Definition of TPE•Removal of large volumes of patient plasma and replacement of the plasma with appropriatefluids.Specialty areas: •Renal and metabolic diseases •Hematologic diseases •Neurologic disorders
Therapeutic Apheresis (TA) Whole blood is removed from the patient into an instrument that separates its components via a centrifugation process. The goal is to selectively remove a substancial proportion of one or more components causing disease while returning the remaining components to the patient, with or without replacement of the removed component.
TA Technologies Membrane Centrifugation Prisma Gambro BCT Asahi Plasma Flow Cascade apheresis for selective plasma component removal Specialized devices
“When it comes to bloodletting four questions must be answered” Who? When? How much? Which Fluids?
Removed with Plasma•Immune complexes•Immunoglobulins (IgG, IgM, IgA)•Abnormal/increased amounts of plasma protein•Cholesterol••Plasma metabolic waste products•Plasma protein bound poisons
Access Plamapheresis is an extracorporeal theapy and as such is dependent on adequate central vascular access. As plasmapheresis results in profound immunosuppression, a tunnelled line is preferred. Baxter/Edwards Bloodlines are used. Apheresis/dialysis-compatible catheter vendors include MedComp, Quinton Intruments, Vascath, Arrow, and Vaxcel.
How much? Volume of exchange • 1-1.5 plasma volume Calculation depends on numerous factors • Frequency of procedures • Duration of therapy
Important Formulas Total Blood Volume= 0.065 x Kg Plasma Volume=(0.065 x Kg) x (1 – Hct in decimal number) Red Cell Volume= Hct in decimal x TBV
Efficiency of Plasmapheresis What is being Efficiency of Plasmapheresis removed? 70 60 • IgG - mainly 50 40 1 plasma vol 1.5 plasma vol extravascular Percent 30 2 plasma vol 20 • IgM – mainly 10 0 intravascular
Frequency of ProceduresDisease specific: IgM removal: Predominantly intravascular Procedure may be done every other day. IgG removal: Predominantly extravascular Procedure may be done daily.
Exchange Fluids 5% Albumin • Best choice • Dilute only with saline Combination of saline and albumin FFP Cryopoor plasma Cryoprecipitate (vWF mediates in recurrent TTP; also used to avoid fluid overload)
Replacement FluidCrystalloids: Contain no protein. Normalsaline 0.9% Ex: in combination with albumin replacementColloids: Contain protein 5% albumin Ex: Guillian-Barré, myasthenia gravisFresh frozen plasma/cryo-poor plasma Ex: TTP, HUS (thrombotic microangiopathies)6% hetastarch, pentastarch
Anticoagulant•ACD-A: Binds to Ca++. Lowers pH of the blood. Inhibits platelet clumping. Acts as an extracorporeal anticoagulant. May cause hypocalcemia.•Heparin: Complexes with antithrombin and increases its activity which inactivates thrombin and other factors and prevents thrombus formation.* Acts as a systemic anticoagulant. There are individual sensitivities and elimination rates. Can cause heparin induced thrombocytopenia.*Essentials of hemostasis and thrombosis drugs used inmanagement of thrombosis.
American Society for Apheresis (ASFA) Guidelines Indications by Category (there are 4 categories). There are 3 levels of evidence. There are 2 grade recommendations.
Category I: Apheresis is considered primaryor standard.Category II: There is sufficient evidence tosuggest efficacy, usually in an adjunctiverole.Category III: Insufficient data to determineeffectiveness. Isolated published studieshave indicated that it may be of benefit as a“last-ditch” effort.Category IV: Controlled trials have notshown benefit.
