Donor reactions and injuries from whole blood donation

Donor Reactions and Injuries From Whole Blood Donation Bruce H. Newman

OMMON and uncommon blood donor reactions and injuries that result from whole blood donation are listed in Table 1. Vasovagal reaction is the most common systemic reaction, and hematoma/bruise is the most common donor injury. Other reactions and injuries are much less common. Donor reactions and injuries are transient, self-limited events. Donors virtually always recover. In very rare exceptions, a donor may sustain permanent damage. The prevalence, characteristics, cause, and clinical significance of donor reactions and injuries is the subject of this review.

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OVERALL PREVALENCE

Based on the data available, 11% to 21% of the blood donor population may have a reaction or injury from their whole blood donation. This includes 9% to 16% who develop a bruise or hematoma, 1,8,9 2% to 5% who have vasovagal symptoms, 27 and less than 0.5% who develop other injuries or reactions. The likelihood of a blood donor sustaining a reaction or injury is unknown. Determination of an exact figure requires documentation of all injuries and reactions, including mild ones. Good telephone followup is required because some donor injuries and reactions occur after the donor leaves the collection site. A few studies in the literature have good follow up. In a 1940s study of 40,000 blood donations using postdonation followup cards, 18% of the donors had one or more complaints.1 Nine percent of the donors had a complaint that related to the mechanics of the venipuncture; overwhelmingly, most complained of a hematoma or bruise. Ten percent complained of vasovagal symptoms, and 4% complained of a lower energy level and the need to limit their activity for a few days after blood donation. Other studies suggest the percent-

From American Red Cross Blood Services, Southeastern Michigan Region, Detroit, Michigan. Address reprint requests to Bruce H. Newman, MD, Medical Directog American Red Cross Blood Services, SE Michigan Region, 100 Mack, Detroit, M148201. Copyright 9 1997 by W.B. Saunders Company 0887-7963/97/1101-000853.00/0 64

age of donors with vasovagal symptoms is much lower, in the 2% to 5% range. 2-7 In two recent studies of blood sample phlebotomy, one in life insurance candidates (n = 4,050) 8 and the other in patients from 630 hospitals (n = 23,700), 9 followup data was collected by telephone or postcard. The prevalence of a hematoma or bruise was 12.3% and 16%, respectively. In the study involving 4,050 life insurance candidates, the syncope rate was 0.69%, whereas in a larger study of 16,200 patients, the syncope rate was 0.16%. 8,m These rates are comparable to reported syncopal rates from whole blood donation. TYPES OF REACTIONS AND INJURIES

Vasovagal reaction Clinical symptoms and reaction classification. Common symptoms and signs of a vasovagal reaction are pallor, lightheadedness, anxiety, diapheresis (perspiration), hyperventilation, irregular breathing, weakness, nausea, vomiting, hypotension, and bradycardia (slow heart rate). The symptoms of a vasovagal reaction usually develop suddenly and generally tend to occur at the end of the phlebotomy or shortly after its completion. In a small percentage of reactions, 3% to 15%, the reaction occurs after the donor leaves the donation site. TM Thus, in some cases, the donor has the reaction back at work, at home, or in other locations. Within American Red Cross blood centers, vasovagal reactions are classified as mild, moderate, and severe. 12 A mild reaction includes any of the above symptoms. If the donor loses consciousness (syncope) or the recovery period is greater than 15 minutes, the reaction is graded as moderate. If the donor develops incontinence, tetany, convulsions, or cyanosis, with or without syncope, the reaction is graded as severe; although severe reactions do not require syncope in fact, virtually all donors with severe reactions have syncope. Prevalence. Although most studies have documented the prevalence of vasovagal reactions to be between 2% and 5%, 2.7 three studies documented higher rates, s,13,14 and one study documented a lower rate, although in the latter the routine volume collected was only 200 mL. 15 Many studies did not Transfusion Medicine Reviews, Vol 11, No 1 (January), 1997: pp 64-75

BLOOD DONOR REACTIONS AND INJURIES Table 1. Classification and Prevalence of Donor Reactions and Injuries Prevalence

Systemic Injury Vascular Vasovagal reaction Vasovagal reaction with syncope Angina, myocardial infarction, stroke

2%-5% 0.1%-0.3% 0.0005% (est)

Local Injury Vascular Hematoma Arterial venipuncture Arterial pseudoaneurysm Arteriovenous fistula Compartment syndrome Neurologic Needle injury Other Local irritation/allergy to tape/antiseptic solution or history of same Local infection Th rombophlebitis/phlebitis

9%-16% 0.001% (est) Rare Very rare Very rare 0.016%

0.5% (est) <0.0005% (est) 0.001%-0.002% (est)

Abbreviation: Est, estimate based on interviews with collection supervisors and collection managers.

address the overall reaction rate but addressed in reaction rates of subset groups such as age, gender, and weight. 16-19 Some studies addressed only specific donor groups such as autologous blood donations, 2~ blood donations by the elderlyY or in those on medication. 26 More recent studies have addressed the subset of moderate and severe vasovagal reactions, which generally includes all donors with syncope. Syncopal reactions are well documented by blood collection organizations. The prevalence of moderate and severe donor reactions has ranged from 0.08% to 0.34%. 27-33 In an informal survey of seven American Red Cross blood centers which collected 1.27 million units in 1994, the moderate/severe donor reaction rate was 0.23%, and the reaction rate varied from 0.10% to 0.34%. The wide variation in the donor reaction rate among the seven blood centers with similar collection protocols is of interest. The variation may relate to differences in the behavior of the blood collection staff, donor demographics, and the use of chairs versus flat beds. Sixty-nine percent of the reactions were moderate, and 31% were severe. No donor reactionrelated deaths were reported in any of the seven blood centers. 33 In an evaluation of 75 severe donor reactions in

