What killed George Floyd: Part 7 — Sickle cell trait and Covid

Dr. Baker also observed sickling of red cells in the body at autopsy and upon further evaluation found that the decedent had sickle cell trait.  Sickle cell is a genetic mutation in the structure of hemoglobin.  The abnormal hemoglobin is called “Hemoglobin S”.   Hemoglobin S causes red blood cells to change shape when they give up their oxygen; the cells form little cups that look like sickles when cut lengthwise and viewed from the side under the microscope.  When the red cells take on that shape, they tend to stack like cups on a shelf.  These collections of stacked red cells can obstruct small blood vessels, and everything downstream becomes oxygen deprived.  People who come from Africa, the Levant, and some parts of southern Europe are prone to this. The survival advantage of this trait is that these cells are resistant to malaria.

Every person has multiple chromosomes that make hemoglobin, with two being predominate.  If both of these chromosomes have the mutation, then almost all of the red cells have hemoglobin S, and the person is said to have “sickle cell disease.”  This  is a very dangerous and painful disease, and people who have it do poorly — though modern therapies make it better than it used to.  If these people go into a state of low oxygen, they can have a so-called “sickle cell crisis” which can be life-threatening.

People who have one normal and one abnormal gene make both normal hemoglobin and abnormal hemoglobin.  The abnormal cells don’t survive as long in the body, and the majority of circulating cells are normal.  These people are said to have “sickle cell trait.”

It used to be believed that people with sickle cell trait were basically completely healthy.  They had a slightly higher rate of a rare form of kidney cancer, but otherwise had normal lifespans, didn’t suffer the sickle crises that people with sickle cell disease had, and were good to go.  People thought it was completely benign.

Then, a few decades ago, folk started noticing that African-American recruits in military training died of sudden cardiac death at a rate 40 higher than white recruits.  It turned out that these young people almost all had sickle cell trait.  Then people started looking at high school and college athletics and found the same thing.  It turned out that sickle cell trait was not quite as benign as people thought.  Under normal circumstances these people didn’t have sickle crises, but under periods of extreme physical stress involving anaerobic exercise, the could.  Other situations where this has been observed have been forced running in a prison boot camp, running from police, and other kinds of exertion.   The author of one review article notes(2):

Military and civilian sickle cell trait-related deaths share many common features. The individuals were usually participating in a physical event that required sustained maximal exertion for at least a few minutes and typically complained of muscle weakness more than pain. Presumably, the collapse is due to generalized weakness unlike the abrupt collapse associated with cardiac dysrhythmias. The larger muscles (calves, quads, hamstrings, glutes) may look and feel normal as compared to the cramping associated with heat cramps. While typically alert and conscious, a cardinal feature is the increasing pain and weakness in the large working muscles. Exertional sickling as a cause of sudden collapse has been under-recognized and often confused with heat stroke or cardiac dysrhythmias.

Dr. Baker considered this diagnosis because he saw sickled cells at autopsy.  However, he discounted it because an antemortem blood smear did not show sickling.  He thus believed that the sickling in tissues represented postmortem artifact.  I respectfully disagree with this, since it has also been shown that sickled cells can “unsickle” when drawn for samples because of exposure to air. As one author notes(2) where “RSC” stands for “reversible sickle cells” (cells that have the ability to return to normal shape when re-oxygenated) and “SCD” is “sickle cell disease”): “Although the presence of RSCs in the blood of patients with SCD has been noted over many decades, their properties have not been studied for various reasons. First, since there was no technology to collect blood samples under physiological oxygen pressures for further studies, most RSCs were fixed in fixing solution at the time of blood collection. Second, when blood is collected by the ordinary method (Exp-blood), cells are exposed to oxygen in the needle, syringe, and Vacutainer, and most RSCs are oxygenated, causing them to assume a normal discoidal shape.” 

Thus, oddly, *both* the presence in tissue and the absence in the antemortem sample can be an artifact.

