Plasmapheresis: Basic Principles
Stuart L. Goldstein
Assistant Professor of Pediatrics
Baylor College of Medicine
Administrative Director, Pheresis Service,
Texas Children’s Hospital
Acknowledgements
• Jun Teruya, MD, Medical Director, Pheresis
Service, Texas Children’s Hospital
• Jean Haas, Gambro (TPE membrane slides)
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.
Continuous vs. Intermittent
• Continuous: COBE Spectra, Fenwall CS3000
• Intermittent: Haemonetics
Blood Components Separated by Centrifugation
Platelets
Plasma
Lymphocytes
Monocytes
Granulocytes
Neocytes
Erythrocytes
Plasma Exchange
TPE: Available techniques
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
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.
Plasma removal is affected by:
• Qb
• Hct
• Pore Size
• TMP
=Plasma effluent
Qb 100-150
Hct 25-45%
Pore Size
TMP <50 mmHg
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.
Efficiency of removal is greatest early in the procedure
and diminishes progressively during the exchange.
Plasma Volume Exchange
Plasma Volume
Exchange
0
0.5
1.0
1.5
2.0
2.5
3.0
Percent Removed
100%
39.3%
63.2%
77.7%
86.5%
91.8%
95.0%
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.
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.
Indication of TPE
Category 1: Standard acceptable therapy
• Chronic idiopathic demyelinating
polyneuropathy (CIDP), cryoglobulinemia,
Goodpasture’s syndrome, Guillain-Barre
syndrome, focal segmental
glomerulonephritis, hyperviscosity,
myasthenia gravis, post transfusion
purpura, Refsum’s disease, TTP
Indication of TPE
Category 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
Indication of TPE
Category 3: Inconclusive evidence of
efficacy or uncertain risk/benefit ratio.
TPE can be considered for the following occasions:
1. Standard therapies have failed.
2. Disease is active or progressive.
3. There is a marker to follow.
4. It is agreed that it is a trial of TPE and when
to stop.
5. Possibility of no efficacy is understood by the
patient.
Indication of TPE
Category 4: Lack of efficacy in controlled
trials.
• Examples: AIDS, amyotrophic lateral
sclerosis, lupus nephritis, psoriasis, renal
transplant rejection, schizophrenia,
rheumatoid arthritis
Replacement Fluid
• Fresh frozen plasma – TTP, liver failure,
coagulopathy with inhibitors, patients
with coagulopathy, immediate post
surgery.
• Cryopoor plasma – TTP
• 5% albumin – Most cases.
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).
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.
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.
Management for TTP
Suspected TTP
vWF-Cleaving Protease
Low
Mixing Study
Correction
Deficiency
FFP Transfusion
No Correction
Inhibitor
Plasma Exchange
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%.
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 1994;331:661-7.)
• 67 yo female developed bloody diarrhea
after vacation in Italy. (Case 17 NEJM
1997;336:1587-94.)
• 49 yo female with TTP developed TRALI
during plasmapheresis. (Case 40 NEJM
1998;339:2005-12.)
Case 19 NEJM 1995;332:1700-7.
• 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.
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.
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 1992;326:1123-9.
Complications - 1
• Death: >50 deaths have been associated
with apheresis (<3/10,000 procedures)
– Cardiac arrhythmias, respiratory
distress syndrome, pulmonary edema.
• Hypotention, hypovolemia, hypervolemia,
anemia
– Association of ACE inhibitor and
hypotension and anaphylaxis has been
reported.
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
Complications – 3
•Dilutional coagulopathy, when albumin is used.
Pre
PT
14.2 sec
Post 1.3
Plasma Volume
Exchange
26.7 sec
PTT
29.9 sec
64.9 sec
Fibrinogen
159 mg/dL
55 mg/dL
Physician’s 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.