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exchange. The United States Government assumes no liability
for its content or use thereof.


16.

17.

18,

19.

20.

21.

22.

23.

24,

25.

26.

27.

28.

29.

30.

31.

32.

Schiff HB, MacSearraigh ETM, Kallmever JC: Nyoglobinuria, rhabdomyolysis
and marathon running. Q J Med 68:463-472, 1978

McArdle B: Myopathy due to failure in muscle glycogen breakdown. Clin
Sei 10:13-35, 1951

Tarui S, Okuno G, Ikura Y, ct al: Phosphofructokinase deficiency in
skeietal muscle. A new type of glycogenosis. Bioch Biophys Res Com
19:517-533, 1965

Rubin E: Muscle damage produced by chronic alcohol consumption. Am J
Pathol 83:4990516, 1976

Henrich WL, Prophet D, Knochel JP: Rhabdomyolysis associated with
Escherichia coli septicemla. Suuth Med J 73:936-937, 1980

Nadel SM, Jackson JW, Ploth DW: Hypokalemic rhabdomyolysis and acute
renal failure. J Am Med Assoc 241:2294-2296, 1979

Adler S: Hyponatremia and rhabdomyolysis. South Med J 73:511-512, 1980

Raifman MA, Berant M, Lenarsky C: Cold veather and rhabdomyolysis.
J Pediatr 93:970-971, 1978

Wright J, Hodges GR: Adenovirus Type 21 infection. Occurrence with
Pneumonia, rhabdomyolysis, and myoglobinuria in an adult. J Am Med Assoc
241:2420-2421, 1979

Dudding BA, Wagner SC, Zeller JA, et al: Fatal pneumonia associated with
Adenovirus Type 7 in three military trainees. N Engl J Med 286:1289-1292,
1972

Saul RA, Vernon M, Roe C, et ai: Khabdomyolysis in a patient with
nonoliguric renal failure: Similarities to the toxic shock syndrome.
South Med J 73:261-263, 1980

Posner MR, Caudill MA, Brass R, et al: Legionnaires’ Disesse associated
with rhabdomyolysis. Arch Intern Ned 140:848-850, 1980

Brite CW, Light RR, Peters BY, et a.: Rhabdomyolysis during treatment with
epsilon-aminocaproic acid, Arch Neurol 37:187-188, 1980

Schlesinger JJ, Gandara D, Bensh KG: hyoglobinuria associated with Herpes~
group viral infections. Arch Intern Med 138:422-424, 1978

Kantor RJ, Norden CW, Wein TP: Infectious mononucleosis associated with
rhabdomyolysis and renal failure. South Med J 71:346-348, 1978

Schretr RW, Henderson HS, Tisher CC, et al: Nephropathy associated with
heat stress and exercise. Ann Intern Med 67:356-376, 1967

Murphy JR: Sickle cell hemoglobin (HbAS) in black football players. J Am
Med Assoc 225:981-982, 1973 .

12



uses supplemental oxygen during the entire flight at
those altitudes .... . (mor)... . . at cabin
pressure altitudes above 15,000 ft (MSL), unless each
occupant of the aircraft is provided with supplemental
oxygen. (Note: The phrase, "cabin pressure altitudes”
is needed here to provide for differences between inside
and outside pressures in the case of pressurized, or
partially pressurized, aircraft.)

If it appears from the above quotation that passengers of commercial
transport aircraft are required to tolerate an altitude of, say, 13,000 ft,
this is not the case at all. As I am sure you have guessed, there are other
Federal Aviation Regulations (e.g., Part 121)* to be considered. Most pas-
senger aircraft are pressurized to at least 8,000 ft. If a decompreasion
were to occur, oxygen masks would be deployed. Even after a sudden decompres-
sion to very high altitudes, everyone, even those with SCT, would have at
least 10 s of useful consciousness, time enough to don a mask. Please note
such severe decompressions are extremely rare. Most decompressions recorded
by the FAA are caused wy a malfunction of the outflow valve, a component of
the cabin pressurizing system. Such decompressions are very slow, and rarely
do cabin pressure altitudes approach 18,000 ft.

