ASFA_Clinical_Appli of TA.ppt [Compatibility Mode]

Clinical Applications ofTherapeutic ApheresisPresentation:Prof. A. Pourazar

TA TechnologiesMembrane• Prisma Gambro BCT• Asahi Plasma FlowCentrifugation• Cascade apheresis forselective plasmacomponent removal• Specialized devices

Apheresis in Clinical PracticeSickle Cell Dis.MalariaThrombocytosisRBCWBCPLTPlasmaLeukemiasCell TherapiesTTPGuillain Barre Syn.Myasthenia GravisGoodpasture’s Syn.Waldenstrom’s

Bloodletting and Plasmapheresis

“When it comes to bloodletting threequestions must be answered”• Who?• When?• How much?Which Replacement fluids

Efficiency of Plasmapheresis• What is beingremoved?• IgG - mainlyextravascular• IgM – mainlyintravascular70605040Percent3020100Efficiency of Plasmapheresis1 plasma vol1.5 plasma vol2 plasma vol

Exchange Fluids• 5% Albumin•Best choice•Dilute only with saline• Combination of saline and albumin• FFP• Cryopoor plasma

Diseases Treated with TAGuillain-Barre Syndrome 11%Myasthenia Gravis 12%CIDP 8%Cryoglobulinemia 30%Anti-GBM Disease 30%Pauci-immune RPGN 13%SLE nephropathy 10%Myeloma kidney 7%Recurrent FSG 5%Renal transplantation 5%

TTP – A Thrombotic Microangiopathy• Microvascular Occlusive Disorder• Platelet thrombi• Thrombocytopenia• Mechanical damage to erythrocytes• 70% of patients are women

TTP – hyaline thrombi inglomerolus

TTP – Mortality Rate90%80%70%60%50%40%30%20%10%0%Before Plasma ExchangeAfter Plasma Exchange

Pathophysiology of TTP• Presence of Unusually Large vonWillebrand Factor Multimers(ULvWFM)• Absence or low levels of ADAMTS13(vWF cleaving metalloprotease)• Presence of auto-antibodies antibodies toADAMTS13

Plasma Exchange in TTPFFP as exchange fluid• Removal of auto-antibodies antibodies to vWFmultimers cleaving enzyme• Infusion of vWF multimers cleavingenzyme

Pathophysiology of TTPNormalTTPCleaved von Willebrand FactormultimersPlatelet aggregatevWF-CleavingEnzymeAuto-antibody tovWF-CleavingEnzymeUncleaved unusuallylarge vWF multimersEndothelial CellEndothelial Cell

DiagnosisFrom Pentad to Triad• Thrombocytopenia• MAHA• CNS symptoms• Renal insufficiency• Fever• Thrombocytopenia• MAHA• LDH elevation

Conditions Associated with TTP• Primary (idiopathic)• Secondary• Systemic autoimmunedisorders• SLE• Rheumatoid arthritis• Scleroderma• Polyarteritis nodosa• Infectious diseases• HIV infection• Bacterial endocarditis• Drugs• Ticlopidine• Clopidrogel• Cyclosporine A• Tacrolimus• Quinine• Neoplastic diseases• Surgeries• Cardiovascular• Intestinal• PBSC transplantation• Pregnancy

Treatment of TTP• Daily plasma exchange• Exchange fluids•FFP•Cryopoor plasma•Detergent treated plasma• Treat until clinical symptoms improve andlaboratory values normalize• Avoid platelet transfusions

Treatment of persistent TTP• Plasma exchange• Corticosteroids• Vincristine• Rituximab• Splenectomy

Treatment of relapsing TTP• Plasma exchange• Treat beyond improvement• Consider adding medications• Splenectomy• Look for other disease association

TTP/HUS (Hemolytic UremicSyndrome)• HUS• MAHA• Renal failure• Classic HUS• Childhood, Escherichia coli 0157:H7 association• Adult HUS• Renal disease is more severe• Difficult to differentiate from TTP• Platelet – fibrin thrombi• Normal ADAMTS 13 (vWF cleaving enzyme) levels• No auto-antibody antibody to ADAMTS• Response to plasma exchange – equivocal results

Rapidly Progressive Glomerulonephritis(RPGN); Crescentic Glomerulonephritis• Subacute deterioration of renalfunction• Crescents in glomeruli• Various etiologies

Rapidly Progressive Glomerulonephritis(RPGN); Crescentic Glomerulonephritis• Goodpasture’s syndrome (Anti-GlomerularBasement Membrane Disease or Anti-GBMDisease)• Pauci immune RPGN (Wegener’sGranulomatosis or microscopicpolyarteritis with antineutrophilcytoplasmic antibodies (ANCA)• RPGN with granular immune complexdeposits sometimes associated withsystemic vasculitis

Goodpasture’s syndrome• Anti-GBM antibodies crossrectivewith alveolar basement membrane

Goodpasture’s Syndrome• Clinical presentation• RPGN• Pulmonary hemorrhage• Anti-GBM antibodies• Treatment• Immunosuppressive drugs• Cyclophosphamide• Corticosteroids• Azathioprine• Plasmapheresis (ASFA Category I)• Daily pheresis for 14 days with 5% albumin, 1-1 ½ plasmavolume• Finish procedure with 1 liter of FFP in cases with pulmonaryhemorrhage and /or renal biopsy

Pauci immune GN

Antineutrophil CytoplasmicAntibodies• ANCA by immunofluorescencemethods• c-ANCA = Wegener’sdisease (60% to 90%)• p-ANCA = microscopicpolyangiitis (MPA)(50% to 80%),UC (40% to 80%), Crohn’s(10% to 40%)Hoffman GS. Arth Rheum. 1998;41(a):1521–1537.

