US3407812A - Method for performing plasmapheresis in situ - Google Patents

Description

v. 5. LUCAS 3,407,812

METHOD FOR PERFORMING PLASMAPHE'RESIS IN SITU Oct. 29, 1968 2 SheetsSheet 1 Filed Nov. 9, 1965 INVENTOR: VICTOR GRlFOLS LUCAS Oct. 29, 1968 v. e. LUCAS 3,

METHOD FOR PERFORMING PLASMAPHERESIS IN SITU Filed Nov. 9, 1965 2 Sheets-Sheet INVENTOR. VICTOR GRIFOLS LUCAS ATT'YS United States Patent 3,407,812 METHOD FOR PERFORMING PLASMAPHERESIS IN SITU Victor Grifols Lucas, Barcelona, Spain, assignor to Dade Reagents, Inc., Miami, Fla., a corporation of Florida Filed Nov. 9, 1965, Ser. No. 502,190 7 Claims. (Cl. 128--214) ABSTRACT OF THE DISCLOSURE A method and apparatus for practicing plasmapheresis in situ, in which a donors vein is first punctured with the needle of a conventional blood collection set and a predetermined quantity of the donors blood is collected in the chamber of a container, such as a standard blood bottle, which has a tapered neck zone. The set is then detached from the bottle Without withdrawing the needle from the donor's vein and the collected blood is immediately centrifuged in the same chamber, with the neck zone thereof facing downwardly, until the red cells migrate peripherally and displace the plasma towards the center of the chamber. The centrifugation is then gradur ally discontinued and the bottle is maintained in inverted stationary position until the peripherally-migrated red cells have settled into the neck zone of the chamber. Finally, with the stationary bottle still in inverted position, the original blood collection set, the needle of which still communicates with the donors vein, is connected to the bottle at the neck zone to draw off the red cells collected in the lower portion of the chamber and to return them to the donor through the same needle, thereby retaining the separated plasma in the chamber of the bottle.

This invention relates to plasmapheresis, and more specifically, to a method for performing plasmapheresis in situ.

In the past, whenever it has been desired to obtain human plasma by plasmapheresis, blood has first been withdrawn from the donor and has then been transmitted to a laboratory where it has been centrifuged to obtain separation of plasma from the red cells. Such a procetime has been characterized by the following disadvantages:

(1) The donor must suffer venipuncture twice; first for withdrawal of blood, and second, for reinjection of the red cells separated from his own blood, the re-injection of such cells serving to speed the process of recuperation so that more frequent donations may be feasible.

(2) Centrifugation of blood in the laboratory requires a detailed control in order to avoid mistakes that may produce shock in the donor if red cells from another person are administered to him.

(3) Repeated handling of the blood and its passage from one container to another, as well as recuperation of the red cells for re-injection, amount to a series of operations which require considerable time and increase the danger of infections and mistakes.

Accordingly, it is an object of the present invention to provide a method for performing plasmapheresis in situ, thereby overcoming many of the important disadvantages and dangers in plasmapheresis as it is now practiced. Specifically, it is an object to provide a method for practicing plasmapheresis in situ, thereby achieving important advantages in safety, asepsis and speed, to insure success with the least possible inconvenience and danger to the donor.

Another object is to provide a method in which Withdrawal of blood, and the centrifugation of such blood, are both carried out in the same container. In this connection, it is a specific object to provide a method in which centrifugation is achieved by rotating the collection bottle on its own axis. A further object is to provide a method in which a blood collection bottle is not only utilized directly in the centrifugation process, but is supported in such a way that re-injection of the red blood cells is greatly facilitated.

Other objects and advantages will be apparent from the specification and drawings, in which:

FIGURE 1 is a perspective view of the complete apparatus embodying the present invention, such apparatus including an electric motor elastically suspended, and a carriage stand mounted for rotation by the motor and adapted to contain a collection bottle in inverted position.

FIGURE 2 is a longitudinal sectional view of the carriage stand.

FIGURE 3 is an exploded perspective view'illustrating structural details of the stand.

FIGURE 4 is a broken perspective view of the lower portion of the bottle retainer showing the lower retaining ring.

FIGURE 5 is a perspective view of a disk adapted to be mounted in the retainers lower retaining ring,

FIGURE 6 is a view in reduced scale illustrating a first step in practicing the method of the present invention;

FIGURE 7 is another view in reduced scale illustrating subsequent steps in practicing such method.