The vilot with SCT has the same minimum time, about 10 9 to don an
oxygen mask. Beyond this time there is a risk of losing consciousness and
control of the aircraft; so the question of sickling is pretty academic.
Regardless of hemoglobin phenotype, the pilot must remain conscious. Remember,
however, that airline pilots receive some :raining in mask donning, and that
yet other regulations (FAR 121.333c) have been issued to assure that there is
at least one conscious pilot at the controls in the event of a decompression.

In our first report on this subject (6) we concluded that, although SCT
seems no threat to the airman, those with the trait should avoid the hypoxic
experience portion of physiological (altitude chamber) training. Frankly,
this conclusion was based on my own personal biases; J am not sure that the
value of this portion of physiological training outweighs the risks from per-
iodic hypoxic exposures throughout a pilot's career, regardless of hemo-
globin type. Perhaps this is an overly conservative opinion. In any case,
since the publication of that report I have been made aware of a number of
people with SCT who have undergone the hypoxic experience to the point of
definite signs and symptoms of hypoxia, with no unusual consequences whatsoever.
We have documented a number of these cases and expect to collect more of them.
Some of these people, of both sexes, have "flown" in our own altitude chamber
in Oklahoma City. Some, before their trait was detected, underwent these
experiences in military chambers. Some of the latter group were members of
Dr. Marchbanks'** own 332d Fighter Group, who flew combat missions during

*FAR 121.327c deals with a variety of cabin pressure altitudes and permissible
exposure times. Physicians concerned for susceptible patients who are plane
ning air travel may wish to consult with the nearest FAA regional flight
surgeon or with a local FAA-designated aviation medical examiner.

**Vance H. Marchbanks, Jr., M.D., Hartford, Connecticut, was one of the first
black flight surgeons. He entered the U.S. Army Medical Corps in 1941, became
rated as a flight surgeon in 1944, and was aseigned to the all-black 332d
Fighter Group. Dr. Marchbanks was a member of the panel whose discussion is
reported here.



VOCATIONAL OPTIONS FOR THOSE WITH SICKLE CELL TRAIT:
QUESTIONS ABOUT HYPOXEMIA AND THE INDUSTRIAL ENVIRONMENT*

INTRODUCTION

It may be characteristic of panel discussions that they seldom follow
the planned form. This is certainly true for the discussion we report here.
Because of the many questions and comments from the floor and from other
panel members, the written form and the title have been changed somewhat to
best represent the tone of our discussion. I hope that those who attended
the actual session will approve.

This section will present some vocational considerations for those who
possess the sickle cell trait (SCT). Dr. Adams will present separately a -
discussion of the profession, and avocation, of diving; here we will consider
other vocations, especially those that may involve exposure to moderate
hypoxia and to industrial chemicals.

In our earliest courses in physiology we learned that hypoxemia can be
caused through a number of mechanisms. Two of these mechanisms ere impor-
tant to the present discussion: (i) oxygen tensions can be reduced on the
arterial side through a reduction of ambient barometric pressure, which low-
ers the partial pressure of oxygen in the alveoli; and (ii) venous and capil-
lary oxygen tensions cap be reduced when tissue oxygen consunption is suf~
ficiently augmented; during certain kinds of physical exertion (e.g., the
hundred-yard dash), this mechanism is compounded in effect by breathholding.

When the blood p02 is lowered sufficiently, erythrocytes containing
hemoglobin S (HbS) will become sickled and so inelastic that they cannot
pass through the smallest vessels. If these vessels are blocked, tissue
oxygen consumption will continue, p02 will be further reduced, more red

cells will sickle, and the vicious cycle of a local or general sickling
crisis will ensue.

In this paper we will evaluate the importance of these hypoxia-induced
effects and of some industrial chemicals to individuals with SCT.

AEROMEDICAL IMPLICATIONS OF SICKLE CELL TRAIT

Although it is now established that most people with SCT are as healthy
and as long lived as those without HbS in their erythrocytes, we still see
occasional reports that associate the trait with a variety of pathological
conditions. For the most part it is unclear whether the authors of these
reports consider SCT to be a cause of these conditions, or merely contributory ———___.
to the morbid consequences of the primary cause. In reports dealing with the *_
effects of high altitude, however, the claim is clearly made: type AS red _——
cells will sickle under hypoxic conditions; collapse at altitude, especially
when there are signs and symptoms of splenic or bowel infarction, is directly

attributable to a sickling crisis. . a
———__

*A portion of the workshop: "Is Sickle Cell Trait a Health Hazard?", held

during the postgraduate course, SICKLE CELL DISEASE: CHALLENGE OF THE ee

EIGHTIES, sponsored by Howard University venter for Sickle Cell Disease,

in cooperation with the Office of Continuing Medical Education, Howard Univer- Codes
sity College of Medicine, : sa/or

