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Chapter VI

Contents

CHAPTER VI

Blood Donors and the Technique of Collectionof Blood

REQUIREMENTS FOR BLOOD DONORS

When the Red Cross Blood Donor Service was inaugurated in 1941, there were two problems concerning donors to be considered. The first was their recruitment (p. 119). The second was their selection. The second problem had two parts, (1) the collection of useful and usable blood, and (2) the protection of the donors from any mischances and sequelae of their donations. In general, the rules which were adopted by the Subcommittee on Blood Procurement, NRC (National Research Council), at the 18 August 1941 (2) meeting remained the basic rules throughout the program, though certain variants were introduced as experience was accumulated.

Initial Specifications

Initial requirements for blood donors were as follows:

1. Donors should be between 21 and 60 years of age.

2. Donations should be accepted from both males and females and from members of all races.

3. No donor should be accepted from whom a donation of 500 cc. could not be expected.

4. The temperature by mouth should not exceed 99.5 F. (39.5 C.).

5. The blood pressure should not exceed 180/100 mm. Hg.

6. The hemoglobin should be 80 percent or more.

7. The pulse should be recorded and note made of bradycardia and any irregularity. In practice, donors with any irregularities were rejected except that no attention was paid to an occasional dropped beat.

8. Women who were pregnant or who had delivered or miscarried within the preceding 9 months were not accepted.

Diabetics were accepted only on the written permission of their personal physicians.

Donors were also asked when they had last given blood and were questioned concerning possible diseases, which are discussed under a separate heading (p. 141).

1Unless otherwise indicated, all data in this chapter are from Dr. G. Canby Robinson's final report of the Red Cross Blood Donor Service in July 1946 (1).


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Later Specifications

As time passed, the following alterations were made in the original specifications for donors:

1. The age was lowered to 18, with the proviso that donors in this age group must present signed permission from their parents or guardians.

2. Donors whose temperature was above 98.4 F. (37 C.) were not accepted.

3. Donors with blood pressures up to 200/100 mm. Hg were accepted.

4. A hemoglobin level of 12.3 gm. percent was required, the determination to be made by a really precise method (p. 160).

5. Both male and female donors must weigh at least 110 pounds.

6. Donors were instructed not to eat within 4 hours before the donation, and in the interim to drink no milk. Originally, the requirement was that no fatty foods must be eaten within a 4-hour period, since at the end of this time, the fat concentration in the blood would be reaching its highest level.

7. The following groups of donors were also not accepted:

a. Those who had had tooth extractions within 24 hours.
b. Those who must return to work with heavy machinery within 8 hours.
c. Those who had been treated for rabies within the previous 5 years.
d. Those who were extremely sensitive to horse serum and similar substances, for fear of passive transfer of sensitivity to the recipient, which would later prevent the effective use of sera for tetanus, gas gangrene, and other conditions. Many observers thought that this risk could be ignored because of the large pools of plasma being used.
e. Military and commercial fliers, including crews as well as pilots.

The understanding was that donors who had been receiving sulfonamides should be evaluated individually. This regulation was honored more in the breach than in the observance. At the 2 June 1944 meeting of the Subcommittee on Blood Substitutes (3), an instance was reported of transfer of sulfathiazole sensitivity from a donor to a recipient who was receiving the drug. Although it was thought that such instances might become more frequent, there were no other reports of the kind.

Even after all the prescribed regulations and restrictions for donors had been met, there were still some questionable cases. In these, the decision for acceptance or rejection was made on an individual basis, by the physician in charge of the center. It was the rule, if any doubt existed after the evaluation, to reject the donor.

Release

Every donor was required to sign a release (fig. 27) stating that he or she was voluntarily furnishing blood through the American Red Cross to the Army and the Navy, and that he or she agreed that neither the Red Cross nor anyone connected with the Blood Donor Service would be held responsible for any event that might follow the donation.

The number of registered donors whose donations were rejected was reported each month by each center to the Technical Director of the program. Of 14,695,836 persons registered, 1,514,085 (10.3 percent) were rejected,


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chiefly for low hemoglobin levels (p. 158) or high blood pressure. The breakdown was as follows:

    5,026 of 932,927 first-time male donors (0.5 percent).
    13,859 of 1,781,481 male re-donors (0.75 percent).
    105,432 of 1,043,833 first-time female donors (10 percent).
    241,694 of 1,849,860 female re-donors (13 percent).

FIGURE 27.-Release signed by donors before they gave blood at American Red Cross blood
donor centers.

DONORS WITH SPECIAL DISEASES

History-Taking

The problem of disease in volunteer blood donors had two aspects, (1) the protection of the donor and (2) the protection of the recipient from transmissible diseases or diseases thought to be transmissible. At the outbreak of the war and the beginning of the blood program, very little specific information was available as to the transmissibility of diseases if blood were drawn during an illness or shortly thereafter. As a precaution, however, donors were not accepted if they had had, or were recently convalescent from, any infectious disease or any other disease of known or unknown etiology.

