Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contact us Login 
  • Users Online:116
  • Home
  • Print this page
  • Email this page

 Table of Contents  
Year : 2017  |  Volume : 5  |  Issue : 1  |  Page : 55-58

Serum cardiac troponin I and alpha fetoprotein levels in adults with sickle cell anaemia in Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Nigeria

1 Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria
2 Department of Medical Laboratory Science, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Anambra State, Nigeria
3 Department of Chemical Pathology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria

Date of Web Publication16-Jun-2017

Correspondence Address:
John C Aneke
Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2321-4848.208214

Rights and Permissions

Background: Several cardiac and hepatic abnormalities have been observed in patients with sickle cell anemia (SCA) which significantly increase disease-related morbidity and mortality. Objective: To determine the levels of cardiac troponin 1 (cTnI) and alpha-fetoprotein (AFP) in adults with SCA and compare with suitable controls. Subjects and Methods: A total of 95 participants, consisting of 30 heterozygous hemoglobin AS (HbAS), 30 homozygous hemoglobin SS (HbSS) (in steady state), 5 HbSS (in crisis), and 30 hemoglobin AA (HbAA), were studied. Five milliliter of venous blood was collected from each participant for cTnI and AFP level estimation (by the enzyme-linked immunosorbent assay technique) and hemoglobin phenotype confirmation (by cellulose acetate electrophoresis). Results: The mean serum level of cTnI was significantly higher in homozygous SCA participants in crisis compared HbAA controls and SCA participants in steady state (1.13 ± 0.46 ng/ml vs. 0.32 ± 0.03 ng/ml and 1.13 ± 0.46 ng/ml vs. 0.27 ± 0.04 ng/ml, respectively, P = 0.01). There were no significant differences in the mean serum levels of cTnI between SCA participant in steady state and HbAS and HbAA (P = 0.33 and 0.58, respectively). Serum AFP levels were not significantly different in SCA (both in crises and in steady state) compared with HbAS and HbAA participants (P values all > 0.05). Conclusion: Cardiac injury may underlie SCA bone pain crisis; assessment of cardiac function may be indicated, particularly in patients with recurrent crises.

Keywords: Bone pain crisis, cardiac enzymes, sickle cell anemia

How to cite this article:
Aneke JC, Manafa PO, Okocha CE, Celestine OC, Manafa VI, Chukwuma GO, Ibeh NC. Serum cardiac troponin I and alpha fetoprotein levels in adults with sickle cell anaemia in Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Nigeria. Arch Med Health Sci 2017;5:55-8

How to cite this URL:
Aneke JC, Manafa PO, Okocha CE, Celestine OC, Manafa VI, Chukwuma GO, Ibeh NC. Serum cardiac troponin I and alpha fetoprotein levels in adults with sickle cell anaemia in Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Nigeria. Arch Med Health Sci [serial online] 2017 [cited 2023 Feb 6];5:55-8. Available from: https://www.amhsjournal.org/text.asp?2017/5/1/55/208214

  Introduction Top

Sickle cell anemia (SCA) is a major health-care and societal problem that affects millions of people worldwide.[1] Nigeria has one of the highest incidences of the disease globally, and this situation has been further exacerbated by the inadequate/appropriate genetic counseling and testing protocol for this condition.[2],[3]

The disorder is inherited following an autosomal recessive pattern, caused by a single-point mutation in the gene encoding the β-globin chain of hemoglobin.[4] The resultant hemoglobin S is responsible for the plethora of complications seen in this condition, including recurrent bone pains, hemolytic anemia, and markedly decreased red cell survival.[5] The clinical severity of presentation has been known to be dependent on factors such as disease haplotype, extent of end-organ dysfunction as well as the concurrent inheritance of α-thalassemia.[5] Indeed proper patient stratification, using established markers of organ dysfunction and disease phenotype, is useful for effective planning of management strategies for patients with SCA.[6],[7]