Special



Technical Kepert Documentation Page

2. Government Accession Ne. Es veote Cotalog No.
AD-AoGk106 (1) :
_Da ernie ~ 5. ’
YOCATIONAL OPTIONS FOR THOSE WITH §ICKLE £ELL TRAIT:
QUESTIONS ABO'NT HYPOXENTA AND THE {NDUSTRIAL ENVIRONMENT
[= Be % a
=F Perlormng Orgenisetion Report No.
Dae wTcenne
9. Pertormng Orgerizetion Nome end Address TO. Werk Unit Ne. (TRAIS)
[FAA Civil Aeromedical Institute
P.O. Box 25082 1, Conteaet or Grent No.
Oklahoma City, Oklahoma 73125
13, Type of Report end
12. Sponsering Agency Neme ond Addrees
loffice of Aviation Medicine —_——- OAM Report
Federal Aviation Administration ~ !
800 Independence Avenue, S.W. 4 A T6. “Sponsoring Agency Code
Washington, D.C. 20591 1, JA i

1S. Supplementary Neves

Work was done under approved task AM~A-80-PHY-113.

¥6, Abetroct

hazardous to them.
in support of any of these beliefs.

SCT have yielded favorable results.

ative ones.

>This report is based on an oral presentation to physicians interested in the
treatment of patients with sickle cell disease.
and siblings who possess the sickle cell trait (SCT), and who often require
not only genetic counseling, but also information. about their own health.

Some have been informed that they cannot pursue careers in aviation.
have been told that they are at special risk from the hypoxemic effects of
heavy exertion, especially the exertion associated with some sports.
believe that certain elements of the industrial environment are unusually

An examination of the literature reveals little evidence

are clouded by faults of various kinds.
based on small numbers of cases; the evidence offered is circumstantial.
the other hand, experiments designed to test the susceptibility of those with

that those with the trait have normal health and normal life expectancy.
Also, there are almost as many favorable anecdotal reports as there are neg-
We must conclude that people with SCT are just as tolerant to
aviation and industrial environments as those who are homozygous for hemo~

globin A. Also, there are strong indications that. those with SCT are not
endangered by heavy physical exertion, including the exertion of athletic
competition.

17, KeyWords 18. Diswibution

Many patients have parents

Some
A few
Most, if not all, unfavorable reports
All of them are of anecdcta. cype,

on

Studies of large populations indicate

Hemoglobin, blood, aeromedical
certification, myopathy, sickle
cell trait, physical. exertion

Document is available to the public through
the National Technical Information Service,
Springfield, Virginia 22161

a

19. Security Clossil, (ef this cepart)

Unclassified

W. Security Clessil. (ol this page)

Unclassified .

Bi No. of Pages
13

22, Price

Form DOT F 1700.7 (#-72)

Reproduction of completed page ovtherized

(264320


Robinson JR, Stone WJ, Asenjorf AC: Exercise capacity of black sickle cell
trait males. Med Sci Sports 8:244-245, 1976

Wenzel RP, McCormick DP, Smith EP, et al: Acute respiratory disease:
Clinical and epidemiologic observations of military trainees. Mil Med
136:873-880, 1971

Severo Rt Genetic teats by industry raise questions on rights of workers.
New York Times. Feb. 3, 1980. Sect. 11, p 1 ~ and cont. on p 36

Severo R: Screening blacks by DuPont sharpens debate on gene tests.
New York Times. Feb. 4, 1980, p 1 - and cont. on p Al3

Severo R: Federal mandate for gene tests disturbs U.S. job safety official.
New York Times. Feb. 6, i980. p i - and cont. on p Al?