Regulations provided that blood donors should be questioned by the registered nurse or the physician in charge of the center concerning their previous history of disease and any current symptoms. On the whole, these regulations were honored, though it must be admitted that their observance depended not only upon the care (or carelessness) of center personnel but also upon the workload. On D-day, for instance, when the centers were crowded with unscheduled as well as scheduled donors, questioning must have been superficial if it was carried out at all.


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The regulations, however, provided for questioning the would-be donor on the following matters (4):

1. Any illness within the past month. Particular note was taken of the presence, or expected development, of upper respiratory infections. The physician in charge was asked to rule in questionable cases.

2. Sinusitis and hay fever. Donors were acceptable if they were not having acute attacks and were otherwise in good health.

3. Septic sore throat within the past 3 months. The physician in charge made the decision.

4. Undulant fever or clinical tuberculosis within the past 5 years. Either disqualified the donor. If he had had extrapulmonary tuberculosis, the physician in charge made the decision.

5. Cardiovascular disease, as evidenced by shortness of breath, swelling of the feet, a persistent cough, or pain in the chest. A history of cardiovascular disease, or the existence of any of these symptoms and signs, disqualified the donor.

6. Jaundice within the past 6 months. Donors with such a history were immediately disqualified. If there was a family history of jaundice, the physician in charge made the decision on the basis of the closeness of contact and the nature of the jaundice. It should be remembered that serum hepatitis did not become a problem until the last year of the blood program (p. 674).

7. Fainting spells and convulsions. The physician in charge made the decision. Such donors were practically always rejected.

8. Rabies. Volunteers who had had treatment for this condition within the past 5 years were rejected.

9. Virus infections such as dengue, yellow fever, atypical pneumonia, and virus exanthemata. These volunteers, who were usually evaluated individually, were not accepted until 6 months had elapsed.

On the basis of a review of the literature, which contained reports of several cases in which leukemic blood had been transfused, it was decided that this disease was not transmissible by this route (5). On the contrary, there were some reports of the treatment of agranulocytosis by leukemic blood. There was also some evidence that sodium citrate was somewhat toxic for the cells of mice with leukemia.

The risk of serum hepatitis from transfused plasma, unsuspected until late in the war, proved the greatest risk of all (p. 674). Early in the war, the chief concern was with syphilis and malaria.

Syphilis

The "Minimum Requirements for Unfiltered Normal Human Plasma," issued by the National Institute of Health on 20 February 1941 (p. 279), specified that an acceptable serologic test for syphilis must be made in a qualified laboratory on a specimen of blood taken at the time of bleeding and that the blood should not be used for the production of normal human plasma unless the result of the test was negative.

At the meeting of the Subcommittee on Blood Substitutes on 13 July 1944, the subject was discussed extensively, and it was agreed that the evidence


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showed that the chance of transmitting syphilis by transfusion was very remote. The life of the spirochete had been demonstrated in laboratory studies with infected testicular tissue to be less than 92 hours in stored blood, and its survival would probably be shorter in organisms occurring naturally in the bloodstream.

The following recommendations were therefore adopted:

1. A serologic test for syphilis should be required on each blood intended for processing into plasma, the test to be performed by a method approved by the Venereal Disease Division of the U.S. Public Health Service.

2. In addition, the Kline exclusion test or the Kahn presumptive test should be performed on bloods to be used in suspensions of red blood cells.

3. Resuspended red blood cells would be acceptable for use only if they were derived from serologically negative blood.

4. Blood cells to be used for resuspension and transfusion should be held for 72 hours at 39 F. (4 C.) before reinfusion, in conformity with existing Red Cross regulations.

Malaria

Malarious donors in the Zone of Interior never furnished the problem that they did in certain oversea theaters (pp. 423 and 597), but they could not be ignored, one reason being that there were then no criteria for the complete cure of malaria (5). It was known that the parasites did not survive either freezing or drying, and that frozen or dried plasma processed from the blood of malarious donors therefore would not transmit the disease.

The matter first came up at the meeting of the Subcommittee on Blood Substitutes on 10 March 1942 (6). A number of lines of investigation were suggested, and the Army and the Navy were advised, for the present, to use caution in processing liquid plasma in malarious districts.

At the 12 May 1942 meeting of the subcommittee (7), the opinion was expressed that the fear of transmission of malaria through plasma had perhaps been overemphasized. Studies on fowl malaria at the Naval Medical School had indicated that this variety of Plasmodium does not survive in dried plasma. Recent observations in Puerto Rico had included a patient who received 10 cc. of unfiltered plasma obtained from a malarious donor and who had clinical signs of malaria and positive smears 25 days after inoculation. Subjects who received the same inocula passed through a Seitz filter did not develop the disease. The plasma used in these experiments was aspirated from citrated blood that had been refrigerated for 48 hours.

