Study of the Incidence and Characteristics of Blood Donor “Reactors”

KOBERT CALLAHAN, ELSA B. EDELMAN, MARY S. SMITH, JAMES J. SMITH From the Department of Physiology, Maryuette University School of Medicine

and the Milwaukee Blood Center, Milwaukee, Wisconsin

Analysis of “reactor” and control groups of blood bank donors reveals from a statistical standpoint younger donors, particularly female, with a previ- ous history O C Cainting are more prone to reaction. The “reactor” group had a tendency toward a higher pulse rate and pulse pressure and a lower diastolic pressure before bleeding. Race, blood type and body temperature did not influence the incidence of reactions. It was three times more likely for a one-time L‘reactor” to have a subsequent reaction than for a control donor. This distinct tendency toward multiple “reactors” makes it very probable that there exists a “reactor-prone” type. The funda- mental cause of the reaction as well as the defect in the “reaction-prone” donor are unknown. Closer study of “multiple reactors” would seem to be a profitable approach to the donor reaction problem.

A SIGNIFICANT number of apparently normal donors experience marked pallor, sweating, dizziness and even fainting and convulsions upon withdrawal of a pint of blood. Although there have been numerous speculations regarding the cause and mech- anism of this response, tangible evidence for any one theory is scarce. In order to explore this question of donor reaction, it was decided to analyze available records of the Milwaukee Blood Center in order to evaluate the incidence and characteristics of the response.

The records reviewed were those of indi- viduals who donated blood between 1958 and 1961 and were subjected to the routine procedures of the Center which handles approximately 50,000 donors per year. About half of these donate blood at the Center itself and the remainder at outlying bloodmobiles. For each donor, trained technicians and nurses under medical super-

Received for publication August 13, 1962; ac- cepted October 18, 19G2.

vision take a history and blood for typing and record oral temperature, blood pres- sure (ausculatory method) and pulse rate. If he has not eaten in the last four hours he is given a fruit juice drink. Individuals with an acute illness, a history of a blood transmissible disorder, blood hemoglobin below 12.5 Gm. per cent in females and 13.5 Gm. per cent in males, and those with evident circulatory disorders are not accepted.

Donors are usually bled within 15 min- utes to an hour after arrival at the Center. While lying flat on the phlebotomy table, a rubber tourniquet is placed firmly about the upper arm, an 18-gauge needle is in- serted into an antecubital vein and about 480 mls. of blood withdrawn into an evac- uated bottle containing 72 mls. of ACD solution. Bleeding time varies from about two to 12 minutes.

To obtain a closer estimate of actual bleeding rates, observations were made on 20 male and ten female donors. The male donors with an average weight of 83.7 f 11.0 kg. had a mean total bleeding time (for 480 mls.) of 3.57 =k 1.22 minutes; they were bled an average of about 5.7 ml./kg. at a rate of about 1.6 ml./kg./min. In the female donors averaging 67.7 k 8.5 kg. in weight, the mean total bleeding time was 5.98 % 2.18 minutes (through a smaller bore tubing). The average bled volume in the females was about 7.1 ml./kg. and the mean bleeding rate was about 1.2 ml./kg./ min.

Thus women are bled about 25 per cent more than men per unit body weight but

76

STUDY 01; 1)ONOR REACTORS 77

at a rate about 25 per cent slower on a bled volume per weight and time basis. Although there were some small variations among individuals, the bleeding rates in these 30 donors were surprisingly constant throughout the entire time of bleeding and a plot of mean volumes of blood withdrawn at different intervals versus duration of these intervals was linear.

General Incidence of Reactors

A tabulation of all the donors between 1958 to 1961 at the Milwaukee Blood Cen- ter (Table 1) indicates a donor reaction rate of 4.5 per cent with a significantly higher rate in females and also a higher rate if the blood is drawn at the Center rather than at an outlying mobile unit.

A “mild” reaction is arbitrarily classified as one with weakness and sweating, a “mod- erate” reaction involved dizziness, nausea or vomiting and in a “severe” case there was either fainting or convulsions; in most instances the reaction occurred during or within a few minutes after the blood with-

T A B L E 1. Donor Reactors at Milwaukee Blood Center Apri l I , 1958 to March 31, I961

To’rAL-Donations 139,260 TOTAL-Reactions 6,257 4.5

Males bled I 14,036 Male reactions

Females bled 25,224 Female reactions 1,358 5.4

Blood drawn-mobile units 72,201 Reactions at mobile units

Blood drawn at blood center Rcactions at blood center 3,263 4.9

Severity of reactions

67,059

Mild 4,079 65.2 Moderate 1,821 29.1 Severe 357 5.7

+**Chi Square significant at the 0.001 level of confidence.