Lockman N: Grading the Test. Boston Globe. Feb. 9, 1980, p 11

Asakura T, Agatwal DL, Relman DA, et al: Oxy~form of sickle hemoglobin.
Nature 244:437-438, 1973

Zinkham WH, Houtchens RA, Caughey WS: Carboxyh-moglobin levels in an
unstable hemoglobin disorder (Hb Zurich): Effect on phenotypic erpression.
Science 209:406-408, 1980

Beutler E: Drug-induced hemolytic anemia. Pharmacol Rev 21:73-103, 1969

Sears DA: The morbidity of sickle cell trait. A review of the literature.
Am J Med 64:1021-1036, 1978

13



Se

another, B142 ALA + VAL. The resulting hemoglobin, besides being susceptible
to sickling, is quite unstable. Moo-Penn and his collaborators were able to
detect it by cellulose acetate electrophoresis, but it seems likely that non-

experts would have difficulty distinguishing it from ordinary HbS. Certainly,

Paper electrophoresis would not be a satisfactory method for detecting this
variant. .

The hypothetical case we have just reviewed represents the type of anec-
dotal evidence upon which former FAA policies were based. Such reports offer

poor evidence iu support of a ruling that can affect careers. As you know,
Present FAA polzcy does not discriminate against the AS phenotype.

As do cells containing only HbS,
HbA and other hemoglobins can also bec
is low enough, but this statement tells us nothing about the threshold alti-
tude for the sickling of SCT cells. Figure 1, taken from the data of Griggs
and Harris (3) is more informative. This chart shows, superimposed on a nor~
mal oxygen-hemoglobin dissociation curve, the oxygen tensions at which various
types of red cells begin to sickle. We can see that there is an impressive
difference between the sickling thresholds of SS and of AS cells, which seem
refractory to sickling above about 10 Torr. Recently, Benesch et al. (4)
have helped to explain this difference by demonstrating that HbF and HbA are
incorporated into the HbS polymer that forms unler hypoxic conditions, and

chat the presence of these other hemoglobins enhances the solubility of the
polymer.

those containing mixtures of it with
ome sickled when the oxygen tension

Using a sorr of physiological Dalton's law, we can recalculate the data

of Figure 1 to find the altitudes equivalent to these threshold oxygen tensions.
Assuming normal values for PH20 and PCOz, 47 and 40 Torr:

Pape ((p02 + pCO2) / 0.21) + p20 = 285.1 Torr

when Py is the total atmospheric pressure
Pressures, and 0.21 is, of course,
air.

» the lower case p denotes partial

the fractional concentration of oxygen in
Using this equation we can calculate that an alveolar pO, of 10 Torr
should result from exposure to an altitude of about 25,000 ft. This is only

an approximation, however, and maybe we have assumed toe much in cur calcula-
tion. We have not taken into account, for example, possible reductions in
alveolar pCO2 that may occur at high altitudes. A more satisfying number would
be one obtained from physiological measurements, not of alveolar tensions but
of those in the capillaries where sickling, if it occurred, would have its
earliest effects. Fortunately, the literature provides us with a fairly useful
number; mean capillary oxygen tensions a little above 20 Torr have been measured
in human subjects while they breathed air at 22,000 ft (5). Because 20 Torr is
twice the tension required to initiate sickling of AS red cells, 22,000 ft seems
a reasonable altitude to set as a limit for long-term exposure of individuals

with SCT. At this altitude, by the way, most individuals will lose conscious—
ness within about 110 s.

. a
The Federal Aviation Regulations (FAR 91.32a) state:

No person may operate a civil aircraft ..... at
cabin pressure altitudes above 14,000 ft (MSL) unless
the required minimum flight crew is provided with and


UNCLASSIFIED

tL al



Koppes et al. make a point of the occurrence of DIC in their patients,
Stating that, “a clinically significant blecding diathesis . . + has not been
described in patients with exertional~induced rhabdomyolysis," but Schreir
et al. (31) reported DIC and muscle involvement in a white patient after he
had exercised in a hot environment. Dudding et al. (25) found consumption
coagulopathies in three U.S. Army recruits who died from an adenovirus Type 7
Pneumonia. Adenoviruses have been reported to induce RML (24). Two of the
Patients studied by Dudding et al. exhibited signs of muscle involvement; in
one, “occasionai muscle fibers had lost cross-striation and were acidophilic.”
Signs of renal involvement were also Present. A mountain climber studied by
Niwa et al. (15) exhibited both DIC and RML; this patient possessed the beta-
thalassemia trait.

