Plasmapheresis: Basic Principles

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Plasmapheresis Basic Principles

• Stuart L. Goldstein
• Assistant Professor of Pediatrics
• Baylor College of Medicine
• Administrative Director, Pheresis Service,
• Texas Childrens Hospital

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Acknowledgements

• Jun Teruya, MD, Medical Director, Pheresis
  Service, Texas Childrens Hospital
• Jean Haas, Gambro (TPE membrane slides)

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Membrane vs. Centrifugation

• In the US, most TPE is performed by
  centrifugation. ? One machine can do all
  apheresis procedures.
• Double filtration method first membrane
  separates plasma from cellular portion and second
  membrane separates globulin from albumin.
• LDL apheresis using membrane coated with
  antibody to LDL, only LDL cholesterol can be
  removed.

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Continuous vs. Intermittent

• Continuous COBE Spectra, Fenwall CS3000
• Intermittent Haemonetics

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Blood Components Separated by Centrifugation
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Plasma Exchange
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TPE Available techniques...
TPE Available techniques

• Cascade or secondary filtration Separated blood
  is perfused through a plasma filter (1) to remove
  certain plasma elements. The second column (2)
  (cascade) absorbs the element and the plasma is
  returned to the patient.

1
2
PATIENT
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Membrane Filtration

• Use semi permeable membrane to separate the
  smallest component (plasma) from larger one
  (cells)
• A negative pressure is applied via the effluent
  pump to remove plasma from the blood side of the
  membrane.

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• Plasma removal is affected by
• Qb
• Hct
• Pore Size
• TMP

Plasma effluent
Qb 100-150
Hct 25-45
TMP lt50 mmHg
Pore Size
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Rationale of Plasma Exchange

• The existence of a known pathogenic substance in
  the plasma.
• IgG, IgM, phytanic acid, cytokines (?)
• The possibility of removing this substance more
  rapidly than it can be renewed in the body.

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Efficiency of removal is greatest early in the
procedure and diminishes progressively during the
exchange.
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Plasma Volume Exchange
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Small vs. Large Volume Exchange

• 1.0 plasma volume exchange minimizes time
  required for each procedure but may need more
  frequent procedures.
• 2.0 3.0 plasma volume exchange greater initial
  diminution of pathologic substance but requiring
  considerably more time to perform the procedure.

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Mechanical Removal of Antibodies

• When antibody is rapidly and massively decreased
  by TPE, antibody synthesis increases rapidly.
• This rebound response complicates treatment of
  autoimmune diseases.
• It is usually combined with immune suppressive
  therapy.

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Indication of TPECategory 1 Standard
acceptable therapy

• Chronic idiopathic demyelinating polyneuropathy
  (CIDP), cryoglobulinemia, Goodpastures syndrome,
  Guillain-Barre syndrome, focal segmental
  glomerulonephritis, hyperviscosity, myasthenia
  gravis, post transfusion purpura, Refsums
  disease, TTP

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Indication of TPECategory 2 Sufficient evidence
to suggest efficacy usually as adjunctive therapy

• ABO incompatible organ transplant, bullous
  pemphigoid, coagulation factor inhibitors, drug
  overdose and poisoning (protein bound),
  Eaton-Lambert syndrome, HUS, monoclonal
  gammopahty of undetermined significance with
  neuropathy, pediatric autoimmune neuropsychiatric
  disorder associated with streptococcus, RPGN,
  systemic vasculitis

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Indication of TPECategory 3 Inconclusive
evidence of efficacy or uncertain risk/benefit
ratio.

• TPE can be considered for the following
  occasions
• Standard therapies have failed.
• Disease is active or progressive.
• There is a marker to follow.
• It is agreed that it is a trial of TPE and when
  to stop.
• Possibility of no efficacy is understood by the
  patient.

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Indication of TPECategory 4 Lack of efficacy
in controlled trials.

• Examples AIDS, amyotrophic lateral sclerosis,
  lupus nephritis, psoriasis, renal transplant
  rejection, schizophrenia, rheumatoid arthritis

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Replacement Fluid

• Fresh frozen plasma TTP, liver failure,
  coagulopathy with inhibitors, patients with
  coagulopathy, immediate post surgery.
• Cryopoor plasma TTP
• 5 albumin Most cases.