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Detroit, most donors had tetany or convulsions whereas incontinence was less common; specifically 54 donors had tetany, 16 convulsions, and 17 incontinence. When tetany occurred, it always ended within 2 minutes and in 32 of 41 cases, it ceased within 30 seconds. Predictive factors. One cannot predict with certainty which donors will or will not have a reaction. There are demographic, physical, psychological, and environmental factors that place a donor at higher risk for a reaction, but in general, these factors have a low predictive value, so even when present, the donor is still unlikely to have a reaction. In contrast, a frequent donor may on occasion have a reaction after many asymptomatic donations. There are at least 27 clinical studies that have evaluated internal and external factors affecting donor reaction rates. 1-7,11,13-23,25-32 Many of these studies were done during or shortly after World War II. Table 2 summarizes the factors that definitely increase the donor reaction rate, factors that probably increase the donor reaction rate, and factors that have no effect on the donor reaction rate. In addition, studies outside of the blood donation setting have noted that exhaustive exercise and certain medications or drugs such as nitrates, furosemide, and alcohol can increase the rate of vasovagal reactions. 34,35 Vasovagal reactions can be triggered by pain, Table 2. Predictive Factors for Vasovagal Reactions in Blood Donors Definitely Associated With Increased Reaction Rates Young age History of previous reaction Anxious (first-time donor) Low weight Epidemic fainting Inattentive or noncommunicative phlebotomist Probably Associated With Increased Reaction Rates Fatigue Lack of food for more than 5 hr Extremes in temperature or humidity Low blood pressure No Effect on Reaction Rates Speed of blood withdrawl Body build Menstruation Hemoglobin level Hypoglycemia "time of the year Gender* Note: *According to most studies

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fear, or any strong emotion. There is a strong psychogenic component associated with blood donation-related vasovagal reactions. For instance, some blood donors faint even before blood collection begins. This is an obvious psychological reaction based on a phobic fear of needles, pain, or the sight of blood. Epidemic fainting, when donors faint in response to seeing other donors faint, may also occur. Hyperventilation is more common in anxious donors, and when present, it can cause or potentiate a donor reaction. Hyperventilation can be recognized as faster breathing, deeper breaths, or an irregular breathing pattern. As a result of hyperventilation, excessive carbon dioxide is exhaled, which causes a decrease in the body's carbon dioxide level and an increase in pH. Both decreased carbon dioxide levels and elevated pH can cause cerebrovascular constriction which decreases the blood supply to the brain. It takes only 1 or 2 minutes of hyperventilation to cause a 40% decrease in the brain's blood supply? 6 This in turn can cause or potentiate dizziness or fainting. Young blood donors, especially those under the age of 20, are much more likely to faint than donors over the age of 30. This has been documented in many studies, 1,2,4-7,11,! 3-! 5,28 including a recent multicenter study in which the moderate/severe donor reaction rate was 10- to 14-fold higher in donors under 20 years. 3~ Some have attributed this phenomenon solely to survivorship of nonreacting donors, but Tomasulo et al 7 evaluated first-time donors and showed clearly that age itself was a key factor. First-time male donors over the age of 50 had a reaction rate of 1.1%, whereas first-time male donors under the age of 30 had a reaction rate of 5.3%. This represents a fivefold increase in the donor reaction rate in younger donors. Similar but less pronounced findings were also found in firsttime young female donors. With increasing age, the body becomes more stable hemodynamically. Neurologic studies have shown fewer vasovagal reactions in elderly individuals compared with young patients. 37-4~ Also, elderly subjects have fewer vasovagal reactions when subjected to a postural tilt test, a test that is designed to induce vasovagal reactions in susceptible individuals. 4~ Low donor weight is another factor associated with increased donor reaction rates. 7,1~,% Donors who weigh close to 110 lb, the minimum acceptable weight in the United States, have a higher

BRUCE H. NEWMAN

probability of a reaction when 450 mL of blood is collected. Although some studies attributed a higher reaction rate to thin body build, it's most likely that low body weight, not build, that is responsible. Similarly, low body weight is largely responsible for reaction rate differences between women and men. Collection of a larger volume also influences donor reaction rates. In one study, the volume collected was changed from 440 mL to 540 mL and the reaction rate increased from 3.8% to 8.5%. 11 In another study, changing the volume collected from 250 mL to 500 mL in donors who weighed less than 150 lb was largely responsible for a doubling of the reaction rate, from 2.3% to 5.7%. 5 In contrast, in a Japanese study in which the collection volume was a mere 200 mL, the donor reaction rate was low, I. 1%. J5 Although our present collection volume is 450 mL _+ 45 mL, most blood centers may switch to a 500 mL +_ 50 mL collection. Although this seems to be a 50 mL increase, it is less because the total volume collected, including the additional sample for postdonation testing, cannot exceed 550 mL. New York Blood Center, in 1994, reported no significant increase in the rate of vasovagal reactions after switching from a 450 mL to 500 mL collection volume (1.28% v 1.36%), nor was any significant increase in moderate and severe reactions found. The center concluded that the change from 450 mL to 500 mL did not have any significant impact on donor reaction rate. 3~ In addition to these factors, there is also individual susceptibility. A history of a past donor reaction places the donor at higher risk for another reaction. 5,6,17,18,27 Brown, et a117 noted that half the donors who fainted had a history of a previous faint in their lives. An English study found that donors who fainted were much more likely to have had a previous history of fainting during a blood donation than controls, 30-43% versus 1-5%. is Nonetheless, having had one reaction does not mean the donor will have a second reaction, and donors with a history of a reaction are generally permitted to donate. A very important factor influencing donor reaction rate is the attitude and actions of the collection staff. Several studies have shown that spending more time with donors decreases the rate of vasovagal reactions. 5,~3,15 Williams ~3 in 1942 noted a lower donor reaction rate in two of four hospitals where the phlebotomy staff spent more time with donors. Maloney 5 in 1946 noted lower reaction

BLOOD DONOR REACTIONS AND INJURIES

rates when more attention was given to donors and when rest times after the phlebotomy were longer. Finally, Ogata et a115 in 1980 noted that talkative, personable nurses had a lower donor reaction rate than noncommunicative nurses, 0.8% versus 1.3%.

