|Year : 2021 | Volume
| Issue : 1 | Page : 32-35
Sickle cell crisis as a cause of death over the past 10 years in Vidarbha Region: A study of 18 cases
Shikha Singh, Bharat Patil, Nitin M Gangane
Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India
|Date of Submission||21-Mar-2020|
|Date of Acceptance||31-Oct-2020|
|Date of Web Publication||29-Jun-2021|
Dr. Bharat Patil
Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Sickle cell disease is a heritable disorder having an autosomal recessive inheritance. The disease arises as a consequence of a single base mutation in the sixth codon of the β-globin gene, which leads to an interchange of valine for glutamic acid. Aim: The aim of this study is to provide an insight to physicians about sickle cell disease being a cause of sudden demise, so that future unexpected deaths due to complications can be avoided. Materials and Methods: This study is a retrospective study conducted over a period of ten years from January 2010 to December 2019. The data was collected from the hospital information system of our institute. A total of 18 cases were collected over a period of ten years. The respective case related findings along with past history were reviewed. Results: Out of 18 cases, 11 cases were males and 7 were females. The youngest person was a nine-year old male and oldest was a 65-year-old male. Four cases were known patients of sickle cell disease, while in the remaining cases no history of sickle cell disease was available. Conclusions: Sickle cell crisis is an important reason of sudden unexplained deaths and this study highlights the role of autopsy in such cases.
Keywords: Autopsy, autosomal recessive inheritance, sickle cell crisis, sudden death
|How to cite this article:|
Singh S, Patil B, Gangane NM. Sickle cell crisis as a cause of death over the past 10 years in Vidarbha Region: A study of 18 cases. J Mahatma Gandhi Inst Med Sci 2021;26:32-5
|How to cite this URL:|
Singh S, Patil B, Gangane NM. Sickle cell crisis as a cause of death over the past 10 years in Vidarbha Region: A study of 18 cases. J Mahatma Gandhi Inst Med Sci [serial online] 2021 [cited 2021 Jul 24];26:32-5. Available from: https://www.jmgims.co.in/text.asp?2021/26/1/32/319834
| Introduction|| |
Sickle cell disease (SCD) is a heritable disorder having an autosomal recessive inheritance. A physician named James Herrick first described the characteristic sickle-shaped red blood cells in students from Grenada in 1910. Linus Pauling was the first to call it a molecular disease in the year 1949 depending on the electrophoretic mobility. Vernon Ingram discovered that sickle hemoglobin forms from a single amino acid substitution in the hemoglobin molecule in the year 1957. The disease results from a single base mutation in the sixth codon of the β-globin chain, which leads to a substitution of valine for glutamic acid, and HbS is formed. Homozygosity for the HbS gene (i.e., HbSS) is the most severe subtype of SCD.
SCD is a genetically transmitted hemoglobinopathy accountable for substantial degree of morbidity as well as mortality. It manifests in two configurations – sickle cell trait and SCD. It results from the point mutation in the genetic code where glutamic acid gets replaced by valine at the sixth position of the beta-globin chain.
In India, SCD is common in Vidarbha, Chhattisgarh, Madhya Pradesh, Orissa, Gujarat, Tamil Nadu, and Andhra Pradesh. The need for hospital care is more in the pediatric population with SCD than the adult age group patients. Children with SCD, especially those between 1 and 3 years of age, are most vulnerable to mortality. Central India region is an epicenter of SCD, and the prevalence in Vidarbha region ranges between 4% and 40%, with an average sickle cell gene frequency being 4.3%.
Despite the improvements in the screening processes, SCD remains a major health concern. This study focuses on the postmortem evaluation in a series of patients wherein the histomorphology showed sickle cell thrombi. The main purpose was to provide an insight to physicians that out of several other causes of sudden death, SCD is also of prime importance and needs to be kept in mind while analyzing the actual cause of demise of a patient. At the same time, the study intends to create awareness among relatives so as to minimize the future unexpected sudden deaths from complications from SCD.
The present study highlights the importance of finding sickle cell thrombi in 18 cases which were either old diagnosed sickle cell cases or were incidentally diagnosed on autopsy.
| Materials and Methods|| |
This is a retrospective study covering a period of 10 years from January 2010 to December 2019. Institutional ethics clearance was taken from the Institutional Ethics Committee. The data were retrieved from the hospital information system of our institute, and all the cases were reviewed thoroughly. As an institutional policy, all cases who present to the hospital as sudden death undergo postmortem. During these 10 years, 18 cases were diagnosed as having sickle cell thrombi on microscopic examination in different organs. No other causes for sudden death were observed during postmortem examination on gross as well as microscopic examination in these cases. These 18 cases were collected and examined. The respective case-related findings along with history were reviewed.
The gross specimens of the brain, heart, lungs, kidney, liver, and spleen were received for histopathological examination in almost all cases. The case-related clinical history, gross findings, and morphological details of all cases were collected and assessed.
| Results|| |
In this study, the presence of sickled red blood cells was found on histopathological examination of the respective organs. Out of 18 cases, 11 cases were male and 7 were female. The youngest person was a 9-year-old male, whereas the eldest was a 65-year-old male. Four cases were known patients of SCD. In the remaining cases, no history of SCD was available [Table 1].
