Note: Descriptions are shown in the official language in which they were submitted.
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The inven~ion relates to treating blood plasma.
It is sometimes desirable to remove substances from blood plasma to
harvest desirable substances from donors or to remove undesirable substances
from a patient's blood.
For example Tsuda et al. United States Patent No.4,243,532 discloses
continuously treating plasma separated from a patient's blood cells by causing
it to flow past a purifying agent to which impurities are adsorbed (e.g.
activated carbon, alumina, silica, alumina-silica, zirconium phosphate,
zeolite, ion-exchange resin), mixing the treated plasma with the separated
blood cells and returning it to the patient.
I have discovered that blood plasma separated from other blood
components can be advantageously treated by adding an agent for precipitating
plasma components to the plasma to form a precipitate, removing the precipitate
from the plasma, and removing the precipitating agent from the plasma, prior to
mixing it with the separated components.
According to OTle aspect of the present invention there is provided
a method for treating a sample of blood plasma comprising:
separating said plasma from other blood components,
adding a precipitating agent for precipitating plasma components
to said plasma to form a precipitate,
removing the precipitate from the plasma,
removing the precipitating agent from the plasma, and
mixing said other blood components with said plasma to provide a
mixture of treated plasma and other blood components.
According to another aspect of the present invention there is
provided an apparatus for treating a patient's blood comprising:
- 1 -
means for continuously receiving plasma components separated from other
blood components,
means for adding a precipitating agent for precipitating plasma
components to said plasma to form a precipitate,
means for removing the precipitate from the plasma,
means for removing the precipitating agent from the plasma, and
means for continuously returning said plasma for mixing with
said other blood components to provide a mixture of treated plasma and other
blood components.
In preferred embodiments the precipitating agent is a salt (most
preferably Na2S04); immunoglobulins are precipitated; blood is continuously
removed from a patient, and the treated plasma is continuously mixed with
the separated blood components and returned to the patient.
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9204-87
The precipitating agent can be added to the plasma
directly or by dialysis, to affect precipitate formation; a make-
up fluid can be added to the treated plasma prior to returning it
to the patient, and the precipitate concentration can be monitored
by measuring the optical density of the plasma after the agent has
been added and before the precipitate has been removed.
The preferred apparatus includes a microporous membrane
device to separate the plasma from other blood components, a
microporous membrane filter for removing the precipi~ate, a
dialyzer for removing the precipitating agent and excess water,
and a bypass shunt valve for directing separated plasma directly
to a return line in the event that the conductivity of the treated
plasma is not within acceptable limits.
The structure and operation of a preferred embodiment
of the invention will now be described, after first briefly
describing the drawing, which is a diagram of an apparatus for
treating blood plasma according to the invention.
Referring to the drawingl there is shown apparatus 10
for continuously treating blood Bi provided by a patient via line
12 and for returning treated blood Bo via line 14. Line 12 is
connected via peristaltic blood pump 16 to membrane separator 18,
which provides plasma P at outlet 20 and concentrated mixture Bc
of other blood components at outlet 22.
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Both plasma line 24, connected to plasma outlet
20, and line 26, connected to a source of 24 gm/100 ml
Na2SO4 salt precipitating agent S, pass through
double-line peristaltic pump 28, the inner diameter of
lines 24, 26 being chosen to provide a ratio of
Na2SO4 flow to plasma flow of-3~9 to 1. After pump
28, plasma line 24 passes through shunt valve 30
(causing plasma line 24 to be directly connected to ~
~ return line 14 in a bypass condition) and ~oins line 26
at junction 32, at which precipitate Ppt including
immunoglobulins forms upon~the mixing of plasma P and
2 4 t S.
Plasma/salt line 34 connects junction 32 to
precipitate filter 36, similar in constr~ction to the
pleated membrane dialyzer shown in U.S. Patent No.
4,239,625 except that a microporous membrane
approximately 0.17 mm thick, and having an average pore
size of 0.6 micron is used, there are Vexar spacers on
both sides of the pleated membrane, and the tips of the
membrane folds need not be potted. The plasma flows in
- a blood port and out a dialysate port (at the other end
of the dialyzer), and the remaining blood port and
dialysate port are blocked.