A letter from Dr. Lowell R. Coggeshall read at the 23 June 1942 meeting of the Subcommittee on Blood Substitutes (8) expressed his own opinion that lyophilized plasma infected with malarial parasites was not dangerous and that there would probably be no infections from the transfusion of liquid plasma over 10 days old if all the red blood cells had been removed. Conclusive laboratory proof of these opinions would be long in forthcoming, but it had already been established that plasma infected with Plasmodium knowlesi was not infective for Rhesus monkeys, even when fresh, if all the red cells


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had been removed. A report from the Malaria Conference stated its official opinion that there was a real hazard from the transfusion of infected plasma, though it was probably safe to use it if all the red cells had been removed by centrifugation.

At the subcommittee meeting on 20 October 1942 (9, 10), Cdr. Lloyd R. Newhouser, MC, USN, reported experiments carried out with Lt. Cdr. Eugene L. Lozner, MC, USN, on 18 patients, none of whom developed malaria after transfusions of 500 cc. of dried plasma infected with different species, with parasite counts of 150,000 per cc. A preliminary report from Dr. Mark C. Boyd, of the Rockefeller Foundation, concerned the intravenous injection of 35 cc. of reliquefied lyophilized plasma prepared from blood with a high density of parasites secured from patients with Falciparum malaria. None of the subjects in a completed experiment had developed malaria, and a second experiment was sufficiently far advanced to indicate that the results would be similar.

The question of the transmission of malaria by transfusion came up again at the 13 July 1944 meeting of the Subcommittee on Blood Substitutes (5), in connection with the blood donor regulations of the New York City Department of Health, already discussed in connection with the possible transmission of syphilis by red blood cell suspensions. It was generally doubted that a physical examination, with reliance upon an enlarged spleen, would identify malarious donors; the Army experience had showed the absence of this finding in many hundreds of men with malaria. The Board for the Coordination of Malarial Studies considered the search for a palpable spleen "a futile gesture."

At this meeting, Commander Lozner reported studies that showed that when only 5-10 cc. of infected blood had been injected after 8 days' storage, infection had followed. If it could be calculated that the parasites died at a rate plotted on a logarithmic curve, then they would probably survive in larger quantities of blood for 2-3 weeks. Transmission of malaria had been reported from donors who had been clinically cured for 15 years.

Dr. Robinson pointed out that the regulation that a donor should be rejected who had had clinical manifestations of malaria within the past 15 years had been made for the protection of the donor from activation of the infection rather than for the protection of the recipient.2

At the end of this discussion, it was recommended that a particularly accurate history on possible malarial infection be obtained from all donors whose blood was intended for preparation of red blood cell suspensions. Any donor with a history even remotely suggesting the possibility of malarial infection, however far in the past, should not be accepted. Donors should be asked not only whether they had had malaria but whether they had been in areas in which the disease was known to be endemic.

2At Grady Hospital, Atlanta, Ga., it was not uncommon for patients who had incurred trauma, sustained hemorrhage, or been given inhalation anesthesia to have temperature charts suggestive of tertian or quartan malaria. Blood smears were done routinely on these patients and frequently revealed the plasmodial parasite.


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ROUTINE OF DONATION

In a program of such magnitude as the Red Cross Blood Donor Service, an assembly line type of production had to be developed (11). This was necessary not only because of the large quantities of blood handled but also because, when as fragile a biologic product as blood was being dealt with, standardization of the operation was essential. It was also necessary for the protection of the vast army of donors that all equipment and all technical details of collections be standardized.

Bleeding was carried out by teams, each of which consisted of a physician, four nurses, a secretary, and one or two shipping clerks. The basis of operation was a unit consisting of two beds and a worktable under the supervision of one nurse. A trained team could easily handle 100 donors in 4-5 hours. The fewer the people who did the bleeding, the less the chances of contamination.

No single person was a more essential part of the team than the secretary. The handling of records had been planned to require as little transcription as possible, but all subsequent handling of the blood depended upon the accuracy of the serial numbering of the medical record, bleeding bottle, and serologic tube. The medicolegal importance of accuracy in this respect needs no elaboration.

The routine of a donation was as follows:

1. The prospective individual donor phoned for an appointment, or, less often, came directly to the donor center. If time and space were available, he was taken at once; otherwise, he was given the earliest possible appointment.