Differences between reactors and non-reactors. The difference between reactors and nonreactors was best described by Philip Ruetz et aP 2 in a study published in 1967. They compared 10 volunteer donors who had at least two donor reactions with 10 volunteer donors who never had a donor reaction. The donors were matched for age, gender, and weight. Both groups underwent psychological tests, a medical history, cardiovascular tests, laboratory tests, and a 480-mL phlebotomy. Psychological tests in both groups were normal, but there were differences between the two groups. The reactor group showed more hypochondriasis and depression. They had heightened awareness in general, were overly concerned with their bodily functions, and were more prone to feelings of uselessness and pessimism. The authors found they could distinguish between the two groups with a 6% error rate with 28 questions from the Minnesota Multiphasic Personality Inventory test. The medical history did not reveal any differences between the two groups, nor did the cardiovascular tests. All laboratory tests were essentially the same in the two groups except that pre- and postphlebotomy alveolar carbon dioxide levels were decreased in the reactor group. This meant that donors in the reactor group were more prone to hyperventilation. The difference in CO2 levels became even more pronounced after phlebotomy. During the actual phlebotomy, 8 of 10 donors in the reactor group had a vasovagal reaction, whereas only 1 of 10 donors from the nonreaction group had a reaction. The reactor group's systolic blood pressure, mean arterial blood pressure, and heart rate were significantly lower during the postphlebotomy period. To summarize, the study showed psychological differences between the two groups, hyperventilation in the reactor group both before and after blood donation, and a lower systolic blood pressure, mean arterial blood pressure, and heart rate in the reactor group after the phlebotomy. These data suggest that donors with a history of two or more donor reactions differ from donors with no history of donor reactions and that hyperventilation plays an important role in the reaction.

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In a very recent study, 20 male blood donors with two or more donor reactions were compared with 20 male controls. 43 In response to pain, the reactors had a blunted blood pressure response, and paradoxically, their heart rate decreased. The study showed that baroreceptors, which help maintain blood pressure, were less sensitive in the reactor group. The author concluded that susceptibility to vasovagal reaction may be associated with decreased baroreceptor sensitivity. Of interest, several studies show that baroreceptor sensitivity is also decreased in healthy young subjects when such individuals are physically or psychologically s t r e s s e d . 44-46

Clinical pathophysiology. The classic vasovagal reaction is thought to be biphasic. In the prodromal stage, the donor's heart rate is increased and the blood pressure is slightly to moderately elevated. This is a normal response to stress and blood volume reduction. However, in a vasovagal reaction, this response is followed by vascular vasodilitation and bradycardia. The vascular vasodilitation causes hypotension and the onset of symptoms. Whatever triggers the vasovagal reaction affects the hypothalamic portion of the brain that then causes the reaction through the autonomic nervous system. Two different neural pathways can stimulate the hypothalamus. In the central pathway, emotions, pain, or stress directly affect the brain, which then stimulates the hypothalamus. This pathway explains why a donor can faint when just thinking about the donation. The second pathway, the peripheral pathway, refers to the effects of peripheral pressure receptors, known as baroreceptots, on the hypothalamus. Baroreceptors are found in the aorta, carotid arteries, and the left ventricle of the heart. The ventricular baroreceptors are the most important. When stimulated by forceful heart contractions or heart distention, the ventficular baroreceptors initiate what is known as the BezoldJarisch reflex. This refers to increased parasympathetic vasovagal output to the heart and decreased sympathetic output to the vasculature in the muscles and viscera. 47-5~The decrease in sympathetic tone to blood vessels has been verified in humans by a low or blunted norepinephrine response, and measurements of sympathetic electrical activity in selected muscles in animals have shown a decrease during a vasovagal reaction and a return in activity when the reaction is over. 5~56 The net result is

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bradycardia and peripheral pooling of blood. The pooling of blood causes hypotension and the onset of symptoms. The main feature of the vasovagal reaction is peripheral blood pooling and hypotension. If the hypotension decreases the brain's blood supply, the donor becomes dizzy, weak, and anxious. When the systolic blood pressure falls below 70mm to 80mm Hg, the donor faints. 59 The greater the hypotension or the longer the hypotension, the more likely the development of either tetany or convulsions. 6~Both result from cerebral hypoxia. Incontinence can also occur but is less common. Incontinence may be related to cerebral hypoxia or it may be related to the active autonomic nervous system because the autonomic nervous system controls the bladder and anal sphincters. Perspiration, nausea, and vomiting can be from either hypotension or stimulation of the autonomic nervous system. Again, the autonomic nervous system controls the sweat glands and the activity of the gut or intestines. Blood is also shunted away from the skin toward the muscles, which explains the donor's pale appearance. Investigators originally thought bradycardia was a major cause of vasovagal reactions, but this has been disproven. In patients experiencing a vasovagal reaction during cardiac catheterization or when reactions were induced, atropine increased the heart rate but did not affect the hypotension or reverse the symptoms. 48,52,57,58 Thus, it seems that bradycardia is not the cause or only has a minor role in causing symptoms. Clinically, a severe vasovagal reaction resembles a patient in shock because the donor is unconscious, appears pale, and may have a thready, barely palpable pulse. However, there are significant differences. In a vasovagal reaction the heart rate is often slow, not fast, cyanosis is rare, and the process spontaneously reverses itself, unlike patients in shock where the process is generally irreversible unless treated. What ends a vasovagal reaction is increased blood supply to the brain. This results when the donor falls to the ground or the collection staff places the donor in a flat or legs-up Trendelenburg position. Eventually the muscular tone in the donor's vasculature returns to normal, and the donor recovers. The teleogical significance of the vasovagal reaction is unclear. As noted, the reaction is paradoxical; one would expect vasoconstriction not vasodilitation in response to a 450mL phlebotomy.

BRUCE H. NEWMAN

A potential explanation may be cardiac protection as the vasodilitation and bradycardia significantly reduces the myocardial oxygen demand. 61Also, the supine position improves cardiac refill and may lead to faster restoration of arterial blood pressure. 62 Treatment. Treatment varies depending on whether the reaction is mild or severe. For mild reactions, it is important to observe the early symptoms because it is possible to reverse the reaction. The phlebotomist's first actions in a mild reaction is to place the donor in a Trendelenburg position and to try to change the donor's breathing pattern. Removing the donor's pillow and raising the donor's legs is a practical means of establishing a Trendelenburg position. One can change the donor's breathing pattern by having the donor cough, hold his breath for 5 seconds, or breathe into a paper bag. The last method may be preferable because it increases the donor's carbon dioxide level. A third action is to physically stimulate the donor with a cold towel around the neck and/or ammonia salts. Nausea can be treated with cola soft drink syrup, which inhibits vomiting, but a handheld basin should be present. Talking to the donor and diverting the donor's attention can also alleviate or reverse the reaction. Only a minority of donor reactions progress to syncope. Severe reactions with syncope, hypotension, and thready pulse can be frightening. When tetany, convulsions, or uncontrolled movements are present, the phlebotomy needle should be removed to prevent harm to the donor. One should also keep the donor from falling off the bed and make sure the airway is intact. After an intact airway is assured, it is important to get the donor into a Trendelenburg position. Cardiopulmonary resuscitation is rarely if ever needed. Although transfusion or intravenous fluids can ameliorate the reaction, starting an intravenous line is rarely needed and generally unnecessary. Blood pressure, pulse, skin color, and mental status should be monitored until the donor is fully recovered. After the reaction, the donor's status should be assessed. Donors who have convulsions rarely hurt themselves; tongue, lip, and needle injuries are possible but rare. Any serious injury such as a fracture or laceration should be referred for immediate medical attention. Closed head injuries should be referred to an emergency center if there is suspicion of a skull fracture or internal injury or if