Cardiac troponin 1 (cTnI) is a component of the cardiac regulatory proteins that control the calcium-mediated interaction between actin and myosin.[8] The protein is found exclusively in the heart, and raised serum levels are accepted as the standard biochemical marker for the diagnosis of myocardial damage as seen in conditions such as myocardial infarction (MI) and acute coronary syndrome.[9] Due to its tissue specificity, cTnI and cardiac troponin T (cTnT) have been shown to be very useful in the detection of cardiac damage even in the presence of elevated total creatine kinase (CK) and CK-MB which may occur in exercise-induced skeletal muscle damage.[10],[11] The importance of cardiac assessment in participant with SCA was emphasized in an earlier report which revealed that evidence of death related to cardiovascular causes was frequently encountered at autopsy.[12]

Alpha-fetoprotein (AFP) is a glycoprotein which is normally produced during fetal development by the hepatocyte and yolk sac and to a lesser extent the gastrointestinal tract. Serum levels are low in adult life but could become elevated in association with primary hepatocellular carcinoma or other yolk sac-derived germ tumors.[13] In clinical practice, it is commonly used as a marker for these tumors and is useful for diagnosis, prognostication, and patient management.[14]

There is paucity of literature on serum levels of CTnI and AFP in adult Nigerian SCA compared with participants with other hemoglobin phenotypes. This study, therefore, was aimed to fill this knowledge gap with a view to highlighting changes in serum levels in participants in steady state compared with those in crises conditions, finding from this work could emphasize the need for more stringent organ function assessment (especially cardiac) in SCA participants, particularly those with recurrent bone pain crises.

  Subjects and Methods Top

Study site

This was a case–control study carried out in at the hematology out-patient clinic (HOPC) of the Nnamdi Azikiwe University Teaching Hospital Nnewi metropolis, Nnewi North Local Government Area of Anambra state, Nigeria.

Study population

A total of 95 participants were recruited for this study, including 30 heterozygous hemoglobin phenotype (heterozygous hemoglobin AS [HbAS]), 30 homozygous SCA in steady state, 5 homozygous SCA in crisis, and 30 hemoglobin AA (HbAA) participants. Steady-state criteria for SCA participants were based on the criteria earlier described by Akinola et al., which stipulate the absence of clinical illness in the past 3 weeks and no blood transfusion in the preceding 3 months.[15]

The steady-state SCA participants were consecutively recruited from our weekly HOPC while those in crises were recruited at the point of presentation at the emergency room. The HbAS and HbAA participants were recruited from consenting members of the hospital community, which included undergraduate students on clinical posting.

Study participants who had extreme physical exertion, were overtly septic, or had clinical features/medical records that were in keeping with concurrent heart failure, pulmonary embolism, end-stage renal disease, pregnancy, Down syndrome, or Edward syndrome were excluded from the study.[16]

Laboratory methods

About 5 ml of venous blood was collected by venipuncture from the participants following standard protocol; 3 ml was dispensed in a plain container and centrifuged at 5000 rpm for 5 min. Serum extracted was used for the estimation of AFP and cTnI levels using enzyme-linked immunosorbent test kits procured from Biocheck ® Inc. Drive Foster City, CA USA. The remaining 2 ml was collected in potassium-ethylenediaminetetraacetic acid specimen containers for hemoglobin phenotype determination, using the cellulose acetate paper electrophoresis (Helena biosciences, UK ®). Samples for participants in crises were taken 12–24 h after presentation to the hospital emergency room; this is the expected time for peak serum cTnI levels to occur in the event of myocardial injury.[17]

Ethical issues

Ethical approval for this study was obtained from Research and Ethics Committee of our institution, and all participants gave written informed consent at the point of recruitment.

Statistical analysis

Data collected were analyzed using the statistical program for social sciences (SPSS) version 20 computer software (SPSS Inc., Chicago, IL, USA). Serum levels of cTn1 and AFP (expressed as means ± standard deviation) were compared among the different hemoglobin phenotypes using the student t-test, and values were deemed significant if P < 0.05.