2. Entry to the center was through a reception room, with an adjoining cloakroom. The donor then passed on to a second room, in which his appointment was checked, and his name and address were entered on a daily booking sheet (fig. 28). A standard, serially numbered registration card (fig. 29) was prepared for him. It contained the questions each donor was asked, space for the replies and for entering other data, and the release which he was later asked to sign (fig. 27).

3. In the succeeding room, the blood pressure, temperature, and pulse were taken and recorded. A hemoglobin determination was made (fig. 30). The registered nurse who had carried out these procedures also asked the necessary questions and recorded the replies. These proceedings were conducted at separate tables, so that complete privacy was assured. When they were completed, the donor signed the release. Later, all data connected with the donation (and subsequent donations) were filed under the donor's name (fig. 31).

4. Bleeding was originally conducted in separate cubicles in the belief that the sight of other donors would be harmful. It was soon found that a common bleeding room (fig. 32), where the donors were in full view of each other, was good psychology and also efficient, in that the physician in charge could keep close check on all donors while bleeding was in progress. As many as 36 bleeding tables or cots were set up in a single room, with a small work stand between each pair.

5. When the original regulations were drawn up (2), it was specified that the donor lie recumbent for at least 10 minutes after the blood was drawn. If there was any sort of reaction, the period of recumbency was prolonged or he was moved to a separate room, in which he was under the supervision of the physician in charge, a nurse, or a nurse's aide, as his condition indicated.


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FIGURE 28.-Reception and registration rooms at American Red Cross blood donor centers. A. Louisville, Ky. B. San Antonio, Tex. C. San Francisco, Calif.


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FIGURE 28.-Continued. D. St. Louis, Mo. E. Fort Worth, Tex. F. Unidentified center (photograph, courtesy American Red Cross).


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FIGURE 29.-Card used by American Red Cross for registration and history of blood donors.

6. After the rest period, the donor was taken to the canteen, operated by the Red Cross Canteen Corps, and, seated at a small table, was given milk, a soft drink, crackers, or other light refreshment (figs. 33 and 34). Whisky was not given.

7. When the donor was ready to leave the center, he was presented with a certificate and emblem (p. 128) attesting the donation, and was also given the opportunity to make an appointment for another donation at the end of 8 weeks.

The reception and treatment of donors at the centers were an important part of the Blood Donor Service. All personnel recognized the importance of treating them courteously in every phase of the procedure. They were welcomed cordially but not effusively. If a volunteer had to be rejected, the reason for the rejection was made clear by careful explanation by the physician or nurse, and, if it seemed practical, the suggestion was made that he reapply at a later date.

The spirit of comradeship among the donors in the centers was notable, although they represented every social, economic, and educational background. The sights and sounds in the canteen after donations suggested groups of old friends rather than persons who shortly before had been complete strangers to each other. The donation of blood without doubt raised the spirits of the donor who had made it, and the donors themselves repeatedly expressed this feeling.

TECHNIQUE OF COLLECTION OF BLOOD

General Considerations

The basic requirement that blood be collected under conditions of absolute asepsis was met by the use of a closed system (4, 12). Standard equipment was used (p. 151). It was decided that gloves, gowns, masks, and caps need


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FIGURE 30.-Determination of donor's hemoglobin and blood pressure, American Red Cross Blood Donor Center, San Antonio, Tex.

not be used, and that sheets and towels need not be sterilized (2). Everything used in the bleeding set, however, was sterilized in an autoclave at 250 F. (121 C.) for 30 minutes. In addition to the equipment prepared daily at each center for the next day's quota, a constant supply of equipment had to be sent to the centers from the processing laboratories, where needles were sharpened, rubber tubing was cleaned, and other procedures were carried out.

The greatest care was exercised in all details of the procedure. A sterile needle was used for each donor, dispensed from an individual test tube or other container from which it could be removed without risk of contamination from air or from the hands of the operator. The Novocain (procaine hydrochloride) for each day's use was dispensed at the beginning of the day, by one nurse, under as nearly aseptic conditions as possible. Diaphragm-stoppered bottles, which permitted multiple withdrawals, were not used.

Details of Technique

Bleeding was usually carried out by a graduate nurse, under supervision of the physician or medical officer in charge. Any problems which arose during the procedure were referred by the nurse to him.


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FIGURE 31.-Fileroom, American Red Cross Blood Donor Center, San Antonio, Tex.

The following technique was employed (fig. 35):

1. With the donor recumbent on a padded table or bed, the arm was bared, and the most suitable site for venipuncture selected. Usually, this was the anterior aspect of the upper forearm.

2. A blood pressure cuff, folded to half its width, was applied to the arm, to serve as a tourniquet. Except during the flow of blood into the bottle, the tourniquet was not released unless a clamp was applied to seal off the inlet tubing completely. Before the vein was entered, the pressure in the cuff was raised to 40-60 mm. Hg.