BLOOD DONOR REACTIONS AND INJURIES

the donor's mental status has changed. If donors with head trauma are sent home, they should be watched carefully by family members for 24 hours for any neurologic change, which should precipitate an immediate visit to the emergency room. Donors should be well-oriented before being sent home. Side effects. The most serious and significant side effect from a vasovagal reaction is a fracture and/or laceration which occurs, when the donor, hits a hard or sharp surface during a fainting. Boynton was aware of 108 scalp and head lacerations, 18 chipped teeth, 5 nose fractures, 2 skull fractures, 3 mandible fractures, 2 finger fractures, 1 fracture of the malar bone, and 1 fracture of the humerus bone.1 American Red Cross National data are similar. 63 It seems that blood donation-related vasovagal reactions rarely, if ever, cause donor deaths. None of three whole blood donor deaths that were reported to the Food and Drug Administration between 1976 and 1985 was associated with an acute vasovagal reaction. 64 To the reviewer's knowledge, no syncopal vasovagal reaction has ever progressed to death. However, cardiac arrests after venipuncture for sample collection have been reported. 65-69 Prevention. Some donors are at higher risk for a vasovagal reaction; these include young donors, first-time donors, and donors who weigh between 110 and 120 lb. Although at higher risk, such donors are usually accepted for blood donation because of the lack of serious sequelae from a donor reaction, because of the fact that most donors in these risk groups will do fine, and because of the chronic need for blood. In general, donor reactions can be prevented by careful and attentive care of the donor from the time the process begins and until the donor departs from the blood donor clinic. 7~Talking to the donor and displaying empathy and warmth while taking care of physical needs inspires confidence and keeps the donor from thinking too much about the donation. The donor's desire to speedily complete the donation process must be balanced with sufficient postdonation rest to minimize reactions. Finally, it is critical that phlebotomists be aware of each donor's mental and physical status so reactions can be quickly recognized and reversed. 4,7~ Pharmacologic agents are not used but can influence donor reactions. In a retrospective study, donors on beta-blocker medication for hyperten-

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sion had a lower donor reaction rate than the general donor population. 26 Beta-adrenergic blockers have a negative inotropic effect and prevent activation of the ventricutar baroreceptors. Other potentially effective agents are scopolamine and disopyramide. Scopolamine has a central depressant effect, and disopyramide has a negative inotropic effect and anti-cholinergic and vasoconstriction properties. These agents significantly decrease reactions during tilt tests and are potentially useful in patients with frequent or severe vasovagal attacks. 71-75In theory, one could also prevent a donor reaction in a very high risk donor with one of these agents.

Serious Systemic Sequelae Associated With Blood Donation (Angina, Myocardial Infarctions, Strokes) Boynton and Taylor ~ reviewed their experience with 7 million blood donations during World War II. No deaths attributable to a cardiovascular cause occurred at any fixed or mobile site. Ten deaths did occur within 48 hours of donation in middleaged donors (age range, 44-58 years) and are detailed in the paper. ~ The deaths were considered to be coincidental. This was supported by life insurance tables that predicted a higher rate of coincidental deaths based on natural causes. In addition, eight donors did not die but developed significant morbidity within a couple of hours of blood collection, including four donors who developed symptoms during the donation. Of the eight donors, four developed a stroke, two developed angina, one developed a myocardial infarction, and one developed congestive heart failure.~ Of interest, six of eight donors would have been deferred by today's Standards from the American Association of Blood Banks because of elevated blood pressure (three donors) or elevated pulse (three donors). 76 It seems that blood donation practices today are more likely to prevent serious acute morbidity. This reviewer is aware of one donation where it appears the donor died during a donation from a "coronary artery occlusion ''77 and a second donation in which the donor had a myocardial infarction during a blood donation and later died. 78 Exact information on the two cases is not readily available, but both appear to be related to myocardial infarction, not vasovagal reactions. Popovsky et al23 recently evaluated 4.1 million American Red Cross blood donations collected

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from July 1993 through March 1994 for serious reactions, defined as reactions requiring hospitalization. Thirty-three donors were hospitalized for significant reactions or injuries. The reasons for hospitalization were vasovagal reaction (73%), angina (12%), and a variety of local injuries (15%) that included compartment syndrome, arteriovenous fistula, phlebitis, and pseudoaneurysm. Although most reactions occurred during the donation process, one third occurred after the donor left the donation site. Hospitalization averaged 2 days, and no deaths occurred. The incidence of hospitalization was almost 12 times greater for autologous blood donors than allogeneic blood donors (1 in 17,000 autologous donors v 1 in 200,000 allogeneic donors). There was also a preponderance of older donors in the autologous group; 48% were older than 60 years in comparison to 4% in the allogeneic donor population. In all, this study provides good information on the incidence of donation-related hospitalizations and shows that autologous and older blood donors are at greater risk for serious reactions than allogeneic blood donors. In summary, practically all blood donationrelated deaths seem to be coincidental events. Although coincidental deaths do occur, they are less likely in allogeneic blood donors than the general population because blood donors are generally healthier. 1

BRUCE H. NEWMAN

ment of a hematoma is direct pressure. A Coban pressure bandage (3M-Medical Surgical Division, St. Paul, MN) can be used for 1 hour after donation. Like all donors, those with a hematoma or bruise should be advised not to do heavy exercise or lifting with the phlebotomized arm for at least 6 hours. This minimizes the risk of breaking the hemostatic seal and developing or enlarging a hematoma.

