CASE REPORT CRIMINALISTICS
Sickle Cell Trait-Associated Deaths: A Case Series with a Review of the Literature* ,†
Jon R. Thogmartin M.D.,
Christopher I. Wilson M.D.,
Noel A. Palma M.D.,
Susan S. Ignacio M.D.,
Mark J. Shuman M.D.,
Lisa M. Flannagan M.D.,
Jon R. Thogmartin M.D.
District Six Medical Examiner Office, 10900 Ulmerton Road, Largo, FL 33778.
Search for more papers by this authorChristopher I. Wilson M.D.
District Six Medical Examiner Office, 10900 Ulmerton Road, Largo, FL 33778.
Search for more papers by this authorNoel A. Palma M.D.
District Six Medical Examiner Office, 10900 Ulmerton Road, Largo, FL 33778.
Search for more papers by this authorSusan S. Ignacio M.D.
District Six Medical Examiner Office, 10900 Ulmerton Road, Largo, FL 33778.
Search for more papers by this authorMark J. Shuman M.D.
District Eleven Medical Examiner Office, #1 on Bob Hope Road, Miami, FL 33136.
Search for more papers by this authorLisa M. Flannagan M.D.
District Two Medical Examiner Office, 1899 Eider Court, Tallahassee, FL 32317.
Search for more papers by this authorJon R. Thogmartin M.D.,
Christopher I. Wilson M.D.,
Noel A. Palma M.D.,
Susan S. Ignacio M.D.,
Mark J. Shuman M.D.,
Lisa M. Flannagan M.D.,
Jon R. Thogmartin M.D.
District Six Medical Examiner Office, 10900 Ulmerton Road, Largo, FL 33778.
Search for more papers by this authorChristopher I. Wilson M.D.
District Six Medical Examiner Office, 10900 Ulmerton Road, Largo, FL 33778.
Search for more papers by this authorNoel A. Palma M.D.
District Six Medical Examiner Office, 10900 Ulmerton Road, Largo, FL 33778.
Search for more papers by this authorSusan S. Ignacio M.D.
District Six Medical Examiner Office, 10900 Ulmerton Road, Largo, FL 33778.
Search for more papers by this authorMark J. Shuman M.D.
District Eleven Medical Examiner Office, #1 on Bob Hope Road, Miami, FL 33136.
Search for more papers by this authorLisa M. Flannagan M.D.
District Two Medical Examiner Office, 1899 Eider Court, Tallahassee, FL 32317.
Search for more papers by this authorAdditional information—reprints not available from author: Jon Thogmartin, M.D. District Six Medical Examiner’s Office 10900 Ulmerton Road Largo, FL 33778 E-mail: [email protected]
†
Presented in part at the 61st Annual Meeting of the American Academy of Forensic Sciences, February 16–21, 2009, in Denver, CO.
‡
Funded in part by the District Six Medical Examiner Office, Largo, FL.
Abstract
Abstract: This study presents a series of 16 carriers of hemoglobin S (HbS) who died during various circumstances. Many of the cases were associated with mild to moderate exertion. The onset and/or duration of symptoms varied from a few minutes to several hours with many displaying a prolonged lucid interval with stable vital signs. Despite seeking medical treatment, sickle cell trait-related micro-occlusive crisis was never considered in the differential diagnosis. Several cases were associated with sudden death. In those deaths which were delayed, high anion gap and uncompensated metabolic acidosis were typical and were not heat related. Also characteristic were large increases in creatine kinase, alanine aminotransferase, and aspartate aminotransferase along with myoglobinemia. Although the antemortem diagnosis of rhabdomyolysis was made, the underlying cause was never deduced by the clinicians. The sickling found at autopsy is not always a postmortem artifact, and in the right circumstances can be diagnostic.
References
- 1 JP Greer, J Foerster, JN Lukens, GM Rodgers, F Paraskevas, B Glader, editors. Wintrobe’s clinical hematology, 11th edn. Philadelphia, PA: Lippincott, Williams & Wilkins, 2004; 1263–4.