3. The selected site was scrubbed mechanically over an area 4 by 4 inches with 50-percent solution of green soap followed by the application of alcohol (70 percent by weight). Iodine (2-percent aqueous solution U.S.P.) was applied, allowed to dry, and then removed with a sponge wet with alcohol. If, for any reason, bleeding had to be delayed, the field was covered with a gauze square soaked in alcohol.

4. Venipuncture was performed without touching the prepared area of the forearm. If introduction of the needle was difficult, it was permissible to palpate the site above and below the puncture after the needle was in situ. If the needle had to be withdrawn after it had penetrated the skin, a fresh bleeding set was used for the second attempt. Not more than two attempts to enter a vein were permitted.


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FIGURE 32.-Collection of blood at various American Red Cross blood donor centers. A. San Diego, Calif. B. Fort Worth, Tex. (showing the last blood donation before the center was closed on 13 October 1944). C. Unidentified center (photograph, courtesy American Red Cross).

5. The actual bleeding occupied about 5 minutes. Every effort was made to collect 500 cc., and no bleeding was counted as such unless the bottle was filled to the 300-cc. level. If suction was necessary, as it occasionally was, a hand pump was used. The bottle was not rotated during the collection of the blood.

6. After the needle was withdrawn, the arm was either kept extended or was elevated; it was never flexed. Pressure was maintained over the venipuncture with a gauze square held in place by the nurse or, more often, by the donor himself. Then a small piece of gauze, held in place by adhesive, was placed over the puncture.

7. While the bleeding was in progress, the bleeding bottle was tagged, as was the serologic tube, with the donor's name and serial number, and the name on each receptacle was checked with the donor. A double card was used for the bleeding bottle.

8. The serology sample was taken at the end of the bleeding. The tube was kept below the level of the bottle, to prevent blood from running back into the bottle, while it was collected.

9. A spring clamp was placed on both steel inserts and both tubes in the stopper of the bleeding bottle (fig. 36), so bent as to constrict the rubber tubes at the bases of the inserts. An eighth of an inch of tubing extended above the edges of the steel inserts, so that there was no danger of their cutting through it. Both inlet tube and airway tube were cut flush with the edge of the stopper.

10. A careful check was made, to be certain that there were no air leaks about the hub of the needle or at the point at which the tubing was connected with the steel tubes. If any leaks were found, or if there was any break in technique in the course of the bleeding, the bleeding tag was marked "P.C.," to indicate potential contamination.


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FIGURE 33.-Canteens, American Red Cross blood donor centers. A. Los Angeles, Calif. B. Clifton, Tex. (mobile setup). C and D. Fort Worth, Tex. E. San Francisco, Calif. F. St. Paul, Minn.

Postbleeding Disposition of Blood

The bottles of blood were moved at frequent intervals from the bleeding room to large refrigerators, the temperature of which was strictly controlled. At the end of the day, all the donations were packed in refrigerator chests (p. 204) by trained blood custodians (fig. 37) and dispatched, by railway express or truck, to a processing laboratory. A daily shipping list, including each donor's name and serial number, was made in triplicate and accompanied each ship-


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FIGURE 34.-Kitchen attached to canteen, American Red Cross Blood Donor Center, Fort Worth, Tex.

ment. Processing, beginning with serologic testing, started the following morning. The blood was moved on prearranged express schedules, so that each lot reached the laboratory within 24 hours after it was collected.

REACTIONS TO DONATIONS

The efficiency of the selection of donors by the regulations outlined is evidenced in the very few fatalities, and the few really serious accidents, which occurred in the course of the program. The accident rate in donor centers, in fact, was far below the accepted accident rate for the population as a whole (11). It was concluded at the end of the war, taking into consideration the millions of people involved, that the donation of a pint of blood was harmless and that among the same group of people, engaged in such presumably innocuous occupations as taking baths, using electrical appliances, or going up or down stairs, the percentage of accidents over the same period was probably much greater.

In April 1943, a member company inquired of the Medical Committee of the Industrial Hygiene Foundation whether the giving of blood affected production and caused absenteeism. It was the unanimous opinion of the committee that there were no undesirable effects at all (13).


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FIGURE 35.-Steps in collection of blood at American Red Cross blood donor centers. A. Application of blood pressure cuff as tourniquet. The donor giving blood (at El Toro, Calif.) is twice-wounded Marine Air Corps Ace, Capt. Don Aldrich, who shot down 20 Japanese planes in the Pacific. B, C. Venipuncture. D. Application of gauze to site of puncture and elevation of arm after blood has been collected. (Photographs A and B, courtesy American Red Cross.)