Accidental Arterial Venipuncture Rarely, an experienced phlebotomist will accidentally puncture the artery instead of the vein. This can be recognized easily because the blood is brighter red than usual, the plastic bag fills rapidly, the needle moves with each heart contraction, and the donor may complain of severe or unusual pain. Unlike a vein that has a thin wall, an artery has a thicker wall that makes it stiff and noncollapsible. A concern with an arterial stick is ongoing blood leakage. Possible complications from leakage are pseudoaneurysm, arteriovenous fistula, and a compartment syndrome. To minimize the possibility of leakage, the phlebotomy must be discontinued immediately and pressure must be applied to the phlebotomy site for at least 10 minutes to help ensure a good hemostatic seal. Afterwards, a pressure bandage must be applied. If these steps are followed, the prognosis for full and immediate recovery is excellent.

Hematomas (bruises) Hematomas are very common after blood donation. Most are noticed after the donor leaves the donation site. The incidence ranges from 9% to 16%.1,8,9 Although hematoma is a self-limited event, the donor may be concerned, especially if the hematoma is associated with a sore arm or the involved area is large or swollen. Hematomas are more common when phlebotomists are untrained, have poor technique, or fail to select the best vein. Having the tourniquet on too tight may increase hematomas. Needle bevel shape and needle size have also been implicated. 79 Donor reactions and a harried environment can also increase the prevalence of hematomas. A hematoma during the donation is often associated with poor blood collection flow or donor discomfort. If the hematoma is small, not growing, and there is no patient discomfort, it may be possible to collect the unit of blood. 8~ Otherwise the blood donation should be discontinued. Treat-

Brachial Artery Pseudoaneurysm Pseudoaneurysm results from leakage of arterial blood as a result of traumatic needle puncture to an artery. On an arteriogram, the collection of blood appears to be an aneurysm, but because there is no vascular wall but just adventitia or surrounding tissues, the lesion is considered a pseudoaneurysm. The lesion is very rare but still more common than an arteriovenous fistula or compartment syndrome, Four of 13 blood center medical directors reported seeing one pseudoaneurysm in their careers, but none had seen an arteriovenous fistula or compartment syndrome. 8 Three pseudoaneurysms were documented in the transfusion medicine literature in the last 2 years, 82-84 and the reviewer is aware of six additional unreported cases. The three reported cases resulted from an accidental puncture of the brachial artery. Two cases were documented as difficult phlebotomies with the phlebotomists unaware that they had

BLOOD DONOR REACTIONS AND INJURIES

performed an arterial venipuncture. The donors developed hematomas and significant blood leakage, and two donors developed paresthesias. Symptoms waxed and waned in the three donors over an extended period of time ranging from 2 weeks to 2 months. Each donor eventually developed a pulsating mass at the point of leakage. Vascular surgery was performed 2 to 8 weeks after blood donation for arterial repair, evacuation of the clot, and relief of symptoms. The donors recovered completely, and peripheral nerve symptoms were reversed.

Arteriovenous Fistula An acquired arteriovenous (AV) fistula can result from penetrating trauma whereby the vein and artery are lacerated and a channel forms between the two vessels either immediately or during the healing process. An AV fistula often presents as a pulsating mass with an associated bruit and palpable thrill because of turbulent blood flow between the artery and vein. Both the bruit and thrill are accentuated with each heart contraction. Distal veins may be dilated and may pulsate. The affected area is warm because of increased blood flow, and the distal part of the limb may be cool if significant shunting of blood is present. An acquired AV fistula after blood donation is extremely rare. A single case was reported in 1971, and the author of the article was unable to find any other case in the world literature up to 1971. 85 In the 1971 case, a 25 year-old male soldier presented during a routine military physical examination with a loud bruit and a palpable thrill over the antecubital fossa area. No venous distention was noted. The patient had donated a unit of blood 6 months earlier, and the records indicated the blood container had filled rapidly, suggesting an arterial venipuncture. The AV fistula was shown with an arteriogram. The fistula was surgically repaired without complications. Another case requiring hospitalization was reported to American Red Cross National Headquarters from 23 million blood donations during a 4-year period. 63 In this case, a male donor donated without incident but complained 3 days later of bruising, stiffness, and soreness of the left arm and swelling at the wrist. Because the swelling persisted, his physician referred him to a cardiovascular surgeon who diagnosed an AV fistula 3 weeks after his blood donation. A pseudoaneurysm was also noted. The patient underwent

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surgery and recovered without further complications. Surgical treatment of an AV fistula is indicated to restore adequate circulation to the distal limb. The timing of surgery may be dictated by the patient's clinical state. If the patient has significant symptoms threatening the limb, immediate surgery is indicated. If the patient's condition is stable, the condition of the limb is optimized and time is allotted for collateral arterial development before surgery is initiated. The goal of surgery is to close the AV fistula and reestablish blood flow in both the artery and vein. The long-term prognosis after direct visual repair is excellent, s6 88

Compartment Syndrome Compartment syndrome after blood donation results from blood leakage. The leakage of significant amounts of blood into a closed cavity eventually leads to increased intracompartmental pressure that causes vascular ischemia as capillaries and small venules close; this may lead to muscle and nerve tissue necrosis. Clinical symptoms and signs include a tense swollen fascial compartment, pain when the limb is moved, and paresthesias and partial paralysis, s9-92 The condition is very rare after blood donation. The reviewer was unable to find a single case in the English literature. However, one case was reported to American Red Cross National Headquarters from 23 million blood donations during a 4-year period. 63 In this case, a 71-year-old female developed swelling at the venipuncture site 1.5 minutes into the donation. The venipuncture was stopped, and 10 minutes of pressure was applied, followed by application of a pressure bandage. Within 4 hours, the donor lost feeling in her right arm and was hospitalized. A 10- • 5- • 3-cm hematoma was identified under the right bicep muscle. The hematoma was surgically evacuated, and a fasciotomy of the upper arm was done. There was no evidence of an arterial venipuncture. Full recovery was expected. Compartment syndrome is diagnosed based on the patient's clinical symptoms. Distal pulses and capillary refill are unreliable indicators of intracompartmental pressure, and the value of direct intracompartmental pressure measurements is controversial. 92 If ischemia is present or suspected, surgical decompression via fasciotomy is indicated to prevent irreversible damage. The operation should be

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accomplished within 12 hours of diagnosis to minimize the risk of permanent damage. 93

