APHERESIS THERAPIES AN OVERVIEW BY DR RASHMI SOOD 2025.pptx

APHERESIS THERAPIES AN OVERVIEW OF DONOR AND PATIENT APHERESIS

1. APHERESIS THERAPIES ( Yr 2025) Presented by Dr Rashmi Sood NABH Assessor Senior Consultant Head Of Department Manipal Hospital ,Palam Vihar , Sector 23 ,Gurugram ,Haryana , India Year (Year .

2. Apheresis Apheresis is word of Greek derivation meaning ‘’SEPARATION Or TAKING AWAY” ” Is an extracorporeal medical treatment Blood of a donor/ patient is withdrawn from him , separated ex-vivo into some /all of its components – the r equired component to be collected/removed is taken away and the remainder is returned to the patients circulation.

3. Apheresis Historical background: In 1660 1st experimental apheresis performed by Richard Lower, Oxford, England. B/W 1902-14, plasmapheresis performed in France,Russia and USA. In 1960, Solomen and Fahey used Manual Therapeutic Plasmapheresis to reduce elevated Ig levels in Hyperviscosity Syndrome. Now a days Automated cell separator machine is used to collect and/or treat blood components in apheresis.

4. APHERESIS TYPES - 1) Donor Apheresis Red Blood Cells(RBCs) : Erythracytapheresis Plasma : Plasmapheresis Various white cells : Leukacytapheresis : Granulocytapheresis , PBSC(HPC ) ,DLI ,CAR-T Platelets : Plateletpheresis Hematopoietic Progenitor Cells (HPC/PBSC) : Stem cell apheresis Multicomponent apheresis : RBCs plus Plasma 2-units RBCs Platelets & RBCs Platelets & Plasma DONOR APHERESIS : Generates Apheresis components for the patients for numerous indications

5. Advantage of Donor Apheresis Advantages of donor apheresis product over whole blood components : Reduced donor exposure Standardized component , leucodepleted filtered Good yield and better dose Safer for donor as well as patients

6. 2)Therapeutic Apheresis PLUS LDL Apheresis and Photopheresis PLUS LDL Apheresis and Photopheresis

7. Therapeutic Apheresis What can be removed : Injurious and noxious large m olecular 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

8. Principle of working A. Centrifugation I. IFC – Intermittent Flow Centrifugation II.CFC – Continuous Flow Centrifugation B. Membrane Filtration

9. Principle of Working   I. IFC Adv:   Smaller in size   Mobile   Single Venipuncture Disadv :   Greater Extracorporeal volume   Procedure time ↑   Variable Volume of Collection   Red Cell Contamination   NOT a Leukocyte Depleted (LD) SDPs

10. Principle of Working II. CFC Adv :   Single/ Double venipuncture   In-process L D Leucodepletion   No chance of Red Cell Contamination   Lesser Extracorporeal volume   Procedure time ↓ Disadv :   Larger and Heavier

11. Membrane Filtration

12. 1. SDP: Apheresis-PC Plateletpheresis : is the process of collecting required platelets and rest of the components are returned back to the donor.  Apheresis platelets can be stored for 5 days at 22±2ºC with continuous agitation.  Can be prepared with/without plasma .  Can boost Platelet Count by 30,000-60,000/ ul .  Procedure Time : 45-90 minutes. Average > 3x1011platelets ( Equivalent to 4-6 RDPCs) in 200-300 ml of plasma / PAS

13. SDP: Apheresis-PC Merits Demerits  Reduced donor exposure : Full transfusion Dose   Trained persons required High Quality Products: More platelets per component collected   Sophisticated equipment required   Leukocytes <5.5x106 / unit   Obviate the need of filtration   Low risk to alloimmunization Donation by Apheresis requires commitment Red cells - Traces   Matching donor to patient   Less exposure to infection   Decreased risk of bacterial contamination & easy handling   Consistent and standardized products (yields)

14. PLATELET RICH PLASMA THERAPY A medical therapy – conditioned plasma Works by injecting a concentrated mixture of platelets ,growth factors and cytokines – leucocyte and fibrin content decides its various types Mostly autologous ,allogenic has been tried Dose of platelets in a good PRP product > 10 lakh / ml ( 3to 5 times physiological level ) Stimulates wound healing ,tissue repair and regeneration Indications : Chronic Tendinitis Rotator Cuff disease Plantar fasciitis Muscle tear - Supraspinatus tear Osteochondral lesion of knee Bone degeneration

