1. (TRANSFUSION MEDICINE & IMMUNOHEMATOLOGY)
APHERESIS
THERAPIES
DR RASHMI SOOD
(TRANSFUSION MEDICINE & IMMUNOHEMATOLOGY)

2. Acute Crisis Refractory Case
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……..………….

3. Evolution –Changing Roles
 Glass bottles
Plastic Bags
Anticoagulant Additives
Whole Blood
Blood Components
Antigens-Antibodies-Immunohematology
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 .

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Blood of a donor/ patient is withdrawn from him , separated ex-vivo into some /all of its components - Required component to be collected/removed is taken away and the remainder is returned to the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

5. APHERESIS - 2 TYPES Includes 1 DONOR APHERESIS :
Generates Apheresis components for the patients for numerous indications
Includes
Platelets- Plateletpheresis
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

6. 2.Therapeutic Apheresis
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.
2.Therapeutic Apheresis
All types- treat diseases by removing substances from the blood causing severe symptoms of disease.
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

7. 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.

8. 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
Therasorb :with antihuman Ig Adsober column
Indian Experience:
Evaflux Columns 2A: Pretransplant and Post Transplant
Evaflux column 5A: LDL Apheresis.

9. 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.   

10. 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

11. 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

12. 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.

13. 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

14. Urgent Plasma Exchange – Emergency
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

15. 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