Neurologic Needle Injury The typical 16-gauge phlebotomy needle can occasionally damage cutaneous branches of the median or ulnar nerve. In a recent study in our blood center, we documented the prevalence of nerve injuries, the types of symptoms, the length of recovery, and any residual damage. 94 Sixty-six blood donors from 419,000 donations or 1 in 6,300 had a peripheral nerve injury based on paresthesias (n = 54), excessive or radiating pain (n = 43), or loss of arm strength (n = 8). Although most donors reported their injury on the day of donation (41%) or within 1 to 10 days (48%), 11% reported the injury weeks to months later. Seventy-eight percent of the affected donors had symptoms on the day of the donation, and 22% did not. Twenty-four percent developed a hematoma, which is higher than expected. The affected blood donor population had more women than the general donor population, 65% versus 47%, and were 8 to 9 years younger on average. After telephone followup on 56 donors, it was found that 70% of the donors recovered completely within 29 days, including 39% who recovered almost immediately or within a couple of days. The recovery period extended 1 month or longer in 30% of the donors, and this included two donors whose recovery period extended into the 6 to 9 month range. The desire for medical consultation correlated with an extended recovery period; almost one third of the donors sought medical consultation. Medical treatment was aimed at relief of symptoms. Despite an extended recovery period for 30%, 52 of 56 donors recovered completely, and the remaining four donors recovered completely except for a small localized patch of numbness. 94 An excellent prognosis was observed also in a small Australian blood center study involving six injuries. Of interest the Australian study suggeSted that Tegretol might be beneficial in these injuries. 95 In all, blood donors with these injuries do well, even when the recovery period is prolonged.

Local Irritants~Allergy Adhesive tape, gauze, and bactericidal skin preparation solutions are used in the phlebotomy process

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and come in contact with the donor's skin. These products are tested by the manufacturer for irritation and sensitization (allergy) properties by standard techniques before FDA approval and release. Irritation and allergic reaction are unusual at the donation site, but occasionally a reaction may occur after the donor leaves the site. More commonly, a donor may give a history of a reaction to adhesive tape or skin preparation solutions. For these cases, hypoallergic tape or alternative skin preparation procedures are available. Perhaps, the most common event is irritation from arm hair being removed or pulled during adhesive tape removal. Nursing care can be adjusted to prevent this problem by attaching tape just to gauze and not to skin.

Infection and Thrombophlebitis There were 18 reports of infection at the venipuncture site from 7 million donations during World War II. This included 15 cases of abscess formation and three cases of acute cellulitis. 1 It must be noted that local anesthetic consisting of novocaine or procaine HCL was used in the 1940s to anesthetize the skin before venipuncture; thus, a blood donation involved two needle sticks. The incidence of infection today would be expected to be lower because no local anesthetic is used. In Detroit, the incidence of infection is estimated to be less than 1 in 200,000 donations, based on interviews with blood center collection managers. Treatment for localized infection includes warm soaks, drainage if pus is present, and possibly antibiotics. Fifteen cases of thrombophlebitis were also reported in the antecubital fossa during World War IIJ None were noted to cause pulmonary emboli. Pulmonary emboli are known to be rare from upper arm veins. Linear red lines are rarely observed today; the incidence in Detroit is estimated to be on the order of 1 in 50,000 to 100,000 donations. Treatment for thrombophlebitis includes heat, aspirin, and observation.

SUMMARY In this review of common and uncommon donor reactions and injuries, donation-associated deaths were found to be extremely rare and generally thought to be coincidental; the rate of coincidental deaths was less than what would be expected based

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on life insurance tables.~ Vasovagal reactions, hematomas/bruises, and history of irritation or allergic reaction to adhesive tape or skin preparations are observed daily in a busy blood collection center. Syncopal vasovagal reactions sometimes resemble shock, but unlike shock, they reverse themselves and do not cause death. Through good management, a blood donor organization can minimize the incidence of syncope. Accidental arterial venipuncture is very uncommon (1 in 100,000), and donors with arterial punctures do well if pressure is applied for an extended period of time. Rarely, a pseudoaneurysm results, and this requires surgery. AV fistulas and compartment syndromes can also occur, but these are extremely rare; most experienced blood center physicians have never observed a case.

Neurologic needle injuries occur approximately once in every 6,300 donations. Although neurologic needle injury complaints are usually received within 10 days of blood donation, 10% of the injured donors may complain weeks to months later. Most donors with needle injuries recover within a month and many within a day or two, but approximately 30% will have a recovery period of greater than 1 month and an occasional case may exceed 6 months. Donors with neurologic needle injuries generally have a full recovery, even when the recovery period may be extended. Thrombophlebitis has a low incidence (1 in 50,000 to 1 in 100,000), and infection at the phlebotomy site is rare. Both are easily treated and have little impact on the donor's health.

REFERENCES 1. Boynton MH, Taylor ES: Complications arising in donors in a mass blood procurement project. Am J Med Sci 209:421436, 1945 2. Greenbury CL: An analysis of the incidence of "fainting" in 5,897 unselected blood donors. Br Med J 1:253-5, 1942 3. Taylor ES: Blood procurement for the army and navy (preliminary report). JAMA 117:2123-2128, 1941 4. Taylor ES: Procurement of blood for the armed forces. JAMA 120:119-123, 1942 5. Maloney WC, Lonnergan LR, McClintock JK, et al: Syncope in blood donors. N Engl J Med 234:114-118, 1946 6. Callahan R, Edelman EB, Smith MS: Study of the incidence and characteristics of blood donor "reactors." Transfusion 3:76-82, 1963 7. Tomasulo PA, Anderson AJ, Paluso MB, et al: A study of criteria for blood donor deferral. Transfusion 20:511-518, 1980 8. Galena HJ: Complications occurring from diagnostic venipuncture. J Faro Pract 34:582-584, 1992 9. Howanitz PJ, Cembrowski GS, Bachner P: Laboratory phlebotomy. College of American Pathology Q-probe study of patient satisfaction and complication in 23,783 patients. Arch Pathol Lab Med 115:867-872, 1991 10. Turkeltaub PC, Gergen PJ: The risk of adverse reactions from percutaneous prick-puncture allergen skin testing, venipuncture, and body measurements: Data from the second National Health and Nutrition Examination Survey 1976-80 (NHANES II). J Allergy Clin Immunol 84:886-890, 1989 11. Poles FC, Boycott M: Syncope in blood donors. Lancet 2:531-535, 1942 12. Blood service directive. Washington, American Red Cross, 1992 13. Williams GE: Syncopal reactions in blood donors. Br Med J 1:783-786, 1942 14. Graham DT: Prediction of fainting in blood donors. Circulation 23:901-906, 1961 15. Ogata H, Iinuma N, Nagashima K, et al: Vasovagal reactions in blood donors. Transfusion 20:679-683, 1980