There is more to be found in the literature on this question than we
have space to cover, but this quick look should satisfy us that the case
against SCT as a cause for rhabdomyolysis, or as a reason for avoiding sports
and other forms of exertion, is tenuous at best. Other facts support this
conclusion. SCT certainly has not been a factor in the selection, for health
or ability, of black players in the National Football League. League players
with SCT number about 8 percent of black athletes, including those who play
most of their games at altitudes greater than 5,000 fc (32). Several athletes
with documented SCT participated in the 1968 Olympiad in Me~ico City, where
they exerted themselves maximally and suffered no untoward consequences (6).
Robinson et al. (33) found no significant differences between the exercise
capacities of 16 male subjects with SCT and 26 matched control subjects. I
hope that you will conclude with me that those cases seen by Zimmerman and
Mummert and by Koppes et al. might just as likely have been associated with
some infectious agent. Organisms capable of causing DIC and RML are known to
be endemic or epidemic in military populations (e.g., 34).

HAZARDS OF THE INDUSTRIAL ENVIRONMENT
EE EE LADUSTRIAL ENVIRONMENT

It seems appropriate to consider also another, more recent, threat to a
free career choice for those with SCT. Beginning early in 1980, there have
appeared a number of newspaper articles referring to "discriminant" policies
of industry toward women, those with inherited enzyme deficiencies and, of
course, toward people with SCT (see, for example, references 35-38). With
such policies have come screening programs, designed to detect various genetic
differences. Those who defend the programs say that they are intended to pro-
tect the worker who may be especially susceptible to working conditions that
are not "normally" hazardous. Those who object to screening point out that:

(i) there may be many susceptible conditions that are not screened for; and

(id) it is yet to be proven that SCT, for example, can increase the hazards of
industrial conditions that are safe for those without it. It is not difficult

to agree with both these latter points. Although Asakura et al. (39) showed

that HbS in solution may become insoluble when shaken and then diluted with a

17 percent isopropanol buffer, this finding does not prove that industrial
solvents present a special danger to those with SCT. I have found no reports

in the literature that HbS-containing red cells become destabilized by other-
wise tolerable levels of any chemical used in industry. On the other hand, it

is known that Hb-Z0xich, a notoriously unstable protein, has a very high a€fin-
ity for carbon monoxide (40), and Beutler (41) points out that Hb-Zrich-containing
red cells are susceptible to a number of drugs and chemicals. Beutler's list of
unstable hemoglobins does not include HbS, but HbS is easily detected. Hemoglobin



World War II; 7 to 8 percent of these men had red cells that would sickle
under hypoxic conditions. Henderson and Thornell (7) reported that four
cadets with SCT tolerated an exposure to 16,000 ft. Some of the group con-
tinued their military flying careers after the war and thus went on to periodic
training exposures at approximately 26,000 ft. Table I presents data on two of
our experimental subjects who were applicants for military flying waivers.

In summary, it is fair to say that sickle cell trait is not a risk factor
in the majority of pilots and passengers who possess it. Reports associating
SCT with collapse during or after flight are clouded with incomplete diagnosis
of hemoglobin phenotype, failure to consider other factors that may have been
involved, poor logic (post hoc ergo propter hoc (6)) and other faults (8,9).

—pitere may be factors that can contribute to a sickling crisis at altitude, but
these factors obviously do not occur in the majority of people with SCT. Anec-
dotal reports are a poor basis fcr policies that deny carcers in aviation, and
the social and economic benefits of those careers, to 8 percent or more of the
world's black people. It is the responsibility of aviation medical examiners
and policymakers to insure that denial of certification is based on real dangers.
An airline pilot, speaking to another medical group about another medical prob-
lem, stated:

The easy way out is to say no, quote the rule book, ground
the pilot, and escape any possible criticism for the decision.
The difficult decision is that of the doctor who says he
believes, on the basis of his training and background, that

a specific condition is not related to safety, and that,
given proper medical surveillance and control, the pilot

can fly. It is usually one of the leaders of your profes-
sion who makes that determinction. ... . (10).

ATHLETICS AND OTHER FORMS OF PHYSICAL EXERTION

In the 1970's there appeared in the literature three reports linking the
trait with pathological consequences of heavy exercise. Jones et al. (11)
reported four cases of sudden death in army recruits during basic training at
an altitude of 4,060 ft. In each case an initial collapse was followed by loss
of consciousness and death. Two recruits died within 8h. In the other two,
who died at 24 and 25 h, there were signs of disseminated intravascular coagu-
lation (DIC). “Electrophoresis” revealed both HbS and HbA, and sickled red
cells were seen at necropsy.