Referring specifically to the drawings, I will now describe in detail the construction and functional characteristics of the apparatus, and the steps of the method, which permit practicing human plasmapheresis in the same place where blood is collected and which also allows immediate re-injection to the donor of his own red cells.

The apparatus shown in FIGURE 1 comprises an electric motor 1 disposed vertically with its shaft 2 projecting downwardly. At the lower end of the motor housing is a horizontal plate or clamping member 3 which is provided along its underside with a resiiient pad or cushion 3a. A second clamping member 4, provided along its upper surface with a similar pad or cushion 4a, is spaced beneath member 3 and is detachably connected thereto by vertical bolts 5 or by any other suitable connecting means. By rotating wing nuts 5a, the distance between plates 3 and 4 may be reduced or increased to either clamp or release a supporting arm 6 having a Y- shaped end portion 6a disposed between the plates.-The opposite end of the arm is firmly secured to a standard (not shown) or other appropriate stationary support means.

Motor shaft 2 extends downwardly through apertures in both clamping plates and is connected at its lower end to an adaptation neck 7 which constitutes a union between the shaft and the upper plate 8 of a bottle retainer or support 9. A pin 10 (FIGURE 2) extends through the lowermost end of the shaft and securely anchors the motor shaft and plate 8 for simultaneous rotation.

A collection bottle B, into which blood withdrawn from a donor is collected and in which centrifugation is thereafter immediately performed, is disposed in inverted position within the cage-like retainer 9. As shown in the drawings, retainer 9 comprises the upper disk 8, lower retaining ring 12 and disk 13, and parallel columns 14 extending between the upper disk 8 and the lower ringdisk assembly 12-13. The four columns are arranged in uniformly and circumferentially spaced relation. On the columns, another disk or plate 15 is slidably mounted and bears against the bottom of inverted bottle B. Disk 15 is urged downwardly by helicoidal expansion springs 16 concentrically mounted on the columns and interposed between upper plate Sand disk 15. The extent of spring expansion is limited by lugs 17 connected to the respective columns. Lugs 17 therefore serve as stops to 'tric power supplied lirnitthe extentof downward movement of disk under the influence of springs 16.

Lower ring 12 is provided on its upper surface with a plurality of uniformlyandcircumferentially spaced notches or recesses 12a. In addition, the inner surface of the ring is provided'with a like number of recesses or openings 12b, such recesses being uniformly spaced from each other and preferably being disposed substantially equal distances .circumferentially between notches 12a. Disk 13 is adapted to fit within the large central opening of ring 12and, as shown clearly in FIGURE 5, has a plurality- -of uniformly and circumferentially spaced ears 18. The ears project outwardly and are; of semi-circular shape, as arethe recesses or openings 12b of ring 12, and the two parts (disk 13 and ring 12) are so mated that the disk may be moved upwardly into the large central opening of the ring'with its ears 18 slidably received within openings or recesses 12b. Disk 13 is also provided with a central opening 19 for receiving the neck of bottle B. i

.It is to be noted that the diameter of the large central opening of ring 12 is greater than the diameter of bottle B. Therefore, the bottle may be introduced into the cage- -like retainer by inserting it upwardly in inverted position until its base engages the undersurface of spring-loaded plate 15. Disk 13 is fitted onto the inverted neck of the bottle, and the plate and bottle are then urged upwardly to compress springs 16 and to permit the ears 18 of the disk to pass upwardly through openings 12b. Thereafter, disk 13 is rotated until ears 18 seat within notches or recesses 12a. The weight of the bottle B, combined with the downward force exerted by springs 16, hold the ears 18 imposition within recesses 12a during the centrifugation step.

It will be observed that when the apparatus is assembled as shown in FIGURE 1, stationary arm 6 supports theunit at aypoint or zone between motor 1 and bottle retainer 9. This arrangement, coupled with the cushioning 'elfectof padded clamping members 3 and 4, substantially eliminates or dampens vibrations which might otherwise occur during centrifugation. As will be brought out later, it is important that vibrations which might produce turbulence of blood during centrifugation, and during the gradual reduction in rotational speed of the retainer following a period of centrifugation, be avoided.

