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Clinical Applications of Therapeutic Apheresis

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Clinical Applications of Therapeutic Apheresis ... and laboratory values normalize Avoid platelet transfusions Treatment of persistent TTP Plasma exchange ... – PowerPoint PPT presentation

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Title: Clinical Applications of Therapeutic Apheresis


1
Clinical Applications of Therapeutic Apheresis
  • Dobri Kiprov, MD, HP
  • Chief, Division of Immunotherapy California
    Pacific Medical Center
  • Medical Director, Apheresis Care Group Fresenius

2
TA Technologies
Membrane
Centrifugation
  • Prisma Gambro BCT
  • Asahi Plasma Flow
  • Cascade apheresis for selective plasma component
    removal
  • Specialized devices

3
Apheresis in Clinical Practice
Sickle Cell Dis. Malaria
Thrombocytosis
RBC
Plasma
WBC
PLT
Leukemias Cell Therapies
TTP Guillain Barre Syn. Myasthenia
Gravis Goodpastures Syn. Waldenstroms
4
Bloodletting and Plasmapheresis
5
When it comes to bloodletting three questions
must be answered
  • Who?
  • When?
  • How much?

Which Replacement fluids
6
How much?
  • Volume of exchange
  • 1-1.5 plasma volume
  • Calculation depends on numerous factors
  • Frequency of procedures
  • Duration of therapy

7
Efficiency of Plasmapheresis
  • What is being removed?
  • IgG - mainly extravascular
  • IgM mainly intravascular

8
Exchange Fluids
  • 5 Albumin
  • Best choice
  • Dilute only with saline
  • Combination of saline and albumin
  • FFP
  • Cryopoor plasma

9
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
10
TTP A Thrombotic Microangiopathy
  • Microvascular Occlusive Disorder
  • Platelet thrombi
  • Thrombocytopenia
  • Mechanical damage to erythrocytes
  • 70 of patients are women

11
TTP hyaline thrombi in glomerolus
12
TTP Mortality Rate
Before Plasma Exchange
After Plasma Exchange
13
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

14
Plasma Exchange in TTP FFP as exchange fluid
  • Removal of auto-antibodies to vWF multimers
    cleaving enzyme
  • Infusion of vWF multimers cleaving enzyme

15
Pathophysiology of TTP
Normal
TTP
Cleaved von Willebrand Factor multimers
Platelet aggregate
vWF-Cleaving Enzyme
Auto-antibody to vWF-Cleaving Enzyme
Uncleaved unusually large vWF multimers
Endothelial Cell
Endothelial Cell
16
Diagnosis From Pentad to Triad
  • Thrombocytopenia
  • MAHA
  • CNS symptoms
  • Renal insufficiency
  • Fever
  • Thrombocytopenia
  • MAHA
  • LDH elevation

17
Conditions Associated with TTP
  • Primary (idiopathic)
  • Secondary
  • Systemic autoimmune disorders
  • 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

18
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

19
Treatment of persistent TTP
  • Plasma exchange
  • Corticosteroids
  • Vincristine
  • Rituximab
  • Splenectomy

20
Treatment of relapsing TTP
  • Plasma exchange
  • Treat beyond improvement
  • Consider adding medications
  • Splenectomy
  • Look for other disease association

21
TTP/HUS (Hemolytic Uremic Syndrome)
  • HUS
  • MAHA
  • Renal failure
  • Classic HUS
  • Childhood, Escherichia coli 0157H7 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

22
Rapidly Progressive Glomerulonephritis (RPGN)
Crescentic Glomerulonephritis
  • Subacute deterioration of renal function
  • Crescents in glomeruli
  • Various etiologies

23
(No Transcript)
24
Rapidly Progressive Glomerulonephritis (RPGN)
Crescentic Glomerulonephritis
  • Goodpastures syndrome (Anti-Glomerular Basement
    Membrane Disease or Anti-GBM Disease)
  • Pauci immune RPGN (Wegeners Granulomatosis or
    microscopic polyarteritis with antineutrophil
    cytoplasmic antibodies (ANCA)
  • RPGN with granular immune complex deposits
    sometimes associated with systemic vasculitis

25
Goodpastures syndrome
  • Anti-GBM antibodies crossrective with alveolar
    basement membrane

26
Goodpastures 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

27
Pauci immune GN
28
Antineutrophil Cytoplasmic Antibodies
  • ANCA by immunofluorescence methods
  • c-ANCA Wegeners disease (60 to 90)
  • p-ANCA microscopic polyangiitis (MPA) (50 to
    80), UC (40 to 80), Crohns (10 to 40)

Hoffman GS. Arth Rheum. 199841(a)15211537.
29
Vasculitis
30
ANCA positive Pauci Immune RPGN
  • Clinical presentation
  • RPGN with or without pulmonary hemorrhage
  • Perinuclear (p-ANCA)-systemic microvasculitis
  • Internuclear (c-ANCA)-Wegeners granulomatosis
  • Treatment
  • Immunosuppressive drugs
  • Plasmapheresis (ASFA Category II) may benefit
    patients with severe renal disease (Cr 9) and
    dialysis dependent patients

31
Immune Complex RPGN (MPGN)
32
Immune Complex RPGN
  • Clinical presentation
  • RPGN
  • Membranoproliferative GN (MPGN)
  • Associations
  • Hepatitis C
  • Cryoglobulinemia
  • Treatment
  • Antiviral drugs
  • Corticosteroids
  • Plasmapheresis (ASFA Category II)

33
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

34
Anti-myelin Antibodies
35
GBS Clinical Course
36
Myasthenia Gravis
Nerve
Acetylcholine (Ach)
Anti-AchR Ab
AchR
Muscle
37
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

38
Myasthenia Gravis
  • Plasmapheresis
  • Acute myasthenic crisis
  • Respiratory insufficiency
  • Failure to respond to medications
  • Side effects of medications (prednisone)
  • Before and after surgery (thymectomy)

39
Myasthenia Gravis
Before plasmapheresis
After Plasmapheresis
40
Hyperviscosity Syndrome
  • Causes
  • Wadenstroms 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

41
Infectious agent
V
APC
IL-4 , IL-6
Antibodies
B-cell
T-cell
Plasma cell
42
(No Transcript)
43
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)

44
SLE
45
Red Cell Exchange
  • Sickle Cell Disease
  • Malaria
  • Babesiosis

46
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 lt30

47
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)

48
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

49
Plateletpheresis
9
  • Thrombocytosis (gt1,000 x 10 /L)
  • Essential
  • Polycytemia vera
  • Clinical picture
  • Microvascular occlusion
  • CNS symptoms
  • Hemorrhage
  • Pulmonary insufficiency
  • Treatment
  • Chemotherapy
  • Plateletpheresis (ASFA Category I)

50
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)

51
Protein A binds IgG
52
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
53
Protocols for Reducing anti-HLA antibodies in
positive CXM and AMR
IVIG 42 patients 30 rejection episodes 89 graft survival at 2 years
Plasmapheresis and IVIG 62 patients 94.2 graft survival at 3 years
AmJTransplant 4(7)1033-1041, 2004
54
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 Edition,
    Bruce McLeod Editor, AABB Press 2003
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