On gross examination, all the organs showed marked congestion. Histopathological examination of each organ was performed, and all the organs showed marked dilation and congestion of vessels which were filled with sickled red blood cells. The spleen showed partial effacement of architecture. The sinusoidal spaces were packed with tactoid cells. The other organs showed a similar microscopic picture [Figure 1]. The conclusive histomorphological diagnosis was the presence of sickle cell thrombi in almost all the organs, especially in the spleen and liver.
|Figure 1: Photomicrograph from (a) lung, (b) liver, (c) kidney, (d) spleen, (e) coronaries, (f) brain showing the presence of sickle cell thrombi (×40)|
Click here to view
| Discussion|| |
SCD is a group of disorders, which include homozygous genotype of hemoglobin HbS and heterozygous genotypes of HbS and the other hemoglobinopathies such as Hb C, D, E, G, and O. Hemoglobinopathy S may also be co-inherited with thalassemia.
Sickle cell anemia (SCA) is one of the most common genetic diseases and is an autosomal recessive condition, in which the normally freely flowing cytosol of red cells is viscous, making them much less deformable and affecting their ability to traverse narrow capillary beds.
The commonly seen genetic constitutions are SS and SC, followed by sickle cell-beta thalassemia. The SS genotype is an incapacitating disease with severe pain crises, hemolysis, increased susceptibility to infections, cerebrovascular events, and chronic organ damage resulting in reduced life span (42 years for males and 48 years for females).
Although SC hemoglobinopathy usually shows a benign clinical behaviour, both SS and SC may present with similar complications., However, hemolysis is less intense, and aplastic episodes as well as cholelithiasis are less common in HbSC. However, proliferating retinitis, osteonecrosis, and acute chest syndrome may present equal or higher incidence in HbSC compared with HbSS.
In general, HbSC patients start manifesting after 20 years of life, and the median age of irreversible organ failure is 10–35 years later than that in SCA. Acute events in SCD include painful vaso-occlusive crisis, infarctive stroke, acute chest syndrome, priapism, aplastic crises, splenic sequestration, hemolytic crises, and infections. The trait patients are mostly asymptomatic, and sickle cell crisis can occur in them only if the patient is exposed to extreme hypoxic conditions.
SCA is a chronically diseased state associated with acute episodes related to vaso-occlusion. Almost every system of the body can get troubled by ischemia resulting from the obstruction of the blood vessels by the aggregates of the sickled red blood cells. The most grounded proof involving intravascular sickling with tissue injury and even demise is excessive exercise, exhaustion with dehydration, and relative hypoxia experienced at higher altitudes.
Complications of SCD are severe, generally associated with high mortality. Among them are pulmonary hypertension and bone marrow necrosis followed by fat embolism syndrome. Pulmonary hypertension can be related to chronic hemolysis, nitric oxide deficiency, chronic hypoxemia, endothelial dysfunction, proliferative vasculopathy, and vaso-occlusive events due to the presence of sickled erythrocytes.,,
There are various studies evaluating the cause of death in SCD. Knowledge regarding the causes of mortality in SCD is essential for improvement in management and treatment practices of these patients. In a study conducted by Manci et al., 33% of deaths occurred in relatively healthy patients who died during a sickle cell crisis and 78% died during an acute painful episode like acute chest syndrome.
Platt et al. studied 3764 patients of SCA and found that 209 adult patients died of SCD and also noted that mortality varies with age. Maximum deaths among children with the disease occurred between 1 and 3 years of age, and deaths among patients younger than 20 years of age were due to pneumococcal sepsis. Eighteen percent of deaths in adults were due to organ failure, and 33% of deaths occurred in relatively healthy patients who died during a classical sickle crisis. Almost 78% died due to acute chest syndrome.
In acute chest syndrome, pulmonary vessels may get occluded by emboli or by platelet thrombi leading to thrombocytopenia as observed by a study done by Anea et al. Autopsy examination of tissues and cytology of bronchial fluid have shown that marrow/fat embolism is a common etiologic factor in SCD crisis and could progress to multi-organ failure.
In a study conducted by Alhumaid et al., the majority of the patients presented with an acute painful crisis as an initial manifestation. The commonly reported manifestations include mild-to-severe anemia, painful crises, frequent infections, hand-and-foot syndrome, and stroke.
Hydroxyurea can be considered the standard of care and ideal agent for treating SCA as it provides multiple therapeutic benefits. According to a study by Quarmyne et al., the use of hydroxyurea upon a group of pediatric patients showed a decrease in hospital admissions, pain incidence, and emergency department visits due to complications.
Failure of early intervention in patients with SCD contributed to most sudden deaths of this group of patients. This was because the disease was unknown until autopsy was conducted. It is necessary that relatives of patients should give consent for autopsy to help the physicians in appropriate management of future patients. Apart from this, the relatives of such patients should be counseled appropriately about the complications and outcomes associated with the disease, so that future comorbidities can be avoided.
