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Clinical Applications of Therapeutic Apheresis. Dobri Kiprov, MD, HP Chief, Division of Immunotherapy California Pacific Medical Center Medical Director, Apheresis Care Group Fresenius. TA Technologies. Prisma Gambro BCT Asahi Plasma Flow

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Clinical Applications of Therapeutic Apheresis

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clinical applications of therapeutic apheresis

Clinical Applications of Therapeutic Apheresis

Dobri Kiprov, MD, HP

Chief, Division of Immunotherapy California Pacific Medical Center

Medical Director, Apheresis Care Group Fresenius

ta technologies
TA Technologies
  • Prisma Gambro BCT
  • Asahi Plasma Flow
  • Cascade apheresis for selective plasma component removal
  • Specialized devices



apheresis in clinical practice
Apheresis in Clinical Practice

Sickle Cell Dis.








Cell Therapies


Guillain Barre Syn.

Myasthenia Gravis

Goodpasture’s Syn.


when it comes to bloodletting three questions must be answered
“When it comes to bloodletting three questions must be answered”
  • Who?
  • When?
  • How much?

Which Replacement fluids

how much
How much?
  • Volume of exchange
    • 1-1.5 plasma volume
      • Calculation depends on numerous factors
    • Frequency of procedures
    • Duration of therapy
efficiency of plasmapheresis
Efficiency of Plasmapheresis
  • What is being removed?
    • IgG - mainly extravascular
    • IgM – mainly intravascular
exchange fluids
Exchange Fluids
  • 5% Albumin
    • Best choice
    • Dilute only with saline
  • Combination of saline and albumin
  • FFP
  • Cryopoor plasma
diseases treated with ta
Diseases Treated with TA

Guillain-Barre Syndrome 11%

Myasthenia Gravis 12%


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

Before Plasma Exchange

AfterPlasma Exchange

pathophysiology of ttp
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
Plasma Exchange in TTPFFP as exchange fluid
  • Removal of auto-antibodies to vWF multimers cleaving enzyme
  • Infusion of vWF multimers cleaving enzyme
pathophysiology of ttp1
Pathophysiology of TTP



Cleaved von Willebrand Factor


Platelet aggregate



Auto-antibody to



Uncleaved unusually

large vWF multimers

Endothelial Cell

Endothelial Cell

diagnosis from pentad to triad


CNS symptoms

Renal insufficiency




LDH elevation

DiagnosisFrom Pentad to Triad
conditions associated with ttp
Primary (idiopathic)


Systemic autoimmune disorders


Rheumatoid arthritis


Polyarteritis nodosa

Infectious diseases

HIV infection

Bacterial endocarditis




Cyclosporine A



Neoplastic diseases




PBSC transplantation


Conditions Associated with TTP
treatment of ttp
Treatment of TTP
  • Daily plasma exchange
  • Exchange fluids
    • FFP
    • Cryopoor plasma
    • Detergent treated plasma
  • Treat until clinical symptoms improve and laboratory values normalize
  • Avoid platelet transfusions
treatment of persistent ttp
Treatment of persistent TTP
  • Plasma exchange
  • Corticosteroids
  • Vincristine
  • Rituximab
  • Splenectomy
treatment of relapsing ttp
Treatment of relapsing TTP
  • Plasma exchange
  • Treat beyond improvement
  • Consider adding medications
  • Splenectomy
  • Look for other disease association
ttp hus hemolytic uremic syndrome
TTP/HUS (Hemolytic Uremic Syndrome)
  • 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 to ADAMTS
  • Response to plasma exchange – equivocal results
rapidly progressive glomerulonephritis rpgn crescentic glomerulonephritis
Rapidly Progressive Glomerulonephritis (RPGN); Crescentic Glomerulonephritis
  • Subacute deterioration of renal function
  • Crescents in glomeruli
  • Various etiologies
rapidly progressive glomerulonephritis rpgn crescentic glomerulonephritis1
Rapidly Progressive Glomerulonephritis (RPGN); Crescentic Glomerulonephritis
  • Goodpasture’s syndrome (Anti-Glomerular Basement Membrane Disease or Anti-GBM Disease)
  • Pauci immune RPGN (Wegener’s Granulomatosis or microscopic polyarteritis with antineutrophil cytoplasmic antibodies (ANCA)
  • RPGN with granular immune complex deposits sometimes associated with systemic vasculitis
goodpasture s syndrome
Goodpasture’s syndrome
  • Anti-GBM antibodies crossrective with alveolar basement membrane
goodpasture s syndrome1
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 plasma volume
      • Finish procedure with 1 liter of FFP in cases with pulmonary hemorrhage and /or renal biopsy
antineutrophil cytoplasmic antibodies
Antineutrophil Cytoplasmic Antibodies
  • ANCA by immunofluorescence methods
    • c-ANCA = Wegener’s disease (60% to 90%)
    • p-ANCA = microscopic polyangiitis (MPA) (50% to 80%), UC (40% to 80%), Crohn’s (10% to 40%)

