1. Clinical Applications of Therapeutic Apheresis

2. 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%

3. TTP – hyaline thrombi in glomerolus

4. TTP – Mortality Rate
Before Plasma Exchange
After Plasma Exchange

5. 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

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

7. 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

8. Diagnosis From Pentad to Triad
Thrombocytopenia
MAHA
CNS symptoms
Renal insufficiency
Fever
Thrombocytopenia
MAHA
LDH elevation

9. 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

10. 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

11. Treatment of persistent TTP
Plasma exchange
Corticosteroids
Vincristine
Rituximab
Splenectomy

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

13. TTP/HUS (Hemolytic Uremic Syndrome)
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

14. Rapidly Progressive Glomerulonephritis (RPGN); Crescentic Glomerulonephritis
Subacute deterioration of renal function
Crescents in glomeruli
Various etiologies

16. 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

17. Goodpasture’s syndrome
Anti-GBM antibodies crossrective with alveolar basement membrane

18. 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

19. Pauci immune GN

20. 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. 18

21. Vasculitis

22. 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

23. Immune Complex RPGN (MPGN)

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

25. 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

26. Anti-myelin Antibodies

27. GBS Clinical Course

28. Myasthenia Gravis
Nerve
Acetylcholine (Ach)
Anti-AchR Ab
AchR
Muscle

29. Myasthenia Gravis Clinical picture Treatment
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

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

31. Myasthenia Gravis
Before plasmapheresis
After Plasmapheresis

32. 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

33. Infectious agent V
APC
IL-4 , IL-6
Antibodies
B-cell
T-cell
Plasma cell

35. 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)

36. SLE

37. Red Cell Exchange
Sickle Cell Disease
Malaria
Babesiosis

38. 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

39. Malaria Cause Clinical picture Traetment
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)

40. 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

41. Plateletpheresis Thrombocytosis (>1,000 x 10 /L) Clinical picture9
Thrombocytosis (>1,000 x 10 /L)
Essential
Polycytemia vera
Clinical picture
Microvascular occlusion
CNS symptoms
Hemorrhage
Pulmonary insufficiency
Treatment
Chemotherapy
Plateletpheresis (ASFA Category I)

42. Rheumatoid Arthritis Chronic inflammatory autoimmune disease Treatment
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)

43. Protein A binds IgG

44. 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): , 2004

45. 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): , 2004