15. PLATELET RICH PLASMA THERAPY Meniscus Injury Hair Loss Dental : Tooth extraction , Periodontal Surgery , Implant Surgery Assisted reproduction Venous Ulcers Diabetic foot ulcers Aesthetic Medicine

16. Response to Platelet Transfusion Monitoring of response:   If platelet transfusion was given to bleeding patient i.e., Therapeutic Transfusion, the CLINICAL RESPONSE is the most important indication of effectiveness of the transfusion.   Responses to a Prophylactic Transfusion should be assessed by measuring the increase in platelet count following transfusion. Percentage Platelet Recovery (PPR) = Platelet increment 10 9/L x blood volume (BV ) x 100 = % Number of platelets transfused (x1011) Corrected Count Increment (CCI) = Platelet increment/ μ l x BSA (m2) x 1011 = = Platelets/ μ l/m2 Number of platelets transfused (x1011)

17. Response to Platelet Transfusion Minimum platelet recovery to define a successful transfusion is considered as: PPR >30% at 1 h post transfusion and >20% at 20-24 h. or a CCI of >7.5x109 platelets/ μ l/m2 at 1 hr and >4.5x109 platelets/ μ l/m2 at 20-24 h.   In practice, a poor response to a prophylactic platelet transfusion can be defined as: Failure to raise the platelet count above the ‘trigger’ platelet count for two consecutive transfusions.

18. 2. Leukapheresis ( Granulocytapheresis ) Role of granulocytes for sepsis is still unclear . However there are certain clinical situations where they may be considered as adjunct therapy to antibiotics . s Factors to be considered Strong evidence of bacterial or fungal septicaemia Absolute neutrophil count < 3000/ ul Indications and Guidelines Neonates & Older Children: Neutropenia or granulocyte dysfunction with bacterial infection and lack of responsiveness to standard therapy .

19. Leukapheresis ( Granulocytapheresis ) ( conti .) Fungal disease not responding to standard therapy. P ost BMT fungal infections resistant to treatment Dose: A typical dose for neonates is 10-15 ml/kg body weight , which is approximately 1-2 X 10 9 PMN/Kg. Older children and adult dose is 1 X10 10 cells/kg. Treatment should be administered daily until an adequate neutrophil count is achieved &/or patient shows clinical

20. Leukapheresis ( Granulocytapheresis ) ( conti .) improvement. Sources: Granulocytapheresis . Buffy coats (about 10 BC ABO matched) Complications: Transfusion reactions TA-GvHD Precautions: ABO & Cross Match Compatible with the patient Irradiated to prevent TA GVHD CMV Negative

21. DLI Donor Lymphocyte Infusion A medical procedure A type of Immunotherapy It involves transferring T lymphocyte cells from a donor to a patients blood stream . The healthy T cells attack cancer cells left behind after bone marrow or Stem Cell Transplant Uses : 1)To treat patients of relapsed leukemia after Hematopoietic Stem Cell Transplantation (HCT) . 2) To treat solid tumor malignancies . 3) To produce prolonged remission of leukemias . Risks : GvHD

22. CAR-T Cell Therapy Chimeric Antigen T cell Receptors Uses T cells engineered with CARs to treat cancer . T cells are modified to recognize cancer cells and destroy them . Application CAR-T therapies account for more than half of all trials for hematological malignancies . B cell derived cancers such as Acute Lymphoblastic Leukemia (ALL) Diffuse large B cell Lymphoma (DLBCL) Follicular Lymphoma Multiple Myeloma Mantle cell lymphoma etc

23. 3. Erythrocytapheresis Erythrocytapheresis is an apheresis procedure by which erythrocytes are separated from whole blood. On-line separation of RBCs and Plasma . Donor Selection Criteria : Same as W.B. Donor except: Hb >14 gm/dl Donation Interval 6 months. Advantages : Standardized , up to 2 units of RBCs mass collection Greater volume of RBCs without hypervolemia Possible to collect rare antigen matched P RBCs in adequate doses for multi transfused patients : Thalassemia Dialysis Cancer