Preferably, the motor is constructed to rotate shaft 2 'and retainer 9 at a speed of between 1500 to 3000 revolutions per minute. It is imperative that the motor be constructed and arranged, or controlled in its operation, so that deceleration of the retainer 9 and the blood-containing bottle B, following a period of centrifugation, occur gradually over an interval in excess of 3 minutes. Such gradual deceleration is necessary the blood and to permit a substantially complete separation of plasma and red cells. The gradual and uniform deceleration may be easily achieved by constructing the rotating parts to spin with minimum. friction and also to possess,-by virtue of their mass, sutficient momentum to spin for a period in excess of 3 minutes and preferably for a period in excess of 4 minutes, after the electric motor has been deenergized. In practice, a deceleration period in the range of 4 to 10 minutes, with an optimum period of approximately 7 to 8 minutes, has been found particularly effective. Periods in excess of 10 minutes are not desirable because they unduly extend the plasmapheresis procedure without any appreciable increase in the degree of red cell and plasma separation.

While gradual deceleration may be achieved as described above, it is to be understood that similar results may be obtained with rotating parts having greater friction and less mass by simply gradually reducing the electo the motor over an interval in excess of 3 minutes and, preferably, in excess of 4 minutes.

To practice plasmapheresis in 'situ, using the apparatus ia-407,812. I

just described, venipuncture is first performed with -the needle 21 of a conventional blood collection set 22, and then collecting the blood in a sterile, partially-evacuated bottle B (FIGURE 6). Bottle B is a standard blood-collectionbottle, having its neck 20 closed with a self-sealing rubber stopper 23'. Blood flows through the collection set into the bottle and, after a predetermined amount of 1 lood (normally 500cc.) has been collected," standard clamp 24 is manipulated to close the blood-collection tube and the filling needle 25 is Withdrawn from the self-sealing stopper 23 and, as indicated in broken lines in FIG- URE 7, is inserted into the drip tube assembly 26 connected to'a suspended bottle '27'containing sterile physiological saline. The sterile saline is allowed to flow-along the tube'22 which connects to the donors vein. This allows (1) some degree of replenishment of the total fluid lost by the donor during the withdrawal of blood and (2) the maintenance of patency of the needle which was previously inserted into the donors vein and which has not been removed therefrom. Failure to maintain a slow flow of physiologically compatible liquid through this needle would result in the formation of a clot within the needle.

Blood bottle B is entirely conventional and contains standard amounts of an approved anti-coagulant substance such as, for example, citrate, heparin, or EDTA.

After the filling needle 25 has been removed from the self-sealing stopper of the blood bottle, the substantially filled bottle is placed within retainer 9, in the position shown in FIGURES 1 and 2, and motor 1 is energized to centrifuge the collected blood for a period of 15 to 20 minutes, including deceleration time. Centrifugation causes the red cells to migrate outwardly against the inside wall surface of the bottle, thereby separating the cells'from the plasma which remains in the bottles axial zone. Following centrifugation, the bottle is allowed to remain undisturbed in the stationary retainer 9 for a further period of 1 to 3 minutes, at which time the red cells which have been driven to the wall of the bottle during centrifugation slide downwardly and occupy the lower portion of the inverted bottle.

As indicated by the solid lines in FIGURE 7, a typical airway needle 28 is then inserted into self-sealing stopper 23 and into communication with the air tube (not shown) within the blood bottle. Thereafter, drip tube assembly 26 is withdrawn from the stopper of the saline bottle 27 and the needle of that assembly is inserted into the stopper of the inverted blood bottle. The contents of the bottle are allowed to flow through the tube system 22 into the donors vein until exactly half the contents of the blood bottle (approximately 250 cc.) have been so administered. The administration procedure is then discontinued by closing clamp 24, and needle 21 is withdrawn from the donors vein.

The residual contents of the blood bottle will consist of plasma contaminated by a certain small proportion of red cells. In practice, this contamination amounts to between 2 to 5% of the 250cc. residual volume. The contaminating red cells are subsequently removed from the plasma by the use of a conventional centrifuge. This degree of red cell loss is quite insignificant and is considered to be small enough to permit a healthy individual to be subjected to the plasmapheresis procedure disclosed herein several times in a week.

