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Clinical Applications of
Therapeutic Apheresis
Diseases Treated with TA
Guillain-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 – hyaline thrombi in glomerolus
TTP – Mortality Rate
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Before Plasma Exchange
After Plasma Exchange
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
Cleaved von Willebrand Factor
multimers
vWF-Cleaving
Enzyme
Endothelial Cell
TTP
Platelet aggregate
Auto-antibody to
vWF-Cleaving
Enzyme
Uncleaved unusually
large vWF multimers
Endothelial Cell
Diagnosis
From Pentad to Triad
 Thrombocytopenia
 Thrombocytopenia
 MAHA
 MAHA
 CNS symptoms
 LDH elevation
 Renal insufficiency
 Fever
Conditions Associated with TTP
 Primary (idiopathic)
 Secondary
 Systemic autoimmune
disorders



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
SLE
Rheumatoid arthritis
Scleroderma
Polyarteritis nodosa
Infectious diseases


HIV infection
Bacterial endocarditis

Drugs







Neoplastic diseases
Surgeries

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Ticlopidine
Clopidrogel
Cyclosporine A
Tacrolimus
Quinine
Cardiovascular
Intestinal
PBSC transplantation
Pregnancy
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
 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 Uremic
Syndrome)
 HUS


MAHA
Renal failure
 Classic HUS

Childhood, Escherichia coli 0157:H7 association
 Adult HUS
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


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
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
 Subacute deterioration of renal function
 Crescents in glomeruli
 Various etiologies
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
 Anti-GBM antibodies crossrective with
alveolar basement membrane
Goodpasture’s Syndrome
 Clinical presentation
RPGN
 Pulmonary hemorrhage
 Anti-GBM antibodies
 Treatment
 Immunosuppressive drugs

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
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
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
Pauci immune GN
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.
Vasculitis
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 (MPGN)
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)

Pathogenesis


Anti-myelin (gangliosides) antibodies GM1, GM1b, GD1a
Clinical presentation

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Ascending paralysis
“albuminocytologic dissociation”
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High CSF protein
No CSF pleocytosis
10-23% require assisted ventilation
Nerve conduction studies show demyelination
dysautonomia
Treatment

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
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
Anti-myelin Antibodies
GBS Clinical Course
Symptom severity
GBS course
Time
Myasthenia Gravis
Nerve
Acetylcholine (Ach)
Anti-AchR Ab
AchR
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


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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
 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
V
APC
IL-4 , IL-6
Antibodies
T-cell
B-cell
Plasma cell
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)
SLE
Red Cell Exchange
 Sickle Cell Disease
 Malaria
 Babesiosis
Sickle Cell Disease
 Clinical picture
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Chronic genetic anemia
Hgb S instead of Hgb A alters the erythrocytes and their membranes
(sickle red cells)
Increased blood viscosity
Microvascular occlusion
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Infarcts in brain, lungs, retina
Pain crisis
Priapism
Acute chest syndrome
Stroke
Treatment

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Red cell transfusions
Hydroxyurea
Red cell exchange (ASFA Category I)
 Aims to maintain Hgb S <30
Malaria
 Cause
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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

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Fever, malaise, headache
Neurologic impairment
Renal failure
ARDS
 Traetment
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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
 Leukocytosis
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
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Acute Myelogenous Leukemia (AML)
Chronic Myelogenous Leukemia (CML)
Acute Lymphocytic Leukemia (ALL)
Chronic Lymphocytic Leukemia (CLL)
 Clinical picture

Hyperviscosity with microvascular occlusion


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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
Plateletpheresis
 Thrombocytosis (>1,000 x 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 Rheumatic Drugs)
 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-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
IVIG
42 patients
Plasmapheresis
and IVIG
62 patients
AmJTransplant 4(7):1033-1041, 2004
30% rejection
episodes
89% graft
survival at 2
years
94.2% graft
survival at 3
years