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Special Communication

Summit on Exercise Collapse Associated with Sickle Cell Trait: Finding the “Way Ahead”

O'Connor, Francis G. MD, MPH, FACSM; Franzos, M. Alaric MD, MPH; Nye, Nathaniel S. MD; Nelson, D. Alan MPAS, PhD; Shell, Donald MD, MA; Voss, Jameson D. MD, MPH; Anderson, Scott A. ATC; Coleman, Nailah J. MD, FACSM; Thompson, Alexis A. MD, MPH; Harmon, Kimberly G. MD, FACSM; Deuster, Patricia A. PhD, MPH, FACSM

Author Information
Current Sports Medicine Reports: January 2021 - Volume 20 - Issue 1 - p 47-56
doi: 10.1249/JSR.0000000000000801
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Sickle cell trait (SCT) and its association with exertional rhabdomyolysis (ER) and exercise-related death (ERD) in warfighters and athletes (WA) are significant and controversial issues confronting sports medicine communities (SMC), the U.S. Department of Defense (DoD), and other health care providers (1–4). Approximately 300 million people worldwide and nearly 7.8% of African Americans in the United States (~3 million individuals) have SCT (5). SCT is not uncommon in military personnel. Singer et al. (6), in retrospective cohort review, identified data that suggested SCT-positive service members deployed more frequently, for greater lengths of time, and remained in service longer when compared with those identified as SCT-negative. Although SCT carrier status is largely considered benign, risks with regard to exertion are increasingly being recognized (1,7).

The deaths of two soldiers in 2010 prompted the convening of a summit by the Consortium for Health and Military Performance (CHAMP) at the Uniformed Services University in Bethesda, Maryland. In collaboration with the American College of Sports Medicine (ACSM), interested DoD entities, the American Medical Society for Sports Medicine (AMSSM), the American Society of Hematology (ASH), and selected members of the SMC met to discuss SCT with particular emphasis on mitigating risk in WA. During that summit the term “Exercise Collapse Associated with Sickle Cell Trait” (ECAST) was introduced, and a plan was proposed for rapid recognition, early treatment, transport to a hospital, and return to duty/play (RTDP) for the WA (8).

A series of ECAST deaths in military personnel in 2019 prompted a reevaluation of current efforts and called for a second consensus conference (9). Thus, on October 8 and 9, 2019, CHAMP convened a second summit to specifically address ECAST. Participants included multiple experts: scientists and physicians from the DoD; representatives from ASH, ACSM, AMSSM; the Collegiate Athletic Trainer Society; the Korey Stringer Institute; the National Heart, Lung, and Blood Institute; National Collegiate Athletic Association (NCAA); and other SMC members. The goal was to again raise questions, engage in discussions, and formulate solutions to include a robust research agenda. Specifically, we described the current literature, reviewed existing policies, discussed educational needs, debated universal precautions, and contemplated the best approaches for managing and returning the WA with an ECAST to duty. Lastly, we deliberated on the key priorities for future research.

Methods and Approach

The summit at CHAMP opened by reviewing the current state of the literature and describing current policies in the military and civilian sectors. Six facilitated discussions followed to develop a “way ahead.” The session topics included: (1) screening and identification of the SCT in WA; (2) education: who, what, when, where and how; (3) universal precautions; (4) management of ECAST; (5) RTDP; and 6) developing a research agenda to address gaps.

Summit Results and Recommendations

ECAST: A Review of the Literature

The distinctive clinical presentations of ECAST events are well described in the literature; generally the result of an intense individual effort. ECAST is described (Fig. 1) as a spectrum of clinical presentations, which varies from ischemic muscle pain to fulminant collapse (2,10). ECAST has been noted in WA across various levels of training/conditioning and competition. In football conditioning, the proximate trigger for ECAST appears to be high-intensity exercise, with the typical setting reported as near maximal exertion, repeated or sustained, with limited recovery. Of the 10 Division-I football players with SCT who died between 2000 and 2010, five had been doing serial sprints and four had been doing fast-tempo, multistation drills, with little or no rest between stations. ECAST in association with football can seemingly occur after finishing an hour-long, fast-tempo station drill or after being on-field only briefly, for example, sprinting “all-out” for only 2 to 5 min (2,11).

Figure 1
Figure 1:
Case Description of an ECAST event.

The first serious attention to ECAST in the military occurred with several case reports on the deaths of four SCT+ recruits during 1968 to 1969 (12). Kark (13) focused on ERD and SCT in 1981 after additional SCT-associated deaths were observed throughout the 1970s. An increase in exertion-related mortality risk associated with SCT in the recruit population was noted in this early research (14). The group also recognized the occurrence of ER with ECAST (15). An association between ER and SCT was further suggested in other work (16).

However, in the same era, no association was seen between SCT and overall mortality in other studies (17,18). Whereas most studies did not focus on active populations for ECAST, the association between SCT and mortality was greeted with some controversy, as SCT was thought to be largely benign (19). In 1982, Kark's group (13) had proposed that U.S. military training expand its approaches to mitigating the effects of heat illness. The measures pursued were “universal” in the sense of being applied to all persons in a given population at risk for exertional collapse, not just to those with SCT. Precautions included a range of primary and secondary prevention techniques, such as wet bulb globe temperature monitoring with associated activity adjustments, closer monitoring of and response to symptoms during exercise participation, and enhanced body cooling resources for first responders during high-risk events, such as large-group runs and ruck marches (20). Kark et al. (21) studied SCT-related death rates among 2.3 million recruits who experienced universal precautions during 1982 to 1991 compared with 1.2 million who did not. They found that excess mortality associated with SCT was absent when such universal precautions were applied. However, this important finding was not broadly published and only released as an abstract (21).

