Splenic sequestration crisis in children with sickle cell disease in the Eastern Region of Saudi Arabia

doi:10.21203/rs.3.rs-5102366/v1

Background:

Splenic sequestration crisis (SSC) is a life-threatening complication of Sickle cell disease (SCD). Studies have shown that patients who carry the African sickle gene haplotypes have more severe SCD than those with the Arab-Indian (AI) haplotype. Our aim was to study the prevalence and the clinical features of SSC among SCD children with both haplotypes living in the same environment in the Eastern region of Saudi Arabia (SA).

Patients and Methods:

A retrospective cohort study of 340 children with SCD, who visited our hospital from 2010 – 2020 was carried out. The collected clinical data of patients with SSC were compared between two groups of children: Eastern and Southwestern (SW) children.

Results:

A total of 50 patients with SSC were enrolled in this study, with a sex ratio of 2.1. There were 38 children from the SW region (African-haplotype group), and 12 from the Eastern region (AI-haplotype group). The overall prevalence of SSC was 14.7%, with no significant difference between the two groups, p.60.

The African-haplotype group were diagnosed with SCD at a younger age than their peers in the AI-haplotype group [median (IQR)]: 8.5 (6-11) v. 30.5 (24-36) months; p<.001.

The median (IQR) steady state HB in the African-haplotype group was significantly lower than that in the AI-haplotype group [8 (7.5-9) v. 9 (8-10) gm/dL]; p<.01.

During the 1^st SSC there was a significant difference between the African-haplotype group and the AI-haplotype group in the following parameters [median (IQR)]: age: 25(12- 48) v. 72(39-134) months, HB 5.1 (4.4-5.9) v. 6.1 (5.9-6.4) gm/dL, Splenic size on admission 5.5 (3-8) v. 8 (6-9.5) cm and upon discharge 3 (2-5) v. 5 (3.5-5.5) cm below the costal margin. The African haplotype group had a significantly greater number of recurrences than did the AI haplotype group [3.5 (2-6) v. 2 (1.5-2.5)]; p<.05.

Conclusion:

The overall prevalence of SSC among SCD children in the Eastern region of SA was 14.7% without a significant difference between Eastern SA (AI-haplotype group) and Southwestern SA (African-haplotype group) who lived in the same environment. SW Children experienced more severe SSC, suggesting that genetic rather than environmental factors are responsible for the severity of these episodes.

sickle cell disease

splenic sequestration

Saudi

children

Eastern region

SCD is one of the most common and severe hereditary blood disorders worldwide[1]. Acute SSC is a potentially life-threatening complication of SCD, usually occurring in young patients under 5 years of age[2]. It is characterized by acute drop in hemoglobin level of 2 g/dL accompanied by splenomegaly[3]. The major episodes are characterized by a greater drop in HB with hypovolemic shock, whereas the minor attacks are characterized by a moderate increase in splenic size with a drop in the HB level of 2–3 g/dL from the steady state. The recurrence rate of SSC tends to reach 50–78% after the first incident[4]. Historically SSC was the second leading cause of death among young children with SCD with a mortality rate of 12–44% in the 1980s. However, over the past forty years, mortality rates have decreased dramatically to less than 1%[3]. Nevertheless, SSC remains an important cause of morbidity and mortality in SCD in developing countries[5].

Saudi Arabia is considered one of the countries with the worst incidence of SCD in the world[6]. In this country, the prevalence of the disease is highest in the Eastern Region, followed by the SW province, with two major clinical and hematological phenotypes. SCD patients originating from the Eastern province of SA are known to have a mild form of the disease because they carry mainly the AI HBB haplotype. In the SW region, SCD patients predominantly carry the African haplotype (Benin), and the disease is more severe[7]. As SCD phenotypes vary widely between different regions of this country, the prediction of disease severity will aid in the risk stratification of patients and the development of appropriate plans for management and counselling.

Information about the variability in SCD phenotypes in SA has been mainly based on studies conducted in each region independently. Research on SSC in SCD is scarce, particularly in this country where information about its prevalence is patchy and may be underestimated [6, 8, 9]. We hypothesized that SSC occurs more among the SW children (with the African haplotype) than among their Eastern peers (with the AI haplotypes). Our aim was to determine the prevalence and clinical characteristics of SSC among children living in Eastern SA with both AI and African haplotypes. We therefore studied a cohort of patients with SCD and compared SSC characteristics between Eastern and SW children living in the same Eastern environment.

This is a retrospective cohort review of children diagnosed with SCD (HBSS/HBSβ⁰ phenotypes) and followed up at King Fahad Military Medical Complex (KFMMC), Dhahran, SA. The hospital provides medical care for military personnel and their dependents living in the Eastern Province of SA. The patients are either indigenous or originated from the SW area. The cohort included 340 patients with SCD: 246(72%) from the SW and 94 (28%) from the Eastern region, of whom 50 children (38 from the SW region and 12 from the Eastern region) had at least one SSC. Compared with SW patients, Eastern patients were more likely to receive treatment in other hospitals near their residences in the Eastern region. This could explain the difference in the number of patients in both groups in our hospital. The inclusion period was from January 2010 – December 2020. The medical records of the patients were reviewed and the data were collected via case report forms.

The original province of the patients was obtained from the family name and confirmed by their ID copy attached to their file. Saudi society is mainly tribal, where the family name indicates the person’s ancestral origin. There is a lack of admixture between the tribal groups due to their conservative attitude in terms of intermarriage with each other. This resulted in a high prevalence of consanguineous marriages in this country[10].

The hemoglobin (HB) genotype was determined via High-performance liquid chromatography (HPLC) electrophoresis, and the patient's HB and hematological indices were determined via an automated coulter counter.

