|Year : 2014 | Volume
| Issue : 2 | Page : 58-63
Impact of urinary schistosomiasis on haematological parameters and frequency of vaso-occlusive crisis among patients with sickle cell disease in northern Nigeria
Sagir G Ahmed1, Modu B Kagu2, Umma A Ibrahim3
1 Department of Haematology, Aminu Kano Teaching Hospital, Kano, Kano State, Nigeria
2 Department of Haematology, University of Maiduguri Teaching Hospital, Maiduguri, Borno State, Nigeria
3 Department of Paediatrics, Aminu Kano Teaching Hospital, Kano, Kano State, Nigeria
|Date of Submission||07-Feb-2014|
|Date of Acceptance||15-Feb-2014|
|Date of Web Publication||30-Aug-2014|
Sagir G Ahmed
Department of Haematology, Aminu Kano Teaching Hospital, PMB 3452, Kano, Kano State 11399
Source of Support: None, Conflict of Interest: None
Background Sickle cell disease (SCD) patients have impaired immunity with vulnerability to infections including parasitic infestations. Majority of SCD patients live in nations where urinary schistosomiasis is also endemic. This study was aimed at determining the impact of urinary schistosomiasis on haematological parameters and frequency of vaso-occlusive crisis (VOC) among patients with SCD.
Materials and Methods We compared the haematological parameters and frequency of VOC among SCD patients with and without schistosomiasis in northern Nigeria.
Result SCD patients with schistosomiasis had lower haematocrit, higher reticulocyte count, higher prevalence of iron deficiency, more intense leucocytosis and thrombocytosis, higher prevalence of bacterial urinary tract infections and higher ESR. The frequency of VOC was significantly higher in SCD patients with schistosomiasis.
Conclusion The results of this study suggest that urinary schistosomiasis adversely affected the severity and prognosis of SCD. SCD patients, the majority of whom live in schistosomiasis endemic countries, should have regular urine tests for early detection and treatment of schistosomiasis in order to avert its adverse interaction with SCD.
Keywords: Sickle, Schistosomiasis, Vaso-occlusive, Crisis
|How to cite this article:|
Ahmed SG, Kagu MB, Ibrahim UA. Impact of urinary schistosomiasis on haematological parameters and frequency of vaso-occlusive crisis among patients with sickle cell disease in northern Nigeria
. Egypt J Haematol 2014;39:58-63
|How to cite this URL:|
Ahmed SG, Kagu MB, Ibrahim UA. Impact of urinary schistosomiasis on haematological parameters and frequency of vaso-occlusive crisis among patients with sickle cell disease in northern Nigeria
. Egypt J Haematol [serial online] 2014 [cited 2022 Sep 30];39:58-63. Available from: http://www.ehj.eg.net/text.asp?2014/39/2/58/139762
| Introduction|| |
Schistosomiasis is a major cause of chronic illness in poor tropical countries, including Nigeria where it is endemic with significant socioeconomic and public health burden , . Urinary schistosomiasis is widespread in both rural and urban communities with prevalence rates of up to 90% in some communities in Nigeria , .
Transmission of the causative agent of urinary schistosomiasis, Schistosoma haematobium, is initiated by the release of ova in the urine of infected persons into freshwater reservoirs. The ova hatch into miracidia that migrate into bolinius snails where they develop into cercariae, which penetrate the skin of human host  . The cercariae migrate to the vesical venous plexus of the urinary tract where they settle and reproduce eggs  . Adult schistosomes are able to evade host immune response through antigenic disguise and immune modulation, which ensure disease persistence and chronicity , .
Oviposition by adult schistosomes may be associated with acute allergic inflammatory reaction characterized by fever, respiratory distress and other systemic symptoms collectively referred to as Katayama syndrome , . The chronic phase is characterized by continuing egg deposition in the bladder leading to epithelial damage, haematuria and iron deficiency , . Epithelial injury caused by S. haematobium predisposes to secondary infections by bacteria, resulting in frequent urinary tract infections (UTIs)  .
