Sudden Death Associated With Sickle Cell Trait Before and After Mandatory Screening

Abstract

Background:

Sickle cell trait (SCT) has been associated with an increased risk of sudden death in athletes during strenuous exercise. In August 2010, the National Collegiate Athletic Association (NCAA) began requiring athletes to be screened for SCT, provide proof of SCT status, or sign a waiver and launched an educational campaign for athletes, coaches, and medical staff. The impact of this program is unknown. The purpose of this study was to determine the incidence of death associated with sickle cell trait (daSCT) in NCAA athletes before and after legislation.

Hypothesis:

NCAA SCT legislation will decrease the incidence of daSCT.

Study Design:

Observational study.

Level of Evidence:

Level 2.

Methods:

A database of NCAA athlete deaths from 2000 to 2019 was reviewed for daSCT. A total of 8,309,050 athlete-years (AY) were included. Incidence of death was calculated before and after legislation.

Results:

The incidence of daSCT in Division I (DI) football athletes before legislation (n = 9) was 1:28,145 AY and after legislation (n = 1) was 1:250,468 AY (relative risk [RR], 0.112; 95% CI, 0.003-0.811; P = 0.022), an 89% reduction in risk after legislation was enacted. The incidence of daSCT in African American DI football athletes before legislation (n = 9) was 1:12,519 AY and after legislation (n = 1) was 1:118,464 AY (RR, 0.106; 95% CI, 0.002-0.763; P = 0.017), also an 89% risk reduction after legislation was enacted. For all NCAA athletes, the incidence of daSCT was 1:489,749 AY before legislation (n = 10) and 1:1,705,780 AY after legislation (n = 2) (RR, 0.288; 95% CI, 0.031-1.347; P = 0.146).

Conclusion:

The incidence of daSCT in DI football athletes has decreased significantly since legislation was enacted. Cases of daSCT outside of football are rare. It is unclear whether the decrease is related to screening for SCT, education, or both.

Clinical Relevance:

This is the first evidence that NCAA SCT legislation may save lives.

Sickle cell trait (SCT) is common, occurring in 7.3% of African Americans (approximately 1 in 14), 0.3% of Caucasians (approximately 1 in 133), and 0.7% of Hispanics (approximately 1 in 145) in the United States.²³ SCT has been reported as a leading cause of exertional death in football athletes, although others have questioned this perspective citing a lack of high-quality studies and concerns over the exact pathophysiologic and pathogenic role SCT plays in causing exertional death.^5,12,26 There are an estimated 840 football athletes and 3500 National Collegiate Athletic Association (NCAA) athletes in all sports participating with SCT each year. After several highly publicized deaths and subsequent lawsuits,^6-8,17,24,27 the NCAA passed legislation requiring that the SCT status of all athletes be documented from previous testing, testing repeated if status was unknown, or a waiver of liability be signed. This went into effect in August of 2010 for Division I (DI) athletes, August of 2012 for Division II (DII) athletes, and August of 2014 for Division III (DIII) athletes. In addition to screening for SCT status, the NCAA required education for athletes, including counseling on the risks and implications of SCT and guidelines for conditioning. The NCAA does not specify how the education be delivered but provides fact sheets for both student-athletes and coaches.²⁵

Deaths associated with SCT (daSCT) appear to occur with extreme exertion without allowance for adequate recovery. This was first observed when a disproportionate number of sudden deaths in military recruits with SCT occurred in 1970.¹³ A later study demonstrated that death in African American military recruits was 28 times more likely in those with SCT compared with those without.¹⁴ Concern of a similar association between SCT and death in NCAA athletes arose after the 1973 death of a college football player and a 2012 study demonstrated the risk of exertional death was 37 times higher in football athletes with SCT compared with those without the trait.¹² Although there appears to be an association between an increased risk of exertional death and SCT, the nature of this relationship, causality, and the mechanism remain subjects of debate.^16,21

The effect of screening and education for SCT in the prevention of sudden death is currently unknown. This study examines the incidence of daSCT in NCAA athletes both prior to and after the enactment of SCT legislation by the NCAA.