The military has continued to study the association between SCT with exertion-related events. A modest association between ER and SCT was seen in later research in the setting of the U.S. Army, which continued to use and augment universal precautions (22). This work supported earlier findings suggesting a SCT-ER relationship by using less robust analyses (16,23). Studies in large military groups have demonstrated mixed findings for the association of SCT and heat illness. One U.S. Army study revealed small effect sizes for SCT and heat illness without statistical significance (24). A further study of the total U.S. military services found a significant and slightly higher effect size for SCT and heat illness (25). With regard to mortality in the active duty population, a large study of U.S. Army soldiers found no association for SCT and overall mortality when universal precautions were used (22). A small nonsignificant association was reported for SCT and mortality in the total U.S. military (6). It is important to note that Kark's early work demonstrated an increased mortality risk involving only recruits, which may be the most vulnerable cohort of the total military population.

ECAST also has been of great concern to athletic programs, particularly among football players. A 2012 study (26) noted a significantly higher mortality risk from exertion among U.S. collegiate football players with SCT than non-SCT players, which was similar to that observed in the military sphere prior to adopting universal precautions. However, after the NCAA implemented universal SCT screening, targeted education, and tailored precautions, the rate of ECAST-related deaths among its athletes decreased markedly (27). Concerns about the contribution of SCT to the risk of ERD among athletes and other active individuals (28) in unrestricted training currently demand prudent recommendations and precautions for WA safety.

Facilitated Discussions

1. Identification and Screening of the SCT Athlete/Warfighter

Identification and Testing

Laboratory testing for the presence of sickle hemoglobin includes isoelectric focusing (IEF), high pressure (also called high performance) liquid chromatography (HPLC), hemoglobin electrophoresis, and/or genetic testing (29,30). Sickle cell solubility tests and sickle prep tests have the added requirement for follow-up confirmatory tests. Hemoglobin electrophoresis, HPLC, and IEF are methods used either for primary identification of SCT or as confirmatory tests. These confirmatory techniques can provide discrimination and relative quantification of hemoglobin types, which allows for differentiation of SCT from other hemoglobinopathies. Hemoglobin electrophoresis is an inexpensive and frequently used technique (31).

Sickle cell testing is available through private and local public health clinics or via a community-based sickle cell disease (SCD) organization. Additionally, the Sickle Cell Disease Association of America (SCDAA) can provide testing locations available in local communities. Hasty adoption of early mass screening programs for SCD, recent implementation of targeted screening mandates for SCT in athletics, and concerns about stigmatization have evoked considerable controversy regarding research and policy decisions for SCT. The historical background of SCD and SCT has provided lessons about how research should be conducted in the modern era to minimize stigmatization, optimize study conclusions, and inform genetic counseling and policy decisions for SCT (32).

Newborn and Adult Screening

In 1987, prompted by government policies and the Prophylactic Penicillin Study, universal screening for hemoglobinopathies for all U.S. newborns was recommended by the National Institutes of Health Consensus Development Conference on Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies (29,33). By the end of 2002, 44 states performed newborn screening for sickle cell, with all states and the District of Columbia screening by 2006 (29,34). Recommendations from the 2008 U.S. Preventive Services Task Force concluded with high certainty a substantial net benefit by including sickle cell screening in newborns (35). Although widespread testing has occurred since 2006, and reporting to families and providers has been successful for SCD, it is variable for SCT status because the program was not designed to address the challenges with SCT. As such, many parents of children with SCT may be unaware of their child's screening status (30), and currently, no national database or repository for SCT status exists. Thus, parents and individuals without information regarding SCT status should be offered screening, as appropriate.

Despite protocols for the newborn screening program in the United States, genetic counseling and follow-up for individuals who test positive for SCT remain poor, secondary to wide variability in state policies regarding notification. In adulthood, screening for SCT may be included as part of preconception counseling (36) or to provide prenatal diagnosis to at-risk couples (37). Also, individuals born before 2006 or immigrants from countries without routine screening may not know their status.

Screening in Athletes

In 2010, the NCAA approved sickle cell testing for its Division I athletes. The policy was adopted as part of a litigation settlement following the ERD of a 19-year-old freshman during intense football training in the setting of an unknown diagnosis of SCT. The NCAA later extended SCT screening policies to Division II (2012) and Division III (2014) (31). The NCAA requires all participating student-athletes to provide confirmation of SCT status through existing documentation from birth or confirmation of recent screening, undergo testing, or provide a written opt-out provision (38,39).

The utility and ethical implications of mandatory screening of athletes are regularly debated. The ASH, SCDAA, American Public Health Association (APHA), Association of Public Health Laboratories, American Society of Clinical Pathology, and the American Society of Pediatric Hematology-Oncology all recommend against screening and instead favor “universal precautions” (30,40). No doubt, mandatory screening will continue to be controversial.


DoD medical policy resides within the office of the Under Secretary of Defense for Personnel and Readiness, with development and implementation assigned to the Assistant Secretary of Defense for Health Affairs (ASD/HA). The current policy for screening for SCT is established in the DoD Instruction (DoDI) 6465.01 Erythrocyte Glucose-6-Phosphate Dehydrogenase Deficiency and Sickle Cell Trait Screening Programs. This DoDI states that sickle cell screening will be done according to service-specific operational requirements. The Army ceased universal sickle cell screening in 1996, whereas the Navy and Air Force apply standard protocols to screen for SCT at enrollment.

Under the authority and direction of the ASD/HA, the Defense Health Agency (DHA) is the execution arm and establishes minimum requirements and criteria for service-specific requirements. The DHA recently released a Procedural Instruction 6025.14 (41) in 2018 to address sickle cell screening of active duty service members (ADSMs). Screening may occur at different points during military service (e.g., at appointment, enlistment or induction, or during military service for service members who meet demographic, clinical, or operational criteria, as developed by each service). Thus, current policy enables sickle cell screening for personnel at the appropriate point of care, which may occur if screening is deemed necessary for a particular assignment or duty, based on the perceived risk of the activity related to SCT. Similar to the civilian population, pregnant female ADSMs are offered sickle cell screening (if not already done), and all newborns are screened for SCT and disease (41).