A sample experience was cited to prove the statement: One company, after an intensive drive among office and shop employees had produced 3,348 donations during the visit of a mobile bleeding unit, did not find a single absence from illness immediately afterward that could be attributed to the donation. One reason, of course, was that the careful predonation check had eliminated the donors likely to be adversely affected. The blood was always drawn after the worker went on the shift, never before. Office workers generally returned to work directly, but shop workers waited for 2 hours.


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FIGURE 36.-Application of clamp to Red Cross donor bottle when collection of blood is complete. A. Airway and bleeding tube. B. Bottle tubes clamped off.

Other companies also reported that they found no absences attributable to the donations, no increased incidence of colds or other upper respiratory infections, and no increase in fatigue. Many reported, on the contrary, that the donation seemed to have provided a stimulus to greater effort and improved morale.

Incidence of Reactions

In order to obtain information directly from the donors concerning the effects of donation, 10,000 postcards were distributed to consecutive donors at each of four centers, with the request that they be filled in and returned within the week. Replies were received from 27,021 donors (68.2 percent), the number probably including most, though not all, of those who had experienced any effects.

Of the 27,021 donors who replied, 81.6 percent had no complaints. Those with complaints usually had more than one. In all, 8.9 percent reported some general ill effects and 10.1 percent had some trouble in the arm from which the


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FIGURE 37.-Shipping room at unidentified American Red Cross blood donor center.

blood was withdrawn, but only 4.1 percent reported limitation of activity within the week after the donation (the figures are overlapping). The percentage of upper respiratory infections, less than 1 percent, was lower than the general incidence of such infections during the period covered by the survey. A good proportion of those who complained of some lassitude and weakness in the 48 hours after the donation were sedentary indoor workers or housewives. The Blood Donor Service was unaware of specific instances of absenteeism, but there is no doubt that occasional persons took advantage of their donations to remain away from work.

Types of Reactions

Accidents and reactions among donors were analyzed by Dr. (later Major, MC) Earl S. Taylor (11) in a presentation to the American Medical Association at its annual meeting in June 1942, by which time 286,197 bleedings had been carried out, with 10,348 reactions (3.5 percent). Later, with Dr. Mary Heiss Boynton, Major Taylor (14) analyzed the reactions which had occurred in the more than 7 million donors who had given blood up to 1 April 1944. The significant data of both analyses were as follows:

Fatalities.-Several fatal illnesses had their inception immediately after donations, the most important being in the group of donors with cardiac or


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other circulatory conditions. In all, there were 10 fatal cardiovascular accidents within 3 to 48 hours after the donors had left the centers, in addition to 1 fatality in a center, caused by a sudden coronary arterial occlusion. The giving of blood was thought to have had little or nothing to do with these deaths.

There were also eight instances of angina pectoris, coronary thrombosis, or cerebral hemorrhage during, or within 2 hours after, the donations; all were followed by recovery.

Fainting-In both the 1941 and 1944 surveys, the most disturbing reaction was impending faintness, actual faintness, or occasionally, a deeper loss of consciousness. Compilation of reports from all bleeding centers at the end of the war gave the number of donors who "fainted or stayed longer than usual" after the donation as 490,000 out of more than 13 million donors (3.7 percent). About half of this group showed definite syncope, though the loss of consciousness was only momentary. A small number presented not only loss of consciousness but generalized convulsions, incontinence, cyanosis, and, occasionally, very striking tetany with carpopedal spasm. All responded rapidly to symptomatic treatment.

All centers were equipped to treat such conditions, and all mobile units carried with them equipment for intravenous administration of saline solution, as well as sedative and other drugs.

The most likely subject for syncope was a young adult weighing between 100 and 110 pounds (later, 110 pounds was the lower limit for a donor). If he was also hypotensive, he was almost certain to have some reaction. Another candidate for syncope was the donor who had worked a long shift at a factory, particularly in warm weather; in such cases, dehydration was also a factor.

Emotional and psychic influences played a major role in fainting. Some donors fainted before bleeding was begun or soon after it was started. In a few instances, the wife or the husband fainted while the spouse was being bled.

Weakness.-Few opportunities arose to pass judgment on donors who complained of limitation of activities because of weakness or lassitude for 7-10 days after the donation. When examinations could be made, no basis was found for the complaints, which seemed to be chiefly of emotional or psychogenic origin.

Lacerations and contusions-A few lacerations, contusions, and fractures occurred in association with fainting, most often in subjects who had refused to rest after the donation.

Local reactions-The most frequent local complication was extravasation of blood into the tissues at the point of venipuncture. The area was discolored, and was sometimes swollen and uncomfortable, for several days. There were a few instances of dermatitis about the venipuncture, but no record of iodine or other burns. There were also about 30 reported instances of local infection. It was reported that one donor had developed a staphylococcic septicemia after the donation, but since he recovered in 5 days, the diagnosis was considered highly unlikely.