Modified McLeod’s Criteria for Evaluation of Efficacy of Therapeutic Apheresis Evidence Mc Leod’s Explanation CriteriaMechanism Plaussible Clear Pathogenesis RationaleCorrection Better Blood Meaningfully CorrectedClinical Effect Perkier Clinically Patients Worthwhile
ASFA 2010 Indication Categories for TA There are 68 diseases. There are many TA accordingly to the diseases. Few of the procedures are: • Total Plasma Exchange (TPE) • RBC Exchange • Extracorporeal Photopheresis (ECP) • Immunoadsorption (IA) • Thrombocytapheresis & Leukocytapheresis • Selective removal methods • Adoptive Cytapheresis • Membrane differential filtration • Cryofiltration apheresis
General Issues to be ConsideredWhen Evaluating a New patient for Initiation of TA Rationale Impact Technical Issues Therapeutic Plan Clinical and/or laboratory end-points Timing & Location
Risks / Side effects of TA The overall rate is < 5%. Transfusion Reactions Nausea/Vomiting Hypotension, hypovolemia, fluid overload Vasovagal reactions Pallor, tachycardia, respiratory distress, muscle spasm, chills, rigors Hematomas, venous sclerosis, thrombosis, bleeding, infection Hypocalcemia from citrate
Use of Calcium in Preventing Symptoms TUMS 1000 mg po 30 minutes prior the procedure and halfway of the procedure (As recommended by Medical Directors Consensus from ARC) Or Use Calcium Gluconate as always.
Use of Magnesium IV Magnesium as per an article from FDA, NIH, Walter Reed ARMY Institute of Research (Salim Haddad et al: Transfusion June 2005; 45: 934-944).
Metabolic Alkalosis due to TPE It’s common in patients with decreased renal function. Secondary to large sodium citrate load given during the procedure. Can be prevented when using 3% albumin and cryoprecipitate rather than FFP’s Pearl RG, Rosenthal MH: American Journal of Medicine 1985 Sep; 79(3): 391-393.
Blood Component Collection by Apheresis Began in the 1970’s. Platelet donors are limited to 24 collections during a rolling 12-month period. RBC’s donors are limited to donate 2 units every 16 weeks. Single whole blood or one PRBC’s unit donor every 8 weeks.
Use in Hematopoietic Stem Cell Transplatation as Mobilization & Collection of PBHPC’s Last Standards & Rules by FDA on 11/24/2004 and effective on 05/25/2005. Goal: To achieve the Product CD34+ cell counts appropriate for infusion to the recipient.
TTP – A Thrombotic Microangiopathy Microvascular Occlusive Disorder Platelet thrombi Thrombocytopenia Mechanical damage to erythrocytes 70% of patients are women
Pathophysiology of TTP Presence of Unusually Large von Willebrand Factor Multimers (ULvWFM) Absence or low levels of ADAMTS13 (vWF cleaving metalloprotease) Presence of auto-antibodies to ADAMTS13
Plasma Exchange in TTP FFP as exchange fluid Removal of auto-antibodies to vWF multimers cleaving enzyme Infusion of vWF multimers cleaving enzyme
Pathophysiology of TTP Normal TTPCleaved von Willebrand Factormultimers Platelet aggregatevWF-CleavingEnzyme Auto-antibody to vWF-Cleaving Uncleaved unusually Enzyme large vWF multimers Endothelial Cell Endothelial Cell
Diagnosis From Pentad to Triad Thrombocytopenia Thrombocytopenia MAHA MAHA CNS symptoms LDH elevation Renal insufficiency Fever
GBS Clinical Course GBS courseSymptom severity Time
Myasthenia Gravis NerveAcetylcholine (Ach) AchR Anti-AchR Ab Muscle
Myasthenia Gravis Clinical picture • Variable degrees of weakness; improved by rest • Thymoma in 15% of patients Treatment • Mestinon • Prednisone • Imuran or other immunomodulatory meds • Plasmapheresis (ASFA Category I) • IVIG 400 mg/kg x 5 days • Thymectomy
Myasthenia Gravis Plasmapheresis • Acute myasthenic crisis • Respiratory insufficiency • Failure to respond to medications • Side effects of medications (prednisone) • Before and after surgery (thymectomy)