With a black population of about 170 million and prevalence rates of about 25 and 3% for sickle cell trait and sickle cell anaemia (SCA), respectively, Nigeria carries the heaviest burden of sickle cell disease (SCD) in the world , . SCA, which is the prototype of SCD, is the homozygous state for the sickle cell gene characterized by red cell sickling, haemolysis, reticulocytosis, leucocytosis and thrombocytosis , . The clinical course of SCD is characterized by variable periods of steady state, which is periodically interrupted by painful vaso-occlusive crisis (VOC) due to red cell sickling and tissue infarcts , . Patients with SCD have impaired immunity and are therefore vulnerable to various infections including schistosomiasis  . Moreover, the majority of SCD patients live in the poorer nations of the world, Nigeria inclusive, where schistosomiasis is also endemic , . There is therefore the need to study the haematological and clinical interactions between urinary schistosomiasis and SCD, which to our knowledge has not been previously reported. Hence, in this report we studied the impact of urinary schistosomiasis on haematological parameters and frequency of VOC among patients with SCD in northern Nigeria.
| Materials and methods|| |
This is a combined prospective and retrospective study carried out during a 7-year period in three tertiary hospitals in northern Nigeria, including Federal Medical Centre, Birnin Kudu (2004), University of Maiduguri Teaching Hospital, Maiduguri (2005-2007) and Aminu Kano Teaching Hospital, Kano (2008-2010).
Patients were diagnosed with SCA on the basis of positive sickling tests and haemoglobin electrophoresis at a pH of 8.6 on cellulose acetate paper  . Consecutive patients who presented at the adult haematology clinics in steady state were recruited with due consents, and all procedures were conducted with institutional ethics committees' approval.
Patients with VOC were excluded, thus eliminating the effect of VOC on haematological parameters and serum ferritin levels  . Patients on long-term transfusion, those taking hydroxyurea and those on erythropoietin for sickle cell nephropathy were also excluded. Patients with diseases such as HIV infection, tuberculosis, hepatitis, malaria or intestinal parasitosis were excluded because these diseases can affect haematological and clinical profiles of SCD , .
Patients were initially screened for schistosomiasis by urine microscopy. Urine samples were collected and analysed by sedimentation and microscopic examination for S. haematobium ova, which are identified by their characteristic terminal spines  . Samples were always collected between 11.00 and 14.00 h, which correspond with the time of greater diurnal yield of S. haematobium ova in infected patients  .
End point of recruitment
Patients were consecutively recruited and screened by urine microscopy during the period of study until a target of 100 eligible SCA patients with documented urinary schistosomiasis were recruited.
Patient categorization on the basis of urine microscopy result for S. haematobium
Patients whose urine tested positive for S. haematobium ova were categorized as 'cases'. Equal number of age-matched and sex-matched individuals were selected from patients whose urine tested negative for S. haematobium ova to serve as 'controls'.
Both 'cases' and 'controls' were subjected to bacterial urine culture, haematological analysis and retrospective analysis of frequency of VOC as detailed below.
The rationale for conducting urine culture was based on the fact that urinary schistosomiasis is frequently complicated by bacterial UTI, which is a common problem in SCD patients in whom it is also a risk factor for VOC , . Urine samples were cultured on blood agar and cysteine lactose electrolyte-deficient agar. After 24 h aerobic incubation at 37°C, the culture plates were read for identifying and isolating bacterial species; and UTI was diagnosed if bacterial count was equal to or greater than 10 5 colony forming units per millilitre of urine sample examined  .
Blood samples were collected in EDTA containers, and the haematocrit, white blood cell (WBC) and platelet counts were determined using automatic blood analysers (Celltac Alpha MEK 6400: Nihon Kohden Corporation, Tokyo, Japan, or Cell-Dyn 3700CS: Abbott Laboratories, Abbott Park, Illinois, USA). Automated WBC count errors due to the presence of circulating nucleated red cells were manually corrected  . Reticulocyte counts were performed manually using brilliant cresyl blue supravital stain  . Erythrocyte sedimentation rates (ESRs) were determined by the Westergren method  . Iron stores of each patient were assessed by serum ferritin estimation using enzyme-linked immunosorbent assay techniques  . Enzyme immunoassay kits (Genway Biotech, Nancy Ridge Drive, San Diego, California, USA, or Clinotech, Horseshoe Way, Richmond, Canada) were used in accordance with kit manufacturer's methodology.