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Other complications-Other complications than those just discussed were minor and infrequent. All rumored reports of profound anemia and prostration were traced to the sources and all were found to be groundless.

REGENERATION OF HEMOGLOBIN

Initial Studies

In June 1941, Dr. Taylor (15) reported an analysis he had received, in a personal communication from E. M. Katzen, of a carefully controlled study of 100 professional male donors of the Blood Transfusion Association, New York City. These 100 men had given 3,617 transfusions, averaging 525 cc. each, over periods ranging from 4 to 14 years and averaging 7 years. They had given from 16 to 101 times during the period of observation, an average of 36 times per donor. They were required to rest 1 week between transfusions for each 100 cc. of blood donated. They had hemoglobin determinations every month they gave blood and a routine checkup every 3 months if they had not donated in the interval.

None of these donors showed any significant failure to regenerate hemoglobin when they were studied at the end of their rest period, and over the years there had been little variation from their original hemoglobin values. This long-term study was taken to indicate that repeated blood donations at stated intervals had no deleterious effects on healthy donors.

At a meeting of the Subcommittee on Blood Substitutes on 23 June 1942 (8), Dr. Taylor pointed out that the immense number of donors recruited by the Red Cross Blood Donor Service offered opportunities for investigation, particularly studies of hemoglobin regeneration, which should not be neglected. At the meeting of the subcommittee on 17 November 1943 (16), he reported the studies of Dr. Charles Doan, Ohio State University College of Medicine, on over 4,000 donors who had given blood from one to five times at the Red Cross donor center at Columbus, Ohio. When blood was given every 8 weeks, about 80 percent of the women donors showed prompt return to their original hemoglobin values. The remaining 20 percent did not, nor did their values return to the original levels even when the interval between donations was as long as 4 months. In view of these facts, it seemed to Dr. Taylor that a certain number of donors would either have to be rejected (and the Tallqvist technique, unfortunately, was difficult to read at the 80-percent level, then the critical level for rejection of donors) or would have to be given iron.

Dr. Doan's data confirmed the observations made by Fowler and Barer (17) at the State University of Iowa College of Medicine on 200 donors, who gave blood for 636 transfusions.

The idea of administering iron to donors was not well received by some of the committee members, who thought it a dangerous policy for Red Cross donor centers to practice medicine. Dr. A. M. Fisher, who was present as a representative of the Canadian National Research Council, said that donations in


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Canada were now limited to five a year. Some Canadian donor centers prescribed iron but others thought it a poor policy to suggest to donors that they might not regenerate blood promptly.

The problem of posttransfusion anemia in women donors was discussed at a subsequent meeting of the Subcommittee on Blood Substitutes (18) and at the Blood Donor Conferences held in December 1943 and January 1944 (p. 119). Captain Taylor reported at these meetings that several studies carried out by the Red Cross had showed that a certain percentage of female donors developed some anemia after blood donations, but he did not consider it justified to say that "medical authorities were becoming worried about possible resultant anemias." At the January 1944 conference, there was general agreement that the incidence of posttransfusion anemia was about 15 percent, but there was opposition to the administration of iron by physicians at the blood donor centers.

Recommendations of Ad Hoc Committee

An ad hoc committee (Dr. Elmer L. DeGowin, Chairman, Captain Taylor, Col. Douglas B. Kendrick, MC, Captain Newhouser, Dr. Max M. Strumia) appointed at the 5 January 1944 meeting of the Subcommittee on Blood Substitutes met on 19 January 1944, with Dr. Doan; Dr. Willis M. Fowler; Dr. Carl V. Moore, Washington University School of Medicine; and Dr. William Thalhimer. It was agreed:

1. That the Tallqvist test for hemoglobin was highly inaccurate and had not been effective in the selection of donors without anemia.

2. That many female donors who should not have given blood had been accepted on the basis of this test.

3. That the Red Cross, to prevent posttransfusion anemia, must devise other standards for the selection of donors. Changes in the technique of selection had been impractical up to this time, particularly in mobile bleeding units, because there had been no quick, accurate, and simple technique available to determine the hemoglobin level.

The ad hoc committee recommended:

1. That the recently devised Thalhimer modification of the copper sulfate technique of Phillips, Van Slyke et al. (p. 257) be used to determine the critical level of hemoglobin for the selection or rejection of donors. This test had the additional advantage of indicating hypoproteinemia; Dr. Doan's data suggested that some women tend to regenerate plasma proteins after transfusion even more slowly than they regenerate hemoglobin.

2. That over the next 6 weeks, Dr. Doan compare the accuracy of the prescribed method with that of the Evelyn colorimeter in the blood donor center at Columbus, Ohio. Final acceptance of the copper sulfate method should await his final report.

