AFERESETEKNIKKER

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AFERESETEKNIKKER
Abid Hussain Llohn
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Apheresis

• aferesis To take away or withdraw
• Removal of whole blood from a patient or donor.
  The components of whole blood are separated
  within the cell separator. One or more of the
  separated portions are then withdrawn and the
  remaining components are retransfused into the
  patient or the donor.

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History

• The Mystique of Dramatic Intervention
• Egyptians Trepanation
• Phlebotomy
• Intestinal wash
• 1660 Richard Lower
• 1914 John Abel
• 1944 First manual plasmapheresis in humane
• 1952 First use in blood component donation
• 1956 Edvin J Cohn
• Freireich, Latham, Judson, Cullis

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Sedimented blood sample
100 90 80 70 60 50 40 30 20 10

Plasma Leukocytes Erythrocytes
Plasma Areas of Platelets predominance Lymphocyte
s predominance Monocyte predominance Granulocyte
predominance Neocytes Erythrocytes
WBC layer
Platelet Rich
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Principle of apheresis
Anticoagulant added
Remaining blood components recombined and returned
Plasma Platelets Lymphocytes Granulocytes Erythroc
ytes
Whole blood
Whole blood
(vein)
(vein)
Blood components separated by centrifugation and
selectively removed
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Apheresis techniques

• Centrifugation
• Intermittent-flow centrifugation (IFC)
• Continuous-flow centrifugation (CFC)
• Photopheresis
• Membrane filtration
• Hollow-fibre filter with Pore diameter 0.2
  to 0.6 um
• Double-lumen vein catheter / AV-fistula
• Continuous-flow 50-200 ml/min
• Plasma removal 20-50 ml/min
• Immunoadsorption

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Intermittent-flow centrifugation

• Procedures are performed in cycles
• More extracorporeal volume
• Smaller and more mobile
• One-arm procedure
• Longer time

Latham bowl
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Continuous-flow centrifugation

• Withdraw, process and return blood simultaneously
• Two venipuncture sites
• Less extracorporeal volume
• Less time required

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Caridian (Gambro) Technology
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Fenwal (Baxter) Technology
PRPPlatelet rich plasma WB whole blood RBC
Erythrocyte
PPP Platelet poor plasma PRP Platelet rich
plasma
Amicus
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Apheresis
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Apheresis

• Donor apheresis
• Erythrocytes
• Platelets
• Plasma
• Progenitor (stem) cells
• Therapeutic apheresis
• Plasma exchange (TPE)
• Selective apheresis
• Cytaphersis
• Erythrocytapheresis
• Leucapheresis
• Thrombocytapheresis
• Extracorporeal photopheresis

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Donor apheresis specific considerations

• Criteria for whole blood donation
• Adequately trained operator
• A physician familiar with all aspects of
  apheresis must be available during the procedure
• Routine premedication of the donors to increase
  the component yield is not recommended
• Collection volume 16 of the donors estimated
  blood volume
• History of thrombosis, Protein C or S deficiency,
  factor V Leiden mutation

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Plasmapheresis

• Not more than 650ml per procedure in the absence
  of volume replacement
• Not more than once in two weeks
• Not more than 15 litres per year
• Protein analysis annually total protein not less
  than 60 g/l

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Donor apheresis specific considerations (cont.)

• Thrombocytapheresis
• Platelet count 150 x 109/l (preferably gt250 x
  109/l)
• Usually not more than once every 2 weeks
• Red cell apheresis
• Interval between two single units is 3 months
• 2 units red cell apheresis(2UD) HB 14 g/dl,
  Body weight 70 Kg
• Interval between 2UD and WBD or another 2UD 6
  months
• Interval between WBD and 2 UD 3 months

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Donor apheresis specific considerations (cont.)

• Total net volume of combined donation in one
  procedure should not exceed 650 ml
• Interval between one plasmapheresis/thrombocytaphe
  resis and WBD/single RC donation (combined or not
  with plasma and/or platelet collection) 48
  hours
• Interval between a WBD/single RC donation/failed
  return of red cells during apheresis and next
  plasmapheresis /throbocytapheresis 1 month

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Donor apheresis Complications

• Local effects venous spasm, hematoma, neuropathy
• Citrate toxicity circumoral paraesthesia,
  vibratory sensations, nausea, vomiting,
  Diarrhoea, tetany
• Syncope, seizures, vasovagal effects
• Hemolysis
• Infections sepsis, phlebitis,
• Chills