- 2 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(5): 704–10.
- 3 Scheinin L, Wetli CV. Sudden death and sickle cell trait. Medicolegal considerations and implications. Am J Forensic Med Pathol 2009; 30(2): 204–8.
- 4 Thogmartin JR. Sudden death in police pursuit. J Forensic Sci 1998; 43(6): 1228–31.
- 5 Jones SR, Binder RA, Donowho EM Jr. Sudden death in sickle cell trait. N Engl J Med 1970; 282(6): 323–5.
- 6 Kark JA, Posey HR, Schumacher HR, Ruehle CJ. Sickle cell trait as a risk factor for sudden death in physical training. N Engl J Med 1987; 317(13): 781–7.
- 7 Koppes GM, Daly JJ, Coltman CA Jr, Butkus DE. Exertion-induced rhabdomyolysis with acute renal failure and disseminated intravascular coagulation in sickle cell trait. Am J Med 1977; 63(2): 313–7.
- 8 Sateriale M, Hart P. Unexpected death in a black military recruit with sickle cell trait: case report. Mil Med 1985; 150(11): 602–5.
- 9 Drehner D, Neuhauser KM, Neuhauser TS, Blackwood GV. Death among US air force basic trainees, 1956 to 1996. Mil Med 1999; 164(12): 841–7.
- 10 Dudley AW Jr, Waddell CC. Crisis in sickle cell trait. Hum Pathol 1991; 22(6): 616–8.
- 11 Wirthwein DP, Spotswood SD, Barnard JJ, Prahlow JA. Death due to microvascular occlusion in sickle cell trait following physical exertion. J Forensic Sci 2001; 46(2): 399–401.
- 12 Kark JA, Ward FT. Exercise and hemoglobin S. Semin Hematol 1994; 31(3): 181–225.
- 13 Gardner JW, Kark JA. Fatal rhabdomyolysis presenting as mild heat illness in military training. Mil Med 1994; 159(2): 160–3.
- 14 Harrelson GL, Fincher AL, Robinson JB. Acute exertional rhabdomyolysis and its relationship to sickle cell trait. J Athl Train 1995; 30(4): 309–12.
- 15 Steen RG, Hankins GM, Xiong X, Wang WC, Beil K, Langston JW, et al. Prospective brain imaging evaluation of children with sickle cell trait: initial observations. Radiology 2003; 228(1): 208–15.
- 16 Gupta AK, Kirchner KA, Nicholson R, Adams JG 3rd, Schechter AN, Noguchi CT, et al. Effects of alpha-thalassemia and sickle polymerization tendency on the urine-concentrating defect of individuals with sickle cell trait. J Clin Invest 1991; 88(6): 1963–8.
- 17 Connes P, Sara F, Hardy-Dessources MD, Marlin L, Etienne F, Larifla L, et al. Effects of short supramaximal exercise on hemorrheology in sickle cell trait carriers. Eur J Appl Physiol 2006; 97(2): 143–50.
- 18 Feldenzer JA, Bueche MJ, Venes JL, Gebarski SS. Superior sagittal sinus thrombosis with infarction in sickle cell trait. Stroke 1987; 18(3): 656–60.
- 19 Austin H, Key NS, Benson JM, Lally C, Dowling NF, Whitsett C, et al. Sickle cell trait and the risk of venous thromboembolism among blacks. Blood 2007; 110(3): 908–12.
- 20 Hedayati B, Anson KM, Patel U. Focal renal infarction: an unusual cause of haematuria in a patient with sickle cell trait. Br J Radiol 2007; 80(953): e105–6.
- 21 Zadeii G, Lohr JW. Renal papillary necrosis in a patient with sickle cell trait. J Am Soc Nephrol 1997; 8(6): 1034–9.
- 22 Selvidge SD, Gavant ML. Idiopathic pulmonary vein thrombosis: detection by CT and MRI imaging. Am J Roentgenol 1999; 172(6): 1639–41.