24. Erythrocytapheresis ( conti ) 130 lb = 58.9 kg 150 lb = 68 Kg 175 lb =79.3 Kg 61 inch = 5 feet 65 inch = 5.4 feet

25. THERAPEUTIC APHERESIS

26. Mc Leod’s criteria for evaluation of apheresis efficacy MECHANISM Current understanding of the di sease process supports a rationale use of apheresis as a treatment CORRECTION The abnormality involved in the disease pathogenesis can be corrected with the apheresis treatment CLINICAL EFFECT There is evidence that apheresis confers a clinical benefit and not just a change in the laboratory parameter ( statistically significant )

27. ASFA Indication c ategories (ASFA indication categories and grading for Therapeutic Apheresis is reviewed and updated every three years 2023) ASFA Category I: Apheresis is standard and acceptable first line therapy , either stand-alone or in conjunction with other therapies . ASFA Category II: Apheresis is accepted as second line therapy , either stand – alone or in conjunction with other therapies . ASFA Category III: Optimum role of apheresis is not established ,therefore decision making should be individualized , based upon the patients clinical situation ASFA Category IV: Evidence demonstrates or suggests that apheresis is ineffective or harmful

28. Grading of Recommendations Assessment, Development and Evaluation (GRADE) system Recommendation Description Methodological quality of supporting evidence Implications Grade 1 A Strong recommendation, High Quality evidence RCTs without important limitations or overwhelming evidence from observational studies Can apply to most patients in most circumstances without reservation Grade 1 B Moderate Quality evidence Inconsistent results, methodological flaws, indirect, or imprecise or exceptionally strong evidence from observational studies “ Grade 1 C Low Quality Evidence Observational studies or case series “ Grade 2 A Weak recommendation, high Quality evidence RCTs without important limitations or overwhelming evidence from observational studies Weak reco ,Best action may differ depending on circumstances or patients’ or societal values Grade 2 B Moderate Quality evidence Inconsistent results, methodological flaws, indirect, or imprecise or exceptionally strong evidence from observational studies “ Grade 2 C Low Quality Evidence Observational studies or case series Other alternatives may be equally reasonable

29. 4. Plasmapheresis and Plasma Exchange: The American Society for Apheresis (ASFA) definitions for these procedures are as follows: Plasmapheresis: A procedure in which blood of a patient or the donor is passed through a medical device , which separates out plasma from the other components of blood , and then this plasma is removed (i.e., less than 15% of total plasma volume/ ap prox 500 ml) , without the use of replacement solution.

30. 4. Plasmapheresis and Plasma Exchange: Plasma Exchange : Therapeutic procedure in which blood of the patient is passed through a medical device which separates out the plasma from other components of blood, the plasma is removed and replaced with a replacement solution such as colloid solution (e.g., albumin and/or plasma) or combination of crystalloid/colloid solution.

31. 4. Plasmapheresis and Plasma Exchange: TREATMENT PLAN

32. Efficiency of TPE Calculation depends on numerous factors – Frequency of procedures – Duration of therapy - What is being removed? – IgG - mainly extravascular – IgM – mainly intravascular Relationship between fraction of unwanted component remaining and proportion of patients plasma volume exchanged – is exponential – continuous mixing in patient plasma of replacement solution . 1PV Ex = Unwanted component reduced to 35% of initial value 2Pv Ex = Unwanted component reduced to 15% of initial value due to diminishing effectiveness , usually 1-1.5 patients plasma volume is exchanged .

33. Fraction of substance remaining after 1 exchange : Exponential Relationship

34. During course of subsequent TPE sessions Calculation depends on numerous factors – Frequency of procedures – Duration of therapy - What is being removed? – IgG - mainly extravascular – IgM – mainly intravascular

35. Molecular weight of removed substances by blood purification therapy

36. PLEX / DIALYSIS

37. PLEX / DIALYSIS

38. Molecular weight of removed substances by blood purification therapy

39. Indications for TPE – Category 1- Indications S NO DISEASE WHERE TPE IN THE FIRST LINE INDICATION SYNONYM RATIONALE PROCEDURE COMMENTS GRADE 1 Acute Inflammatory Demyelinating Polyradioculoneuropathy GB Syndrome Circulating Myelin Antibodies TPE / Immunoadsorption Evidence suggests : 1) Improvement in clinical grade 2) Shortening of recovery time 3) Improvement even in mildly affected patients as well 1A/1B                             2 Acute Liver Failure TPE for Hepatitis Virus induced acute liver failure Rapid removal of aromatic aminoacids ,amoniac endotoxins ,Mercaptans ,Activated coagulation factors ,FDPs ,TPAs ,Phenols TPE   1A              

