Transcript Document
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
SLE
Rheumatoid arthritis
Scleroderma
Polyarteritis nodosa
Infectious diseases
HIV infection
Bacterial endocarditis
Drugs
Neoplastic diseases
Surgeries
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
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
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
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
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
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
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)
White Cell Depletion
Leukapheresis
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
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