Downstream of precipitate filter 36 is
precipitating-agent-removing dialyzer system 38, three
serially-connected dialyzers each similar in
construction to that shown in U.S. Patent No. 4,239,625,
except that in the first two dialyzers the membranes are
Enka 280 HDF l.9-square meter high-flux membranes.
Dialyzer sy6tem 38 is connected to dialysate preparàtion
and supply apparatus (e.g., similar to the Centry 2
system of Cobe Laboratories, Lakewood, Colorado, shown
in U.S. Patent No. 3,990,973). The dialysate is similar
to standard dialysate.
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9204-87
Downstream of dialyzer system 38 is double-line
peristaltic return pump 40, through which plasma line 42 and make-
up fluid line 44 both pass~ Lines 42, 44 are of the same size,
so that there will be equal flow rates through each when both are
unclamped. On line 44 there is air detector 46 and valve 48,
used to prevent flow through line 44 when make up fluid is not
being added. Lines 42, 44 join at junction 50, connected by line
52 to junction 54 via shunt valve 30 (which, in the bypass condi-
tion, in addition to connecting plasma line 24 to return line 14,
also connects line 52 to junction 32). Return line 14 is connected
to junction 54.
Collection bag connecting lines 56, 58 and associated
valves 60, 62 are provided on lines 34, 42 for taking samples.
Conductivity sensor 64 is provided on line 42.
In operation, a patient is connected to lines 12, 14.
Blood pump 16, double-line plasma pump 28, return pump 40 and
separator 18 are controlled to provide the desired separation of
plasma and blood cells in separator 18 without damage to the
cells. At junction 32, 3.9 parts of 24 gm/100 ml Na2SO4 are
diluted by one part of plasma to result in approximately 19 gm/100
ml Na2SO4 in the plasma/salt combination in line 34. At this
Na2SO4 concentration, immunoglobulin and other protein precipitates
form quickly, and the precipitates are filtered out at precipitate
filter 36, which has sufficient capacity, owing to its spacers
on the upstream side of the membrane, to collect the immunoglobulin
precipitate
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removed durin~ treatment of a single patient with normal
immunoglobulin concentrations. The Na2SO4 and
excess water (caused by mixing 3.9 parts of salt
solution with one part plasma at junction 32) are
removed at dialyzer system 38, and the treated plasma is
pumped via pump 40 to jUnCtiQn 54, where it mixes with
the high blood cell concentration mixture sc and is
returned to the patient. Pump 40 is operated at a rate
related to that of pump 28, typically at ~he same rate
i~ valve 48 is closed or at one half the rate of pump 28
if valve:48 is open, so th~at the volume returned to the
patient is the same as that removed. The rate of pump
40 can also be varied to affect the ultrafiltration
achieved in dialysis sytem 38.
- If during operation an improper conductivity is
sensed by sensor 64, shunt valve 30 is activated to
direct plasma in line 24 directly to junction 54 and to
connect line 52 to junction 32.
In the presently most preferred embodiment, the
treating apparatus does not include the means for
separating plasm~ from other blood components but is
instead designed for connection to Cobe Laboratories
Therapeutic Plasma Exchange System (TPE) described in
the above-mentioned patent appllcation. In this
embodiment, plasma line 24 is connected to receive
plasma fro~ the plasma pump of the TPE system; line 52
is connected to the junction of the TPE system
corresponding to junction 54, and shunt valve 30 is
replaced by a shunt valve between line 24 upstream of
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pump 28 and line 52. This embodiment could also be used
with other means for separatin~ plasma from other blood
components.
Also, other precipitating agents or other
concentrations can be used to affect the types of
precipitates that form. Othe~r 6alts reported to
precipitate proteins are those that include ions in the
Hofmeister series, incl~lding S042, P043, F 1, Cl 1,
Br~l, I-l, NO31, C1041, CNS 1 (listed in
decreasing ability to promote precipitation; Franks, F.,
"Solvent Mediated Influence on Conformation and Activity
of Proteins", p. 45 (Symposium Press, London). Also,
the precipitating agent can be added more gradually,
e.g., by usinq a dialyzer instead of junction 32, to
affect the formation of precipitates. Also, other means
can be used to remove the precipitate and precipitating
agent or to separate plasma from the other blood
components.