40. Indications for TPE - Category 1- Indications                             3 Acute glomerular basement membrane disease Good Pastures Syndrome   Antibodies attatched to the basement membrane of blood vessels of kidneys and lungs 1)Diffuse alvelor hemorrhage 2) Dialysis Independence TPE   1C/1B                             4 Catastrophic Antiphospholipid Syndrome   Anti phospholipid antibodies such as lupus anticoagulant ,anti cardiolipin ,anti beta2 glycoprotein   TPE   2C                             5 Chronic acquired demyelinating polyneuropathies   IgG /IgA/IgM related TPE   1B                            

41. Indications for TPE - Category 1- Indications                             6 Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)   Removal of Antibodies to Myelin Protein Antigen TPE /Immunoadsorption 1) Especially in patients not responding to or tolerating steroids 2) Comparable to IVIG 1B                             7 Familial Hypercholesterolemia Homozygotes Low density lipoproteins and cholesterol   Esp in homozygotes , esp in patients aged less than 10 years   1A                             8 Focal Segmental Glomerulosclerosis   Removal of c irculating antibodies that damage the glomeruli in the kidneys   TPE /Immunoadsorption Is recurrent in kidney transplants 1B                            

42. Indications for TPE - Category 1- Indications               9 Hyperviscosity in Hypergammaglobulinemia 1) Hyperviscosity : When serum viscosity > 3 centipoise greater than water esp with neurological signs 2) Cellular causes of Hyperviscosity ( Hyperleucocytosis ,Thrombocytosis ) 1) IgM paraproteins (WM) 2) Multiple Myeloma   1) Single session reduces plasma viscosity by 20-30% 2) Rapid recovery of renal functions                   Symptomatic     TPE   1B                 Prophylaxis for rituximab     TPE   1C                            

43. Indications for TPE - Category 1- Indications               10 Myasthenia Gravis Anti Ach receptor antibodies   at the neuro muscular junction   1 Acute short term treatment with TPE /DFPP/IA - Category I indication 2Long term treatment with TPE /DFPP/IA - Category II indication 1 Especially useful for rapid symptomatic improvement ,esp those with breathing ,swallowing ,walking compromise 2 Useful for those intolerant or unresponsive to other therapies 3Useful for patients who are negative for the antibody 4Useful to optimize muscle function before thymectomy or other surgery 5 In comparison with IVIG ,median response time is significantly shorter                

44. Indications for TPE - Category 1- Indications               11 N-Methyl -D- Aspartate receptor antibody encephalitis     1) Removal of autoantibodies 2) Decreases inflammatory response to antibodies TPE/IA                                 12 Thrombotic microangiopathy - Drug Induced - Ticlopidine     Removal of thromogenic and antifibrinolytic molecules and replenishing the deficient anticoagulants and profibrinolytics                                   13 Thrombotic microangiopathy - Thrombotic Thrombocytopenic Purpura     Removal of thromogenic and antifibrinolytic molecules and replenishing the deficient anticoagulants and profibrinolytics TPE   1A                            

45. Indications for TPE - Category 1- Indications               14 Transplantation -Kidney - ABO compatible                           Antibody mediated rejection     TPE/IA   1B                               Desensitization /Prophylaxis - Living Donor     TPE/IA   1B                             15 Transplantation -Kidney - ABO incompatible                                         Desensitization - Living Donor     TPE/IA   1B                            

46. Indications for TPE - Category 1- Indications               16 Transplantation - Liver                                         Desensitization - ABO incompatible - Living Donor     TPE   1C                             17 Wilsons Disease - Fulminant     TPE   1C                            

47. Replacement fluids a) 5% Albumin Best choice Dilute only with saline b) Combination of saline and albumin c) FFP d) Cryo poor plasma