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Therapeutic Plasma exchange

• Rationale
• The existence of a known pathogenic substance in
  the plasma
• The possibility of removing this substance more
  rapidly than it can be renewed in the body

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TPE Target

• Removal of antibodies
• Alloantibodies anti-HPA-1a, anti-D,
  anti-P, anti-HLA, anti A / B
• Autoantibodies anti-AchR, anti-GBM,
  platelet aab, myelin aab, ANCAs
• Removal of immune complexes / macromolecules
• Removal of monoclonal proteins
• Removal of excess plasma constituent
• Replacement of a specific plasma component

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Indications Categories (ASFA and AABB)

• Category I Diseases for which therapeutic
  apheresis is standard and acceptable, either as a
  primary therapy or a valuable first-line adjunct
  therapy
• Category II Diseases for which therapeutic
  apheresis is generally accepted but considered to
  be supportive or adjunctive to other, more
  definitive treatments, rather than a first-line
  therapy
• Category III Diseases in which there is a
  suggestion of benefit for which existing evidence
  is insufficient, either to establish the efficacy
  of therapeutic apheresis or to clarify its
  risk/benefit ratio.
• Category IV Diseases in which there is lack of
  efficacy in controlled trials

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TPE Indications Category I

• Guillain-Barre Syndrome
• Chronic inflammatory demyelinating polyneuropathy
• Myasthenia Gravis
• Homozygous familial hypercholesterolemia
• Heterozygous refractory to medicines
• Goodpasture syndrome
• Thrombotic thrombocytopenic purpura
• Post-transfusion Purpura
• Phytanic acid storage disease

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TPE Indications Category II

• Cryoglobulinemia
• Hyperviscosity syndrome (Waldenstrøm)
• Rapidly progressive glomerulonephritis (ANCA-Pos)
• Coagulation factors inhibitors (factor VIII)
• Myelomatosis with renal involvement
• Idiopathic thrombocytopenic purpura
• Acute vascular rejection after heart transplant
• Reumatoid Arthritis
• ABO-mismatched marrow transplant (recipient)

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TPE Indications category III

• Hemolytic uremic syndrome
• Recurrent focal glomerulosclerosis
• Heart transplant rejection
• Acute hepatic failure
• Raynauds phenomenon
• Vasculitis
• Scleroderma
• SLE
• HDN
• Platelet alloimmunization and refractoriness
• Multiple sclerosis
• Paraneoplastic neurologic syndrome

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TPE Indications category IV

• AIDS
• Amyotrophic lateral sclerosis
• Systemic amyloidosis
• Acute rejection of renal transplant
• Psoriasis
• Schizophrenia
• Lupus nephritis

Ref. Transfusion 200343820-822
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TPE

• Vascular access
• Peripheral vein, AV fistulae, Catheter
• Anticoagulants
• Citrate 0.8 mL/min/L TBV
• Heparin
• Priming
• 0.9 saline
• Blood (ECV10, anemic hemodynamically
  unstable patients)
• Replacement fluid
• 4 albumin
• FFP
• Combination (0.9 saline, 4 albumin,
  plasma)

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Orignal component
Volumes of fluid exchanged
100 80 60 40 20

• IgM75 intravascular, 90 reduction after 2
  TPE
• IgG 45 intravascular, 90 reduction after 5
  TPE in 7-10 days

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63
Component removed
78
86
92
95
1.0
1.5
2.0
2.5
3.0
0.5
Number og volumes exchanged
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Complications of TPE

• Vascular access complications
• Fall in Plasma protein levels
• (Ig, C3, ALP, SGOT)
• Coagulation factors
• (Antithrombin III)
• Citrate toxicity
• Allergic reaction
• Fall in blood pressure
• Increased risk for infections
• TRALI
• Mortality?

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Citrate Toxicity

• Metabolism in mitochondria (Liver, Kidney,
  muscle)
• Ca
• Normal value Ca 1.05 to 1.3 mmol/L (total
  calcium 2.25 to 2.75 mmol/L)
  
• Mg K pH
  HCO3
• Causes
• Citrate given too quickly
• Citrate given faster than it can be
  metabolised
• Citrate accumulation due to duration of the
  procedure

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Hypocalcemia
1.3 1.2 1.1 1 0.9 0.8 0.7 0.6 0.5
- - - - - - - - -
ACD-A 0,8 mL/min/L TBV
Tingling
Ionized calcium (mmol/L
1.0 mL/min/L TBV
1.2 mL/min/L TBV
Myocardial Depression
I I I I I
I I I I
I I I I
0 10 20 30 40 50 60 70 80 90 100 110 120
Time (min)
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Hypocalcemia Signs Symptoms