3 Jon Fob Mot April May June July Aug Sspi Oci Nor Der

FIG. I . Mean: Donor reaction rate by month in period 1958-1961 (additional points show average rates for individual years).

drawal. Only rarely are these “delayed” reactions reported as occurring hours after the donation. As might be anticipated there was a predominance of the milder type of reaction.

A running graph of the mean monthly reaction rate for this three-year period is shown in Figure 1. There was a large amount of variation between the years but there are apparent tendencies toward peak rates in the months of April, July and November with relatively low rates prev- alent in January and September.

Study of Reactor Group In order to obtain further information,

an analjsis was made of a group of reactors and controls during a “normal” year, i.e. 1960. Of the approximately 2,000 “reac- tors” of 1960, the records of 872 and 870 controls were withdrawn from the files. For each reactor the next alphabetical name was taken as a control. All available data was coded, recorded on IBM cards and ana- lyzed at the Marquette University Com- puting Center with the help of an IBM 650 digital computer. T h e more relevant data from this analysis are summarized in Table 2.

It is evident that the “reactor” is younger and unmarried, with a significantly higher heart rate, with a significantly lower dias-

78 CALLAHAN, E T AL.

TABLE 2. Analysis of Random Group of “Reactors” and “Controls” from Milwaukee Blood Center Records of 1960

(Mean values and standard deviation of the distribution)

Control group Reactor group Significance S.D. S.D.

No. of subjects Age (mean)

Sex-Male Female

Race-White Colored

Marital status Married Single Other

Below 30 yrs. of age

Pulse rate (mean per min.) Art. blood pressure

(mean mms. Hg.) Systolic Diastolic Pulse pressure

Mean no. of prior donations (including present one)

No. of donors with at least one previous reaction

No. of donors with a t least two previous reactions

No. of donors with three or more previous reactions

870

358 (41.2%) 674 196 (22.57,) 847 23

33.6

652 I97 21 84.4

129.2 79.6 49.6 3.3

47 (5.473

5 (0.6%)

872

489 (56.1%) 673 199 (22.8%) 856

16

9.9 30.3

622 242

8 3.9 85.6

16.9 128.8 10.6 78.1 16.0 50.6 2.9 2.2

163 (18.7%)

31 (3.6%)

9.3 ***

N.S.

N.S.

t

3.6 ***

14.0 N.S. 10.9 12.7 N.S. 2.2 *I*

* #

tt t

ttt

tt ** “t” significant at the 0.01 level.

*** “t” significant at the 0.001 level. t Chi Square significant at the 0.05 lcvel.

tt Chi Square significant at the 0.01 level. ttt Chi Square significant at the 0.001 levcl. N.S. Difference not significant.

tolic blood pressure antl with a tendency toward a higher pulse pressure-at least prior to blood withdrawal. Also, the reac- tor group has given significantly fewer do- nations than the control group. Taking this finding into account, a further breakdown of these two groups reveals that even at the first donation, the reactor group is clearly younger.

There were no significant differences be- tween the control and reactor groups in distributions of blood types. Of the reac- tions experienced, 517 (59.8%) were mild,

294 (34.0%) were moderate and 54 (6.2%) were severe; t!ie frequency roughly paral- leled the incidence in the total group tabu- lated in Table 1. The mean body tempera- ture of the two groups was identical (in controls the mean was 98.27 F. f 2.95” antl in the reactors 98.27 F. f 3.02”). There were no differences in frequency of reaction between colored and white donors.

Reactor Type The tendency for “reactors” to have had

a previous reaztion is unequivocal; indeed i t is at least three times more likely that a

STUDY OF DONOR REACT’ORS 79

member of the reactor group (selected be- cause they had a reaction in 1960) will have had a previous reaction than it is for a member of a randomly selected group of donors. Stated somewhat differently, there is about one chance in six that a previous reactor will have another reaction com- pared to about one chance in eighteen ot a random donor having a reaction. Because of the relatively fewer total donations given by reactors as compared to controls, it is probable that this tendency toward “re- peat” reactions is conservatively estimated by these statistics.