  Results Top

The mean ages of SCA, HbAS, and HbAA participants were 24.29 ± 8.05, 20.17 ± 4.25, and 22.10 ± 6.15 years, respectively.

The means of serum cTnI level in HbSS (in steady state), HbAS, HbAA, and HbSS (in crisis) participants were 0.27 ± 0.04, 0.26 ± 0.13, 0.32 ± 0.03, and 1.13 ± 0.46 ng/ml, respectively [Table 1]. Serum levels were significantly higher in HbSS participants in crisis compared with those with HbAA and HbSS in steady state [P = 0.01, respectively, [Table 1].
Table 1: Comparison of serum cardiac troponin 1 levels among different hemoglobin phenotypes

Click here to view

The means of serum AFP levels in HbSS (in steady state), HbAS, HbAA, and HbSS (in crisis) participants were 1.55 ± 0.57, 1.54 ± 0.61, 1.50 ± 0.61, and 1.49 ± 0.24 ng/ml, respectively [Table 2]. There were no statistically significant differences in serum levels among participants with different hemoglobin phenotypes in this study [P values all > 0.05, [Table 2].
Table 2: Comparison of serum alpha-fetoprotein levels among different hemoglobin phenotypes

Click here to view

  Discussion Top

Autopsy features suggestive of MI but devoid of morphological evidence of coronary artery disease (CAD) are well described in patients who died from sickle-related crises.[11] Sickle vaso-occlusive crises typically present with limb as well as chest pain; there is, however, increasing likelihood that patients may have underlying myocardial injury arising from sickle-related obstruction of the coronary microcirculation, in addition to the body pains.[18] Due to increased survival and longevity of patients with SCA, sickle-related cardiovascular dysfunction (as well as other complications resulting from end-organ dysfunction) is becoming increasingly recognized in routine clinical practice.[19],[20] Indeed abnormalities such as cardiomegaly, chest hyperactivity, and heart murmurs have been documented in SCA patients and are thought to occur secondary to the effects of chronic anemia, pulmonary arterial hypertension, microcirculatory obstruction (related to vasculopathy), and cardiac iron overload.[21],[22]

In the present study, the mean serum level of cTnI was significantly higher in homozygous SCA participants in crisis compared with HbAA participants [P = 0.01, [Table 1]. This in keeping with the report of Aslam et al. which showed that serum cTn1 was elevated in SCA patients in crisis probably secondary to myocardial ischemia resulting from microvascular coronary obstruction which occur in sickle cell crisis.[18] Correspondingly, it has equally been shown that serum troponin levels (particularly serum cTnT levels) was significantly elevated and had strong positive correlation with the pain severity scores (r = 0.64, P = 0.011) among children with SCA in Ile-Ife, South West Nigeria.[23] In contrast, Rajpal et al. observed elevated serum troponin levels in just a fraction of SCA patients with chest pain and concluded that serum levels were not significantly associated with cardiovascular risk factors and obstructive CAD.[24] In addition, the study emphasized that elevated serum troponin levels in SCA may actually be a marker for pulmonary hypertension and correlated more with indices of hemolytic burden.[24]

The elevation in cTnI observed in our work maybe due to the widespread vaso-occlusion of the microvasculature including those of the heart, which occur in SCA, particularly in crises situations. Troponin release from the myocardium into the circulation is thought to be either due to transient leakage as seen in reversible ischemia or on a continuous basis as a result of irreversible ischemic damage.[25] We believe that the higher serum cTnI levels in this study might have occurred as a result of reversible myocardial ischemia due to crisis (leading to transient release) as opposed to necrosis (sustained release) because levels were not significantly different in homozygous hemoglobin SS (HbSS) in steady state compared with HbAA participants [P = 0.58, [Table 1]. This line of argument has equally been reiterated by another report which showed that cTns may be released by ischemia alone, and this is thought to be enabled by the presence of membranous blebs in cardiac myocytes.[26]