SCT screening policy in the military is dynamic. Recently, Tri-Service and Coast Guard representation on the Council on Recruit Basic Training recommended its desire that “all at-risk recruits be given the Hemoglobin S Evaluation prior to arriving at basic training.” Screening options may include requiring recruits born on or after 2006 to access and provide newborn, prenatal, or athletic participation SCT test results. Above all, policy and programmatic decisions requiring SCT screening must not result in stigmatization or the loss of opportunity, unless warranted, to protect the health and well-being of the service member. The development and implementation of future sickle cell screening programs must consider the following questions:

  1. Will requiring at risk or population-based sickle cell screening reduce morbidity or mortality of clinical complications (exercise-related exertional injury, renal abnormalities, venous thromboembolism) associated with SCT?
  2. Will requiring population-based sickle cell screening have an operational impact on readiness, resiliency, retention, and deployment of service members?
  3. How many recruits and service members need to be screened over a given time period to prevent one death or adverse event associated with SCT?
  4. What are the budgetary and manpower requirements associated with policies and programs requiring screening for SCT?
  5. Will testing for SCT result in the stigmatization of service members testing positive and adversely impact opportunities for career advancement?

2. Education: Who, What, When, Where, and How

Education is the foundation for prevention and early intervention in ECAST, yet awareness is limited. Studies from the last decade suggest that only 16% of polled individuals are aware of their own SCT status (42), and only 37% of parents report having been directly notified about the SCT status of their children (43). Screening has not been successful so education is key. Physician engagement increased after the NCAA implemented screening with 99% of pediatricians reporting SCT status to parents. However, only 71% counseled their patients on medical implications beyond reproductive, 59% ordered confirmatory testing (e.g., hemoglobin electrophoresis), and 27% were aware of the NCAA policy (44). Education on SCT is critical for clinic/hospital-based health care professionals, first responders, athletic trainers or instructors, team members, and the WA with SCT (and their caregiver if the WA is underage).

The topic of “who” should know the SCT status of the WA is an important ethical question not specifically discussed at this Summit. Policies developed by the various organizations that require screening will need to make decisions based on their environment on how to effectively identify those at risk and determine who needs access (e.g., medical providers, first responders, cadre, leaders, teammates) to such personal health information. Multiple online educational resources available at Human Performance Resources by CHAMP, the NCAA, and other organizations are presented in Table 1.

Table 1 - Selected web site resources for ECAST and universal training precautions.
▪ CHAMP Sickle Cell Trait Awareness
▪ CDC Keeping Workers Hydrated and Cool Despite the Heat
▪ Heat Work/Rest Sample Schedules
▪ Heat Stress Acclimatization
▪ CDC Acclimatization
▪ Ranger & Airborne School Students Heat Acclimatization Guide
▪ ACH Sickle Cell Trait
▪ OSHA About Work/Rest Schedules
▪ NCAA Student Athlete Fact Sheet — Sickle Cell Trait
▪ NCAA Coach Fact Sheet — Sickle Cell Trait

Education of the First Responders and Health Care Professionals

All first responders should be educated about the risks associated with SCT to include splenic infarction, pulmonary embolism, and ECAST (e.g., ER, ERD), as well as the universal training precautions outlined in Section 3. Likewise they should be clearly informed on the management of ECAST (Section 4 below), as well as on the ethical implications of screening (44–46). In addition to following standard protocols for collapse, first responders also must appreciate the potential benefit of delivering oxygen to the SCT positive WA even with normal oxygen saturation. Because extreme hypoxia is known to precipitate vaso-occlusive events in SCT individuals and in vitro studies show abnormal blood rheological changes with modest reduction in oxygen thresholds, early application of oxygen may reduce exertional sickling in the microvasculature (47–49).

ECAST victims that survive to hospital-based care often display a recalcitrant metabolic crisis. When ECAST is suspected, a radio report to the receiving emergency department should include concern for a metabolic emergency in a WA with SCT (see link to CHAMP's training for first responders and cadre in Table 1). Although awareness of ECAST is increasing in sports medicine and pediatric circles, health care professionals in primary, emergency, and critical care also should receive training beyond the reproductive implications of SCT.

Education of the Coach, Trainer, or Instructor

The coach, trainer or instructor (training recruits or monitoring fitness testing) also must understand the ECAST prodrome and apply universal training protocols outlined below. Excessive motivation is equally important to recognize as a risk factor, as an individual can push too hard while ignoring the onset of physical signs and symptoms of distress. Ideally, leadership creates an environment supportive of WA with SCT to report signs and symptoms as trainers/instructors understand the physical fitness of their WA and know when to stop or modify exercise when they observe someone struggling. If they witness a conscious collapse and the individual is too weak to stand back up, they must activate the emergency medical system.

Education of the SCT-positive WA

Because of the significant misunderstanding surrounding the possible implications of SCT and concerns with stigma, degree of awareness, polarized opinions and the like, the SCT-positive WA should receive standardized counseling upon entry into an athletic or military program, regardless of prior knowledge of SCT status (50,51). In addition to explaining the reproductive and familial repercussions, the SCT-positive WA should be counseled on universal precautions (see below in section 3) and the rare, but serious, associated complications of an ECAST event (45). Potential Risk factors can be personal, environmental, or external. Some of the personal risk factors may include the following: dehydration, recent or current illness, accumulated fatigue, poor baseline conditioning, a predisposing or underlying cardiac condition, asthma, recent vaccination, excess body fat (body mass index over 30 kg/m2), and prior exercise-related collapse (24,25,52–54). Environmental factors may include lack of appropriate environmental acclimatization, change to higher altitude, high ambient temperature, and humidity.

External factors may include prescription and over-the-counter medications (sympathomimetic antihistamines, antipsychotics, decongestants, and statins) (22,24) and dietary supplements containing stimulants (e.g., for weight loss or preworkout, energy drinks). The degree to which these risks can be mitigated through following and maintaining the universal training precautions described next continues to be studied. However, leadership is perhaps the most important consideration and critical for minimizing ECAST risk (55). Importantly, because awareness may wane with time, it is reasonable to reinforce these precautions periodically with leadership and the WA, such as during the military's annual periodic health assessment or after a prolonged break in training for the student athlete.

