Apheresis: Clinical Indications
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- Deborah Lora Hodges
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1 PART 2
2 Apheresis: Clinical Indications Clinical Vignettes: Hematology Cardiology/Vascular Neurology Solid Organ Transplantation Anatomy of an ASFA Fact Sheet
3 Hematology 40 yo M presenting to the Emergency Room: I woke up and saw blood all over my pillow Vital Signs Stable + Epistaxis Labs: CBC: Hb 9gm/dl. Platelets 5000/micL LDH Haptoglobin- Undetectable What should we do?
4 Blood Smear
5 Hematology Diagnosis: Thrombotic Thrombocytopenic Purpura Deficiency of ADAMTS13 enzyme (cleaves multimeric vwf) typically due to an autoantibody Treatment: (a) Remove evil humor (autoantibody): TPE (b) Provide ADAMTS13 enzyme: TPE (c) Suppress autoantibody formation (eg. Steroids)
6 TTP TPE: ASFA Category I Frequency typically once daily with or without a taper PV per exchange Clinical and Laboratory monitoring (Platelets, Hb, LDH, haptoglobin, ADAMTS13 activity) Lifesaving and primary treatment in this disease
7 Hematology-II AA male brought to the ED with symptoms of slurred speech and hemiplegia Labs: Hb 8. Bilirubin elevated History of multiple admissions for pain crisis No family history of disease Hb electrophoresis: 97% HbS Is there a role for Apheresis?
8 Pathogenesis of Sickle cell Single nucleotide substitution in the beta chain of hemoglobin results in an amino acid change 6(Glu->Val); 2 S 2 Changes the charge at a critical pocket Glu (-ve); Val (neutral) loss of negative charge Disease
9 CLINICAL MANIFESTATIONS Painful crises - Bones, Viscera Acute chest syndrome CNS disease: Strokes, Chronic ischemic white matter disease Priapism Acute/chronic sequestration Aplastic crises
10 Treatment Options for SCD Current therapies: Hydration Antibiotics Analgesics for pain crisis Hydroxyurea (Increases HbF levels) Allogeneic Stem Cell Transplantion (SCT) remains the only curative treatment Red Cell Exchange
11 Erythrocytapheresis Highly effective in sickle cell disease the treatment of sickle cell disease In the setting of Sickle Cell dx, used for: Prevention/recurrence of stroke (Cat I) Acute chest syndrome (Cat II) Multiorgan failure (Cat III) Priapism
12 Probability of Stroke Recurrence with Chronic Blood Transfusions Adams RJ et al, NEJM 2005 & Verduzco & Nathan, Blood, 2009
13 Cardiac/Vascular Doc, I have high cholesterol and a family history of premature heart disease 35 yo M with both parents deceased due to complications of CAD One angioplasty procedure performed previously Labs: Cholesterol 500. LDL 250 On maximal doses of statins
14 Xanthomas on knees Courtesy G Dargo, ITxM
15 Xanthoma on right elbow Courtesy G Dargo, ITxM
16 Treatment Alternatives for Severe Hypercholesterolemia Plasma exchange LDL Apheresis Rarely: Liver transplantation
17 Plasma Exchange Removes LDL-C but: Non-specific and removes the beneficial parts of plasma - HDL-C (good cholesterol) - Clotting factors
18 LDL Apheresis A form of apheresis that eliminates the low density lipoprotein cholesterol fraction from blood by one of two methods: Works by leading venous blood through a column which removes LDL cholesterol By precipitating LDL with heparin at low ph
19 How It Works Heparin Pump Re-Priming Solution Regeneration Solution Regeneration Pump Blood Pump Plasma Pump Plasma Separator LIPOSORBER Columns Blood Return Plasma Line Waste Line LIPOSORBER SYSTEM 19
20 LDL-C Removed 20 LIPOSORBER SYSTEM
21 Saw tooth Pattern of Lowering LDL-C with regular treatment LDL-C Diet Therapy Diet & Drug Therapy LIPOSORBER Treatment Pre Time Average Post Time LIPOSORBER SYSTEM
22 Neurology 35 yo F presenting with difficulty swallowing and ambulation, and with droopy eyelids Laboratory values: Within Normal Limits Tensilon test: Positive AChR antibody: Positive Diagnosis?
23 Myasthenia Gravis Patient develops autoantibodies to the ACh receptor in the motor neuron junction Results in weakness Thymomas often associated with MG Can progress to respiratory distress that can become life threatening ASFA Category I (1) Moderate-Severe MG (2) Prethymectomy
24 Solid Organ Transplantation 42 yo male presenting with hemodynamic instability H/O Cardiac transplantation. High PRA. Recurrent rejection episodes Cardiac Biopsy: Evidence of Acute Cellular Rejection Treatment with immunosuppressives and steroid boluses ineffective Can apheresis be useful?