Retrospective analysis of vaso-occlusive crisis
One of the aims of this study was to evaluate the impact of schistosomiasis on the frequency of VOC among SCA patients. In view of the chronic nature of schistosomiasis, it was not possible to precisely determine the duration of schistosomiasis at the time of patient recruitment. Nonetheless, an empirical period of 3 years was retrospectively reviewed with respect to the occurrence of VOC in the recruited patients. The medical case note of each patient was scrutinized to determine and enumerate the number of documented episodes of VOC in the previous 3 years. In each case note, VOC was diagnosed if the patient presented with acute pain episodes in the extremities, back, chest, abdomen or head region  .
Calculations and statistical analysis
The cases and controls categories were comparatively analysed with respect to mean and SDs of haematological parameters, prevalence and relative frequencies of bacterial UTIs and the frequencies of VOC in the previous 3 years. The frequency of VOC (number of VOC per patient) was determined for each patient category by dividing the cumulative number of VOC by the number of patients. Statistical analyses were performed using computer software SPSS version 11.0 (SPSS Package for Windows 11.0 software, SPSS Incorporated, Chicago, Illinois, USA), and comparisons between values of studied parameters for the two patient groups were based on the χ2 -test and a P-value of less than 0.05 was taken as significant.
| Results|| |
The demographic data and haematological parameters of patients studied are shown in [Table 1]. Patients with schistosomiasis had lower mean haematocrit in comparison with those without schistosomiasis (0.22 vs. 0.27 L/L, P < 0.05). Mean reticulocyte count was higher among patients with schistosomiasis in comparison with those without schistosomiasis (16 vs. 11%, P < 0.05). Patients with schistosomiasis had higher quantitative leucocytes changes in comparison with those without schistosomiasis: mean WBC count (14.4 vs. 11.2 × 10 9 /l, P < 0.05), mean neutrophil count (10.4 vs. 7.6 × 10 9 /l, P < 0.05), mean eosinophil count (0.4 vs. 0.2 × 10 9 /l, P < 0.05) and prevalence of eosinophilia (53 vs. 0%, P < 0.05). Lymphocyte, monocyte and basophil counts were normal with no significant differences in both patient groups. Patients with schistosomiasis had higher mean platelet count in comparison with those without schistosomiasis (567 vs. 460 × 10 9 /l, P < 0.05). The mean ESR values were higher among patients with schistosomiasis in comparison with those without schistosomiasis (62 vs. 21 mm/h, P < 0.05).
Prevalence of bacterial UTI and frequencies of bacterial species isolated from patients studied are shown in [Table 2]. The prevalence of culture-proven UTI among patients with and without schistosomiasis was 49 and 8% (P < 0.05), respectively. Isolated bacterial species and their relative frequencies in patients with and without schistosomiasis include Escherichia coli (46.9 vs. 50%, P > 0.05), Klebsiella (34.7 vs. 37.5%, P > 0.05), Staphylococcus (12.2 vs. 12.5%, P > 0.05) and Salmonella (6.1 vs. 0%, P < 0.05).
|Table 1: Demographic data and haematological parameters of sickle cell anaemia patients with and without urinary schistosomiasis|
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|Table 2 Prevalence of urinary tract infection and relative frequencies of causative bacterial species among sickle cell anaemia patients with and without urinary schistosomiasis|
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The variations in serum ferritin levels among the patients studied are shown in [Table 3].
|Table 3 Serum ferritin levels of sickle cell anaemia patients with and without urinary schistosomiasis|
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Normal serum ferritin levels were found in 60 and 63% (P > 0.05) of patients with and without schistosomiasis, respectively. The prevalence of low serum ferritin was much higher in patients with schistosomiasis (38%) in comparison with those without schistosomiasis (3%, P < 0.05). Elevated serum ferritin levels were found in 8 and 40% (P < 0.05) of patients with and without schistosomiasis, respectively.
The frequencies of VOC among the patients studied are shown in [Table 4]. Patients with schistosomiasis had higher frequency of VOC (2.53 vs. 0.98, P < 0.05) in comparison with those without schistosomiasis.
|Table 4 Cumulative numbers of episodes and frequency of vaso-occlusive crisis in sickle cell anaemia patients with and without urinary schistosomiasis in the previous 3 years|
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| Discussion|| |
The pathophysiology of SCD is characterized by red cell sickling, chronic haemolysis, anaemia and reticulocytosis  . However, this study showed that SCD patients with schistosomiasis had lower haematocrit and higher reticulocyte count due to the additional effect of haemorrhage (haematuria). Haemorrhage by itself would cause anaemia and induce reticulocytosis, thus aggravating the background haemolytic anaemia and reticulocytosis due to SCD  . Reticulocytes play significant role in the pathogenesis of VOC. Sickle reticulocyte membrane has abundant expression of the a-4 b-1 integrin complex, which binds endothelial VCAM-1 receptors as a primary event in the initiation of VOC in SCD  . Hence, the higher reticulocyte counts seen in patients with schistosomiasis would partly account for the higher frequency of VOC observed in that group.