3. Universal Training Precautions

The concept of universal training precautions (UTP) for mitigating SCT emerged in the 1990s after selected ECAST deaths were shown to be associated with dehydration and exercise in the heat. However, the concept of UTP per se is illusive as no formal guidelines exist for implementation. Importantly, UTP would apply to all and would reduce the risk of any and all exertion-related events: heat illness, ER, ECAST, ERD, and the like. If one considers the spectrum of precautions that might be taken to protect any service member or civilian athlete from exertion-related events a long list will emerge. The most common considerations are briefly described.

Fitness Status and Exercise Progression

Physical fitness status and exercise progression are extremely important for mitigating exertion-related events and, in particular, ECAST (56). For all WA, progressive and graduated increases in load/intensity should be tailored to their current fitness level. Fitness/sports specialists/instructors can be taught the signs and symptoms of an impending ECAST event. The bottom line is always that exercise training “should represent a priority in strategies related to lifestyle modification” (57). The benefits of exercise far outweigh the risks, and we must be careful not to marginalize those with SCT — exercise is critical to military performance, sports participation, and overall health (56).

Environmental Conditions

The two primary environmental conditions of interest are heat and altitude, as evidence suggests, they are potential risk factors for ECAST (24,25,58–60). Leadership and the WA should be made aware of these risks and be given time to sufficiently acclimate/acclimatize (61–63). To date, no standard guidelines for acclimating either to heat or at altitude have been established, but the U.S. Army recommends 2 wk of daily heat exposure for about 2 h·d−1 (can be broken into two 1-h exposures) combined with physical exercise (marching or jogging) to induce heat acclimatization (see Table 1). Likewise, no definitive guidelines for acclimatizing to altitude are available, in part because the process depends on the altitude where the WA would be working/playing. Also, the proposed schedules differ for low, moderate, and high altitude. However, general guidelines would suggest that acclimatization is elevation specific, such that full acclimatization at one altitude would only partially confer acclimatization to a higher altitude (64). The U.S. Army has a technical bulletin — TB MED 505 —with excellent information for acclimatizing at altitude (65). Online resources for environmental considerations are presented in Table 1.

Hydration and Work/Rest Cycles

Hydration is a well-accepted precaution against multiple exertion-related events and guidelines for both military members and athletes have been put forward. For example, legislative bodies in North America, such as the Occupational Safety and Health Administration (OSHA) and the American Conference of Governmental Industrial Hygienists recommend replacing fluids frequently when exposed to heat stress, with one cup (250 mL) every 15 to 20 min when working in warm environments being a consistent recommendation (66). The composition of the fluid also may be very important if strenuous work takes place under warm/hot conditions, as workers/WA do not always ingest sodium-sufficient foods during meals. Thus, electrolyte replacement may be needed during hot weather physical activities (66). This would be a leadership recommendation but could be critical for protecting workers and WA from untoward events.

The concept of work/rest cycles also has been used for many years by the military and occupational safety specialists. Table 2 presents the current hydration/fluid replacement and work/rest cycle recommendations for the military.

Table 2 - Fluid replacement and work-rest cycle guidelines for training in warm and hot environments. *
Easy Work (250 W) Moderate Work (425 W) Heavy Work (600 W) Very Heavy Work (800 W)
Heat Category WBGT Index (°F) Work-Rest Water Intake (qt·h−1) Work-Rest Water Intake (qt·h−1) Work-Rest Water Intake (qt·h−1) Work-Rest Water Intake (qt·h−1)
1 78–81.9 NL* ½ NL ¾ 50/10 ¾ 25/35 1
2 (Green) 82–84.9 NL ½ NL ¾ 40/20 1 20/40 1
3 (Yellow) 85–87.9 NL ¾ NL ¾ 35/25 1 20/40 1
4 (Red) 88–89.9 NL ¾ 50/10 ¾ 25/35 1 15/45 1
5 (Black) >90 NL 1 35/25 1 20/40 1 10/50 1
*NL, no limit to work time per hour (up to 4 h); Rest, minimal activity and in shade if possible;
Hourly fluid intake should not exceed 1.5 qt and daily fluid intake should not exceed 12 qt.
Easy work: 250 W ~ 3.5 kcal·min−1 Maintaining weapon; drills and ceremonies; walking a dog; yoga; raking; washing clothes; golfing Moderate work: 425 W ~ 6 kcal·min−1
Patrolling with 25 lb load; Stair climbers; rowing 5 km·h−1.; cutting wood; biking 15 km·h−1; hiking; low and high crawl; tennis
Heavy Work: 600 W ~ 8.4 kcal·min−1 Walking and climbing briskly up hills; patrolling with 45 lb. load; 4-person litter carry; jogging 9 km·h−1; cycling 25 km·h−1; cross-country skiing 7 km·h−1; Very Heavy Work: 800 W. ~ 11.2 kcal·min−1 Obstacle course; 2-person litter carry (150 lbs.); basketball game; jogging 11 km·h−1; judo; skipping rope 100 steps per minute; swimming 3.5 km·h−1
*Adapted from TB Med 507, Table 3-2.

Drugs, Medications, and Dietary Supplements

Another UTP should be a careful and individualized evaluation of drugs, medications, and dietary supplements containing combinations of stimulants and selected other ingredients that impact the cardiovascular system (22,24,67–69). As noted in the education section, many of these products contain various sympathomimetic, caffeine, herbal/other ingredients/drugs that can mediate vasodilation and increase heart rate and metabolic heat load (70). All prescription drugs/dietary supplements should be carefully reviewed and cleared, and any product containing caffeine in excess of 300 mg should be prohibited. Service members and athletes should be discouraged from taking weight loss, preworkout, and other drugs/dietary supplements containing one or multiple stimulants (71). This precaution should be enforced for WA with and without SCT.

