U.S. patent number 3,802,432 [Application Number 05/254,609] was granted by the patent office on 1974-04-09 for apparatus for filtration-leukopheresis for separation and concentration of human granulocytes.
Invention is credited to Isaac Djerassi.
United States Patent |
3,802,432 |
Djerassi |
April 9, 1974 |
APPARATUS FOR FILTRATION-LEUKOPHERESIS FOR SEPARATION AND
CONCENTRATION OF HUMAN GRANULOCYTES
Abstract
Apparatus is provided for continuous withdrawal of blood from a
human donor, separation preferably of granulocytes therefrom by
extracorporeal circulation and filtration of the blood and return
of leucocyte-poor whole blood to the donor, controls being provided
for the flow of the blood within the apparatus so that the volume
of the blood processed can be known and controlled at any
particular time.
Inventors: |
Djerassi; Isaac (Philadelphia,
PA) |
Family
ID: |
22964931 |
Appl.
No.: |
05/254,609 |
Filed: |
May 18, 1972 |
Current U.S.
Class: |
604/6.03; 422/44;
604/6.06; 604/6.11; 604/6.09 |
Current CPC
Class: |
A61M
1/3679 (20130101); A61M 2202/0057 (20130101); A61M
2202/0441 (20130101); A61M 2202/0441 (20130101) |
Current International
Class: |
A61M
1/36 (20060101); A61m 001/03 (); A61m 005/00 () |
Field of
Search: |
;128/213,214R,214E,214F,214.2 ;23/258.5 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Ingram, "Some Contributions of Leukocyte Balance Studies," U. of
Rochester, 11/56, pp. 1-16..
|
Primary Examiner: Truluck; Dalton L.
Attorney, Agent or Firm: Wobensmith, 2nd; Zachary T.
Claims
I claim:
1. Apparatus for filtration-leukopheresis comprising
a venous blood supply connection adapted to be connected to a
donor,
a venous blood return connection adapted to be connected to the
donor,
a leukocyte separating and retaining filter interposed in series
with said connections and in fluid communication therewith for
extracting leucocytes from blood passing therethrough,
a permanently vented receptacle in continuous communication with
the atmosphere interposed in series between said filter and said
return connection and in fluid communication therewith, and
power driven pump means upstream of the vented receptacle
continuously delivering blood from said supply connection to and
through said filter and to said vented receptacle.
2. Apparatus for filtration-leukopheresis comprising
a blood supply connection adapted to be connected to a donor,
motor driven pump means for delivering blood from the supply
connection to a receptacle;
leukocyte separation filters to which blood from said receptacle is
delivered for circulation through said filters,
means for receiving blood from said filters including receptacles
with valved inlet and delivery connections,
weight responsive members associated with each of said second
mentioned receptacles,
members controlled by said weight responsive members for
controlling the flow to and from said second mentioned receptacles,
and
means for returning the blood from said delivery connections to the
donor by increased gravity flow and venting of admixed air
including a blood return connection adapted to be connected to the
donor.
3. Apparatus for filtration-leukopheresis as defined in claim 2 in
which
said last mentioned means includes a motor driven pump interposed
between said blood return connection and said delivery connection
for the purpose to raise the blood to the level of the blood return
connection and increase the flow by gravity back into the
donor.
4. Apparatus for filtration-leukopheresis as defined in claim 2 in
which
said blood return connection has air collecting and venting means
interposed therein.
5. Apparatus for filtration-leukopheresis as defined in claim 2 in
which
said flow controlling members include solenoid controlled
valves.
6. Apparatus for filtration-leukopheresis as defined in claim 2 in
which
independent control means is provided for said first mentioned
motor driven pump means.
7. Apparatus for filtration-leukopheresis as defined in claim 3 in
which
independent control means is provided for said second mentioned
motor driven pump.
8. Apparatus for filtration-leukopheresis as defined in claim 5 in
which
independent control means is provided for the solenoid controlled
valves for at least one of said filter connected receptacles.
9. Apparatus for filtration-leukopheresis as defined in claim 2 in
which
said leukocyte separation filters are positioned for flow of blood
also by gravity through said filters.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to apparatus for filtration-leukopheresis
for separation and concentration of large amounts of normal human
granulocytes, primarily for the purpose of transfusion to
individuals in need of such treatments.
2. Background of the Prior Art
It has heretofore been proposed to extract blood from a human doner
for use as whole blood, for separation of plasma and for separation
of granulocytes or other blood components.