48. 5. Immuno adsorption Principle : WB → Cell Separator(Plasma filter ) →Pump ↑ ↓ Rvr ← Plasma ← Affinity column or Filter (Immunoadsorption Column )

49. 5. Immuno adsorption An extracorporeal blood purification technique that enables the selective removal of Immunoglobulins from separated plasma through high-affinity adsorbers. Can be used as an alternative to plasma exchange in certain conditions esp. in autoimmune conditions were TPE failed to be effective. Lack of controlled t rials for Immunoadsorption

50. 5. Immuno adsorption Devices available in market : Non selective adsorbers : Selesorb : Dextran sulphate column : Drug Resistant SLE ,APLA ,Cryoglobulinemia Semi-selective: Prosorba , Immunosorba : with Staphylococcal protein A-agarose column : Cardiomyopathy Selective : Therasorb : with antihuman Ig Adsober column : Familial Hypercholesterolemia , Autoimmune Diseases Indian Experience: Evaflux Columns 2A: Pretransplant and Post Renal Transplant Evaflux Columns 5A: LDL Apheresis.

51. Immuno adsorption Merits : a) More specific alternative b) Advantageous safety profile- reduced plasma substitution solutions c) Reduced length of stay in hospital d ) Cases refractory to TPE Demerits : Cost Complications : Allergic reactions to the column Dizziness Nausea Feeling cold

52. Immuno adsorption

53. Selective Adsorption (Immunoadsorption ) Type of column Effectiveness Remarks Staphylococcus Protein A Sepharose (PAS) Column ( Ligasorb ) Binds IgG1, IgG2, IgG4, Immune complexes Process up to 6L of plasma and remove up to 20 mg of IgG per treatment of session Peptid - GAM Ligand Columns ( Globaffin ) Higher affinity to IgG1, IgG2, IgG4 Regenerative and is effective up to 20 sessions Antihuman polyclonal Immunoglobulin columns ( TheraSorb and Ig Adsopak ) IgG, IgA, IgM, IgE , immune complexes TheraSorb : 10 sessions Ig Adsopak : 20 sessions Dextran-Sulphate Column ( Selesorb ) DNA antibodies, anticardiolipin antibodies Intended use: SLE complicated by RPGN or CNS disease Drug-resistant SLE APLA,Cryoglobulinemia Tryptophan Polyvinyl Alcohol Gel Column (Immusorba TR) Phenylalanine Polyvinyl Alcohol Gel Column ( Immusorba PH) Greater removal capacity for AchR antibodies, Fibrinogen Single treatment (MG)

54. Selective Adsorption (Immunoadsorption ) ABO Specific Immunoadsorption ABO incompatible transplantations One use removes more than 90% of isohemagglutinins Ig E Immunoadsorption Atopic dermatitis Severe allergic asthma 86% reduction β2 Micro globulin Column Dialysis related Amyloidosis It can be used simultaneously with dialysis

55. Selective Adsorption (Immunoadsorption )

56. LDL Apheresis Approved for patients with : 1Homozygous form of familial hypercholesterolemia 2 When LDL > = 200mg/dl and there is documented coronary heart disease 3 When LDL>= 300mg/dl despite medical therapy 4those who are intolerant to medical therapy .

57. LDL Apheresis TPE DFPP LDL antibody Immunoadsorption Hemoperfusion Thermofiltration

58. 6. Photopheresis Buffy Coat is separated from whole blood, chemically treated with Methoxalen ( Uvadex ), then exposed to ultraviolet A light, and returned to the patient. Therakos Photopheresis System (J & J)

59. 6. Photopheresis

60. 6. Photopheresis

61. 7. Red Cell Exchange Sickle Cell Disease: (The Author has hands on experience ) Clinical picture Chronic anemia Hgb S instead of Hgb A - alters the erythrocytes and their membranes (sickle red cells) Increased blood viscosity Microvascular occlusion Infarcts in brain, lungs, retina Pain crisis Priapism Acute chest syndrome Stroke

62. 7. Red Cell Exchange Treatment Red cell transfusions Hydroxyurea Red cell exchange (ASFA Category I) Aims to maintain Hgb S <30 Malaria/Babesiosis Severe malaria or babesiosis with parasitic index >10%