Myasthenia GravisBefore plasmapheresis After Plasmapheresis
Systemic Lupus Erythematosus (SLE) Systemic autoimmune disease with the presence of autoantibodies and immune complexes (anti-DNA, anti-DS-DNA) Multiple organ involvement including the kidneys Controlled clinical trials failed to show benefit from plasmapheresis in lupus nephropathy Plasmapheresis (ASFA Category III)
Red Cell Exchange Sickle Cell Disease Malaria Babesiosis
Sickle Cell Disease Clinical picture • Chronic genetic 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 • Treatment Red cell transfusions Hydroxyurea Red cell exchange (ASFA Category I) • Aims to maintain Hgb S <30
Malaria Cause • Plasmodium falciparum, vivax, ovale, malariae • Transmitted by female anopheline mosqito • Infected RBC adhere to endothelial cells of capillaries and postcapillary venules via surface knobs • Microvascular obstruction of brain, kidneys,lungs Clinical picture • Fever, malaise, headache • Neurologic impairment • Renal failure • ARDS Traetment • Chloroquine, quinine, quinidine • Red cell exchange (ASFA Category III) • Plasmapheresis for removal of cytokines to prevent or treat lactic acidosis, hypoglycemia (NR)
Protocols for Reducing anti-HLA antibodies in positive CXM and AMR IVIG alone Plasmapheresis and IVIG Plasmapheresis, IVIG and anti-CD20 antibody (splenectomy) AmJTransplant 4(7):1033-1041, 2004
Protocols for Reducing anti-HLA antibodies in positive CXM and AMR 30% rejectionIVIG 42 patients episodes 89% graft survival at 2 yearsPlasmapheres 62 patients 94.2% graftis and IVIG survival at 3 years AmJTransplant 4(7):1033-1041, 2004
LDL Apheresis Using Liposorber or HELP system For LDL > 300 mg/dl or LDL > 200 mg/dl plus CAD Can be used in severe hypertriglyceridemia.
Extracorporeal photopheresis Immunomodulatory effect Cellex or TheraKos Using 8MSO 0.6 mg/kg For: • CTCL • Graft vs. Host Disease • Solid organ transplant rejection • Crohn’s Disease • Scleroderma
Quality & Audit Management cGMP, cGTP, SOP’s, CFR FDA requirements & AABB standards OSHA, CMS, Joint Commission CAP CLIA Foundation for the Accreditation of Cellular Therapy (FACT)
Summary Therapeutic Apheresis is an outpatient or inpatient procedure that usually takes two to three hours and the blood components causing illness are removed from circulation saving lifes. The risks or side effects are manageable or preventable. Its under used. Future review of the guidelines is recommended & encouraged.
References Journal of Clinical Apheresis, Vol.15, No.1/2, 2000, Special Issue, Clinical Applications of Therapeutic Apheresis Journal of Clinical Apheresis 2000-2006 APHERESIS, Principles and Practice, 2nd & 3rd Editions from 2003 & 2010 respectively, Bruce C. McLeod Editor, AABB Press
Cont. References R Bambauer, R Latza, R Schiel: Therapeutic Apheresis in the Treatment of Hemolytic Uremic Syndrome in View of Pathophysiological Aspects. Ther Apher Dial 15(1): 10-19, 2011. ZM Szczepiorkowski et al: Guidelines on the use of therapeutic apheresis in clinical practice-evidence based approach from the Apheresis Applications Committee of the American Society for Apheresis. Jounal of Clinical Apheresis 25: 83-177, 2010. SG Shelat: Practical Considerations for Planning a Therapeutic Apheresis Procedure. The American Journal of Medicine 123(9): 777-784, 2010. Lamont Williams (AABBR Staff Writer): Plasma exchange in Organ Transplantation. AABB News, 8-19, April 2010. K. El-Gharini & DJ. Unsworth: Therapeutic apheresis – pasmapheresis. Clinical Medicine, 6(4): 343-347, July/August 2006. RB Striker, RG Miller & DD Kiprov: Role of plasmapheresis in acute disseminated (postinfectious) encephalitis. J Clin Apher 7(4):173-179, 1992.
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