Leucocytosis due to neutrophilia is a common haematological feature of SCD, even in steady state, and is partly due to redistribution of neutrophils from marginal to circulating pool  . Other factors that may contribute to leucocytosis in SCD include increased marrow neutrophil mobilization and antiapoptotic effect of raised levels of interleukin-8 and decreased neutrophil apoptosis due to diminished levels of caspase-3 , . However, the result of this study revealed a much higher leucocytosis and neutrophilia among SCD patients with schistosomiasis in comparison with those without schistosomiasis. This finding was interpreted to be a reflection of additional effects of haemorrhage (due to haematuria) and greater inflammatory response due to higher prevalence of UTI among patients with schistosomiasis  . In addition, more than half of the patients with schistosomiasis had eosinophilia, which further escalated the leucocyte count  Leucocytosis increases blood viscosity, which is an important risk factor for VOC  . Moreover, cytoadherence involving neutrophils, eosinophils, vascular endothelial cells and sickled erythrocytes contributes towards the development of VOC ,, . It can therefore be deduced that intense leucocytosis due to the combined effect of neutrophilia and eosinophilia had contributed to the higher frequency of VOC observed in patients with schistosomiasis.
Thrombocytosis is a common feature of SCD that is generally attributed to elevated erythropoietin level due to the effect of haemolytic anaemia and autosplenectomy  . In this study, the intensity of thrombocytosis was higher among patients with schistosomiasis in comparison with those without schistosomiasis. This disparity may be related to additional effect of reactive thrombocytosis due to haemorrhage, vesical inflammation and high prevalence of bacterial UTI seen among patients with schistosomiasis  . Thrombocytosis can adversely affect blood viscosity and predispose to red cell sickling and VOC  . VOC invariably leads to vascular endothelial damage with subsequent exposure of subendothelial microfibrils and collagen, both of which cause platelet activation and aggregation, thereby re-enforcing vaso-occlusion , . We therefore infer that the presence of more intense thrombocytosis among patients with schistosomiasis might have contributed to the higher frequency of VOC recorded for that group.
More than one-third of patients with schistosomiasis had low serum ferritin in comparison with only 3% of patients without schistosomiasis. This is consistent with iron depletion as a result of chronic blood loss due to haematuria  . Conversely, elevated serum ferritin levels were seen in more than one-third of patients without schistosomiasis in comparison with only 8% of patients with schistosomiasis. Elevation of serum ferritin levels in patients without schistosomiasis can be attributed to previous blood transfusions, which is a major cause of iron overload among SCD patients  . The paradoxical finding of a few cases of elevated serum ferritin among patients with schistosomiasis can be explained on the basis of the well-known behaviour of ferritin as an acute-phase reactant that rises during inflammation  . The high prevalence of iron deficiency observed among patients with schistosomiasis in this study must have contributed to the lower haematocrit seen in that group of patients. Iron deficiency has been shown to raise plasma viscosity and enhance red cell aggregability in previous studies  . Increased plasma viscosity and red cell aggregability are undesirable in SCD, as they are associated with increased sickling, which increases the frequency and severity of VOC as exemplified in SCD patients with myeloma  . Hence, the high prevalence of iron deficiency in the schistosomiasis group might have contributed to the higher frequency of VOC documented for that group.
The greater elevation of ESR observed in patients with schistosomiasis was attributed to the considerably higher prevalence of secondary bacterial UTI leading to acute-phase reaction and higher blood viscosity, which is a potent trigger of VOC in SCD  . It is noteworthy that most of the causative bacterial species of the UTI in our patients with and without schistosomiasis were the 'usual' urinary tract pathogens, including E. coli, Klebsiella and Staphylococcus spp.  . However, Salmonella spp. that are rather 'unusual' urinary tract pathogens occurred exclusively in patients with schistosomiasis with a relative frequency of 6.1%. This finding is consistent with previous studies, which revealed that salmonella bacteria adhere to the tegument of S. haematobium in an intimate symbiotic relationship that contribute to recurrence and persistence of salmonella UTI and bacteraemia in patients with urinary schistosomiasis ,, . The presence of salmonella UTI among SCD patients with schistosomiasis is important because it creates a recalcitrant reservoir for salmonella infection, which would be particularly undesirable in SCD patients in whom infection is a major risk for VOC  . Moreover, Salmonella spp. have special predilection for SCD patients in whom they are known to cause both localized and disseminated infections ,, . High prevalence of UTI, due to both usual and unusual urinary bacteria, was therefore a contributory factor for the increased frequency of VOC seen among patients with schistosomiasis in this study.