Methods

This study was approved by the University of Washington Division of Human Subjects Institutional Review Board in Seattle, Washington (reference No. 42077). A database of daSCT from July 2000 to June 2019 was developed from multiple sources, including the NCAA All-Cause Mortality Database,¹⁰ data from the National Center for Catastrophic Sports Injury Research, reports on SCT deaths in the literature,¹ and articles in the media. An athlete-year (AY) was defined from July 1 of one year to June 30 of the next. Deaths were considered to be associated with SCT if an autopsy report attributed causality to SCT or if the athlete was known to have SCT and there was reliable reporting, based on medical record support or report from school medical staff and/or officials, of a history consistent with exertional collapse associated with SCT. All cases were reviewed by authors with expertise in differentiating the etiology of sudden death in athletes, and disagreement was resolved by consensus among the panel of authors. NCAA participation statistics were obtained from the NCAA demographics database.²⁰ The database of daSCT used from July 2000 to June 2019 included a total of 8,309,050 athlete-years (AY). The athletes were divided into 2 groups: “before legislation,” which included DI athletes from July 1, 2000, through July 30 2010; DII athletes from July 1, 2000, through July 30, 2012; and DIII athletes from July 1, 2000, through July 30, 2014; and “after legislation,” which included DI athletes August 1, 2010, through June 30, 2019; DII athletes August 1, 2012, through June 30, 2019; and DIII athletes August 1, 2014, through June 30, 2019.

Case characteristics, including demographics, whether SCT was diagnosed (known/unknown at time of sport play), and activity at time of death, were recorded. Information was collected from the NCAA, media reports, university statements, and publicly available documents associated with legal action. Statistical analysis was conducted using Open Source Epidemiologic Statistics for Public Health at http://www.openepi.com. Summary statistics, incidence, and relative risk (RR) ratios comparing daSCT in NCAA athletes before and after legislation were calculated. Statistical significance was defined at P < 0.05.

Results

There were 10 total cases of daSCT before legislation: 9 in DI football athletes and 1 case in a DII basketball athlete. There were 2 cases of daSCT (1 DI football, 1 DI track) after legislation (Table 1). All cases were in African American male athletes with a mean age of 19.8 years (range, 18-23 years). For all NCAA athletes, the incidence of daSCT was 1:489,749 AY in the prelegislation period (n = 10) and 1:1,705,780 AY in the postlegislation period (n = 2) (RR, 0.288; 95% CI, 0.031-1.347; P = 0.146). The postlegislation group included an athlete trying out for a DI track team who had not submitted sickle cell status confirmation or been tested.

Table 1.

Deaths associated with sickle cell trait in NCAA athletes, 2000-2019

Demographics	Institution	Date of Incident, MM/DD/YYYY	SCT Status	Division	Sport
Age: 19 y Sex: Male Race: African American	Tennessee Tech University	08/13/2000	Unknown	I	Football—collapsed first day of conditioning test
Age: 18 y Sex: Male Race: African American	Florida State University	02/26/2001	Known	I	Football—collapsed during conditioning drills
Age: 18 y Sex: Male Race: African American	Bowling Green State University	09/15/2004	Unknown	I	Football—collapsed during practice
Age: 19 y Sex: Male Race: African American	University of Missouri	07/12/2005	Unknown	I	Football—collapsed during practice
Age: 19 y Sex: Male Race: African American	Rice University	09/24/2006	Unknown	I	Football—collapsed after conditioning
Age: 19 y Sex: Male Race: African American	University of Central Florida	03/18/2008	Known	I	Football—collapsed after conditioning
Age: 22 y Sex: Male Race: African American	North Carolina A&T University	05/28/2008	Unknown	I	Football—collapsed during conditioning
Age: 20 y Sex: Male Race: African American	Western Carolina University	07/08/2009	Unknown	I	Football—collapsed during conditioning
Age: 20 y Sex: Male Race: African American	University of Mississippi	02/19/2010	Known	I	Football—collapsed during conditioning
Division I NCAA legislation—August 2010
Age: 19 y Sex: Male Race: African American	North Carolina A&T University	08/19/2010	Unknown	I	Track & field—collapsed during tryouts
Age: 23 y Sex: Male Race: African American	Slippery Rock University	9/10/2011	Unknown	II	Basketball—collapsed during conditioning
Division II NCAA legislation—August 2012
Age: 21 y Sex: Male Race: African American	University of California, Berkeley	2/7/2014	Known	I	Football—collapsed during conditioning
Division III NCAA legislation—August 2014

NCAA, National Collegiate Athletic Association; SCT, sickle cell trait.

Before legislation.After legislation.

In DI football, the incidence of daSCT in the prelegislation period was 1:28,145 AY compared with 1:250,468 AY in the postlegislation period. The RR of daSCT after required testing or confirmation of status was 0.112 compared with before the SCT legislation was enacted (95% CI, 0.003-0.811; P = 0.022). The incidence of daSCT in African American DI football athletes in the prelegislation period was 1:12,519 AY compared with 1:118,464 AY in the postlegislation period. The RR of daSCT after required testing or confirmation of status was 0.106 compared with before legislation (95% CI = 0.002-0.763; P = 0.017), an 89% risk reduction after legislation was enacted.