General Precautions

A variety of other general procedures (some of which may be controversial) that could be incorporated into UTP include:

  • Provide a cool-down period wherein exercise continues for 5 to 10 min, but at a much slower pace and reduced intensity
  • Have a buddy system that serves to stop a teammate when that teammate is clearly in distress and ignoring signs and symptoms
  • Recognize undue pressure (whether from a peer or a superior) to finish a high-intensity workout or physical fitness test (72)
  • Educate staff and peers on what to look for in terms of early signs of distress and having them ready to call for medical assistance
  • Know how to activate emergency medical services (EMS) and access the appropriate level of medical care
  • Have access to an automated external defibrillator (AED) and oxygen available in case of an emergency

Selected web sites with useful information relating to universal precautions and acclimatization are provided in Table 1.

4. Management of Exercise Collapse Associated with SCT

ECAST is a term describing an observed event with a varied, yet distinctive, clinical presentation; clinical recognition is fundamental to the event's management and emergency action plan (8). Although many case reports detailing ECAST have commonalities, they can be unique (2,56). Perhaps, the most striking commonality reported is the initial “conscious” collapse (10). That being stated, some reports detail an abrupt collapse event (73). A second commonality identified in recently observed ECAST events with subseqent death is the report of an initial “nonshockable rhythm” by providers on the scene; this suggests pulseless electrical activity. The working group agreed upon a case defnition to assist with future clinical and research efforts (Fig. 1). Core to any potential life-saving intervention is the clinical differentiation of an ECAST event. Eichner and Anderson (74) have identified clinical clues to assist the provider in distinguishing ECAST from other etiologies of collapse that may occur in WA (see Table 3).

Table 3 - Differentiating features of common causes of exertional collapse*.
ECAST Muscle Cramping Exertional Heat Stroke Cardiac Collapse
Slumps to the ground Hobbles to a halt Variable from bizarre behavior to collapse Falls like a rock
Weakness > pain Pain > weakness Fuzzy thinking No cramping
Can talk at first Yelling in pain Variable cognitive dysfunction Unconscious
Muscles normal Muscles locked up Variable Flaccid or seizing
Temperature, <103°F Temperature, <103°F Temperature, >104°F Temperature, nonspecific
Can occur early in exercise Usually occurs later in exercise Usually occurs later in exercise Limited to no warning
*Adapted from Eichner and Anderson (74).

No evidence-based guidelines for managing an ECAST event are currently available. The management of a WA with suspected ECAST involves a “chain of survival” and proper execution of emergency action plans. The plan should consist of rapid recognition, early treatment, transportation to a hospital (if not responsive to initial treatments or unconscious), and communication with emergency room staff regarding the suspected diagnosis, likely threats, possible treatment course, and suggested interventions (Fig. 2).

Figure 2
Figure 2:
Management of an ECAST event.

Communication with the receiving emergency room staff is critical to the management of ECAST. The receiving facility must be made aware of the differential diagnosis and likelihood of ECAST with accompanying hypermetabolic state and explosive ER. Interventions in the emergency room include aggressive fluid and electrolyte management, blood gas monitoring to rule out metabolic acidosis, cardiac monitoring, and possibly dialysis to control hyperkalemia. Patients with severe ECAST may rapidly develop hyperkalemia and lethal cardiac arrhythmias within minutes to hours of presentation (11,53). Any reasonable treatment to avert these outcomes should be instituted.

Evidence based guidance to assist in the prehospital management of an ECAST event is limited (75). The National Athletic Trainers' Association published a consensus document in 2007 that recommended the initiation of high flow oxygen in ECAST, but no controlled trials either support or refute this intervention. Additional military and civilian consensus publications support administering oxygen, along with consideration of intravenous hydration and making emergency equipment available in the event of cardiac arrest (76,77). However, a clear need exists for validating: 1) oxygen requirements, 2) the value of initiating intravenous hydration, and 3) the optimal strategy for managing cardiac arrest with particular attention to ECAST-induced pulseless electrical activity.

5. Return to Duty/Play

RTDP decisions are among the most challenging issues confronting the team and military physician (78). Ideally, the RTDP decision would be directed by high-quality, patient-oriented evidence. However, in many situations, the evidence is sparse or lacking, and a general framework must be used to guide RTDP decisions. The framework should consist of medical factors and sport- or duty-specific risk factors/modifiers and include elements that may modify decision making (79). Ultimately, each RTDP decision must be individualized based on the specific facts and circumstances to include risks to teammates and, for the military provider, risk to the mission.

Currently, no evidence-based RTDP guidelines exist for an episode of ECAST (78). However, the consensus opinion during the 2011 CHAMP summit was that RTDP should not be considered until the WA was asymptomatic at rest and had normal end-organ function (8). During the 2019 summit, considerable discussion validated a return to normal baseline status and additionally addressed the question of subsequent ECAST risk. To date, the risk of the WA with a prior ECAST event experiencing a future event remains unknown (8,25).

At the 2019 CHAMP summit, intrinsic and extrinsic factors proposed as suggestive of recurrence included the following: (the inability to concentrate urine >450 mOsm·kg−1 under water-deprived conditions), early chronic kidney disease, other associated hemoglobinopathies, an underlying metabolic myopathy, or a heretofore undescribed genetic variant or mutation. Hydration has been directly implicated in abnormal hemorheology, which may contribute to sickling and an increase in RBC viscosity. Accordingly, the presence of hyposthenuria may be a potential risk factor for ECAST recurrence. Hyposthenuria is a universal finding in patients with SCD but also may be identified in those with SCT (80).