Although Jones et al. reported no muscle involvement in their patients,
Zimmerman and Mummert (12) and Koppes et al. (13) found rhabdomyolysis (RML)
following severe exertion in a total of five young recruits with SCT. All
four of the patients studied by Koppes et al. exhibited signs of DIC; two of
them died after admission to the hospital. Interestingly, the two survivors
collapsed after exercising at an altitude of 7,200 ft. Both were athletes in
excellent condition before their problems occurred and, presumably, had not
experienced similar problems in the past at this same altitude. No defi-
eiencies in muscle phosphorylase or phosphofructokinase were found ii the two
survivors, but carnitine palmityl transferase (CPT) was not measured; defi-
eiencies in CPT are reportedly associated with familial exertional RIL. Many
other factors have also been incriminated (sec Table It).



be

There have been quite a few of these reports. Rather than consider them
individually, let me summarize them in a single hypothetical case:

A civilian pilot, flying under instrument flight rules,
is within 2 h of his destination when he is called by
Air Route Traffic Control Center and informed of severe
weather ahead. The Center directs him to a new heading
to avoid the storm, and instructs him to ascend from his
Present altitude of 9,000 ft to an altitude of 11,000 ft,
Although he does not have oxygen equipment aboard, this
higher altitude is of no concern because the Federal Avia-
tion Regulations (Part 91.32) do not require him to use
oxygen until he flies above an altitude of 12,500 ft (and
below 14,000 fe) for over 30 min.

Later, the pilot calls Center to inform them that he is

on the new course and at the higher altitude. However,

he has encountered severe weather and turbulence is extreme.
His transmission is interrupted and radio contact is per-
manently lost. Next morning the crash site is located and
the pilot's body found in the wreckage. Autopsy protocol
reveals severe impact trauma; in fact, not all of the tis~
Sues can be found. Samples of blood and tissues age sent
to the FAA's Aviation Toxi logy Laboratory in Oklahoma
City; tests for drugs, Gfcohol, and carbon monoxide are
negative. Later histological examination, however, reveals
sickle-shaped red cells in some organs, and paper electro-
phoresis results indicate the presence of both HbS and HbA.

The important fact to recognize from this case is that if HbS had not been
detected, we might have concluded that the most Probable cause of this accident
was the weather; the pilot had, after all, reported extreme turbulence just
before contact was lost. “How much weight should we give to the finding of

and rule instead that the pilot had become incapacitated by a sickling crisis
at 11,000 ft? We might, if we forgot a well-known fact: there is little oxy-
gen left in a cadaver several hours after death. This fact, and the tendency

other possible causes, including alcohol abuse, drugs, and trauma. Rosenheim
(1) has warned us that approximately 8 percent of all black people will exhibit
sickled red cells at necropsy, and that this finding has no value in establish-
ing the cause of death.

How should we interpret the electrophoretic findings in our hypothet—
teal case? It shoud be enough to say, after considering the litera~
ture on the subject, that electrophoresis can fool us Sometimes, especially
Paper electrophoresis. This is particularly true if we are a bit naive
concerning technique. For example, our pilot might have possessed, instead
of a pure sickle cell trait, some other, electrophoretically "silent" double
mutation, such as Hb-Travis, reported by Moo-Penn et al. (2), in the red
cells of an airman who collapsed during a transoceanic flight. This hemo-
globin contains two beta substitutions, the B6 substitution of HbS and


AD A098 706

(( FILE COPY

ml

_. LEVEL

VOCATIONAL OPTIONS FOR THOSE WITH SICKLE CELL TRAIT:
QUESTIONS ABOUT HYPOXEMIA AND THE INDUSTRIAL ENVIRONMENT

Jess M. McKenzie

Civil Aeromedical Institute
Federal Aviation Administration
Oklahoma City, Oklahoma

DTIC
ELECTE
MAY 14 1981.

E_.

November 1980

Document is available to the public through the
National Technical Information Service,
Springfield, Virginia 22161

Prepared for
U.S. DEPARTHENT OF TRANSPORTATION
Federal Aviation Administration
Office of Aviation Medicine
Washington, D.C. 20591

815 11 024


TABLE II. Reported Causal Factors in Rhabdomyolysis. Some examplee.