- 23 Eichner ER. Sickle cell trait and the athlete. Sports Sci Exchange 2006; 19: 1–6.
- 24 Adams JQ. Sudden death in pregnancy due to sickle cell trait. South Med J 1957; 50(7): 898–901.
- 25 http://www.cdc.gov/healthyweight/assessing/bmi/ (accessed June 30, 2010).
- 26 Pretzlaff RK. Death of an adolescent athlete with sickle cell trait caused by exertional heat stroke. Pediatr Crit Care Med 2002; 3(3): 308–10.
- 27 Scoville SL, Gardner JW, Magill AJ, Potter RN, Kark JA. Nontraumatic deaths during U.S. armed forces basic training, 1977–2001. Am J Prev Med 2004; 26(3): 205–12.
- 28 Khan FY. Rhabdomyolysis: a review of the literature. Neth J Med 2009; 67(9): 272–83.
- 29 Moeckel-Cole SA, Clarkson PM. Rhabdomyolysis in a collegiate football player. J Strength Cond Res 2009; 23(4): 1055–9.
- 30 Lin AC, Lin CM, Wang TL, Leu JG. Rhabdomyolysis in 119 students after repetitive exercise. Br J Sports Med 2005; 39(1): e3.
- 31 Dekeyser B, Schwagten V, Beaucourt L. Severe rhabdomyolysis after recreational training. Emerg Med J 2009; 26(5): 382–3.
- 32 Greenhaff PL. Cardiovascular fitness and thermoregulation during prolonged exercise in man. Br J Sports Med 1989; 23(2): 109–14.
- 33 Lim CL, Byrne C, Lee JK. Human thermoregulation and measurement of body temperature in exercise and clinical settings. Ann Acad Med Singapore 2008; 37(4): 347–53.
- 34 Febbraio MA, Snow RJ, Stathis CG, Hargreaves M, Carey MF. Blunting the rise in body temperature reduces muscle glycogenolysis during exercise in humans. Exp Physiol 1996; 81(4): 685–93.
- 35 Harmon J. The army pushed too hard, says widow of soldier who died trying to be a Ranger. A game out of hand? Atlanta J Atlanta Constitution (Atlanta Constitution ed) 1992:Sect.C:1.
- 36 McDermott BP, Casa DJ, Ganio MS, Lopez RM, Yeargin SW, Armstrong LE, et al. Acute whole-body cooling for exercise induced hyperthermia: a systematic review. J Athl Train 2009; 44(1): 84–93.
- 37 Choi JS, Ahn DW, Choi JK, Kim KR, Park YS. Thermal balance of man in water: prediction of deep body temperature change. Appl Hum Sci 1996; 15(4): 161–7.
- 38 Castro RR, Mendes FS, Nobrega AC. Risk of hypothermia in a new Olympic event: the 10-km marathon swim. Clinics (Sao Paulo) 2009; 64(4): 351–6.
- 39 Varghese GM, John G, Thomas K, Abraham OC, Mathai D. Predictors of multi-organ dysfunction in heatstroke. Emerg Med J 2005; 22(3): 185–7.
- 40 Dincer HE, Raza T. Compartment syndrome and fatal rhabdomyolysis in sickle cell trait. WMJ 2005; 104(6): 67–71.
- 41 Anzalone ML, Green VS, Buja M, Sanchez LA, Harrykisson RI, Eichner RE. Sickle cell trait and fatal rhabdomyolysis in football training: a case study. Med Sci Sports Exerc 2010; 42(1): 3–7.
- 42 Hofmann N, Waldherr R, Schwenger V. Is the sauna a common place for experiencing acute renal failure? Nephrol Dial Transplant 2005; 20(1): 235–7.
- 43 Emmett M, Narins RG. Clinical use of the anion gap. Medicine (Baltimore) 1977; 56(1): 38–54.
- 44 Kaplan LJ, Frangos S. Clinical review: acid–base abnormalities in the intensive care unit—part II. Crit Care 2005; 9(2): 198–203.