• Neuromuscular
• Paresthesia (peri oral, peripheral)
• Chills, shivering
• Chest wall vibrations
• Twitching, muscle cramps, tremors
• Spasm (laryngeal, abdominal muscles), tetany
• Neurological
• Anxiety, confusion, irritability leading to
  seizures
• Cardiac
• ECG changes Prolonged QT interval, arrhythmias
• Decreased cardiac output, hypotension

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Citrate toxicity Signs Symptoms

• Hypomagnesaemia
• Paesthesia, foot leg cramps, tremors,
  twitching, tetany, breathing difficulties,
  nausea, vomiting, dysphagia, confusion, seizures,
  depression, arrhyhmias, ECG changes
• Hypokalemia
• Skeletal muscle weakness (in legs) to paralysis
  (could involve respiratory muscles),
  paresthesias, leg muscle cramps, Weak irregular
  pulse, orthostatic hypertension, cardiac arrest
• ECG changes flattened T wave, depressed ST
  segment
• Metabolic Alkalosis
• Muscle twitching, weakness, paresthesia, tetany,
  nausea, vomiting, arrhyhmias, confusion, apathy

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Citrate Toxicity Management

• Ask the patient to report tingling or numbness
• Monitor vitals and watch for ECG changes
• Underlying disease?
• Treatment Based on the severity
• Oral calcium
• Pause the system
• Reduce the inlet flow rate
• Consider
• -Calcium I.V. 0.5 mg of Ca/mL of ACD-A
  (Rate of infusion 14-36 mg/min)
• 10 mL of 10
  CaCl 270 mg Ca
• 10 mL of 10
  Ca-gluconate 90 mg Ca
• - Magnesium I.V. (0.15 mg/mL of ACD-A)
• - Potassium oral or I.V. (0.1 mmol/kg/h)

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Therapeutic Cytapheresis

• Leucapheresis
• Acute hyperleucocytic leukemias Leukocyte
  counts gt100 X 109/L
• When chemotherapy is contraindicated
• To reduce the tumour load before chemotherapy
• Plateletpheresis
• Thrombocytose gt 1000 X109/L
• Myeloproliferative disorders

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Erythrocytapheresis

• RBC Depletion
• Hemochromatosis
• Polycythemia vera
• RBC Exchange
• Sickle cell disease
• Malaria
• Babesiosis
• Thalassemia
• Carbon monoxide poisoning

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Photopheresis

• 8-Methoxy-psoralen per os Intermittent-flow
  centrifugation UVA Treated cell return
  to the patient
• UVAR-XTS
• Indications Cutaneous T-cell lymphoma
• Pemphigus
  vulgaris
• Graft versus host
  disease
• Acute chronic
  graft rejection
• SLE
• RA
• Psoriasis
• Scleroderma
• Juvenile
  dermatomyositis
• Severe atopic
  dermatitis

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Cytapheresis Indications categories (AABB)
Transfusion 200343820-822

• Category I
• ABO-mismatched marrow transplant (removal av RBCs
  from marrow)
• Polycythemia vera / erythrocytosis
• Symptomatic thrombocytosis / leukocytosis
• Sickle cell disease
• Cutaneous T-cell Lymphoma
• Category II
• Rhematoid Arthritis
• Category III
• Malaria / babesiosis
• Multiple sclerosis (progressive)
• Category IV
• Dermatomyositis / Polymyositis, Inclusion-body
  myositis

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Immunoadsorption

• Columns containing adsorptive matrices
• Selective binding affinity
• Plasma modulation
• Protein A-agarose column
• binds strongly to IgG antibodies to factor
  VIII and IX, HLA autoantibodies in patient
  awaiting renal allografting
• Protein A-Silica column
• ITP, RA
• Charcoal removes bile acid
• A and B antigens remove ant-A anti-B, DNA
  removes ANA, immune complexes

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Selective LDL apheresis

• Homozygous familial hypercholesterolemia
• Hetrozygous familial hypercholesterolemia
• drug treatnment not effective
• complications with plasma exchange
• Dextran-sulphate Cellulose column

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LDL-apheresis
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LDL-apheresis
Kaneka M03 Twin Columns-regeneration mod
Unlimited blood volume processing Heparin as
anticoag. Effective reduction of LDL/VLDL
Preservation of HDL other plasma
components Smaller extracorp. Volume
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LDL-apheresis
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LDL-apheresis