Aggressive screening is the need of the hour for SCD. The knowledge regarding the precipitating factors such as dehydration and physical stress has to be provided to the individuals, and a word of caution to refrain from exposure to such factors is needed.
| Conclusion|| |
SCD is the most common hereditary hematological disorder associated with increased mortality. The aim of this study is to create a sense of awareness among physicians and relatives on the importance of autopsy so as to minimize future unexpected deaths from complication or crisis. This study shows that sickle cell crisis is an important cause in the list of causes of unexpected sudden deaths. Hence, it should always be kept in mind as a differential by the histopathologists and clinicians. Community awareness and marriage counseling programs should be emphasized upon in endemic areas, as they are helpful in preventing SCD.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Serjeant GR, Serjeant BE. Sickle Cell Disease. 3rd ed. New York: Oxford Univ Press; 2001. p. 792.
Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet 2010;376:2018-31.
Stuart MJ, Nagel RL. Sickle-cell disease. The Lancet. 2004. p. 1343-60.
Colah RB, Mukherjee MB, Martin S, Ghosh K. Sickle cell disease in tribal populations in India. Indian J Med Res 2015;141:509-15.
] [Full text]
Frenette PS, Atweh GF. Sickle cell disease: Old discoveries, new concepts, and future promise. J Clin Invest 2007;117:850-8.
Shrigiriwar M, Ghormade S, Tingne C. Death due to sickle cell anaemia: Autopsy diagnosis. J Indian Acad forensic Med 2013;35:383-5.
Leikin SL, Gallagher D, Kinney TR, Sloane D, Klug P, Rida W. Mortality in children and adolescents with sickle cell disease. Coop Stud Sickle Cell Dis Pediatrics 1989;84:500-8.
Balgir RS. The burden of haemoglobinopathies in India and the challenges ahead. Curr Sci 2000;79:1536-47.
Pereira SA, Brener S, Cardoso CS, Proietti AB. Sickle cell disease: Quality of life in patients with hemoglobin SS and SC disorders. Rev Bras Hematol Hemoter 2013;35:325-31.
Azar S, Wong TE. Sickle cell disease: A brief update. Med Clin North Am 2017;101:375-93.
O'Keeffe EK, Rhodes MM, Woodworth A. A patient with a previous diagnosis of hemoglobin S/C disease with an unusually severe disease course. Clin Chem 2009;55:1228-31.
Pasquini R, Zago MA, Falcão RP. Hematology: Fundamentals and practice. São Paulo: 1st ed. Atheneu. 2004. p. 295-97.
Nagel RL, Fabry ME, Steinberg MH. The paradox of hemoglobin SC disease. Blood Rev 2003;17:167-78.
Powars D, Chan LS, Schroeder WA. The variable expression of sickle cell disease is genetically determined. Semin Hematol 1990;27:360-76.
Benz E, Ebert B. Hemoglobin structural variants associated with haemolytic anemia, altered oxygen affinity and methemoglobinemias. In: Hematology: Basic Principles and Practice. 6th
ed. Philadelphia: Elsevier Health Sciences; 2013. p. 573-81.
Mitchell BL. Sickle cell trait and sudden death – Bringing it home. J Natl Med Assoc 2007;99:300-5.
Kato GJ, Gladwin MT, Steinberg MH. Deconstructing sickle cell disease: Reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev 2007;21:37-47.
Villagra J, Shiva S, Hunter LA, Machado RF, Gladwin MT, Kato GJ. Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin. Blood 2007;110:2166-72.
Machado RF, Gladwin MT. Pulmonary hypertension in hemolytic disorders: Pulmonary vascular disease: The global perspective. Chest 2010;137:30S-38S.
Manci EA, Culberson DE, Yang YM, Gardner TM, Powell R, Haynes J Jr., et al
. Causes of death in sickle cell disease: An autopsy study. Br J Haematol 2003;123:359-65.
Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, et al
. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med 1994;330:1639-44.
Anea CB, Lyon M, Lee IA, Gonzales JN, Adeyemi A, Falls G, et al
. Pulmonary platelet thrombi and vascular pathology in acute chest syndrome in patients with sickle cell disease. Am J Hematol 2016;91:173-8.
Gangaraju R, Reddy VV, Marques MB. Fat embolism syndrome secondary to bone marrow necrosis in patients with hemoglobinopathies. South Med J 2016;109:549-53.
Alhumaid A, Aleidi A, Alfakhri A, Alosaimi N, Ali Y, Alzahrani M. Clinical features and outcome of sickle cell anemia in a tertiary center: A retrospective cohort study. J Appl Hematol 2018;9:22. [Full text]
Singh A, Xu YJ. The cell killing mechanisms of hydroxyurea. Genes (Basel) 2016;7:99.
Quarmyne MO, Dong W, Theodore R, Anand S, Barry V, Adisa O, et al
. Hydroxyurea effectiveness in children and adolescents with sickle cell anemia: A large retrospective, population-based cohort. Am J Hematol 2017;92:77-81.