16. Frazer WF, Fowweather FS: Tetany in blood donors. Br Med J 1:759-760, 1942 17. Brown H, McCormack P: An analysis of vasomotor phenomena (faints) occurring in blood donors. Br Med J 1:1-5, 1942 18. Fainting in blood donors: A report to the Medical Research Council prepared by a subcommittee of the Blood Transfusion Research Committee. Br Med J 1:279-283, 1944 19. Beal RW: Vasovagal reaction in blood donors: an investigation of 222 cases. Med J Australia 2:757-760, 1972 20. McVay PA, Andrews A, Kaplan EB, et al: Donation reactions among autologous donors. Transfusion 30:249-252, 1990 21. AuBuchon JR Popovsky MA: The safety of preoperative autologous blood donation in the nonbospital setting. Transfusion 31:513-517, 1991 22. Haley NR, Feller IT: Comparison of donation reactions between autologous and allogeneic blood donors. Transfusion 35S:14S, 1995 (abstr) 23. Popovsky MA, Whitaker B, Arnold NL: Severe outcomes of allogeneic and autologous blood donation: frequency and characterization. Transfusion 35:732-737, 1995 24. Scott E: The safety of blood donation-is it what it should be? Transfusion 35:717-718, 1995 (editorial) 25. Pindyck J, Avorn J, Kuriyan M: Blood donation by the elderly: clinical and policy considerations. JAMA 257:11861188, 1987 26. Newman B, Gedie J, Perkins J, et al: The effect of beta blocker anti-hypertensive agents on whole blood donor reaction rates. Transfusion 29S:61S, 1989 (abstr) 27. Lin JT, Ziegler DK, Lai CW, et al: Convulsive syncope in blood donors. Ann Neurol 11:525-528, 1982 28. Kasprisin DO, Glynn SH, Taylor F, et al: Moderate and severe reactions in blood donors. Transfusion 32:23-26, 1992 29. Stehling L, Parker N: Moderate and severe reactions in blood donors. Transfusion 34S: 13S, 1994 (abstr) 30. Bianco C, Robins JL: Whole blood collection volumes

74

and donor safety: equivalence between 450 mL and 500 mL collections. Transfusion 34S: 15S, 1994 (abstr) 31. Trouern-Trend JJ: Personal communication, 1996 32. Trouern-Trend JJ, Cable RG, Badon SJ, et al: Role of weight, blood pressure, and pulse in donor reactions with syncope-A multicenter study. Transfusion 1996 (abstr), in press 33. Blood center survey. American Red Cross Washington, 1995 34. Fleg JL, Lakatta EG: Prevalence and significance of postexercise hypotension in apparently healthy subjects. Am J Cardio157:1380-1384, 1986 35. Semple PF, Thoren R Lever AF: Vasovagal reactions to cardiovascular drugs: the first dose effect. J Hypertens 6:601606, 1988 36. McHenry LC, Fazekas JF, Sullivan JF: Cerebral hemodynamics of syncope. Amer J Med Sci 241:173, 1961 37. Martin GJ, Adams SL, Martin HG, et al: Prospective evaluation of syncope. Ann Emerg Med 13:499-504, 1984. 38. Lipsitz LA, Pluchino FC, Wei JY, et al: Syncope in institutionalized elderly: the impact of multiple pathological conditions and situational stress. J Chronic Dis 39:619-630, 1986 39. Kapoor W, Snustad D, Peterson J, et al: Syncope in the elderly. Am J Med 80:419-428, 1986 40. Lipsitz LA, Marks ER, Koestner J, et al: Reduced susceptibility to syncope during postual tilt in old age. Arch Intern Med 149:2709-2712, 1989 41. Imholz BP, Dambrink JH, Karemaker JM, et al: Orthostatic circulatory control in the elderly evaluated by noninvasive continuous blood pressure measurement. Clin Sci 79:73-79, 1990 42. Ruetz PP, Johnson SA, Callahan R, et al: Fainting: a review of its mechanisms and a study in blood donors. Medicine 46:363-384, 1967 43. France C: Baroreflex sensitivity during noxious stimulation in vasovagal reactors to blood donation. Int J Psychophys 19:13-22, 1995 44. Steptoe A, Sawada Y: Assessment of baroreceptor reflex function during mental stress and relaxation. Psychophysiology 26:14-147, 1989 45. Steptoe A, Vogele C: Carotid baroreflex function during postural change assessed using non-invasive spontaneous sequence analysis in young men. Cardiovasc Res 24:627-632, 1990 46. Vogele C, Steptoe A: Anger inhibition and family history as modulators of cardiovascular responses to mental stress in adolescent boys. J Psychosom Res 37:503-514, 1993 47. Van Lieshout JJ, Wieling W, Karemaker JM, et al: The vasovagal response. Clin Sci 81:575-586, 1991 48. Weissler AM, Warren JV: Vasodepressor syncope. Am Heart J 57:786-794, 1959 49. Adams RD, Victor M: Faintness and syncope, in Principles of Neurology (ed 5). New York, McGraw-Hill, 1993, pp 319-330 50. Ziegler MG, Echon C, Wilner KD: Sympathetic nervous withdrawl in the vasodepressor (vasovagal) reaction. J Auton Nerv Sys 17:273-278, 1986 51. Burke D, Sundlof G, Wallin BG: Postural effects on muscle nerve sympathetic activity in man. J Physiol (London) 272:399-414, 1977 52. Goldstein DS, Spanarkel M, Pitterman A, et al: Circula-