Genetic variation also has been postulated to impact ECAST risk. Alpha thalassemia has been proposed as a potential “lifesaver” that may mitigate ECAST risk by decreasing the percentage of HbS. Specifically, coinheritance of α-thalassemia gene deletions with SCT decreases the percentage of HbS in a dose-dependent manner, such that individuals with a higher number of α-thalassemia deletions demonstrate the lowest percentage of HbS (32). On the other hand, Thein (81) has identified the increased risk associated with a co-inheritance of pyruvate kinase deficiency. Pyruvate kinase, one of the final steps of glycolysis, converts phosphoenolpyruvate to pyruvate, which generates more than 50% red blood cell ATP. Of particular relevance to SCD, a reduction in pyruvate kinase activity leads to accumulation of upstream substrates that decrease oxygen affinity and favor polymerization of deoxy-HbS. In these cases, genetic testing for potential associated abnormalities and consultation with an appropriate specialist familiar with SCT and exercise are recommended (7). Figure 3 represents a consensus clinical algorithm developed at the summit to guide military providers with RTDP decision making.

Figure 3
Figure 3:
ECAST return to duty algorithm.

6. Developing a Research Agenda to Address Gaps

Despite considerable research since ECAST was first defined in 2011, the SMC and public health organizations continue to debate about the best way forward. Real-world risk management can combine multidisciplinary perspectives by applying clinical insights from the SMC into a public health approach for preventing ECAST events in real time. The three core functions in public health are assessment, policy development, and assurance. Prioritizing future research can address each function while considering the maturity of different lines of investigation, the feasibility of implementation, and the level of prevention (e.g., primary, secondary, and tertiary). Importantly, the public health approach is not static, sequential, or limited to a specific stakeholder. Instead, these functions are ongoing, collaborative, and iterative. Figure 4 helps summarize open questions across the functions and prevention levels. As we look to the next decade of ECAST research and mitigation, we also need to plan for sustainment so a third ECAST summit is not prompted by a tragic cluster of deaths but by a shared commitment to continued implementation of UTP and sharing of new information.

Figure 4
Figure 4:
Proposed iterative way forward.


ECAST is a clinical challenge for WA and leaders in the military and SMC. Consensus strategies are presented, to include use of UTP, clinical management, and RTDP considerations. However, further basic science and clinical research are urgently needed to determine the mechanisms and origin of ECAST. Research will assist in unraveling the etiology of, genetic contributions to, and advancing clinical interventions for managing ECAST. These actions will allow us to improve our current clinical guidance and existing policies. It is our expectation that this guidance and research agenda will ensure and enhance the safety of WA with SCT to participate and enjoy sports and service in the military without stigma.

The authors would specifically like to acknowledge the contribution of the following individuals to the ECAST conference: Keith W. Hoots, MD, NHLBI; LaGwyn Durden, ATC, NCAA; Clifford Marc Madsen, DO; Christopher Meyering, MD; Steve Blivin, MD; William B. Adams, MD; Rakhi Naik, MD, MHS; Brendon McDermott, PhD, KSI; Swee Lay Thein, MD, NHLBI; Aaron Pitney, MD; Neil Page, MD; Bryant Webber, MD MPH; Valerie Castle, DO, MPH; Carlton Covey, MD; Ms. Stephanie Van Arsdale; David W. DeGroot, PhD; and Benjamin Buchanan, MD.

The authors declare no conflict of interest and do not have any financial disclosures.

Disclaimer: The views expressed herein are those of the authors and do not reflect the official policy or position of the Uniformed Services University, Defense Health Agency, Department of the Air Force, Department of the Army, Department of Defense, or the U.S. Government.