- 45 Rosenthal MA, Parker DJ. Collapse of a young athlete. Ann Emerg Med 1992; 21(12): 1493–8.
- 46 Dean JB. Metabolic acidosis inhibits hypothalamic warm-sensitive receptors: a potential causative factor in heat stroke. J Appl Physiol 2007; 102(4): 1312.
- 47 Wright CL, Boulant JA. Carbon dioxide and pH effects on temperature sensitive and insensitive hypothalamic neurons. J Appl Physiol 2007; 102(4): 1357–66.
- 48 Okoli K, Irani F, Horvath W. Pathophysiologic considerations for the interactions between obstructive sleep apnea and sickle hemoglobinopathies. Med Hypotheses 2009; 72(5): 578–80 [Epub 2009].
- 49 Niebanck AE, Pollock AN, Smith-Whitley K, Raffini LJ, Zimmerman RA, Ohene-Frempong K, et al. Headache in children with sickle cell disease: prevalence and associated factors. J Pediatr 2007; 151(1): 67–72.
- 50 Diep BN, Scheirman K, Reeves WB, Mask DR, Eichner ER. Splenic infarction in a white man with sickle cell trait. South Med J 1979; 72(12): 1611–13.
- 51 Shalev O, Boylen AL, Levene C, Oppenheim A, Rachmilewitz EA. Sickle cell trait in a Jewish family presenting as splenic infarction at high altitude. Am J Hematol 1988; 27(1): 46–8.
- 52 Lane PA, Githens JH. Splenic syndrome at mountain altitudes in sickle cell trait. Its occurrence in nonblack persons. JAMA 1985; 253(15): 2251–4.
- 53 Nussbaum RL, Rice L. Morbidity of sickle cell trait at high altitude. South Med J 1984; 77(8): 1049–50.
- 54 Oksenhendler E, Bourbigot B, Desbazeille F, Droz D, Choquenet C, Girot R, et al. Recurrent hematuria in 4 white patients with sickle cell trait. J Urol 1984; 132(6): 1201–03.
- 55 Franklin QJ, Compeggie M. Splenic syndrome in sickle cell trait: four case presentations and a review of the literature. Mil Med 1999; 164(3): 230–3.
- 56 Carr JA, Shurafa M, Velanovich V. Surgical indications in idiopathic splenomegaly. Arch Surg 2002; 137(1): 64–8.
- 57 Swerdlow PS. Red cell exchange in sickle cell disease. Hematology Am Soc Hematol Educ Program 2006; 48–53.
- 58 Pepple DJ. Sickle cell trait: dual picture on blood films. Med Hypotheses 1995; 44(3): 165–6.
- 59 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 Hematol 2006; 81(1): 26–35.
- 60 Wilson CI, Hopkins PL, Cabello-Inchausti B, Melnick SJ, Robinson MJ. The peripheral blood smear in patients with sickle cell trait: a morphologic observation. Lab Med 2000; 31(8): 445–7.
- 61 Thogmartin JR, Wilson CI, Palma NA, Ignacio SS, Pellan WA. Histological diagnosis of sickle cell trait. A blinded analysis. Am J Forensic Med Pathol 2009; 30(1): 36–9.
- 62 Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 1998; 339(1): 5–11.
- 63 JP Greer, J Foerster, JN Lukens, GM Rodgers, F Paraskevas, B Glader, editors. Wintrobe’s clinical hematology, 11th edn. Philadelphia, PA: Lippincott, Williams & Wilkins, 2004; 1286–311.
- 64 Helzlsouer KJ, Hayden FG, Rogol AD. Severe metabolic complications in a cross-country runner with sickle cell trait. JAMA 1983; 249(6): 777–9.
- 65 Le Gallais D, Bile A, Mercier J, Paschel M, Tonellot JL, Dauverchain J. Exercise-induced death in sickle cell trait: role of aging, training, and deconditioning. Med Sci Sports Exerc 1996; 28(5): 541–4.
Citing Literature
