Double Filtration Plasmapheresis

(DFPP)- an alternative to Therapeutic

Plasma Exchange (TPE) approved
by the American Society for
Apheresis (ASFA).

The Experience
of the Clinical Emergency County
Hospital Sibiu

M. Sava, A. Bereanu, I. Ilie

What means apheresis?

Apheresis = separation
 Greek apairesos / Roman aphairesis: “to
take away”
 Process in which blood is removed from a
patient and continuously separated into
component parts; allowing a component to be
retained while the remainder is returned to
the patient.
 Cascade filtration: Definitions
 Cascade filtration - 2 steps process during which plasma is first
extracted from the blood and then circulated through a second filter,
the plasma fractionator.
 The plasma fractionator - membrane pore size 10 folds smaller
than a plasmafilter and retains larger substances - IgG/IgM and
LDL-cholesterol.
 Cascade filtration - the separation of plasma from blood can be
obtained by centrifugation or filtration.
 Double filtration plasma is extracted from blood by filtration. As the
second step is also done by filtration the process in this case can be
named double filtration.
 Double filtration is often named DFPP (Double Filtration
PlasmaPheresis)
 Plasma exchange vs. cascade
filtration
Plasma exchange - plasma is discarded and replaced by fluids such as
albumin or FFP.
Cascade filtration - plasma is filtered to retain targeted substance (antibodies
or cholesterol) before being returned to blood.
TPE Cascade Filtered
Filtration plasma
Plasmafilter

Plasma
fractionator
Discarded plasma Replacement fluid
Principles of Double Filtration
Plasmapheresis (DFPP)
Molecular weight and sieving coeffcients

SMALL MEDIUM LARGE

substances
ß2 microglobulin
sucrose
myoglobin HDL
creatinine urea
IL-6
albumin
ionic
compounds inulin IgG
IL-8
LDL
Vit
B12
TNF IgM
IL-1

10 102 103 104 105 106 MW (Daltons)

Hemofilter Plasmafilter
Fractionator
 Substances removed by
DFPP
Fractionator Plasma proteins Plasma filter
passing cutoff
HCV (55-65nm)
range
Substances
HBV (42 nm) targeted by
H2O Albumin DFPP
HIV
CI- K+ (100 nm) RBC
Globulin

LDL Corona virus

Glucose
(80-220 nm) WBC
IgM Platelet
(33-35 nm)

10-1
1 10 102 103 104 nm
Nadler’s formula + hematocrit or:
 Cascade filtration clearance
according to the sieving coefficient

Removed with Removed with

SC of Medopen 10 1 plasma volume 1.5 plasma
(10 nm pores) volume
Albumin : 0.62 33% 48%
IgG : 0.18 52% 63%
Fibrinogen : 0 63% 77%

Removed with Removed with

SC of Medopen 30 1 plasma volume 1.5 plasma
(30 nm pores) volume
Albumin : 0.86 10% 14%
Fibrinogen : 0.32 48% 63%
HDL : 0.86 17% 24%
LDL : 0.02 55% 72%
 Journal of Clinical Apheresis 31:149–338
(2016)
Guidelines on the Use of Therapeutic
Apheresis in Clinical Practice—Evidence-
Based Approach from the Writing Committee
of the American Society for Apheresis: The
Seventh Special Issue

Joseph Schwartz et. al.

 Indications for Therapeutic Apheresis–
ASFA 2016
Category Description
Disorders for which apheresis is accepted as first-line
therapy, either as a primary standalone treatment or in
I conjunction with other modes of treatment.
Ex: TPE in Guillain-Barre S. as 1st-line standalone therapy; TPE in
myasthenia gravis as 1st-line in conjunction with
immunosuppression and cholinesterase inhibition

Disorders for which apheresis is accepted as

secondline therapy, either as a standalone treatment
II or in conjunction with other modes of treatment.
Ex: TPE as standalone secondary treatment for acute
disseminated encephalomyelitis after high-dose IV corticosteroid
failure
 Indications for Therapeutic Apheresis–
ASFA 2016
Category Description

Optimum role of apheresis therapy is not established.