This study had shown that urinary schistosomiasis in SCD patients was associated with increased frequency of VOC. The clinical significance of this finding is underscored by the fact that increased frequency of VOC has a prognostic implication in SCD. Earlier studies had shown that increased frequency of VOC was a significant indicator of disease severity and correlated with multiorgan damage and early death among patients with SCD  . Therefore, the results of this study suggest that urinary schistosomiasis adversely affected the severity and prognosis of SCD.
| Conclusion|| |
S. haematobium infection in patients with SCD is associated inflammatory response, UTI, haemorrhage, iron deficiency, lower haematocrit and increased frequencies of VOC. Hence, urinary schistosomiasis had an adverse effect on prognosis of SCD. Patients with SCD, most of whom live in schistosomiasis endemic countries, should have regular urine examination for early detection and treatment of schistosomiasis.
| Acknowledgements|| |
| References|| |
|1.||World Health Organization. Schistosomiasis, fact sheet no. 115. Geneva: World Health Organization; 2012. |
|2.||King CH. Parasites and poverty: the case of schistosomiasis. Acta Trop 2010; 113 :95-104. |
|3.||Ugbomoiko US, Ofoezie IE, Okoye IC, Heukelbach J. Factors associated with urinary schistosomiasis in two peri-urban communities in south-western Nigeria. Ann Trop Med Parasitol 2010; 104:409-419. |
|4.||Barnabas BB, Aliyu MB, Gbate M, Attairu AA. Survey of schistosomiasis and other intestinal helminthiases among school-aged children in Agaie, Niger State, Nigeria. J Pharm Biomed Sci 2012; 15 :1-5. |
|5.||Ross AG, Bartley PB, Sleigh AC. Schistosomiasis. N Engl J Med 2002; 346 :1212-1220. |
|6.||McLaren DJ. Disguise as an evasive stratagem of parasitic organism. Parasitology 1984; 88 :597-611. |
|7.||Van Riet E, Hartgers F C, Yazdanbakhsh M. Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiology 2007; 212 :475-479. |
|8.||Ross AG, Vickers D, Olds GR, et al. Katayama syndrome. Lancet Infect Dis 2007; 7 :218-224. |
|9.||Baharoon SA, Al-Jahdali HH, Bamefleh HS, Elkeir AM, Yamani NM. Acute pulmonary schistosomiasis. J Glob Infect Dis 2011; 3 :293-295. |
|10.||Fu CL, Odegaard JI, Herbert DR, Hsieh MH. A novel mouse model of Schistosoma haematobium egg-induced immunopathology. PLoS Pathog 2012; 8 :e1002605. doi: 10.1371/journal.ppat.1002605. |
|11.||Friedman JF, Kanzaria HK, McGarvey ST. Human schistosomiasis and anemia: the relationship and potential mechanisms. Trends Parasitol 2005; 21 :386-392. |
|12.||Nmorsi OP, Kwandu UN, Ebiaguanye LM. Schistosoma haematobium and urinary tract pathogens co-infections in a rural community of Edo State, Nigeria. J Commun Dis 2007; 39 :85-90. |
|13.||United Nations Population Fund. World Population Report, October 31, 2011: (http://foweb.unfpa.org/SWP2011/reports/EN-SWOP2011-FINAL.pdf). |
|14.||Galadanci N, Wudil BJ, Balogun TM, Ogunrinde GO, Akinsulie A, Hasan-Hanga F. Current sickle cell disease management practices in Nigeria. Int Health 2013; 6: 23-28. doi: 10.1093/inthealth/iht022 |
|15.||Flint J, Harding RM, Boyce AJ, Clegg JB. The population genetics of the haemoglobinopathies. Baillieres Clin Haematol 1993; 6 :215-222. |
|16.||Ahmed SG, Ibrahim AU, Hassan AW. Haematological parameters in sickle cell anaemia patients with and without priapism. Ann Saudi Med 2006; 26 :439-443. |