25 1) Blood is drawn into instrument ECP steps 5) Treated WBCs returned to patient 4) WBCs photoactivated with UVA light UVADEX 2) Whole blood centrifuged; RBCs and plasma returned to the patient 3) WBCs collected and treated with 8-MOP
26
27 ECP:What s in the bag? Lymphocytes Plasma Buffy Coat RBCs B cell T cell Platelets NK cell Granulocytes a THERAKOS company Macrophage Dendritic cell Antigen Presenting Cells
28 Photoactivation After buffy coat is collected, 8-MOP directly injected into the bag. Cells exposed to 1-2 J/cm 2 of UVA light Photoactivation time depends on: Treatment volume Hematocrit of the buffy coat Intensity of the light bulb
29 Nucleus Mechanism of Action DNA Cytoplasm 8 MOP Modified from Gasparro FP.
30 Photoactivation of 8-MOP Methoxsalen Nucleus DNA Cytoplasm 1) Cell membrane damage 2) Irreversible binding to DNA Adapted from Gasparro FP.
31 ECP in Cardiac Transplantation Successful use of ECP in human cardiac transplant recipients was first published in 1992 A multicenter, international, randomized, double-blind study on ECP use in rejection prophylaxis was published in 1999
32 Cardiac Rejection: Prophylaxis 60 consecutive eligible recipients of primary cardiac transplants 2 Arms: Standard vs ECP Photopheresis group received a total of 24 ECP treatments (over 6 mo) Barr et al, NEJM, 1999
33 Cardiac Rejection: Prophylaxis After 6 mo: Mean episodes of acute rejection per patient was higher in standard-therapy arm More patients in the ECP arm had one rejection episode or none, and Fewer patients in the ECP arm had two or more rejection episodes Barr et al, NEJM, 1999
34 ECP in Cardiac Rejection Several reports show beneficial effects of ECP in the management of cardiac rejection (biopsy proven) All studies are retrospective Used to treat refractory rejection (typically cellular)
35 ECP Decreases Risk of Rejection With Hemodynamic Compromise Kirklin J et al. J Heart Lung Transplant 2006;25:283
36 ECP-Treated Cells Transferred to Another Mouse Confer Increased Cardiac Transplant Survival George J. J Heart Lung Transplant 2008;27:616
37 ECP Induces Tolerogenic Dendritic Cells In Vitro and Regulatory T Cells In Vivo Lamioni A et al. Transplantation. 2005; 79:846
38 Cardiac Transplantation & ECP: ASFA Recommendations Category I: Cardiac Rejection Prophylaxis Category II: Treatment of Cardiac Rejection (Cellular Rejection)
39 Transplantation: Renal I need a kidney 55 M Hypertensive male with ESRD Blood group O. Wife is Blood group A and wants to donate her kidney Can apheresis enable this transplant?
40 Plasmapheresis Transplantation Waitlist Demand (~100,000) exceeds supply (~15,000) for solid organs April 2009 (US Renal Tx waitlist): Total ~84,000 O 44,385 A 23,779 B 13,672 AB 2,363
41 Why do we need ABOi renal Tx? Longer average wait for blood group O and B individuals B 5.8 yrs O 5.2 yrs A 3.4 yrs AB 2.4 yrs In the US, the probability that a pair of individuals will be ABO incompatible is 36%
42 ABO Incompatible Renal Transplants Plasma Exchange Protocols Goal is to reduce preformed anti-donor antibodies to prevent hyperacute rejection at the time of transplant Goal is to maintain low antibody titers immediately post-transplant to allow for graft accommodation
43 Plasmapheresis Protocols Tobian et al.. Transfusion 2008;48:
44 Plasmapheresis Protocols Pre-transplant: Number: Determined by ABO titer: in most published series with a target of < 8 or < 16 at time of transplant Frequency: Johns Hopkins protocol Every other day Mayo protocol - Daily Tobian et al.. Transfusion 2008
45 Pre-Transplant Plasmapheresis p=0.04 Padmanabhan et al. Transplantation 2009
46 ABOI titers- Response to PEX * * Initial Initial PreTx PreTx Initial Initial PreTx PreTx IgM IgG ABOI ABOI+XM Padmanabhan et al. Transplantation 2009
47 Post-Transplant Plasmapheresis p=0.05 Padmanabhan et al. Transplantation 2009
48 ASFA FACT SHEET Diseases listed in alphabetical order Single Page Consistent layout/ information for each disease Goal is to be practical
49 ASFA FACT SHEET
50 Anatomy of a Worksheet-I Incidence Procedure Recommendation Category Number of patients Type of study Type of Evidence
51 ASFA Categories
52 Level of Evidence
53 Grading Recommendations
54 ASFA FACT SHEET
55 Anatomy of a Worksheet-II Description of Disease Current Management & Treatment Rationale for Therapeutic Apheresis Technical Notes Duration/Discontinuation and Number of Procedures References
56
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