Introduction Effects of Age and Sex on Sickle Cell Disease Avascular Necrosis

Volume 2 | Issue


Volume 2 | Issue 1
Journal of Hematology and Blood Disorders This is a retrospective study in which the data were collected from our institute's electronic database in the years 2008-2015 for 68 patients with SCD.Both male and female patients with age from 4 to 78 years were included; of these, 41 underwent bone scintigraphy (BSc), and 27 underwent magnetic resonance imaging (MRI) for different reasons.Our exclusion criteria were bone diseases due to factors other than SCD such as tumors and endocrinology disorders, steroid therapy, irradiation treatment, or alcohol consumption.The patients were divided into two groups based on the SCD genotype as follows: the Hb S-thalassemia (SCTh) and HbSS (SCA) groups.In both groups, AVN was tested for significant relationships with age (child and adult) and sex (female and male).The patients' medical charts were reviewed for complete blood count, high performance liquid chromatography (HPLC), and AVN.Bone scintigraphs were retrieved electronically for all patients in this study and were examined for AVN.Infinia Hawkeye 4.0 SPECT-CT camera (GE Healthcare) was used.For bone scans, technetium-99m hydroxymethylene diphosphonate (HDP) was administered intravenously.For MRI, Echelon apparatus was used.Statistical analysis was performed by using SPSS; the crosstab statistical analysis test was conducted to find the significant values of age and sex in both SCA and SCTh groups.
Bone AVN is a frequent outcome in patients with SCD.The objective of the current study was to check if age and sex were associated risk factors for AVN development in patients with SCD including both the genotypes SCA and SCTh; the patients underwent BSc and MRI for different reasons.We collected the data of 68 subjects that represented both the SCD genotypes SCTh and SCA.In all the patients, AVN was a common complication observed in both the types of SCD.

Results
In SCTh 93.3% male patients compared to 50% female patients developed AVN.Similarly, among patients with SCA, 78.3% male patients compared to 65% female patients developed AVN.Number of AVN observed in 25 patients with SCTh 19 (76%).Number of AVN observed in 43 patients with SCA 31 (72 %).However in SCTh the age effect on AVN in SCTh (p=0.546) and the Sex effect on AVN (p=0.013).In SCA the age effect on AVN in SCA (p=0.783) and the Sex effect on AVN in SCA (p=0.334)(Table 1).The HPLC results (Table 2) showed the HbF mean values in SCTh 12% (13.6 in children, 10.6 in adults, 12.1 in females and 11.9 in males), while it is in SCA 17% (20.5 in children, 15.2 in adults, 18.2 in females and 15.8 in males).Further the HPLC results showed the HbA2 mean values in SCTh 4.9% (4.9 in children, 4.9 in adults, 4.8 in females and 4.9 in males), while it is in SCA 2.1% (1.9 in children, 2.4 in adults, 2.1 in females and 2.3 in males.