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Thrombotic Thrombocytopenic Purpura (TTP)

• Pentad Thrombocytopenia, microhemangiopathic
  hemolytic anemia, renal dysfunction, CNS
  symptoms, fever
• Etiology Platelet activation by unusually large
  multimers of von Willebrand factor (vWF). vWF
  cannot be cleaved due to the absence of cleaving
  enzyme, metalloprotease ADAMTS 13 (a
  disintegrin and metalloprotease, with
  thrombospondin-1-like domains).

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TTP vs. DIC

• TTP - platelet activation
• Platelet activating factor is unusually large
  vWF.
• Platelet aggregates stain for vWF.
• DIC - coagulation activation
• Platelet aggregates stain for fibrinogen.
• Hypercoagulability and consumption coagulopathy.
• No primary DIC.

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Congenital TTP vs. Primary TTP

• Congenital TTP Hereditary deficiency of
  metalloprotease. ? Transfusion of FFP every 2-3
  weeks.
• Primary TTP Autoantibody against
  metalloprotease. ? Removal of the antibody and
  replacement with cryopoor plasma or FFP.

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Management for TTP
FFP Transfusion
Plasma Exchange
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TPE for Primary TTP

• Medical emergency.
• DDx Malignant hypertension, DIC
• 1.3 plasma volume exchange everyday until 3-5
  days after normal platelet count and normal LDH.
• Replacement fluid cryopoor plasma, FFP
• Overall response 81 (182/224), refractory 19
  (42/224), early relapse 27, late relapse 10.

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Cases of TTP in CPC, NEJM

• 41 yo female received platelet transfusion for
  hematuria. She developed acute myocardial
  infarction during TPE and died. (Case 33 NEJM
  1994331661-7.)
• 67 yo female developed bloody diarrhea after
  vacation in Italy. (Case 17 NEJM
  19973361587-94.)
• 49 yo female with TTP developed TRALI during
  plasmapheresis. (Case 40 NEJM 19983392005-12.)

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Case 19 NEJM 19953321700-7.

• 55 yo female with history of breast carcinoma
  developed acute respiratory distress and
  thrombocytopenia. Requested for TPE.
• Hct 37, schistocytes 2-5, WBC 13,800, PLT
  34,000, PT 13.2 sec, PTT 32.1 sec, D-dimer 2-4
  mg/mL, LDH 3,525 U/L, uric acid 9.7 mg/dL
• Anatomical diagnosis pulmonary embolic and
  lymphangitic carcinomatosis of breast origin.

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Guillain-Barre Syndrome

• Acute inflammatory demyelinating polyneuropathy.
• Positive anti peripheral nerve myelin in most
  patients.
• Triggered by common cold or vaccination.
• Indication for TPE progressive disease, an
  inability to ambulate, decreased respiratory
  capacity, bulbar symptoms.

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TPE for Acute GBS

• 1.3 plasma volume exchange 6 times over 1-2
  weeks.
• 85 patients respond, 10 left with severe
  disability, 5 death.
• IVIG or TPE is controversial.
• Dutch Guillain-Barre Group. A randomized trial
  comparing IVIG and plasma exchange in GBS. N Engl
  J Med 19923261123-9.

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Complications - 1

• Death gt50 deaths have been associated with
  apheresis (lt3/10,000 procedures)
• Cardiac arrhythmias, respiratory distress
  syndrome, pulmonary edema.
• Hypotention, hypovolemia, hypervolemia, anemia
• Association of ACE inhibitor and hypotension and
  anaphylaxis has been reported.

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Complications - 2

• Effects on the circulation
• Tiredness and malaise, presumably due to the
  shifts in fluid balance and extracorporeal
  circulation.
• Citrate toxicity (most common)
• Plasma protein levels
• Decrease in immunoglobulins, cholesterol, C3,
  alkaline phosphatase, AST
• Alteration of pharmacodynamics
• Restlessness, agitation

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Complications 3

• Dilutional coagulopathy, when albumin is used.

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Physicians Procedure Note

• Reviewed and evaluated the pertinent clinical lab
  data relevant to the treatment of the patient
  that day.
• Made decision to perform the procedure on the
  day.
• Saw and evaluated the patient during the
  procedure.
• Remained available to respond in person to
  emergencies or other situations throughout the
  procedure.