63. 8.Leukocytapheresis Leukocytosis Acute Myelogenous Leukemia (AML) Chronic Myelogenous Leukemia (CML) Acute Lymphocytic Leukemia (ALL) Chronic Lymphocytic Leukemia (CLL) Clinical picture Hyperviscosity with microvascular occlusion : WBC levels > 100X103/ uL CNS symptoms Hemorrhage Pulmonary insufficiency

64. 8.Leukocytapheresis Treatment Combination chemotherapy ( tumor cell lysis leads to metabolic imbalance and ARDS) Leukapheresis (ASFA Category I) The role of therapeutic leukapheresis is to initially and rapidly decrease the burden of leukocytosis on the body by 50-60% whilst chemotherapy is commenced. Pre treatment of leukocytosis Prevention of tumor cell lysis syndrome (Japan ) Inflammatory Bowel Disease : selective removal of granulocytes ,monocytes /macrophages from whole blood (Pro inflammatory cytokines ) by selective adsorption : Columns containing cellulose diacetate (Japan ) RA

65. 9. Thrombocytapheresis Thrombocytosis (>1,000 x 109 /L) Essential Polycythemia vera Clinical picture : Microvascular occlusion CNS symptoms Hemorrhage Pulmonary insufficiency

66. 9. Thrombocytapheresis Treatment: Chemotherapy Plateletpheresis (ASFA Category I) Aim: To prevent the development of thrombotic and hemorrhagic complications until conventional therapy can control platelet production. Note: It should be noted that in disease process, which result in thrombocythemia, the platelets are generally atypical and function poorly and therefore platelet transfusions post apheresis may be indicated (though rare).

67. 10. Peripheral Blood Stem Cell (PBSC) Harvesting by Apheresis Background First successful transplants— late1960s 30,000-40,000 transplants performed yearly worldwide > 20,000 patients have survived >5 years Hematopoietic stem cell Responsible to maintaining marrow function throughout the life of individual. Stem cells are undifferentiated cells with the capacity for u nlimited or prolonged self-renewal & the ability to give rise to differentiated cells   Totipotent : give rise to entire organism   Pluripotent: give rise to most cells

68. 10. Peripheral Blood Stem Cell (PBSC) Harvesting by Apheresis Gives rise to (any) blood cells : RBC, PLT, WBC. Re-establish hematopoietic function in patients with damaged/defective bone marrow or immune systems Potentially curative for a wide variety of disorders Lazarus HM. Autologous and allogeneic transplantation procedures for hematologic malignancies. Manual of Clinical Hematology , 3rd edition 2002:399-409

69. INDICATIONS - PBSC Congenital Immune deficiency : Severe combined Immunodeficiency , Wiskott -Aldrich syndrome Chronic granulomatous disease Severe Aplastic Anemia : Fanconi anemia , Bone marrow failure syndrome Hemoglobinopathies : Thalassemia , Sickle cell disease Inherited metabolic disorders : Mucopolysaccharidosis , Osteopetrosis Malignant diseases of the bone marrow : Acute and Chronic leukemia , Lymphoma and Multiple Myeloma ,MDS Solid Tumors : Neuroblastoma ,Germ Cell Tumors ,Sarcomas ,Wilms Tumor Auto Immune Disorders

70. NEWER MODALITIES DFPP / Rheopheresis /Membrane Differential / Cascade Filtration Cryofiltration AN69- based oxiris membrane Couple Plasma Filtration-Adsorption (CPFA) Double plasmafiltration molecular adsorption system (DPMAS) Molecular adsorbent recirculating system (MARS)

71. Is a semi selective Plasma Exchange technique based on mTPE . It uses two filters to remove pathogenic /unwanted substances from the plasma . As a first step , a plasma separator separates the plasma from blood cells . DFPP / Rheopheresis /Membrane Differential / Cascade Filtration

72. DFPP / Rheopheresis /Membrane Differential / Cascade Filtration Thereafter , a plasma component separator fractionates /concentrates and removes fractions containing pathogenic substances like large molecular weight immunoglobulins , cryoglobulins , immune complexes and return the remaining(small molecular weight components such as albumin ) plasma to the body DFPP is designed to remove molecules with sizes between the pore sizes of the first (plasma separator ) and second membrane ( plasma fractionator ) By selecting the optimal pore size model for the plasma component separator , DFPP can be applied to various disorders .