The sickle cell trait issue is an interesting one when it comes to accusations of racism.   If one does not observe its importance, then one is racist because one discounts a life-threatening process that is present primarily in those of African descent.  If one does observe it’s importance, the one is a racist because it becomes a vulnerability in sudden death that interferes with a desired narrative in death in custody.  This has been a particular conundrum in the US military over the years.  The author of the review I referenced, Dr. Bruce Mitchell, is a Navy physician (or at least ex-Navy physician) who is African-American with sickle trait.  I chose his reference because he wrote a very personal article about it in 2007, which is pretty gutsy(3), and it’s interesting to see how his perspective evolved over the following decade.

But, be that as it may be, the fact is that sickle trait can be life-threatening under conditions of stress.  Personally, I don’t think it’s a key player in this case.  Here’s why.   Exertional sickle deaths seem to occur in fairly specific settings.  It happens when the victim exercises to his or her limit, and then pushes over it.  Often it’s an issue of exercise followed by a sprint or running as a last “heroic” effort.  That’s why it’s such a problem in military training and athletics, since that’s exactly what DIs and coaches do.  They push you to your limit and then just a bit more – – because that’s how you move your limit.  But it’s that last “heroic effort” that kills the victim.  As one study notes (where where SCT is an acronym for “Sickle Cell Trait,” ECAST is an acronym for “exercise collapse associated with SCT,” and WA is an acronym for “warfighters and athletes ”: (4)

“ECAST appears to be a spectrum presentation in WA with SCT because it varies from severe muscle pain to fulminant collapse. Although ECAST has been noted in both military and sport settings at various levels of training/conditioning and competition, American football conditioning appears to account for the majority of ECAST events. In football conditioning, the proximate trigger for ECAST appears to be high-intensity exercise.

The typical setting reported for precipitation of-ECAST is an athlete near maximal exertion—repeated or sustained—for a short time. Of the 10 Division I football players with SCT who died in the past decade, five had been doing serial sprints for 5 to 30 min and four had been doing fast-tempo, multi-station drills, with little or no rest between stations, for 12 to 60 min. In five of the earlier football players with SCT who died, sprinting for only 2-5 min reportedly led to ECAST (two players had newly arrived at altitude). ECAST 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 2-5 min.

A review of case reports revealed that typical training settings include the following: day 1 of conditioning, newly arrived at altitude, just returning from a vacation, or a sudden increase in the intensity of a conditioning drill. All ECAST events appear to involve a “perfect storm” of high-intensity exercise, sustained for at least a few minutes, and a “heroic effort” beyond what may be the physical limits of the athlete on that particular day. 

Mr. Floyd’s dynamic wasn’t like that.  If he had vigorously fought the police, escaped, ran for two blocks and then collapsed, I’d be more likely to weigh sickle trait as important. But that’s not the story here.

Similary, COVID-19 is all in the news, of course, but Mr. Floyd was aysmptomatic.  At autopsy, histologic evaluation of the lungs did not reveal any evidence of Covid pneumonitis, and there was no evidence in any section of Covid-related coagulation problems, myocarditis, or other Covid-related anatomic finding.  So, it’s a non-issue also.

Next up: That “incidental” tumor might not have been so incidental.

  1. Mitchell, B.L. Sickle Cell Trait and Sudden Death. Sports Med – Open 4, 19 (2018). https://doi.org/10.1186/s40798-018-0131-6 .
  2. Obata K, Mattiello J, Asakura K, Ohene-Frempong K, Asakura T. Exposure of blood from patients with sickle cell disease to air  changes the morphological, oxygen-binding, and sickling properties of sickled erythrocytes.” Am J Hematology. 2006 81:26-35.
  3. Mitchell, Bruce L. “Sickle cell trait and sudden death–bringing it home.” Journal of the National Medical Association 99.3 (2007): 300.
  4. O’connor. F. G., M. F. Bergeron, J. Cantrell, P. Connes, K. G. Harmon, E. Ivy, J. Kark, D. Klossner,P. Lisman, B. K. Meyers, K. O Brien, K. Ohene-Frempong, A. A. Thompson, J. Whitehead, And P. A. Deuster. ACSM and CHAMP Summit on Sickle Cell Trait: Mitigating Risks for Warfighters and Athletes. Med. Sei. Sports Exerc, Vol. 44, No. 11, pp. 2045-2056, 2012

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