Hoffman GS. Arth Rheum. 1998;41(a):1521–1537.

anca positive pauci immune rpgn
ANCA positive Pauci Immune RPGN
  • Clinical presentation
    • RPGN with or without pulmonary hemorrhage
    • Perinuclear (p-ANCA)-systemic microvasculitis
    • Internuclear (c-ANCA)-Wegener’s granulomatosis
  • Treatment
    • Immunosuppressive drugs
    • Plasmapheresis (ASFA Category II) may benefit patients with severe renal disease (Cr 9) and dialysis dependent patients
immune complex rpgn
Immune Complex RPGN
  • Clinical presentation
    • RPGN
    • Membranoproliferative GN (MPGN)
  • Associations
    • Hepatitis C
    • Cryoglobulinemia
  • Treatment
    • Antiviral drugs
    • Corticosteroids
    • Plasmapheresis (ASFA Category II)
acute inflammatory demyelinating polyradiculoneuropathy aidp guillain barre syndrome gbs
Acute Inflammatory Demyelinating Polyradiculoneuropathy (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, 1-1 1/2 plasma volume exchange with 5% albumin
myasthenia gravis
Myasthenia Gravis


Acetylcholine (Ach)




myasthenia gravis1
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 gravis2
Myasthenia Gravis
  • Plasmapheresis
    • Acute myasthenic crisis
    • Respiratory insufficiency
    • Failure to respond to medications
    • Side effects of medications (prednisone)
    • Before and after surgery (thymectomy)

Myasthenia Gravis

Before plasmapheresis

After Plasmapheresis

hyperviscosity syndrome
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 agent



IL-4 , IL-6




Plasma cell

systemic lupus erythematosus sle
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
Red Cell Exchange
  • Sickle Cell Disease
  • Malaria
  • Babesiosis
sickle cell disease
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
  • 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)
white cell depletion leukapheresis
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 metabolic imbalance and ARDS)
    • Leukapheresis (ASFA Category I)
      • Ptreatment of leukocytosis
      • Prevention of tumor cell lysis syndrome


  • Thrombocytosis (>1,000 x 10 /L)
    • Essential
    • Polycytemia vera
  • Clinical picture
    • Microvascular occlusion
      • CNS symptoms
      • Hemorrhage
      • Pulmonary insufficiency
  • Treatment
    • Chemotherapy
    • Plateletpheresis (ASFA Category I)
rheumatoid arthritis
Rheumatoid Arthritis
  • Chronic inflammatory autoimmune disease
    • Arthritis
    • Rheumatoid nodules
    • Serum rheumatoid factor
  • Treatment
    • DMARD (Disease Modifying Anti Rheumatic Drugs)
    • Anti-TNF alpha monoclonal antibodies
    • Apheresis
      • Plasmapheresis (ASFA Category IV)
      • Lymphoplasmapheresis (ASFA Category II)
      • Prosorba column (ASFA Category II)
protocols for reducing anti hla antibodies in positive cxm and amr
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 amr1
Protocols for Reducing anti-HLA antibodies in positive CXM and AMR

AmJTransplant 4(7):1033-1041, 2004

  • 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 Edition, Bruce McLeod Editor, AABB Press 2003