1. Key NS, Derebail VK. Sickle-cell trait: novel clinical significance. Hematology Am. Soc. Hematol. Educ. Program. 2010; 2010:418–22.
2. Eichner ER. Sickle cell considerations in athletes. Clin. Sports Med. 2011; 30:537–49.
3. Tsaras G, Owusu-Ansah A, Boateng FO, Amoateng-Adjepong Y. Complications associated with sickle cell trait: a brief narrative review. Am. J. Med. 2009; 122:507–12.
4. Goldsmith JC, Bonham VL, Joiner CH, et al. Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications. Am. J. Hematol. 2012; 87:340–6.
5. Jordan LB, Smith-Whitley K, Treadwell MJ, et al. Screening U.S. college athletes for their sickle cell disease carrier status. Am. J. Prev. Med. 2011; 41:S406–12.
6. Singer DE, Chen L, Shao S, et al. The association between sickle cell trait in U.S. service members with deployment, length of service, and mortality, 1992–2012. Mil. Med. 2018; 183:e213–8.
7. Xu JZ, Thein SL. The carrier state for sickle cell disease is not completely harmless. Haematologica. 2019; 104:1106–11.
8. O'Connor FG, Bergeron MF, Cantrell J, et al. ACSM and CHAMP summit on sickle cell trait: mitigating risks for warfighters and athletes. Med. Sci. Sports Exerc. 2012; 44:2045–56.
9. Keilman J. After 2 boot camp deaths at Great Lakes base, Navy urges vigilance for recruits with sickle cell trait. Chicago Tribune. May 21, 2019.
10. Hughes RL, Feig J. Sickle cell trait-related exertional deaths: observations at autopsy and review of the literature. Mil. Med. 2015; 180:e929–32.
11. Eichner ER. Sickle cell trait. J. Sport Rehabil. 2007; 16:197–203.
12. Jones SR, Binder RA, Donowho EM Jr. Sudden death in sickle-cell trait. N. Engl. J. Med. 1970; 282:323–5.
13. Kark JA [Internet]. Sickle cell trait. [cited 2020 Nov 10]. Available from:
14. Kark JA, Posey DM, Schumacher HR, Ruehle CJ. Sickle-cell trait as a risk factor for sudden death in physical training. N. Engl. J. Med. 1987; 317:781–7.
15. Gardner JW, Kark JA. Fatal rhabdomyolysis presenting as mild heat illness in military training. Mil. Med. 1994; 159:160–3.
16. Harrelson GL, Fincher AL, Robinson JB. Acute exertional rhabdomyolysis and its relationship to sickle cell trait. J. Athl. Train. 1995; 30:309–12.
17. Stark AD, Janerich DT, Jereb SK. The incidence and causes of death in a follow-up study of individuals with haemoglobin AS and AA. Int. J. Epidemiol. 1980; 9:325–8.
18. Castro O, Rana SR, Bang KM, Scott RB. Age and prevalence of sickle-cell trait in a large ambulatory population. Genet. Epidemiol. 1987; 4:307–11.
19. Naik RP, Smith-Whitley K, Hassell KL, et al. Clinical outcomes associated with sickle cell trait: a systematic review. Ann Intern Med. 2018; 169(9):619–27.
20. Dorn E. Sickle Cell Policy. 1996, p 2.
21. Kark J, Garder J, Ward F, Virmani R. Prevention of exertional heat illness protects recruits with sickle cell trait from exercise-related death. In: Proceedings of the Sickle Cell Disease Program, National Institute of Health. Washington, DC.; 1999.
22. Nelson DA, Deuster PA, Carter R 3rd, et al. Sickle cell trait, rhabdomyolysis, and mortality among U.S. army soldiers. N. Engl. J. Med. 2016; 375:435–42.
23. Deuster PA, Contreras-Sesvold CL, O'Connor FG, et al. Genetic polymorphisms associated with exertional rhabdomyolysis. Eur. J. Appl. Physiol. 2013; 113:1997–2004.
24. Nelson DA, Deuster PA, O'Connor FG, Kurina LM. Sickle cell trait and heat injury among US army soldiers. Am. J. Epidemiol. 2018; 187:523–8.
25. Singer DE, Byrne C, Chen L, et al. Risk of exertional heat illnesses associated with sickle cell trait in U.S. military. Mil. Fortschr. Med. 2018; 183:e310–7.
26. Harmon KG, Drezner JA, Klossner D, Asif IM. Death associated with sickle cell trait in National Collegiate Athletic Association football athletes. Br. J. Sports Med. 2012 Apr; 46:325–30.
27. Buchanan BK, Siebert DM, Zigman Suchsland ML, et al. Sudden death associated with sickle cell trait before and after mandatory screening. Sports Health. 2020; 12:241–5.
28. Mitchell BL. Sickle cell trait and sudden death. Sports Med Open. 2018; 4:19.
29. Ojodu J, Hulihan MM, Pope SN, Grant AM. Incidence of sickle cell trait—United States, 2010. MMWR Morb. Mortal. Wkly Rep. 2014; 63:1155–8.
30. Vichinsky EP. Sickle cell trait. UpToDate. 2019.
31. Naik RP, Haywood C Jr. Sickle cell trait diagnosis: clinical and social implications. Hematology Am. Soc. Hematol. Educ. Program. 2015; 2015:160–7.
32. Raffield LM, Ulirsch JC, Naik RP, et al. Common alpha-globin variants modify hematologic and other clinical phenotypes in sickle cell trait and disease. PLoS Genet. 2018; 14:e1007293.
33. Gaston MH, Verter JI, Woods G, et al. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N. Engl. J. Med. 1986; 314:1593–9.
34. US Government Accountability Office. Newborn screening: characteristics of state programs. 2003. [cited 2020 Nov 10]. Available from:
35. US Preventive Services Task Force. Screening for sickle cell disease in newborns: recommendation statement. Am. Fam. Physician. 2008; 77:1300–2.
36. Center for Disease Control and Prevention. Fact sheet: get screened to know your sickle cell status. 2019. [cited 2020 Nov 10]. Available from:
37. Health supervision for children with sickle cell disease. Pediatrics. 2002; 109:526–35.
38. 2014–15 NCAA Sports Medicine Handbook. 2014. [cited 2020 Nov 10]. Available from:
39. NCAA. NCAA Sickle Cell Trait (SCT) Testing - What You Need to Know. 2014. [cited 2020 Nov 10]. Available from:
40. American Society of Hematology. Statement on Screening for Sickle Cell Trait and Athletic Participation. 2012. [cite 2020 Nov 10]. Available from:
41. Defense Health Agency. Procedural Instruction 6025.15. In: Active Duty Service Member (ADSM) Erythrocyte Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Sickle Cell Trait (SCT) Screening. DHA Publications; 2018.
42. Kavanagh PL, Wang CJ, Therrell BL, et al. Communication of positive newborn screening results for sickle cell disease and sickle cell trait: variation across states. Am. J. Med. Genet. C: Semin. Med. Genet. 2008; 148C:15–22.
43. Treadwell MJ, McClough L, Vichinsky E. Using qualitative and quantitative strategies to evaluate knowledge and perceptions about sickle cell disease and sickle cell trait. J. Natl. Med. Assoc. 2006; 98:704–10.