III Decision making should be individualized.
Ex: plasma exchange in patients with sepsis and multi-organ
failure

Disorders in which published evidence demonstrates

IV or suggests apheresis to be ineffective or harmful.
Ex: plasma exchange for active rheumatoid arthritis
 ASFA 2016 – Category I 20
 Myasthenia gravis
 Acute inflammatory demyelinating polyradiculoneuropathy
(Guillain-Barre S.)
 Chronic inflammatory demyelinating polyradiculoneuropathy
 Thrombotic thrombocytopenic purpura

 Acute liver failure - TPE-HV

 Renal transplantation, ABO compatible - antibody mediated
rejection, desensitization when LD
 Renal transplantation, ABO incompatible - desensitization
when LD
 Liver transplantation - desensitization, ABOi LD
ASFA 2016 – Category I 20

 Anti-glomerular basement membrane disease

(Goodpasture’s syndrome)
 ANCA- associated rapidly progressive
glomerulonephritis
 Focal segmental glomerulosclerosis
 Familial hypercholesterolemia - LDL Apheresis or TPE
 Hereditary hemachromatosis
 Hyperviscosity in monoclonal gammopathies
ASFA 2016 – Category I 20

 N-methyl D-aspartate (NMDA) receptor antibody

encephalitis
 Paraproteinemic demyelinating neuropathies/chronic
acquired demyelinating polyneuropathies IgG/IgA, IgM
 Progressive multifocal leukoenchephalopathy
associated with natalizumab
 Thrombotic microangiopathy - complement mediated,
Factor H autoantibodies
 Thrombotic microangiopathy, drug associated -
Ticlopidine
 Wilson’s disease, fulminant
ASFA 2016 – Category II 18

 Acute disseminated encephalomyelitis

 Severe cold agglutinin disease
 Cryoglobulinemia
 Familial hypercholesterolemia
 Hashimoto’s encephalopathy
 Hematopoietic stem cell transplantation, ABO
Incompatible
 Lambert-Eaton myasthenic syndrome
 Lipoprotein (a) hyperlipoproteinemia
 Multiple sclerosis (Acute CNS inflammatory
demyelinating)
ASFA 2016 – Category II 18

 Myeloma cast nephropathy

 Neuromyelitis optica spectrum disorders (NOSD)
 Mushroom poisoning
 PANDAS exacerbation
 Phytanic acid storage disease (Refsum’s disease)
 Renal transplantation, ABO incompatible
 Severe systemic lupus erythematosus
 Vasculitis
 Voltage-gated potassium channel antibodies
ASFA Indications → DFPP

 Age related macular degeneration, dry

 Familial hypercholesterolemia- LDL Apheresis

 Lipoprotein (A) Hyperlipoproteinemia - LDL

Apheresis
 LDL cholesterol removal
apheresis systems
 1. immunoadsorption columns containing matrix-bound sheep
anti-apo-B antibodies;
 2. dextran sulfate columns to remove apo-B lipoproteins from
plasma by electrostatic interaction;
 3. heparin extracorporeal LDL precipitation (HELP) to precipitate
apo-B in the presence of heparin and low pH;
 4. direct adsorption of lipoprotein using hemoperfusion to remove
apo-B lipoproteins from whole blood through electrostatic
interactions with polyacrylatecoated polyacrlyaminde beads;
 5. dextran sulfate cellulose columns: same mechanism as (2)
above but treats whole blood; and
 6. membrane differential filtration to filter LDL from plasma.
ASFA Indications → DFPP
(alternative)
 Myasthenia gravis
 Neuromyelitis optica spectrum disorders
(NMOSD)
 Renal transplantation, ABO incompatible
 Goodpasture’s syndrome
 Cryoglobulinemia
 Hyperviscosity in monoclonal gammopathies
 Phytanic acid storage disease (Refsum’s
Disease)
ASFA Guidelines
Apheresis Contraindications:

 Patients who cannot tolerate central line placement.

 Patients who are actively septic or are
hemodynamically unstable.
 Patients who have allergies to fresh frozen plasma or
albumin depending on the type of plasma exchange.
 Patients with heparin allergies should not receive
heparin as an anticoagulant during plasmapheresis.
 Patients with hypocalcemia are at risk for worsening
of their condition because citrate is commonly used to
prevent clotting and can potentiate hypocalcemia.
 2013
TPE DFPP

Number of patients 2 --

Number of sessions 6

S. Guillan-Barre --
Diagnostic
Multiple myeloma
-- --
Outcome
 2014
TPE DFPP

Number of 5 1
patients

Number of 16 3
sessions

Acute inflammatory demyelinating Amyloidosis with

Diagnostic polyradiculoneuropathy (Guillain- Kappa
Barre S.) 2 pt.