Blood removal and collection apparatus has taken various forms and
reference may be had to the U.S. patents to Strumia, No. 2,845,929;
Gewecke et al., No. 2,757,669; Welch, Jr., No. 2,982,286; Rieutord
et al., No. 2,757,375; Portras, No. 2,784,932; Erikson, No.
2,597,715; Judson et al., No. 3,489,145.
The delivery of blood plasma and the like to a patient for
transfusion can be effected by gravity or by applied pressure as
shown in the U.S. patent to Rundhaug, No. 2,842,123.
The methods in current use for separation and concentration of
platelets and leukocytes for transfusion rely on differential
centrifugation. Note Judson et al., U.S. Pat. No. 3,489,145.
The harvesting of normal granulocytes with special continuous flow
centrifugation (Freireich, E.J. et al., Separation and collection
of leukocytes. Cancer Res. 25:1516-1520 (1965) is difficult, costly
and of low efficiency.
It has heretofore been ascertained that granulocytes adhere to
foreign substances such as siliconized glass wool and many of the
newer synthetic plastics. A filter of the latter type and employing
nylon fibers is available under the name Leuko Pak -- Leukocyte
Filter from Fenwal Laboratories, Division of Travenol Laboratories,
Inc., Morton Grove, Illinois. These filters have heretofore been
used for administration of leukocyte-poor whole blood to
multitransfused patients with antileuko-cyte antibodies.
The adhering takes place when the medium carrying the granulocytes
is heparinized blood and when the filter is perfused with more acid
medium (example ACD or Citrate-Dextrose Plasma) the granulocytes
are eluted and can be recovered in the outflowing carrier fluid and
then separated therefrom.
It has heretofore been undertaken to withdraw blood from a donor,
in a plastic bag with a mixture of heparin, saline and sodium
citrate selectively delivered to the plastic bag and then
transferring the fluid through leukocyte filters and then advance
the blood by manual manipulation to another plastic bag for return
through a tube to the donor, a source of saline solution being
connected to the return tube to keep it open when not in use. The
respective tubes were controlled by hemostats for manual regulation
and the entire procedure was manual.
Very close supervision and control by trained personnel has been
required and the time for the filtration-leukopheresis has required
about some 4 hours or more with each individual donor.
Leukocyte transfusions using granulocytes obtained from patients
with chronic myelogenous leukemia have been used to support
patients with infections who lack adequate numbers of granulocytes
(Schwarzenberg, L. et al.: Study of factors determining the
usefulness and complications of leukocyte transfusions. Amer. J.
Med. 43:206, 1967; and Morse, E.E. et al.: Effectiveness of
granulocyte transfusion from donors with chronic myelocytic
leukemia to patients with leukopenia. Cl. Res. 9:32, 1961). The use
of such transfusions is limited by the availability of donors with
chronic myelogenous leukemia and the frequency of preexisting or
developing antileukocyte antibodies in the recipient leading to
severe and often life-threatening transfusion reactions.
Normal leukocyte "buffy coats" have also been used for support of
infected leukopenic patients with inconclusive results. The
transfusion of "buffy coats" from normal donors is handicapped by
the need for each transfusion of large numbers of leukocyte
concentrates (all ABO type specific) and especially by their low
content of granulocytes. The latter sediment on centrifugation of
the whole blood with the top layer of the red cells and are not
included in the buffy coat which consists mainly of lymphocytes and
platelets.
Even if adequate yields of granulocytes are harvested from each
unit of whole blood, large numbers of donors are needed for each
single transfusions thus greatly increasing the risk of sensitizing
the patient to subsequent transfusions of granulocytes thus
increasing the risk of severe reactions as well as of hepatitis and
other infections.
Large amounts of granulocytes, all obtained from one donor as much
as possible compatible with the recipient, could however be given
repeatedly to leukopenic patients in order to prevent or overcome
already existing infections. Obtaining normal granulocytes for
transfusion using continuous flow centrifuges is limited by the low
efficiency of separation by centrifugation (Freireich, E.J., et
al.: Separation and collection of leukocytes. Cancer Res. 25:1516,
1965). Simple methods and suitable apparatus for repeated
harvesting of large amounts of granulocytes from single donors,
applicable to standard blood banks and donor centers, are needed to
use transfusions of granulocytes routinely.
SUMMARY OF THE INVENTION
In accordance with the present invention apparatus is provided for
harvesting granulocytes from a single donor and within a relatively
short time period and which includes structure for withdrawal of
blood from the donor and transferred under pressure, the pressure
application being effective to transfer the blood to filters for
retention of the granulocytes by selective absorption-elution. The
filters are connected to leukocyte-poor whole blood collecting
receptacles from which a connection is provided to pumping
apparatus for return through an air vented bottle to the donor.