|17.||Ballas SK. Pain management of sickle cell disease. Hematol Oncol Clin North Am 2005; 19 :785-802. |
|18.||Ahmed SG, Kagu MB, Abjah UA, Bukar AA. Seasonal variations in frequencies of acute vaso-occlusive morbidities among sickle cell anaemia patients in northern Nigeria. J Blood Disord Transfus 2012; 3 :120. doi:10.4172/2155- 9864.1000120. |
|19.||Salawu L, Orimolade EA, Durosinmi MA. Immuno-haematological characteristics of Nigerian sickle cell disease patients in asymptomatic steady state. Eur J Gen Med 2009; 6 :170-174. |
|20.||Dacie JV, Lewis SM, White JM, Marsh GW. Investigation of abnormal haemoglobins and thalassaemia. In: Dacie JV, Lewis SM, (eds). Practical haematology. London, Churchill Livingstone, 1991; 227-257. |
|21.||Brownell A, Lowson S, Brozovic M. Serum ferritin concentration in sickle cell crisis. J Clin Pathol 1986; 39 :253-255. |
|22.||Ahmed SG, Bukar AA, Jolayemi B. Hematological indices of sickle cell anaemia patients with pulmonary tuberculosis in northern Nigeria. Mediterr J Hematol Infect Dis 2010; 2 :e2010014. |
|23.||Ahmed SG, Uraka J. Impact of intestinal parasites on haematological parameters of sickle cell anaemia patients in Nigeria. East Mediterr Health J 2011; 17 : 710-713. |
|24.||Cheesbrough M. Examination of urine. In: Cheesbrough M, (ed). District Laboratory Practice in Tropical Countries, Part-2. Delhi, Cambridge University Press, 2006; 105-115. |
|25.||Doerhring E, Vester U, Ehrich JH, Feldmeier H. Circadian variation of ova excretion, proteinuria, hematuria, and leukocyturia in urinary schistosomiasis. Kidney Int 1985; 27 :67-71. |
|26.||Mava Y, Timothy SY, Zailani SB, Ambe JP. Significance of pyuria in the diagnosis of urinary tract infection in children with sickle cell anaemia in Maiduguri, Nigeria. Afr J Clin Exp Microbiol 2012; 13 :103-109. doi: http://dx.doi.org/10.4314ajcem.v13i2.8. |
|27.||Evatt, BL, Gibbs WN, Lewis SM, McArthur JR. Diagnostic Methods. In: Evatt BL, Gibbs WN, Lewis SM, (eds). Fundamental diagnostic hematology (anemia). Geneva, World Health Organization, 1992; 63-124. |
|28.||Platt OS, Thorington BD, Brambilla DJ. Pain in sickle cell disease: rates and risk factors. N Engl J Med 1991; 325 :11-16. |
|29.||Raphael RI, Vichinsky EP. Pathophysiology and treatment of sickle cell disease. Clin Adv Hematol Oncol 2005; 3 :492-505. |
|30.||Noble NA, Xu QP, Hoge LL. Reticulocytes II: re-examination of the in vivo survival of stress reticulocytes. Blood 1990; 75 :1877-1882. |
|31.||Brittain JE, Han J, Ataga KI. Mechanism of CD47-induced α4β1integrin activation and adhesion in sickle reticulocytes. J Biol Chem. 2004; 279 : 42393-42402. |
|32.||Boggs DR, Hyde F, Srodes C. An unusual pattern of neutrophil kinetics in sickle cell anemia. Blood 1973; 41 :59-62. |
|33.||Almeida CB, Favero ME, Pereira-Cunha FG, Lorand-Metze I, Saad STO, Costa FF, Coran N. Alterations in cell maturity and serum survival factors may modulate neutrophil numbers in sickle cell disease. Exp Biol Med 2011; 236 :1239-1246. |
|34.||Conran N, Almeida CB, Lanaro C, Ferreira RP, Traina F, Saad STO, Costa FF. Inhibition of caspase-dependent spontaneous apoptosis via a cAMP-protein kinase A dependent pathway in neutrophils from sickle cell disease patients. Br J Haematol 2007; 139 :148-158. |