Myasthenia gravis 2 pt.

Severe cold agglutinin disease 1 pt.

Outcome overall good overall good

 2015
TPE DFPP

Number of 6 3
patients

Number of 20 7
sessions

Guillan-Barre S. 2 pt. Meningoencephalitis with

West Nile virus 1 pt.
Transverse Neuromyelitis 2 pt.
Diagnostic Paraneoplastic mielitis 1 pt.
Myasthenia gravis 2 pt.
Myasthenia gravis 1 pt.

Outcome overall good overall good

 2016
TPE DFPP
Number of 9 5
patients

Number of 32 13
sessions

S. Guillan-Barre 2 pt. S. Guillan-Barre 3 pt.

Myasthenia gravis 1 pt. Myasthenia gravis 1 pt.

Diagnostics Severe cold agglutinin PTT 1 pt.

disease 1 pt.

Thrombotic
microangiopathy 1 pt.

Outcome overall good overall good

 2017 (Jan - May)
TPE DFPP
Number of 5 2
patients

Number of 20 6
sessions

S. Guillan-Barre 3 pt.
S. Guillan-Barre 1 pt.
Neuromyelitis optica
Diagnostics spectrum disorders (NOSD) Neuromyelitis optica spectrum
1 pt. disorders (NOSD) 1 pt.

Myasthenia gravis 1 pt.

Outcome overall good overall good

Double filtration plasmapheresisi
(DFPP) – pathogenic treatment of
a patient with West Nile virus
encephalitis

M. Sava, A. S. Bereanu

A III-a Conferință de Plasmafereză

Terapeutică. Asociația Medicală Română
pentru Plasmafereză.
București, 08-09.10.2015
Plasmapheresis and Double
Filtration Plasmapheresis in Severe
Neuroimune Disorders –
A Retrospective study

C. Roman-Filip, A. Lăzăroae, M. Sava

Al XIV-lea Congres a Societății de

Neurologie din România
18-21.05.2016, București
Double filtration plasmapheresis and
Therapeutic plasma exchange in
severe neuroimune diseases, a case
series

A. Lazaroae, I.-R. Carcalici, M. Sava,

C. Roman-Filip
3rd Congress of the European Academy of
Neurology. June 2017, Amsterdam

Conference: Abstracts of the 3rd Congress of the European Academy of Neurology, Amsterdam,
The Netherlands, June 2017 At: Ansterdam,Netherlands Volume: European Journal of
Neurology,Volume 24, Issue Supplement S1
AN ALTERNATIVE THERAPY TO HIGH DOSE
IMMUNOGLOBULINS IN SEVERE NEUROIMMUNE
DISORDERS - THERAPEUTIC PLASMA EXCHANGE
AND DOUBLE FILTRATION PLASMAPHERESIS
C. Roman-Filip, M. Sava, A. Bereanu, A. Lăzăroaie, F. Gligor
 20 patients
Revista Farmacia,with
datasevere
in press neurologic diseases requiring
TPE or DFPP (Nov. 2012 – Dec. 2016)
 GBS, MG, NMO, CIDP
 Indication, complications and efficacy of these
procedures were analysed
 Neurological improvement was recorded in 80% of the
patients
 5% had no improvement
 Mortality was 15%.
AN ALTERNATIVE THERAPY TO HIGH DOSE
IMMUNOGLOBULINS IN SEVERE NEUROIMMUNE
DISORDERS - THERAPEUTIC PLASMA EXCHANGE
AND DOUBLE FILTRATION PLASMAPHERESIS
 Neurological improvement rate is similar to other
studies.
 No patient presented catheter related
complications.
 Systemic complications (hypocalcemia,
hyponatremia, hypokaliemia, hypotension) were
mild, transient and completely reversible.
 Death was secondary to sepsis not related to the
apheresis procedure (nosocomial pneumonia)
TPE and DFPP
 In many disorders - first line therapy
 Cheaper then IVIG
 Safe and efficient
 Relatively easy to perform
 Low complication rate
 DFPP
 No need or little need for substitution
 No allergic rections
 No complications of FFP infusion