. Intensity of Treatment Aggressive A: Daily treatment : 3 to Indefinite Routinue R: 3times a week:5-7tts Prolonged P: 1-2 times/week: 3-8 weeks Chronic C: Every 1-4weeks: Indefinite

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Comparing TPE and IVIG : 1.Slow onset of action 2.Malaise associated with high-dose IVIG 3.Risk of IVIG associated aseptic meningitis 4.Risk of acute kidney injury 5.Risk of anaphylaxis and stroke Trends : In UK and Canada: IVIG is being conserved for indications were there is no alternate treatment option available ,eg Immunodeficiency state. In USA,use of IVIG discouraged for economic reasons when TPE can be an equally good alternative Our Experience at SCH: Guillain Barre Syndrome Wegners Granulomatosis(cANCA pos ) Myasthenia Gravis Anti GBM (24 procedures) disease CIDP SLE Adverse Effects : Continuous Observation ,Proper Monitoring of patients Required Throughout Rarely serious complications in ICU patients (2.16% procedures) Ref: Complications;Anaesthiology Intensive Therapy 2013,vol45,no1,7-13. Common AE : Arterial BP fall Arrythmias Anxiety/Agitation Sensation of cold/paresthesias Allergic Reactions Lowe Limb pain Fever Abdominal pain

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