Provision is made for weighing the leukocyte-poor blood in the
collecting receptacles and for limiting the amount by weight in the
system so as to limit the total amount of blood out of the donor at
any time and to provide knowledge of the volume of blood already
processed.
It is the principal object of the invention to provide apparatus
for harvesting granulocytes from human blood of a donor with return
of the leukocyte-poor blood to the donor which will be effective in
its action, will protect the donor against excessive withdrawal of
blood at any time, will insure effective filtration of the blood
and its safe return to the donor, which will reduce the burden upon
the attendant and which will permit of relatively rapid cycling,
thus allowing the processing of larger volumes of blood within the
time available to the donor.
It is a further object of the invention to provide apparatus of the
character aforesaid which will be reliable in its action, fool
proof in regard to potential harm to the blood donor and which can
be readily made available for use.
Other objects and advantageous features of the invention will be
apparent from the description and claims.
BRIEF DESCRIPTION OF THE DRAWINGS
The nature and characteristic features of the invention will be
more readily understood from the following description taken in
connection with the accompanying drawing forming part hereof, in
which:
FIG. 1 is a diagrammatic view of a preferred form of apparatus in
accordance with the invention;
FIG. 2 is a schematic diagram of the electrical circuitry employed;
and
FIG. 3 is a view of a modified form of circuitry.
It should, of course, be understood that the description and
drawings herein are illustrative merely and that various
modifications and changes can be made in the structure disclosed
without departing from the spirit of the invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now more particularly to FIG. 1 of the drawings, a fluid
connection 10 in the form of plastic tubing is shown which has a
needle (not shown) of well known type, and preferably of 15 gauge,
on its free end for insertion into a vein in one arm A1 of the
donor for withdrawing blood.
The fluid connection 10 preferably extends to the fluid inlet of an
electric motor driven pump 12. The outlet or delivery connection of
the pump 12 is connected by a fluid connection 14 to an elevated
vessel 15 suspended above the location at which the donor is
situated. The pump 12 can be of any desired type, rotary or tandem
diaphragm or piston, but is preferably of a variable speed type to
provide the desired rate of withdrawal from the donor and delivery
to the vessel 15.
The vessel 15 is connected by a fluid connection 20 and branch
pipes 21 to a plurality of leukocyte filters 22, four being
preferred. The filters 22 are connected by fluid connections 23
through infusion chambers 24 which allow observation of the blood
dripping or flowing out of the leukocyte filters after retention of
the granulocytes. The filters 22 can be of any suitable type which
separate and retain granulocytes and permit the passage of
leukocyte-poor whole blood for return to the donor, Leuko-pak
Leukocyte Filters available from Fenwal Laboratories, Division of
Travenol Laboratories, Inc., Morton Grove, Ill. having been found
satisfactory.
The infusion chambers 24 are connected by interconnected branch
tubes 25 which is connected by a flexible tube 26 and flexible
tubes 27 and 28 to collection bags 29 and 30 which are resting on
scales of the spring or lever type. The tubes 27 and 28 have
solenoid controlled valves 32 and 33 therein.
The collection bags 29 and 30 are carried on weighing scales 34 and
35 having normally open switches 55 and 56 closed when a
predetermined weight is effective in either bag 29 or 30.
The collection bags 29 and 30 are connected by flexible pipes 35
and 36 which have solenoid controlled valves 38 and 39 therein to a
fluid connection 40 which extends to the fluid inlet of an electric
motor driven pump 42.
The pump 42 is preferably similar to the pump 12.
The delivery side of the pump 42 is connected by a fluid connection
43 to a vented receptacle 44 with a vent pipe 45 communicating with
the atmosphere. The receptacle 44 has a fluid connection 46
extending therefrom which has a needle (not shown) of well known
type and preferably of 15 gauge on its free end for insertion into
a vein in the other arm A2 of the donor for the return of
granulocyte-poor whole blood to the donor.
Referring now to FIG. 2, one form of electrical circuitry is shown
suitable for control of the system shown in FIG. 1.
A suitable source of electric energy such as 115 volt 60 Hz
alternating current is connected by a conductor 50 through a main
power control switch SW 1 and conductor 51 and blood pump control
switch SW2 conductor 53, and contact arms 54 and 55 of a manually
positioned blood pump selector switch SW3 engageable with contacts
56 and 57 connected to conductors 58 and 59 to one terminal of each
of the motor driven pumps 12 and 42. The other terminals of the
pumps 12 and 42 are connected to return conductor 60.