Discussion
SCD is a group of disorders that affects both men and women.Those face a chronic disease, with onset in childhood leading to devastating consequences [1].In spite of the impressive improvements in the survival of patients with SCD, scientific advances in chronic bone diseases are still lagging [12,13].AVN, which refers to bone destruction due to subchondral oxygen deficiency, remains Journal of Hematology and Blood Disorders Volume 2 | Issue 1 the leading cause of crippling disability and the most common manifestation in patients with SCD [14,15].Approximately 50% of the individuals with SCD are likely to develop some form of bone fragility syndrome by the age of 35 years [3].In Jamaica, Lee et al. reported that the likelihood of developing AVN was 82% between the age of 10 and 29 years [16].Little attempt has been made to survey age and sex-based differences in AVN in individuals with SCD.
Very few studies have shown the high incidence of AVN in male patients, and to our knowledge, none have stressed on sex as a factor associated with AVN and management of patients with SCD.The results of our study indicated a significant relationship between AVN and sex (p = 0.013) in SCTh, such that, male patients had more tendency to develop AVN than the female patients did.In patients with SCTh, 93.3% male patients compared to 50% female patients developed AVN.Similarly, in patients with SCA, 78.3% male patients compared to 65% female patients developed AVN.The female patients with SCTh had a lower tendency to develop AVN (50%) than the female patients with SCA did (65%).
We studied the significant effects of age and sex on AVN in patients with SCD.Pertaining to age, we have observed no significant differences between children and adults in both the sexes affected with SCD.Our finding is not in agreement with the recent studies on SCD that have suggested a lower prevalence (26%) of AVN among children with Hb SS (mean age, 9.8 years) compared to adults (48.6%) with a mean age of 26.7 years.In a study by Ware et al. 41% of adults with Hb SS over the age of 15 years had bone AVN [17].However, Koduri et al. reported that silent AVN occurred in 41% children aged 4-28 years with the spine and shoulder being involved in 27% and 28% cases, respectively [18].This indicates that there is an underestimation of AVN prevalence in children because of asymptomatic AVN or insensitive AVN investigation by using radiography [19].Earlier studies on AVN prevalence in patients with SCD were grossly underestimated, particularly, since 47% and 79% patients with hip and shoulder disease, respectively had no symptoms at the diagnosis time [20] for that reason bone scintigraphy is recommended to detect the silent and the multifocal AVN [21].We screened for AVN in our study by both the following methods: bone nuclear scintigraphy by utilizing the radionuclide technetium-99m, which is the most sensitive technique, and MRI, which is considered as the gold standard technique that is the most sensitive and specific one for the diagnosis of this condition.Therefore, our estimation of AVN prevalence in both the adults children was accurate.Pertaining to sex-based differences in AVN, prevalence in male versus female patients, we observed that the phenotypic heterogeneity of SCA, especially, in terms of AVN development was not linked to sex.The high Hb F level considered a protective factor in SCD [22] .
To date, there is no well-established consensus among providers on the management of SCD complications partly because of lack of evidence and because of differences in the experience of the providers [23].We strongly emphasize on the idea of screening all patients with SCD for AVN to monitor these complications; we hope to establish it as a routine protocol for all patients with SCD, in order to reduce the complications and disability associated with this disease.Additionally, the attention of physicians treating patients with SCD must be drawn to the possibility of AVN in order to prevent or avoid this serious complication, especially in male patients who are presented with frequent pain crises.By knowing the risk factors, patients with symptomatic SCD who are at risk for AVN can be identified and additional evaluations can be performed [24].
The HPLC results showed the mean HbF value in sex groups is higher than normal in both SCTh 12% (male 11.9 ± 7.76, female 12.1 ± 4.38) and SCA 17% (male 15.8 ± 8.23, female 18.2 ± 4.69).It is known that Hb F is high in SCTh as part of this genetic disorder.However, the high Hb F in SCA is most likely due to hydroxyurea treatment such patients commenced on.The higher HbF in SCA correlated with lower AVN 72% than in SCTh where the AVN was 76%.Although the HbF was almost similar between both sexes in SCTh and SCA group, but the male was more affected due to, sex factors which going with our hypothesis in this study (Table 2).The HbA2 mean value as expected is within normal in SCA 2.1%, while it was higher than normal in SCTh 4.9%.This need more research work to detect if it has any influnce on the higher incidence of AVN in SCTh.
No significant relationship was found between AVN and age in both SCTh and SCA, also no significance was found between SCA and sex.However, in SCTh a significant relationship was detected between AVN and sex, where males had more tendency to develop AVN.Female patients with SCTh had less tendency to develop AVN than the female patients with SCA.The higher HbF in SCA than in SCTh might be due to hydroxyurea treatment which could decreased the AVN incidence in SCA.The AVN prevalence in this study was more than in other studies that could be because of bone scintigraphy technique used which is the most sensitive technique which could detect the silent and the multifocal AVN in SCD.

Conclusion
We are grateful to the staff of the nuclear medicine department in Amiri Hospital and Mubarak Al-Kabeer Hospital for their efforts in performing scintigraphy.

Table 1 :
Effects of age and sex as possible associated risk factors for AVN development in patients

Table 2 :
The HPLC result for each group of sickle cell disease patients having avascular necrosis