Further breakdown of the data and com- parisons by sex yielded confirmatory statis- tical evidence that in reactors, diastolic blood pressure tends to be lower and pulse pressure antl heart rate higher. There is a tendency toward a lower systolic pressure but only among the female reactors. On the basis of our data, “multiple reactors” do not differ significantly in their hemo- dynamic patterns from the “one-time’’ reactors.

Body Weight

In considering the predisposition of cer- tain individuals toward a reaction, the question of body weight must be considered. It is known that the greater the blood with- drawn per unit body weight, the greater the stress, although the exact relationship between these two is not well defined. As mentioned previously it is evident that reactors are younger. Do reactors perhaps have smaller body weights and are they therefore inordinately stressed? Additional

information was obtained on this point by selecting 125 controls and 125 reactors from the groups described in Table 2 on the basis of random selection. These donors were then individually contacted for supple- mentary information including their weight and height. Replies were obtained from approximately half of each group and the results are summarized in Table 3. It is noted that while the controls tend to be older, taller and heavier, these differences are not statistically significant. A break- down of this sample by sex yielded similar results. Such a statistical result on a rather limited sample does not make it certain that the weight and height differences in our two groups are necessarily negligible lrom a physiological standpoint; it does strongly suggest, however, that these factors are not the critical variables in determining the occurrence or non-occurrence of reac- tion in the members of our two groups.

History of Fainting

In the course ol the medical history at the Milwaukee Blood Center, the donor is asked when antl under what circumstances he last fainted. A tabulation of all such cpisotles revealed that a history of fainting (regardless of the cause or circumstances) was present in 91 (10.4y0) of the 870 con- trols and in 169 (19.4%) of the reactor group. This difference as tested with chi square test is significant (p = 0.001).

A comparison was also made within the reactor group of the severity of reactions among the “fainters” antl “non-fainters” and the results shown in Table 4. It is

TABLF 3. .4ge, Height and Weight of n Rundondy Selected Group of Controls nnd Reuctors (Mean values antl standard deviation of distribution)

Controls Reactors

Number Age (years) Height (inches) Weight (Ihs.)

77 74 34.83 f io.nli 32.31 & 9.65 N.S. 69.48 2 3.22 GX.23 2 8.59 N.S.

1G8.17 2 27.28 163.65 f 23.87 N.S.

CALLAHAN, E T Al.. 80

I’ABLL 4. Incidence and Severity of Donor Reactions in Relation to Histoiy of Faiiztitig

Previous history Entire group of fainting

Control group 870 91 (10.4%) Males 674 (77.5y0) 44 (48.4%) Females 196 (22.5%) 17 (51.Gyo)ttt

Reactor group 872 169 (19.4%)

Females 199 (22.8%) 55 (32.6%) Males 673 (77.2%) 114 (G7.4%Jttt

Severity of Reactions-Reactor group Total 872 1G9

Type 1 520 (59.7%) 79 (46.7%)

Type 2 298 (34.2%) 75 (44.-I%)ttt Typc 3 54 (6.1%) 15 (8.97,)

ttt Chi Square significantly different from the “entire group” figure at the 0.001 level.

seen that not only do donors with a history of fainting have a higher reaction rate but also that the ensuing reactions are more severe. Fainting is more frequent among the female donors. It is also of interest that of the 872 reactors, 46 were perma- nently rejected as blood donors because of the reaction that occurred. Fifteen of these 46 had a history of fainting. Of 24 donors in the reactor group with convulsions, nine had a history of fainting.

Discussion

Two broad categories of conditions which affect the donor’s reaction to blood with- drawal can be postulated-the stress ex- ternally imposed upon the donor and the internal response of the donor to the stress. Age, height, weight, sex, amount of blood withdrawn and racial background are com- mon “stress” factors since these are external factors outside the control of the donor. Blood pressure, pulse pressure, heart rate, intrinsic and either physiological or psycho- common “response” factors since these are temperature, hemodilution and anxiety are logical. In such terminology, there is some overlap between “stress” and “response” factors; yet this distinction serves a useful

purpose when considering the question of the cause and mechanism of donor reactions to blood withdrawal.