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tory control mechanisms in vasodepressor syncope. Am Heart J 104:1071-1075, 1982 53. Eckberg DL, Sleight P: Human Baroreflexes in Health and Disease. Oxford, Oxford University Press, 1991 54. Yatomi A, Iguchi A, Uemura K, et al: A rare case of recurrent vasodepressive attacks of 2-hours duration analysis of the mechanisms by muscle sympathetic nerve activity recording. Clin Cardiol 12:164-168, 1989 55. Esler M, Jennings G, Lambert G, et al: Overflow of catecholamine neurotransmitters to the circulation: source, fate and functions. Physiol Rev 70:963-985, 1990 56. Wallin BG, Sundlof G: Sympathetic outflow to muscles during vasovagl syncope. J Auton Nerv Syst 6:287-291, 1982 57. Greene MA, Boltax AJ, Ulberg RJ: Cardiovascular dynamics of vasovagal reactions in man. Circulation Res 9:12-17, 1961 58. Murray Rh, Shropshire S: Effect of atropine on circulatory responses to lower body negative pressure and vasodepressor syncope. Aerosp Med 41:717-722, 1970 59. Bernat JL, Vincent JL: Syncope, in Neurology: Problems in Primary Care (ed 2). Los Angeles, Medical Economics Books, 1993, pp 115-128 60. Pedley TA, Ziegler DK: Syncope and seizures, in Merritt's Textbook of Neurology, (ed 9). Baltimore, Williams and Wilkins, 1995, pp 12-18 61. Abboud FM: Ventricular syncope: Is the heart a sensory organ? N Engl J Med 320:390-392, 1989 62. Bjurstedt H, Rosenhamer G, Ballidin U, et al: Orthostatic reactions during recovery from exhaustive exercise of short duration. Acta Physiol Scand 119:25-31, 1983 63. Haley NR: Written personal communication, 1996 64. Sazama K: Oral personal communication, 1996 65. Engel GL: Psychologic stress, vasodepressor (vasovagal) syncope, and sudden death. Ann Intern Med 89:403-412, 1978 66. Tizes R: Cardiac arrest following routine venipuncture. JAMA 236:1846-1847, 1976 67. McIntosh HD: The stabilizing and unstabilizing influences of neurogenic and vascular activities of the heart as related to sudden cardiac death. J Am Coll Cardiol 5:105-10B, 1985 68. Maloney JD, Jaeger FJ, Fouad-Terazi FM, et al: Malignant vasovagal syncope: prolonged asystole provoked by head-up tilt. Cleveland Clin J Med 55:542-48, 1988 69. Milstein S, Buetikofer J, Lesser J, et al: Cardiac asystole: a manifestation of neurally mediated hypotension-bradycardia. J Am Coll Cardiol 14:1626-1632, 1989 70. Rutman RC, Di Pfascuale-Barrios S: Donor reactions, in Green TS, Steckler D (ed): Donor Room Policies and Procedures. Arlington, American Association of Blood Banks, 1985, pp 81-90 71. Ferguson DW, Thames MD, Mark AC: Effects of propranolol on reflex vascular responses to orthostatic stress in humans. Circulation 67:802-87, 1983 72. Waxmand MB, Yao L, Cameron DA, et al: Isoproterenol induction of vasodepressor-type reaction in vasodepressor-. prone person. Am J Cardiol 63:58-65, 1989 73. Almquist A, Goldenberg IF, Milstein, et al: Provocation of bradycardia and hypotension by isoproterenol and upright posture in patients with unexplained syncope. N Engl J Med 320:346-351, 1989 74. Jaeger FJ, Fouad-Tarazi FM, Abi-Samra F, et al: Transder-

BLOOD DONOR REACTIONS AND INJURIES

mal scopolamine for the treatment of vasovagal syncope. Clin Res 35:832A, 1987 (abstr) 75. Milstein S, Buetikofer J, Dunnigan A, et al: Usefulness of disopyramide for prevention of upright tilt-induced hypotensionbradycardia. Am J Cardiol 65:1339-1344, 1990 76. Klein H (editor and compiler): Standards for blood banks and transfusion services (ed 17). Bethesda, MD, American Association of Blood Banks, 1996 77. Kendrick DB: Blood program in World War II. Washington, Office of the Surgeon General, Department of the Army, 1964, pp 156-157 78. Sazama K: Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion 30:583-590, 1990 79. Grindon AJ: Adverse Reactions to Whole Blood Donation and Plasmapheresis. CRC Press, 17:51-75, 1982 80. Sataro PA: Blood collection, in Kasprisin C, Laird-Fryer B (eds): Blood Donor Collection Practices. Bethesda, American Association of Blood Banks, 1993, pp 83-103 81. ARC blood center medical director e-mail survey, 1996 82. Popovsky MA, McCarthy S, Hawkins RE: Pseudoaneurysm of the brachial artery: a rare complication of blood donation. Transfusion 34:253-254, 1994 83. Newman B, Popovsky M: Pseudoaneurysm after blood donation. Transfusion 34:935, 1994 (letter) 84. Kumar S, Agnihotri SK, Khanna SK: Brachial artery pseudoaneurysm following blood donation. Transfusion 35:791, 1995 85. Lung J, Wilson S: Development of arteriovenous fistula following blood donation. Transfusion 11: 145-146, 197 l

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86. Keeley JL, Schairer AE, Pesek IG: Peripheral arterial aneurysms and arteriovenous fistulas. Surg Clin NAmer 40:97110, 1960 87. Lyerly HK, Sabiston D: Arteriovenous fistulas, in SaNston D (ed): Textbook of Surgery (ed 14). Philadelphia, W.B. Saunders, 1991, pp 1630-1637 88. Green R, Ourrel K: Peripheral arterial disease, in Schwartz S (ed): Principles of Surgery (ed 6) New York, McGraw-Hill, 1994, pp 976-977 89. Mubarak SJ, Owen CA, Hargens AR: Acute compartment syndromes: Diagnosis and treatment with the aid of the Wick catheter. J Bone Joint Surg 60A: 1091-1095, 1978 90. Matsen FA, Winquist RA, Krugmire RB: Diagnosis and management of compartment syndromes. J Bone Joint Surg 62A:286-291, 1980 91. Mubarak SJ, Hargens AR: Acute compartment syndromes. Surg Clin North Am 63:539-565, 1983 (review) 92. Jacobs L: Arterial compression syndromes, in Greenfield L (ed): Surgery. Philadelphia, Lippincott, 1993, pp 1498-1500 93. Nixon RG, Brindley GW: Hemophilia presenting as compartment syndrome in the arm following venipuncture. A case report and review of the literature. Clin Orthop Rel Res 244:176-181, 1989 94. Newman BH, Waxman DA: Blood donation-related neurologic needle injury: Evaluation of 2 years' worth of data from a large blood center. Transfusion 36:213-215, 1996 95. Berry PR, Wallis WE: Venipuncture nerve injuries. Lancet 1:1236-1237, 1977