3. That arrangements be made to procure the solutions used in the copper sulfate test and to procure photoelectric colorimeters to use for occasional quantitative determinations of hemoglobin in multiple donors and for checking the accuracy of the copper sulfate technique.

4. That the minimum level of hemoglobin for acceptable donors of both sexes be tentatively placed at 11.5 gm. percent. By this criterion, if Dr. Doan's data were correct, about 25 percent of all females and about 20 percent of all males living in conditions similar to those in Ohio would be rejected. Final action on this point would be taken after receipt of further studies by Dr. Doan on multiple donors.


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5. That Drs. Doan and Moore be permitted to prescribe iron at their discretion in the blood donor centers at Columbus and St. Louis. Dr. Doan wished to give iron only to re-donors who regenerated hemoglobin slowly. Dr. Moore wished to test its effect on the incidence of rejections of re-donors. Both physicians were asked to observe the effect of its prescription on relations of the centers with the local medical profession.

No action would be taken, until additional data were available, on the volume of blood to be collected from female donors; on the incidence of rejection of female donors in the age group 18-21 years; and on an increase of intervals between donations in women. At the urgent request of Captain Taylor, who thought it highly undesirable to question women on this point, no recommendations were made concerning donations during menstruation.

In further discussion of iron therapy, it was concluded that since medical practice varied in different localities, the local technical supervisor was in the best position to judge the repercussions of any given policy on the local medical profession and on the procurement of donors. There was general agreement that repeated bleedings undoubtedly produced iron-deficiency anemia in some women and that the Red Cross, because of its publicity concerning the safety of blood donations, was morally if not legally responsible for it.

Followup Actions

By 21 April 1944 (19), all blood donor centers had been supplied with materials for the Thalhimer-Phillips-Van Slyke copper sulfate test. The solutions were adjusted to a hemoglobin concentration of 12.3 gm. for all donors, since it had been found in over a thousand males tested that only 5 had hemoglobin levels below 13.5 gm. percent. With a minimum standard of 12.4 gm. percent, about 10 percent of prospective female donors had been rejected, the incidence being slightly higher at the Columbus Blood Donor Center than at others. The correlation between the Evelyn and the copper sulfate techniques was reported as good. The solutions were regularly checked for accuracy.

In view of these data, it was recommended that a single standard of hemoglobin, 12.3 gm. percent, be used as a minimum for donors of both sexes.

Statistics averaged for several centers for May 1944, covering a total of 12,545 prospective women donors, showed a rejection rate of 17 percent (3). The rate was 10 percent for 6,000 first-time donors, which was the expected figure arrived at on the basis of a large series of determinations by the photoelectric cell colorimeter. On their initial appearance, only 0.3 percent of male donors were found to have hemoglobin values below the minimum of 12.3 gm. percent. The male rejection rate on re-donation varied from 0.2 to 8 percent. The rejection rate in female donors ranged from 12 to 55 percent.

No further changes were made in the minimum hemoglobin level during the remainder of the war.


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References

1. Robinson, G. C.: American Red Cross Blood Donor Service During World War II. Its Organization and Operation. Washington: The American Red Cross, 1 July 1946.

2. Minutes, meeting of Subcommittee on Blood Procurement, Division of Medical Sciences, NRC, 18 Aug. 1941.

3. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 2 June 1944.

4. Phalen, J. A.: The Blood Plasma Program. Division of Medical Sciences, NRC. Washington: Office of Medical Information, 1944.

5. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 13 July 1944.

6. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 10 Mar. 1942.

7. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 12 May 1942.

8. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 23 June 1942.

9. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 20 Oct. 1942.

10. Lozner, E. L., and Newhouser, L. R.: Studies on the Transmissibility of Malaria by Plasma Transfusions. Am. J. M. Sc. 206: 141-146, August 1943.

11. Taylor, E. S.: Procurement of Blood for the Armed Forces. J.A.M.A. 120: 119-123, 12 Sept. 1942.

12. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 18 July 1941.

13. What About Blood Donations by War Workers? A Discussion by the Medical Committee of Industrial Hygiene Foundation and Other Medical Specialists. Pittsburgh: Industrial Hygiene Foundation, April 1943.

14. Boynton, M. H., and Taylor, E. S.: Complications Arising in Donors in a Mass Blood Procurement Project. Am. J. M. Sc. 209: 421-436, April 1945.

15. Taylor, E. S.: Blood Procurement for the Army and Navy. Preliminary Report. J.A.M.A. 117: 2123-2129, 20 Dec. 1941.

16. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 17 Nov. 1943.

17. Fowler, W. M., and Barer, A. P.: Rate of Hemoglobin Regeneration in Blood Donors. J.A.M.A. 118: 421-427, 7 Feb. 1942.

18. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 5 Jan. 1944.

19. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 21 Apr. 1944.

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