The present study primarily examines “stress” factors in its analysis of a group of donor reactors and a comparable control group of donors. In reviewing the results, the data highlights the importance of sev- eral stress factors but emphasizes the ex- istence of a “reaction-prone’’ individual.

Incidence

The reaction ratc of 4.5 per cent found in this study is comparable to that occur- ring in most blood bank operations31 10.14

although rates as high as 10 per cent have been reported.’ When actual fainting is regarded as the cnd point, rates are more likely to be 1 per cent to 3 per cent.2, 11

Age, Sex and Race

Other studies support the significant find- ing that reaction rates are higher in the younger age groups4-6, 101 111 16 and in women.s+ 10, 14.16 However, one study re- ports no age differences between reactors and normals14 and three other studies no sex differences.4.6. 11 In our study, there was no difference in the reaction rate of colored and white donors but the number

STUDY OF DONOR REACTORS 81

of subjects in the colored group was com- paratively small. Graham has previously reported lesser reaction rates among colored donors.4

Site of Withdrawal, Temperature and Humidity

In a large number of blood donations over a three-year period, the reaction rate was significantly lower when blood was withdrawn at outlying “mobile units”; ac- counting lor such a difference is rather difficult though it is conceivable that the more informal and perhaps more person- alized approach at the outlying unit may be a factor as has been suggested by Moloney et al.1” in discussing relative reac- tion rates ol the two groups in their study.

The monthly reaction rates in our series though showing some peaks do not suggest any decisive climatic association. I t has been a long standing clinical impression that high heat and humidity predispose to fainting but the apparently very limited efforts that have been made to assess these factors do not bear this out.10, 11

Amount and Speed of Blood Withdrawal Previous investigators have established

beyond doubt that the amount of blood withdrawn is a major factor in determining the incidence of “fainting.”2, 7, 11, 12 The fainting rate varies from practically nil with a 250 ml. blood withdrawal15 to about 80 per cent if the bleecling approaches

In distinction to the amount of blood drawn, the speed of withdrawal within ordinary limils seems to exert only a doubt- ful effect on reaction rate. Brehm et aZ.2 in their study on blood withdrawal of rather large amounts of blood (811 mls. to 1,950 mls.) stressed the importance of withdrawal rate in causing collapse but their groups do not always have equivalent amounts of blood withdrawn. Poles and Boycott11 indi- cated that speed of withdrawal had no evident effect and Heckel et al.7 reported

1,200 mis.13

that cardiac minute outpul was apt to de- crease more with a faster withdrawal rate but that this factor seemed to have no appreciable effect on the reaction rate.

Fatigue and Blood Sugar Levels

Fatigue has been generally suggested as predisposing to fainting” but the tangible evidence is slight. Lawrence and Plaut found no relationship between blood glu- cose levels and incidence of fainting;* al- though i t is a common clinical feeling that fasting predisposes to reaction,6 neither the prior feeding of glucose11 nor fasting” had an apparent effect on the incidence of fainting.

History of Fainting

The prevalence of previous “fainters” in our reaction group indicates a definite asso- ciation between these two factors. Other authors have also noted this tendency and most have recommended rejecting donors with such a history.“), 14, 16

Multiple Reactors

The tendency 01 one-time reactors to have a second reaction seems unmistakable; this significant finding suggests that inde- pendent of extrinsic or “stress” factors, there exists a type of donor with a clear predisposition toward reaction.

Our statistical results would indicate that these individuals are usually under 30 years of age, female, unmarried, with a somewhat higher pulse rate and pulse pressure, a lower diastolic pressure and with a previous history of fainting. A higher pulse pres- sure3 and pulse rate3-4 have been previ- ously noted in fainters. Other investigators have also associated reaction tendency with “nervousness”3~ 4 9 6 and vasomotor instabil- ity.16 Graham4 has suggested that fainting is a biphasic response, the first phase being the anxiety and the second being the vaso- vagal storm9 resulting in an abrupt drop in peripheral vascular resistance and brady-

CAl.I.AHAN, E T AL. 82

cardia,’ which represents the second phase or relief from anxiety.

Such a description of a “donor reactor” lacks sufficient definition from a statistical standpoint to be ol practical use in blood bank operations. However, one implication of this study-namely the existence of a reaction-prone individual-is that closer in- vestigation of the response factors, physio- logic and psychologic, would allow clearer understanding of the determinants of such reactions.