73. DFPP / Rheopheresis /Membrane Differential / Cascade Filtration 1)Transplant of antibody incompatible kidneys – ABO blood group incompatibility and Donor Specific antibody positive - as part of pretransplant desensitization protocol for the recipients . 2) Severe triglyceridemia associated acute pancreatitis – DFPP removes oxidized and inflammatory Lipoproteins . 3) Age related macular degeneration : Removes high molecular weight molecules ( eg Fibrinogen ,LDL ,alpha 2 macroglobulin ,LDL cholesterol ,IgM ,Fibronectin ,von Willebrands factor ) : which may impair retinal microcirculation ,contribute to chronic inflammation . 4) Peripheral vascular disease 5) Sudden sensorineural hearing loss : Improvement of inner ear microcirculation and hair cell function , by acute reduction of fibrinogen and cholesterol levels . 6) Waldenstorms Macroglobulinemia : Type of cancer affecting two types of B cells : Lymphoplasmacytoid cells and plasma cells : Is charaterised by high levels of circulating IgM made by these cells .

74. DFPP / Rheopheresis /Membrane Differential / Cascade Filtration (A Popular Procedure In Japan ) DIFFERENCE FROM CONVENTIONAL THERAPEUTIC PLASMA EXCHANGE 1) Volume of replacement is significantly reduced as compared to conventional TPE . So places with limited blood resources have the advantage of DFPP over TPE . 2) Lesser chances of hyperacute allergic reactions with DFPP as compared to TPE 3) Lesser chances of hypocalcemia (induced by sodium citrate in FFP ) 4) Lesser chances of microorganism transmission caused by massive infusion of FFP (incidence 3 - 46.8%)

75. Cryofiltration Removes cryoproteins including cryoglobulins and cryofibrinogen , from the plasma at low temperatures Patients with Cryoglobulinemia , Rheumatoid arthritis , Cold hemagglutinin disease , Ulcerative colitis Patients not able to tolerate high volume DFPP Before HLA as well as ABO - antibody incompatible renal transplantation

76. AN69- based oxiris membrane In patients with sepsis or septic shock reduces lactate levels, SOFA score and concentrations of endotoxin and cytokines while improves hemodynamic parameters and clinical outcomes

77. Couple Plasma Filtration-Adsorption (CPFA) Lower velocity than the blood flow, allowing better contact time for the toxins with the resin Excess fluid and small molecular weight toxins

78. Double plasmafiltration molecular adsorption system (DPMAS) a neutral macroporous adsorption resin (HA330–II) which can adsorb medium‐ and macro‐molecular toxins such as inflammatory mediators and an ion exchange resin (BS330) which is a specific adsorbent for bilirubin. first –line treatment for HBV -induced acute on chronic liver failure and for cholestatic hepatitis. It can also act as bridge for liver transplantation

79. Molecular adsorbent recirculating system (MARS) It is also known as extracorporeal liver dialysis system and is used mainly in ICUs for acute liver failure (ALF) as fulminant viral hepatitis and drug/toxin- induced ALF or decompensate chronic liver disease for recovery therapy or as bridge therapy for transplantation

80. Complications of Apheresis Apheresis / Plasma Exchange : Citrate toxicity – IV Calcium gluconate in 100 ml Normal Saline Vascular access complications (hematoma, sepsis, phlebitis, neuropathy) Vasovagal reactions – Trendelberg position Hypovolemia (more common with saline-albumin infusion) Allergic reactions - Pruritus & Urticaria – FFP Related Air embolus – Central Vein related Depletion of clotting factors –Restored in 4 hours Circulatory and respiratory distress – TRALI or TACO Transfusion-transmitted disease – If not tested Depletion of proteins and immunoglobulins –Temporary – restored in 48 hours

81. Complications of Apheresis PBSC: Citrate Toxicity Thrombocytopenia : 30-40% PLT loss. G-CSF Related : Flu like syndrome Bone pain Hypercoagulable state Ref: 1.Shemin D, Briggs D, Greenan M: Complications of therapeutic plasma exchange: a prospective study of 1,727 procedures. A Clin Apher . 2007; 22(5):270-6. 2. Denise M. Harmening ,Modern blood banking and transfusion practices, Philadelphia : F.A. Davis, 2005