It will be noted that throughout the plasmapheresis procedure, needle 21 remains in position in the donors vein. Only a single venipuncture occurs and, since the entire procedure is conducted at the donors bedside, there is no danger that the red cells returned to the donor may have been taken from someone else. The entire procedure is performed safely and relatively quickly, in 25 minutes or less, with no discomfort to the donor except possibly for that occasioned by the single venipuncture.

While in the foregoing I have disclosed the method of the invention in considerable detail for purposes of illustration, it will be understood that many of these details may be varied without departing from the spirit and scope of the invention.

I claim:

1. In a method for practicing plasmapheresis in situ, the steps of puncturing a donors vein with the needle of a blood collection set and collecting a predetermined quantity of the donors blood in a blood bottle having a tapered neck zone, then detaching the set from said blood bottle without withdrawing said needle from the donor and immediately centrifuging the collected blood by rotating the same bottle in inverted position about its axis until the red blood cells migrate peripherally and displace the plasma towards the center of the bottle, then gradually reducing the rotational speed of the bottle and permitting downward migration of the red cells under the influence of gravity into the neck zone of the inverted bottle without turbulence, and then, with the stationary bottle still in inverted position, reconnecting said set to said bottle at said neck zone to draw off the red cells collected in the lower portion of the bottle and return them to the donor through the same needle, retaining the separated plasma in the blood bottle.

2. The method of claim 1 in which the step of gradually reducing the rotational speed of the bottle is performed over a period in excess of 3 minutes.

3. The method of claim 1 in which the bottle is rotated at a speed within the range of approximately 1500 to 3000 revolutions per minute, the speed of the bottle being thereafter gradually reduced to zero over a speed-reducing interval of between approximately 4 to minutes.

4. In a method for practicing plasmapheresis in situ, the steps comprising: puncturing a donors vein with the needle of a blood collection set and collecting a predetermined quantity of the donors blood in a partiallyevacuated blood bottle having a tapered neck zone and containing a standard anti-coagulant; then detaching the set from said bottle without withdrawing the needle from the donors vein; then immediately centrifuging the collected blood by rotating the same bottle in inverted position in the immediate vicinity of the donor until the red cells have migrated peripherally and have displaced the plasma toward the center of the bottle; then gradually and uniformly reducing the rotational speed of the bottle over a deceleration interval in excess of 3 minutes; then maintaining the bottle in stationary inverted position until the peripherally-migrated red cells settle into the neck zone of the bottle; and then, with the stationary bottle still in inverted position, reconnecting said set to said bottle to draw off the red cells collected in the lower portion of the bottle and return them to the donor through the same needle, retaining the separated plasma in the bottle.

5. The method of claim 4 in which there is the additional step of attaching the needle of said set to a saline administration bottle to administer physiological saline to the donor while the collected blood in being centrifuged.

6. The method of claim 4 in which the blood bottle and its contents are centrifuged at a rotational speed falling within the range of approximately 1500 to 3000 revolutions per minute, said centrifuging and decelerating steps occurring over an interval within the range of approximately 15 to 20 minutes.

7. In a method for practicing plasmapheresis in situ, the steps of drawing a quantity of blood through a venipuncture in a donor and collecting said blood in a chamber having a tapered end zone, then rotating said chamber about a vertical axis extending through said end zone and while said chamber is oriented with said end zone facing downwardly until the red blood cells migrate peripherally and displace the plasma towards the axis of rotation, then gradually reducing the rotational speed and permitting downward migration without turbulence of the red cells into said end zone under the influence of gravity, and then, without altering the orientation of said chamber, and immediately upon discontinuance of rotational movement, drawing off the red cells from said tapered end zone and directly returning them to the donor through said venipuncture.

References Cited UNITED STATES PATENTS 2,758,597 8/1956 Elder 128-214 2,876,769 3/1959 Cordova 128-214 3,096,283 7/1963 Hein 128-214 3,140,714 7/1964 Murphy 128-214 3,145,713 8/1964 Latham 128-214 3,190,546 6/ 1965 Raccuglia 1'28-214 XR 3,211,368 10/1965 Shanley 233-1 3,243,105 3/1966 Anderson 233-1 OTHER REFERENCES The Journal of the American Medical Association, Red Cell Reinfusion and the Frequency of Donations, vol. 124, No. 6, p. 331, Feb. 5, 1944.

RICHARD A. GAUDET, Primary Examiner.

M. F. MAJESTIC, Assistant Examiner.

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