plasmapheresis: basic principles stuart l. goldstein assistant professor of pediatrics baylor...
TRANSCRIPT
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Plasmapheresis: Basic Principles
Stuart L. GoldsteinAssistant Professor of Pediatrics
Baylor College of MedicineAdministrative Director, Pheresis Service,
Texas Children’s Hospital
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Acknowledgements
• Jun Teruya, MD, Medical Director, Pheresis Service, Texas Children’s 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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PlasmaPlatelets
Lymphocytes
Monocytes
GranulocytesNeocytes
Erythrocytes
Blood Components Separated by Centrifugation
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Plasma Exchange
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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
TPE: Available techniques
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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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Qb 100-150
Hct 25-45%
TMP <50 mmHg
=Plasma effluent
Plasma removal is affected by:• Qb• Hct• Pore Size• TMP
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
Plasma Volume Exchange
Percent Removed
0 100%
0.5 39.3%
1.0 63.2%
1.5 77.7%
2.0 86.5%
2.5 91.8%
3.0 95.0%
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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 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
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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:
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.
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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
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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
Suspected TTP
vWF-Cleaving Protease
Low
Mixing Study
Correction No Correction
Deficiency Inhibitor
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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 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.)
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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 g/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 1992;326:1123-9.
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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.
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• 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 - 2
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Pre Post 1.3 Plasma Volume
Exchange
PT 14.2 sec 26.7 sec
PTT 29.9 sec 64.9 sec
Fibrinogen 159 mg/dL 55 mg/dL
Complications – 3•Dilutional coagulopathy, when albumin is used.
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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.