This study revealed no significant difference in the mean serum level of AFP in SCA participants in crises and in steady state and even among those with HbAS and HbAA [P values all > 0.05, [Table 2]. This observation is consistent with previous reports which emphasized the fact that serum AFP levels remain mainly unchanged in SCA, even in those with sickle-related hepatopathy and thus is a poor marker of hepatic dysfunction.[27],[28]

  Conclusion Top

cTns are tissue-specific enzymes which have been shown to be elevated in a number of critical disease conditions associated with myocardial injury or necrosis. The significant increase in cTnI in SCA participants in crises (compared with steady-state controls) may signify crises-related ischemic cardiac injury; the functional significance of this observation in our patient population will need to be further investigated (using electrocardiography and echocardiography) in follow-up studies.

Limitation of the study

Few SCA participants presented in crises (and fulfilled the inclusion criteria) during the study period. This accounted for the small participants in crises (5) that were studied. We hope that our findings will stimulate further work on this topic, using larger numbers of adult SCA participants in crises.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Piel FB, Patil AP, Howes RE, Nyangiri OA, Gething PW, Dewi M, et al. Global epidemiology of sickle haemoglobin in neonates: A contemporary geostatistical model-based map and population estimates. Lancet 2013;381:142-51.  Back to cited text no. 1
Aneke JC, Okocha CE. Sickle cell disease genetic counseling and testing: A review. Arch Med Health Sci 2016;4:50-7.  Back to cited text no. 2
  [Full text]  
Okocha C, Onubogu CU, Aneke J, Onah C, Ajuba I, Ibeh N, et al. Prevalence of sickle cell gene among apparently healthy under-two South-East Nigerian children: What is the role of parental premarital counseling and socio-demographic characteristics? Niger J Med 2016;25:176-81.  Back to cited text no. 3
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.  Back to cited text no. 4
Hassan SM, Al Muslahi M, Al Riyami M, Bakker E, Harteveld CL, Giordano PC. Sickle cell anemia and α-thalassemia: A modulating factor in homozygous HbS/S patients in Oman. Eur J Med Genet 2014;57:603-6.  Back to cited text no. 5
Okocha EC, Onwubuya EI, Osuji CU, Ahaneku G, Okonkwo UC, Ibeh NC, et al. Serum ferritin and severity scores in sickle cell disease patients in Nnewi (South East Nigeria). Br J Med Med Res 2016;11:1-7.  Back to cited text no. 6
Okocha E, Onwubuya E, Osuji C, Ahaneku G, Okonkwo U, Ibeh N, et al. Disease severity scores and haemogram parameters in Nigerian sickle cell disease patients. J Blood Disord Transfus 2015;6:324.  Back to cited text no. 7
Sharma S, Jackson PG, Makan J. Cardiac troponins. J Clin Pathol 2004;57:1025-6.  Back to cited text no. 8
Robertson IM, Sun YB, Li MX, Sykes BD. A structural and functional perspective into the mechanism of Ca2+- sensitizers that target the cardiac troponin complex. J Mol Cell Cardiol 2010;49:1031-41.  Back to cited text no. 9
Shave R, Dawson E, Whyte G, George K, Ball D, Collinson P, et al. The cardiospecificity of the third-generation cTnT assay after exercise-induced muscle damage. Med Sci Sports Exerc 2002;34:651-4.  Back to cited text no. 10
Nnadi E, Manafa P, Okocha E, Chukwuma G, Aneke J. Evaluation of creatine kinase activity and inorganic phosphate concentration in adult Nigerian homozygous and heterozygous hemoglobin phenotypes. Ann Med Health Sci Res 2014;4:697-700.  Back to cited text no. 11