44. Koopmans J, Ross LF. Identification and management of sickle cell trait by young physicians. J. Natl. Med. Assoc. 2012; 104:299–304.
45. Ferrari R, Parker LS, Grubs RE, Krishnamurti L. Sickle cell trait screening of collegiate athletes: ethical reasons for program reform. J. Genet. Couns. 2015; 24:873–7.
46. Acharya K, Benjamin HJ, Clayton EW, Ross LF. Attitudes and beliefs of sports medicine providers to sickle cell trait screening of student athletes. Clin. J. Sport Med. 2011 Nov; 21:480–5.
47. Kumar R, Kapoor R, Singh J, et al. Splenic infarct on exposure to extreme high altitude in individuals with sickle trait: a single-center experience. High Alt. Med. Biol. 2019; 20:215–20.
48. Lu X, Chaudhury A, Higgins JM, Wood DK. Oxygen-dependent flow of sickle trait blood as an in vitro therapeutic benchmark for sickle cell disease treatments. Am. J. Hematol. 2018; 93:1227–35.
49. Connes P, Renoux C, Romana M, et al. Blood rheological abnormalities in sickle cell anemia. Clin. Hemorheol. Microcirc. 2018; 68:165–72.
50. Creary S, Adan I, Stanek J, et al. Sickle cell trait knowledge and health literacy in caregivers who receive in-person sickle cell trait education. Mol Genet Genomic Med. 2017; 5:692–9.
51. Acharya K, Lang CW, Ross LF. A pilot study to explore knowledge, attitudes, and beliefs about sickle cell trait and disease. J. Natl. Med. Assoc. 2009; 101:1163–72.
52. Tripette J, Loko G, Samb A, et al. Effects of hydration and dehydration on blood rheology in sickle cell trait carriers during exercise. Am. J. Physiol. Heart Circ. Physiol. 2010; 299:H908–14.
53. Bergeron MF, Cannon JG, Hall EL, Kutlar A. Erythrocyte sickling during exercise and thermal stress. Clin. J. Sport Med. 2004; 14:354–6.
54. Loosemore M, Walsh SB, Morris E, et al. Sudden exertional death in sickle cell trait. Br. J. Sports Med. 2012 Apr; 46:312–4.
55. O'Connor FG, Grunberg NE, Harp JB, Deuster PA. Exertion-related illness: the critical roles of leadership and followership. Curr. Sports Med. Rep. 2020; 19:35–9.
56. Liem RI. Balancing exercise risk and benefits: lessons learned from sickle cell trait and sickle cell anemia. Hematology. 2018; 2018:418–25.
57. Mendes R, Sousa N, Reis VM, Themudo-Barata JL. Prevention of exercise-related injuries and adverse events in patients with type 2 diabetes. Postgrad. Med. J. 2013; 89:715–21.
58. Franklin QJ, Compeggie M. Splenic syndrome in sickle cell trait: four case presentations and a review of the literature. Mil. Med. 1999; 164:230–3.
59. Sheikha A. Splenic syndrome in patients at high altitude with unrecognized sickle cell trait: splenectomy is often unnecessary. Can. J. Surg. 2005; 48:377–81.
60. Thiriet P, Le Hesran JY, Wouassi D, et al. Sickle cell trait performance in a prolonged race at high altitude. Med. Sci. Sports Exerc. 1994; 26:914–8.
61. Daanen HAM, Racinais S, Periard JD. Heat acclimation decay and re-induction: a systematic review and meta-analysis. Sports Med. 2018; 48:409–30.
62. Rahimi GRM, Albanaqi AL, Van der Touw T, Smart NA. Physiological responses to heat acclimation: a systematic review and meta-analysis of randomized controlled trials. J. Sports Sci. Med. 2019; 18:316–26.
63. Saunders PU, Garvican-Lewis LA, Chapman RF, Periard JD. Special environments: altitude and heat. Int. J. Sport Nutr. Exerc. Metab. 2019; 29:210–9.
64. Reeves JT, McCullough RE, Moore LG, et al. Sea-level PCO2 relates to ventilatory acclimatization at 4300 m. J Appl Physiol (1985). 1993; 75:1117–22.
65. Department of the Army. Altitude Acclimatization and Illness Management. In: Dot Army editor. Headquarters 2010.
66. Kenefick RW, Sawka MN. Hydration at the work site. J. Am. Coll. Nutr. 2007; 26(5 Suppl):597s–603s.
67. Brown AC. An overview of herb and dietary supplement efficacy, safety and government regulations in the United States with suggested improvements. Part 1 of 5 series. Food Chem. Toxicol. 2017; 107(Pt A):449–71.
68. Martinez M, Devenport L, Saussy J, Martinez J. Drug-associated heat stroke. South. Med. J. 2002; 95:799–802.
69. Mladenka P, Applova L, Patocka J, et al. Comprehensive review of cardiovascular toxicity of drugs and related agents. Med. Res. Rev. 2018; 38:1332–403.
70. Ely BR, Ely MR, Cheuvront SN. Marginal effects of a large caffeine dose on heat balance during exercise-heat stress. Int. J. Sport Nutr. Exerc. Metab. 2011; 21:65–70.
71. Figueredo VM. Chemical cardiomyopathies: the negative effects of medications and nonprescribed drugs on the heart. Am. J. Med. 2011; 124:480–8.
72. Raleigh MF, Barrett JP, Jones BD, et al. A cluster of exertional rhabdomyolysis cases in a ROTC program engaged in an extreme exercise program. Mil. Med. 2018; 183(suppl_1):516–21.
73. Fajardo KA, Tchandja J. Exercise-induced cardiac arrest in a sickle cell trait-positive Air Force recruit: a case report. Mil. Med. 2015; 180:e372–4.
74. Eichner ER, Anderson S. Exertional Sickling. In: DJ C, editor. Preventing Sudden Death in Sport and Physical Activity. Sudbury (MA): Jones & Bartlett Learning; 2012. p. 131–41.
75. Casa DJAS, Baker L, et al. The inter-association task force for preventing sudden death in collegiate conditioning sessions: best practices recommendations. J. Athl. Train. 2012; 47:477–80.
76. Webber BJ, Casa DJ, Beutler AI, et al. Preventing exertional death in military trainees: recommendations and treatment algorithms from a multidisciplinary working group. Mil. Med. 2016; 181:311–8.
77. Casa DJ, Almquist J, Anderson SA, et al. The inter-association task force for preventing sudden death in secondary school athletics programs: best-practices recommendations. J. Athl. Train. 2013; 48:546–53.
78. Asplund CA, O'Connor FG. Challenging return to play decisions: heat stroke, exertional rhabdomyolysis, and exertional collapse associated with sickle cell trait. Sports Health. 2016; 8:117–25.
79. Herring SA, Kibler WB, Putukian M. The team physician and the return-to-play decision: a consensus statement—2012 update. Med. Sci. Sports Exerc. 2012; 44:2446–8.
80. Naik RP, Derebail VK. The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait. Expert. Rev. Hematol. 2017; 10:1087–94.
81. Alli N, Coetzee M, Louw V, et al. Sickle cell disease in a carrier with pyruvate kinase deficiency. Hematology. 2008; 13:369–72.
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