|35.||Dale DC. Neutropenia and neutrophilia. In: Kaushansky K, Lichtman M, Beutler E, Kipps TJ, Seligsohn U, Prchal J, (eds). Williams Hematology. New York, McGraw-Hill; 2010, 939-950. |
|36.||Wardlaw AJ. Eosinophils and their disorders. In: Kaushansky K, Lichtman M, Beutler E, Kipps TJ, Seligsohn U, Prchal J, (eds). Williams Hematology. New York, McGraw-Hill, 2010; 897-913. |
|37.||Ho CH. White blood cell and platelet counts could affect whole blood viscosity. J Chin Med Assoc 2004; 67 :394-397. |
|38.||Hofstra TC, Kalra VK, Meiselman HJ, Coates TD. Sickle erythrocytes adhere to polymorphonuclear neutrophils and activate the neutrophil respiratory burst. Blood 1996; 87 :4440-4447. |
|39.||Turhan A, Weiss LA, Mohandas N. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc Natl Acad Sci USA 2002; 99 :3047-3051. |
|40.||Canalli AA, Conran N, Fattori A. Increased adhesive properties of eosinophils in sickle cell disease. Exp Hematol 2004; 32 :728-734. |
|41.||Kaushansky K. Reactive thrombocytosis. In: Kaushansky K, Lichtman M, Beutler E, Kipps TJ, Seligsohn U, Prchal J, (eds). Williams hematology. New York, McGraw-Hill, 2010; 1929-1932. |
|42.||Ibanga IA. Significance of platelet activation in sickle cell anaemia. Niger J Med 2006; 15 :148-150. |
|43.||Wun T, Paglieroni T, Rangaswami A. Platelet activation in patients with sickle cell disease. Br J Haematol 1998; 100 :741-749. |
|44.||Hafsia R, Belakhal F, Ben Salah N, Gouider E, Elborgi W. Iron overload in sickle cell anemia: a study of 94 patients. Tunis Med 2011; 89 :548-552. |
|45.||Vanarsa K, Ye Y, Han J, Xie C, Mohan C, Wu T. Inflammation associated anemia and ferritin as disease markers in SLE. Arthritis Res Therap. 2012; 14: R182. doi:10.1186/ar4012. |
|46.||Khaled S, Brun JF, Wagner A, Mercier J, Bringer J, Préfaut C. Increased blood viscosity in iron-depleted elite athletes. Clin Hemorheol Microcirc 1998; 18 :309-318. |
|47.||Lemonne N, Connes P, Romana M, Vent-Schmidt J, Bourhis V, Lamarre Y, Etienne-Julan M. Increased blood viscosity and red blood cell aggregation in a patient with sickle cell anemia and smoldering myeloma. Am J Hematol 2012; 87 : E129. doi: 10.1002/ajh.23312. |
|48.||Ahmed SG. The role of infection in the pathogenesis of vaso-occlusive crisis in patients with sickle cell disease. Mediterr J Hematol Infect Dis 2011; 3 : e2011028. doi: 10.4084/MJHID.028. |
|49.||LoVerde PT, Amento C, Higashi GI. Parasite-parasite interaction of Salmonella typhimurium and schistosoma. J Infect Dis 1980; 141 :177-185. |
|50.||Gentilini M, Robineau M, Letonturier P, Boussougant Y, Domart A. Urinary infection due to Salmonella paratyphi C during Schistosoma haematobium schistosomiasis. Bull Soc Pathol Exot Filiales 1972; 65 :430-434. |
|51.||Gendrel D. Salmonella - schistosoma interactions. Rev Prat 1993; 43 :450-452. |
|52.||Wong VK, Lissack ME, Turmezei TD, Maitland JA. Salmonella pyomyositis complicating sickle cell anemia: a case report. J Med Case Rep. 2010; 4 : 198. doi:10.1186/1752-1947-4-198. |
|53.||Anand AJ, Glatt AE. Salmonella osteomyelitis and arthritis in sickle cell disease. Semin Arthritis Rheum 1994; 24 :211-221. |
|54.||Hann G, Roberts-Harewood M, Yardumian DA, Wilkey O. Salmonella bacteraemia in children with sickle cell disease. Arch Dis Child 2012; 97 : A89. doi:10.1136/archdischild-2012-301885.213. |
[Table 1], [Table 2], [Table 3], [Table 4]