[PUBMED]  [Full text]  
Norris S, Johnson CS, Haywood LJ. Sickle cell anemia: Does myocardial ischemia occur during crisis? J Natl Med Assoc 1991;83:209-13.  Back to cited text no. 12
Hidaka M, Takatsuki M, Soyama A, Adachi T, Kitasato A, Kuroki T, et al. I. Diagnosis and treatment for hepatoma. Gan To Kagaku Ryoho 2013;40:1297-300.  Back to cited text no. 13
Kumagawa M, Matsumoto N, Watanabe Y, Hirayama M, Miura T, Nakagawara H, et al. Contrast-enhanced ultrasonographic findings of serum amyloid A-positive hepatocellular neoplasm: Does hepatocellular adenoma arise in cirrhotic liver? World J Hepatol 2016;8:1110-5.  Back to cited text no. 14
Akinola NO, Stevens SM, Franklin IM, Nash GB, Stuart J. Subclinical ischaemic episodes during the steady state of sickle cell anaemia. J Clin Pathol 1992;45:902-6.  Back to cited text no. 15
Korff S, Katus HA, Giannitsis E. Differential diagnosis of elevated troponins. Heart 2006;92:987-93.  Back to cited text no. 16
Daubert MA, Jeremias A. The utility of troponin measurement to detect myocardial infarction: Review of the current findings. Vasc Health Risk Manag 2010;6:691-9.  Back to cited text no. 17
Aslam AK, Rodriguez C, Aslam AF, Vasavada BC, Khan IA. Cardiac troponin I in sickle cell crisis. Int J Cardiol 2009;133:138-9.  Back to cited text no. 18
Maioli MC, Soares AR, Bedirian R, Alves UD, de Lima Marinho C, Lopes AJ. Relationship between pulmonary and cardiac abnormalities in sickle cell disease: Implications for the management of patients. Rev Bras Hematol Hemoter 2016;38:21-7.  Back to cited text no. 19
Aneke JC, Adegoke AO, Oyekunle AA, Osho PO, Sanusi AA, Okocha EC, et al. Degrees of kidney disease in Nigerian adults with sickle-cell disease. Med Princ Pract 2014;23:271-4.  Back to cited text no. 20
Vasconcelos MC, Nunes MC, Barbosa MM, Fernandes BM, Passaglia LG, Silva CM, et al. Left ventricular remodeling in patients with sickle cell disease: Determinants factors and impact on outcome. Ann Hematol 2015;94:1621-9.  Back to cited text no. 21
Gladwin MT, Sachdev V. Cardiovascular abnormalities in sickle cell disease. J Am Coll Cardiol 2012;59:1123-33.  Back to cited text no. 22
Adegoke OA, Adegoke SA, Okeniyi JA, Smith OS. Serum cardiac troponin T (cTnT) in Nigerian children with sickle cell anaemia: An index of myocardial injury? Int J Med Med Sci 2013;3:376-80.  Back to cited text no. 23
Rajpal S, Hilbun J, Dwary A, Smith T, Mina G, Reddy PC, et al. Troponin elevation correlates with pulmonary hypertension and hemolytic burden in sickle cell pain crisis. Eur Heart J 2013;34 (Suppl_1):297. doi: 10.1093/eurheartj/eht307.P297.  Back to cited text no. 24
Hamm CW, Giannitsis E, Katus HA. Cardiac troponin elevations in patients without acute coronary syndrome. Circulation 2002;106:2871-2.  Back to cited text no. 25
Hickman PE, Potter JM, Aroney C, Koerbin G, Southcott E, Wu AH, et al. Cardiac troponin may be released by ischemia alone, without necrosis. Clin Chim Acta 2010;411:318-23.  Back to cited text no. 26
Ahn H, Li CS, Wang W. Sickle cell hepatopathy: Clinical presentation, treatment, and outcome in pediatric and adult patients. Pediatr Blood Cancer 2005;45:184-90.  Back to cited text no. 27
Gardner K, Suddle A, Kane P, O'Grady J, Heaton N, Bomford A, et al. How we treat sickle hepatopathy and liver transplantation in adults. Blood 2014;123:2302-7.  Back to cited text no. 28


  [Table 1], [Table 2]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Subjects and Methods
Article Tables

 Article Access Statistics
    PDF Downloaded191    
    Comments [Add]    

Recommend this journal