In the prelegislation period, 20% of the daSCT cases occurred during practice, 80% of the daSCT cases occurred during conditioning, and no cases occurred during competition. After legislation, 1 case occurred during a tryout and 1 case occurred during conditioning. Overall, the SCT status of 4 of the athletes who died was known, and in 8 of the athletes it was unknown.

Discussion

Our study is the first evidence that the legislation passed by the NCAA has been effective in reducing daSCT, specifically in football. Although there was a 71% decrease in risk among all NCAA athletes, this was not statistically significant because the overall prevalence of SCT in the total NCAA population is quite low. All athletes who died prior to 2011 were football athletes, and all athletes who died were African American. Some have argued that screening should be limited to higher risk groups, either football players or African American athletes.¹¹

The exact pathophysiology of daSCT is unknown. It is hypothesized that a combination of high-intensity exercise, dehydration, and thermal strain may lead to erythrocyte sickling in athletes with SCT.¹⁶ Sickling in the microvasculature is thought to lead to hypoxemia, muscle cell death, release of potassium from within the cell, hyperkalemia, and arrhythmic death. In many cases, an explosive fulminant rhabdomyolysis presentation has been noted. daSCT is most often noted in settings where activity is not self-regulated, such as athletic conditioning or in military physical fitness training and testing, both situations where the individual is encouraged by another individual to push oneself to or beyond one’s limit. Exertional collapse associated with SCT has hallmark presenting features of profound muscle weakness causing collapse of a conscious athlete.²²

SCT was first addressed with an NCAA guideline in 1975. However, intermittent deaths continued with a total of 23 daSCT among NCAA athletes in the past 56 years.¹⁵ The NCAA guideline has been revised in 1982, 1992, 2002, 2008, and 2009,¹⁵ and in 2007 the National Athletic Trainers’ Association published a consensus statement recommending each institution carefully consider the decision to screen for SCT status in the absence of documented newborn screening results.¹⁸ Most recently, NCAA legislation requiring confirmation of SCT status with either prior documentation or repeat testing with the option for the student-athlete to decline testing and sign a written release was enacted in the fall of 2010 for DI athletes, 2012 for DII, and 2014 for DIII.

The mandate was met with criticism from the American Society of Hematology, the Sickle Cell Disease Association of America, and others citing concerns about the lack of evidence that screening decreases death, the potential for discrimination against athletes with SCT, concern that nonathletes with SCT may think they should not exercise, and the reported effectiveness of universal precautions implemented in the military.^2,9,26 Kark, in an unpublished study comparing 1.8 million recruits in an intervention group to 1.1 million recruits in a control group, reported that the implementation of universal heat acclimatization and hydration precautions reduced the number deaths in those with SCT to 0 from an expected 13.⁹ Deaths later increased, causing the military to reexamine its policies.²²

Since the legislation passed, there has been 1 death of a football athlete who had been screened and whose SCT status was known by medical and conditioning staff. This athlete died while participating in a workout that was not in compliance with NCAA recommendations, reinforcing that knowledge of SCT status alone is not enough to prevent all deaths. Screening must continue to be accompanied by prudent policies and appropriate education for athletes, coaches, and strength and conditioning and medical staffs.

All deaths occurred while practicing or conditioning. Although one may expect competitions to be the most intense activity, in many sports, especially football, there are built-in recovery periods between plays. Targeted modifications of training and conditioning to avoid repetitive, intense activity should be implemented as well as adequate acclimatization, fluid intake, and rest breaks.^3,4 There should be individualized workout plans that do not exceed an athlete’s fitness level, and there should be an awareness of heat and humidity, with modifications of practice and conditioning as needed.^3,4 These precautionary practices and a culture of not continuing to push a struggling athlete should be adopted in all sports. Each institution needs a specific emergency action plan, and medical personnel need to be familiar with and regularly rehearse it.

Limitations

There are several limitations to this study. The educational component required by the NCAA is broad and is potentially administered differently by each institution.¹⁹ It is unclear whether athletic teams implemented new strategies for mitigating risk to their athletes with SCT outside of the education and whether the decrease in daSCT is related to screening for SCT, education, or both. It is also difficult to clarify the variation of load exposure to each athlete in each case. Finally, data are not available specifying how many total athletes tested positive for SCT and how many athletes signed waivers in lieu of testing.

Conclusion

This is the first evidence that the NCAA SCT legislation may save lives. The incidence of daSCT has decreased by 89% in DI football, the sport in which the vast majority of deaths occur. It is unclear whether the decrease is related to screening for SCT, education, or both. Additional studies are needed to better understand the relative value of screening versus education, what the correct educational narrative is and to whom it should be given, and the value of a similar policy in other groups such as high school athletes and whether it would show comparable benefit.