APHERESIS

THERAPIES

DR RASHMI SOOD (TRANSFUSION MEDICINE & IMMUNOHEMATOLOGY)

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 CrisisRefractory Case

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 BagsAnticoagulant Additives Whole Blood Blood Components Antigens-Antibodies-Immunohematology

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Blood of a donor/ patient is withdrawn from him , separated ex-vivo into some /all of its components - Required component to be collected/removed is taken away and the remainder is returned to the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

1 DONOR APHERESIS :Generates 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 apheresisMulticomponent 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

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

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.

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.

Patient Parameters to be monitored :

1. Metabolic Functions2.Acid-Base Balance3.Respiratory Function(esp intubated patients with FFP exchange)4.Cardiocirculatory function(removal of drugs during the procedure)Heart rate,Rhythmn ,BP monitored5. signs of Transfusion Reactions6. 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)GULLIAN BARRE SYNDROME Evidence suggests : Improvement in

Clincal GradeShortening of Recovery TimeDocumented 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

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 signs2) Cellular causes of Hyperviscosity(Hyperleucocytosis;Thrombocytosis)

IgM paraproteins(WM) ; Multiple MyelomaSingle session reduces plasma viscosity by 20-30%Rapid recovery of Renal Functions

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 engraftmentPost 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 avoidedPost 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.

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

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 CategoriesCategory I: Standard first line TherapyCategory II: Second -line therapyCategory III: Uncertainty of effects of tt due to inadequate dataCategoryIV: Negative data from controlled trails or ancedotal reports

Available Machines: Amicus ; ALYX;COM-TEC;Spectra;Optia;MCS+ etc..

Intensity of TreatmentAggressive A: Daily treatment : 3 to IndefiniteRoutinue R: 3times a week:5-7ttsProlonged P: 1-2 times/week: 3-8 weeks Chronic C: Every 1-4weeks: Indefinite

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

ThroughoutRarely serious complications in ICU patients (2.16% procedures) Ref: Complications;Anaesthiology Intensive Therapy 2013,vol45,no1,7-13.

Common AE: Arterial BP fallArrythmiasAnxiety/Agitation Sensation of cold/paresthesiasAllergic ReactionsLowe Limb painFeverAbdominal pain