The contact arms 54 and 55 of SW3 can also be selectively connected
to contact 62 connected to conductor 58 and to contact 63 when
operation of pump 12 only is desired.
The contact arms 54 and 55 of the switch SW3 can also be
selectively connected to contact 64 and to contact 65 which is
connected to conductor 59 when operation of pump 42 only is
desired.
A spare blood pump 70 can also be provided if desired and which can
be substituted by shifting of fluid inlet and delivery connections
thereto. The pump 70 can be energized by normally open switch 71
connecting the conductor 53 through the pump 70 to the return line
60.
The conductors 51 and 60 are also preferably connected to the
primary of a step-down transformer T.
The secondary of the transformer T has one terminal thereof
connected to a conductor 73 the other terminal being connected by a
conductor 74 through a normally open contact 75 of switch SW5 to
one terminal of solenoid winding K1 thereof which has the other
terminal connected to conductor 73. The secondary of the
transformer T is also connected by a conductor 76 connected to the
conductor 74 and through a normally open contact 77 of switch SW6
to one terminal of winding of solenoid K2, the other terminal of
which is connected to conductor 73.
The winding of solenoid K1 controls a contact arm 78 which in its
down position engages a contact 79 which is connected by a
conductor 80 to one terminal of each of the solenoid valves 32 and
39.
The contact arm 78 in its up position engages a contact 82 which is
connected by a conductor 84 to one terminal of the winding of
solenoid K2, the other terminal of which is connected to conductor
73.
The winding of solenoid K2 controls a contact arm 85 which is
connected to conductor 74 and which in its up position engages a
contact 86 which is connected by a conductor 87 to conductor 74 and
thence to one terminal of the winding of the solenoid K1, the other
terminal of which is connected to conductor 73.
The winding of solenoid K2 controls the contact arm 85 to a down
position in engagement with a contact 88 which is connected by
conductor 89 to energize the windings of the solenoid valves 33 and
38.
The transformer T also has a conductor 90 which is connected by
conductors 91, 92, 93, and 94 to the solenoid valves 32, 33, 38 and
39.
A manually operable override SW7 with simultaneously operable
contact arms 95 and 96 controls the independent energization of the
solenoid valves 32 and 33 for closing these valves.
A manually operable override switch SW8 with simultaneously
operable contact arms 97 and 98 controls the independent
energization of the solenoid valves 38 and 39 for closing these
valves.
In normal operation with switches SW1 and SW2 closed, and with the
switch SW3 in normal operating position as shown in FIG. 2 the
pumps 12 and 42 will be operated. With the switch SW5 in closed
position and the switch SW6 in open position the solenoid K1 will
be energized so that solenoid valves 32 and 39 will be closed for
delivery of blood to the receptacle 30, the valves 33 and 38 being
open. As blood is delivered to the receptacle 30 the switch SW6
will be closed to energize the solenoid K2. The flow of blood from
the receptacle 29 and the closing of the contact 77 by the weight
of the blood in the receptacle 30 will effect a reversal of the
control of the valves 33 and 38 so that delivery to the receptacle
44 through valve 39 will be effected with the valves 33 and 38
closed. The alternating operation will be repeated as desired.
The blood from the receptacle 15 will pass by gravity through the
filters 24 and will have the granulocytes extracted therefrom for
subsequent separation and utilization.
The blood delivered by the pump 42 to the receptacle 44 is then
preferably returned by gravity to the donor, any air in the blood
being separated out in the receptacle 44.
A modified form of circuitry is shown in FIG. 3 in which the scale
switches includes a switch SW5a with normally open contact arm 75a
and switch SW6a with normally closed contact arm 77a to both of
which conductor 74 is connected. A single solenoid K is employed
with conductor 90 from switch SW5a connected to one terminal
thereof, the other terminal being connected to conductor 73. A
conductor 91 extends from switch SW6a to the normally closed
contact arm 92 which when engaged with contact 93 connected to
conductor 90 for energizing the winding of the solenoid K.
A normally down contact arm 94 when in engagement with a contact 95
is connected by a conductor 96 to both the solenoid valve 32 and
the solenoid valve 39 for energizing the same, and when in an up
position in engagement with a contact 97 is connected by a
conductor 98 to both the solenoid valve 33 and the solenoid valve
38.
The alternating opening and closing of the valves controlling the
delivery to and discharge from the receptacles 29 and 30 is similar
to that previously described, initiated and continued by alternate
closing of the scale switches SW5a and SW6a, these switches opening
when the weight thereon is removed.
The processing of blood for separation and collection of
granulocytes is greatly facilitated.
* * * * *