Acknowledgments

I t is a pleasure to acknowledge the encour- agement and assistance of Dr. T. J. Greenwalt, Medical Director, Mrs. Virginia B. Jefferson, Executive Director and the Staff of the Mil- waukee Blood Center as well as that of Miss J o h n Hanke and the staff of the Marquette University Computer Center for notable as- sistance with the statistical analysis.

References 1. Barcroft, H. and 0. G. Edholm: On the vaso-

dilatation in human skeletal muscle during post-hemorrhagic fainting. J. Physiol. 104: 161, 1945.

2. Brehm, H., A. G. Gathof, and J. Krzywanek: Experimentelle Untersuchungen iiber die Ent- stehung des Rlutspenderkollapses und dessen Verhiitung. Metl. \Yelt 51: 2700, 1960.

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Brown, II. and P. McCormack: An analysis of vasoniotor phenomena occurring in blood donors. Brit. Med. J. 1: 1, 1942.

Graham, D. T.: Prediction of fainting in bloocl donors. Circulation 23: 901, 1961.

Greenbury, C. L.: Analysis of incidencc of “fainting’ in 5,897 unselected blood donors. Brit. Med. J. 1:253, 1942.

Hasse, \V.: Vorkommnisse beim Blutspender wYhrend und nach der Blutentnahme. Bibl. Haeinat. 5: 151, 1956.

Heckel, K., C. G . Bar and K. T. Schricker: 0 ber Kreislaufverlnderungen wiihrend des Atlerlasses. Aertzl. Wschr. 13: 523, 1958.

I.awrence, B. J . and G. Plaut: T h e effect of bleetling on the blood-sugar levcl .in bloocl donors. Brit. Med. J. 4: 8, 1942.

I.cwis. T.: Vasovagal syncope and the carotid sinus mechanism. Brit. Med. J. 1: 873, 1932.

Moloney, W. C., I.. R. L.onnergan and J. K. McClintock: Syncope in bloocl donors. N. Engl. J . Med. 234: 114, 1916.

Poles, 1:. C. and M. Boycott: Syncope in hloocl donors. Lancet 2: 531, 1942.

Shenkin, H. A., R. H. Cheney, S. R. Govons, J . D. Hardy, A. G. Fletcher and I. Starr: On the diagnosis of hemorrhage in man. Am. J. Med. Sci. 208: 241, 1944.

Stead. E. A,: Physiological adjustments of nor- mal subjects to sudden loss of blootl. J. Clin. Invest. 1 9 776, 1940.

Subcommittee of the Blood Transfusion Re- search Committee: Fainting in blood donors. Rrit. Med. J . 1: 279, 1944.

Talwar, C. L., C. P. Sawhney and B. S. Handa: Effects of blood letting on donors. Indian J . Med. Sci. 13: 206, 1959.

\Yilliams, G. E. 0.: Syncopal reactions in blood donors: Investigation of 222 cases. Brit. Sled. J . 1: ?83, 1942.

Comprehensive Laboratory Survey Under Auspices of College of American I’athologists

Nationwide surveys held each year under the auspices of the Standards Committee, College of American Pathologists are a means of evaluating status of laboratory procedures. After each survey appropriate recom~nendations arc made by the Com- mittee and by a National Advisory Council appointed to review results. Furthermore, comparison of data from one survey with those of preceding years allows the Com- mittee to evaluate the effectiveness of its programs directed to areas where deficiencies are known to exist. Participating hospitals bcnefit in that the survey is a means of checking the accuracy and precision of their procedures with laboratories throughout the country. Growing interest in the Survey Program has prompted the Standards Committee to offer a Comprehensive Laboratory Survey in May 1963. This survey is designed to evaluate procedures in immuno-hematology, bacteriology, parasitology, antl chemistry. Specimens will be provided for the following studies: serum bilirubin (2 samples), cholesterol (2), sodium, potassium, carbon dioxide, urea: hemoglobin (2); blood group and type (2); blood smear evaluation; spinal fluid protein antl

chloride; stool culture: parasite identification. All Pathologists and Laboratory Directors will be invited to participate. Inquiries

may be addressed to: Comprehensive Survey, College of American Pathologists, I’rutlential Plaza, Chicago 1, Illinois.