FACTOR COMMENT REFERENCE®
Carnitine Palmityl 14
Transferarce Defic.

Sickle Cell Trait 12,13
B-Thalassemia Trait 15
Byperuricemia ke
Trauma/ Ischemia : (Many)
Phosphorylase Defic. McArdle's Synd. uy
Phosphofructokinase Tarui's Synd. 18
Defic.

Alcohol Abuse/ 49
Sensitivity

Bacteremia e@.ge, E. coli 20
Hypokalemia 21
Hyponatremia 22
Cold Exposure 23
Adenovirus Infection Several Types rz)
Toxic Shock Synd. 26
Legionnaires’ Dis. 27
Epsilon Amino For hemrorrhage 28
Caproic Acid Ther.

Herpesvirus Inf. 29
Epstein-Barr Virus 30

*Citations are given as examples only and are not inteuded to indftate

priority of publication.


REFERENCES

Rosenheim SH: Sickle cell trait and sudden death (Cont.). N Engl J Med
283:2229-1230, 1971

Moo-Penn WF, Schmidt RM, Jue DL, et al: Hemoglobin S-Travis: A sickling
hemoglobin with two amino acid substitutions (B6(A3) glutamic Acid
valine and 3142(H20) alanine —> valine). Eur J biochem 77:561-566, 1977

Griggs RC, Harris JW: The biophysics of variants of sickle cell disease.
Arch Intern Med 97:315-326, 1956

Benesch RE, Rohinton E, Reneach R, et alt. Solubilization of hemoglobin $
by other proteins. Proc Natl Acad Sci USA 77:5130-5134, 1980

Ernsting J: Respiration and anoxia, in Gillies JA(ed): A Textbook of
Aviation Physiology. Oxford, Pergamon, 1965, pp 214-263

McKenzie JM: Evaluation of the hazards of sickle trait in aviation.
Aviat Space Environ Med 48:753-762, 1977

Henderson AB, Thornell HE: Observations on the effect of lowered oxygen
tension on sicklemia and sickle cell anemia among military flight personnel.
J Lab Clin Med 21:769-776, 1946

Addae RO: Alleged intestinal infarction in sickle cell trait during flight.
Ghana Med J 11:93~94, 1972

Konotey-Ahulu FID: An international sickle cell crisis. Ghana Med J
11:4-7, 1972

Gilstrap RW: Medical excellence and airline pilots. In: Cardiovascular
Problems Associated With Aviation Safety. Eighth Bethesda Conference of
the American College of ‘ardiology. FAA Office of Aviation Medicine Report,
FAA-AM-78-38: pp 59-66, 1978

Jones SR, Binder RA, Donowhoe EM: Sudden death in sickle cell trait. N Eng)
J Med 282:323-325, 1970

Zimmerman J, Mummert K: Sickle crisis Precipitated by exercise rhabdomyolysis.
Mil Med 139:313-315, 1974

Koppes GM, Daly JJ, Coltman CA, et al: Exertion-induced rhabdomyolysis with
acute renal failure and disseminated intravascular coagulation in sickle cell
trait. Am J Med 63:313-317, 1977

Patten BM, Wood JM, Harati Y, et al: Familial recurrent rhabdomyolysis cue
to carnitine palmityl transferase deficiency. Am J Med 67:167-171, 1979
*

Niwa T, Imoto M, Okubo M, et al: Acute renal failure due to rhabdomyolysis
in B-thalassemia trait. Lancet 2:476, 1979

11

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Zurich is not easily detected, and as far as 1 know, no screening programs
for it have been instituted. .

CONCLUSIONS

Sickle cell trait has been associated in the medical literature with
a variety of pathological conditions.* With the possible exception of
malaria, the trait has not been Proven to protect against any disease;
therefore, it is not surprising that people with the trait have in che past,
and will in the future, become i11 or injured, The most convincing evidence,
based on studies of large populations and on controlled experiments, inaicaces
that people with the trait are not unusually susceptipie wv the moderace hypoxemia
of altitude or of competitive sports. There are hemoglobin phenotypes that may
confer abnormal susceptibility to certain industrial po}tutants, but HbS has not
been proven to be one of these hemoglobins.

*For sther references dealing with SCT and health see the review by Sears (42).

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