Vasculitis

ANCA positive Pauci Immune• Clinical presentationRPGN•RPGN with or without pulmonary hemorrhage•Perinuclear (p-ANCA) ANCA)-systemic microvasculitis•Internuclear (c-ANCA) ANCA)-Wegener’sgranulomatosis• Treatment•Immunosuppressive drugs•Plasmapheresis (ASFA Category II) maybenefit patients with severe renal disease (Cr9) and dialysis dependent patients

Immune Complex RPGN (MPGN)

Immune Complex RPGN• Clinical presentation•RPGN•Membranoproliferative GN (MPGN)• Associations•Hepatitis C•Cryoglobulinemia• Treatment•Antiviral drugs•Corticosteroids•Plasmapheresis (ASFA Category II)

Acute Inflammatory DemyelinatingPolyradiculoneuropathy (AIDP)‘Guillain-Barre Syndrome (GBS)• Pathogenesis• Anti-myelin (gangliosides) antibodies GM1, GM1b, GD1a• Clinical presentation• Ascending paralysis• “albuminocytologic dissociation”• High CSF protein• No CSF pleocytosis• 10-23% require assisted ventilation• Nerve conduction studies show demyelination• dysautonomia• Treatment• Supportive care• IVIG 400mg/kg x 5 days• Plasmapheresis (ASFA Category I)• Start within 14 days of onset• 5-6 Q.O.D. procedures, 1-11 1/2 plasma volume exchange with 5% albumin

Anti-myelin Antibodies

GBS Clinical CourseGBS courseSymptom severityTime

Myasthenia GravisAcetylcholine (Ach)NerveAchRAnti-AchRAbMuscle

Myasthenia Gravis• Clinical picture•Variable degrees of weakness; improved byrest•Thymoma in 15% of patients• Treatment•Mestinon•Prednisone•Imuran or other immunomodulatory meds•Plasmapheresis (ASFA Category I)•IVIG400 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 plasmapheresisAfter Plasmapheresis

Hyperviscosity Syndrome• Causes• Wadenstrom’s macroglobulinemia 50%• Multiple myeloma 5%• Clinical presentation• Neurologic symptoms• Bleeding diathesis• Retinal hemorrhage and papilledema• Hypervolemia• Congestive heart failure• Treatment• Plasmapheresis (ASFA Category II)• Chemotherapy

Infectious agentAPCVIL-4 , IL-6AntibodiesT-cellB-cellPlasma cell

Systemic Lupus Erythematosus(SLE)• Systemic autoimmune disease with thepresence of autoantibodies and immunecomplexes (anti-DNA, anti-DS-DNA)DNA)• Multiple organ involvement including thekidneys• Controlled clinical trials failed to showbenefit from plasmapheresis in lupusnephropathy• Plasmapheresis (ASFA Category III)

SLE

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 theirmembranes (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

Malaria• Cause• Plasmodium falciparum, vivax, ovale, malariae• Transmitted by female anopheline mosqito• Infected RBC adhere to endothelial cells of capillaries andpostcapillary 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 treatlactic acidosis, hypoglycemia (NR)

White Cell DepletionLeukapheresis• Leukocytosis• Acute Myelogenous Leukemia (AML)• Chronic Myelogenous Leukemia (CML)• Acute Lymphocytic Leukemia (ALL)• Chronic Lymphocytic Leukemia (CLL)• Clinical picture• Hyperviscosity with microvascular occlusion• CNS symptoms• Hemorrhage• Pulmonary insufficiency• Treatment• Combination chemotherapy (tumor cell lysis leads to metabolicimbalance and ARDS)• Leukapheresis (ASFA Category I)• Ptreatment of leukocytosis• Prevention of tumor cell lysis syndrome

Plateletpheresis• Thrombocytosis (>1,000x 10 /L)•Essential•Polycytemia vera• Clinical picture•Microvascular occlusion• CNS symptoms• Hemorrhage• Pulmonary insufficiency• Treatment•Chemotherapy•Plateletpheresis (ASFA Category I)9

Rheumatoid Arthritis• Chronic inflammatory autoimmune disease•Arthritis•Rheumatoid nodules•Serum rheumatoid factor• Treatment•DMARD (Disease Modifying Anti RheumaticDrugs)•Anti-TNF alpha monoclonal antibodies•Apheresis• Plasmapheresis (ASFA Category IV)• Lymphoplasmapheresis (ASFA Category II)• Prosorba column (ASFA Category II)

Protein A binds IgG

Protocols for Reducing anti-HLAantibodies in positive CXM andAMR• IVIG alone• Plasmapheresis and IVIG• Plasmapheresis, IVIG and anti-CD20antibody (splenectomy)AmJTransplant 4(7): ):1033-1041, 2004

Protocols for Reducing anti-HLAantibodies in positive CXM and AMRIVIG 42 patientsPlasmapheresis and IVIG30% rejectionepisodes89% graftsurvival at 2years62 patients 94.2% graftsurvival at 3yearsAmJTransplant 4(7): ):1033-1041, 2004

References• Journal of Clinical Apheresis, Vol.15,No.1/2, 2000, Special Issue, ClinicalApplications of Therapeutic Apheresis• Journal of Clinical Apheresis 2000-2006• APHERESIS, Principles and Practice,2 nd Edition, Bruce McLeod Editor,AABB Press 2003