SSC occurred when a sudden drop in the steady-state HB level of at least 20% is associated with an increase of at least 2 cm in palpable spleen size, accompanied by an increase in the reticulocyte count[11]. During the study period, the KFMMC adopted a strategy to manage SSC following the Evidence-Based Management of Sickle Cell Disease Expert Panel Report[12].

In our study, the following information was collected from the medical records:

Baseline data: date of birth (age), sex, consanguinity, province of origin, glucose-6-phosphate-dehydrogenase (G6PD) status, splenic size (if palpable before SSC), Hb level, reticulocytes, and initial HB electrophoresis.
During the 1st SSC: Age, HB level, reticulocytes, concomitant signs and symptoms, and splenic size on admission and upon discharge.
Post-1st SSC Follow-up until the age of 14: the number of SSC recurrences, whether the blood transfusion program was used, and splenic status: surgical removal, auto splenectomy, or persistent enlargement.

In this study, if the spleen was documented to be palpable and measured in centimeters below the left costal margin on the mid-clavicular line, it was considered enlarged. The steady-state splenic size was the average of three measurements taken during three routine clinic visits. The steady-state hematological data; including hemoglobin (HB), mean corpuscular volume (MCV), and reticulocyte percentage (Retic%); were calculated from the average of three complete blood counts (CBC) during routine clinic follow up visits

Statistical Analysis: The patients were categorized into 2 groups based on the province of origin: southwestern and eastern. The quantitative data were presented as mean (± SD), median (IQR), and graphs in IBM SPSS version 28. For normally distributed data, comparisons between groups were done via the chi-square (or Fisher exact) test for categorical data, and for continuous data, Student’s t-test (or Wilcoxon Mann-Whitney U test) was used. Univariate analysis was carried out to determine factors that are correlated with SSC. Multivariate logistic regression analysis, expressed as the adjusted odds ratio (OR) and its 95% confidence interval (CI), included all significant parameters identified in the univariate analysis. In all statistical tests, the P value was considered statistically significant if it was < 0.05.

Over the period between January 2010 and December 2020, 340 children with SCD attended KFMMC, of whom 50 patients had at least one SSC. The overall prevalence was 14.7% with15.5% among the SW (African haplotype) group and 12.7% among the Eastern group (AI haplotype); the difference was not statistically significant, (p = 0.60).

Table (1) shows the main demographic data and management of the patients with SSC. There were 34 boys and 16 girls (sex ratio: 2.1). Among these 50 children, 38 (78%) had homozygous SCD (HB SS), and 11(22%) had Sβ⁰ Thalassemia. Twenty-seven (54%) patients had a positive family history of SCD. Three pairs of siblings with consanguineous parents had SSC. Nine (18%) patients had G6PD deficiency,16 (32%) had normal enzyme, and the G6PD status of 25 (50%) children was unknown. The table also shows no significant difference in these parameters between the two groups.

The patients received supportive care during the episodes, including small aliquots of PRBCs, followed by offering a temporizing transfusion program. Eighteen (36%) patients received a chronic blood transfusion. The program was irregular for many children as their families had to move between East SA and South SA from time to time. After the age of five, 10 (20%) children had not experienced any new SSC, possibly because of auto-splenectomy, and 15 (30%) patients had no SSC but maintained a persistently enlarged spleen. A third group (25 children, 50%) continued to have recurrent sequestration until surgical splenectomy was performed.

Three patients with SSC from the SW group presented with hypovolemic shock, one of whom developed acute chest syndrome and stroke within 24 hours. One patient from the Eastern group presented with fainting and hypotension as the SSC commenced. No one died because of SSC at KFMMC during the period of study.

The most common symptoms accompanying SSC were: fever (23 patients; 46%), and pallor (22 patients; 44%). Five (10%) patients presented with other symptoms, eg, abdominal pain, cough, and diarrhea.

Table (1): Comparison between the SW and Eastern groups of SCD children.

The neonatal sickle cell screening program was not implemented in our hospital during the study period. SCD was diagnosed when the patient presented with the first symptom or when the parents are concerned because of positive family history of the disease. Table (2) describes the hematological and splenic changes in the steady state and during the 1st SSC among the children of both groups. There were significant differences between the two groups in the following parameters: age at both SCD diagnosis and at onset of 1st SSC, HB in the steady state and during the 1st SSC, Splenic size on admission for the 1st episode and upon discharge after stabilization of the patient, and the number of SSC relapses. The results also revealed a geater HBS and reticulocyte percentage in the SW group, whereas HBF, steady-state splenic size and the interval between episodes were greater in the Eastern group; however, these differences were not statistically significant.

Table (2): Comparison between the SW and Eastern groups of SCD children according to features of the 1st SSC

The SSC appeared more severe in the SW group than in the Eastern group as shown in Figs. 1–6. The steady-state HB was significantly lower in the SW group, which also experienced the 1st SSC at an earlier age with a greater decrease to a lower level in HBs than their Eastern peers did; p < .05. Interestingly, the splenic size of the Eastern patients was larger on admission and upon discharge during the 1st episode (compared with the SW group); p < .05. However, the SW group had more SSC recurrences; p < .05.

Figure (1)

Figure (2)

Figure (3)

Figure (4)

Figure (5)

Figure (6)

Univariate analysis of factors associated with the occurrence of SSC (Table 3) revealed that a lower steady-state HB level, hemolytic crisis, and splenomegaly were associated with a history of SSC (P < 0.05). Age, VOC, MCV and HU (P > 0.05) were not associated with risk of sequestration. In the multivariate analysis (Table 4), both splenomegaly (P = 0.00) and hemolytic crisis (P = 0.01) remained significant factors associated with SSC.

Table (3) Univariate analysis of SSC and measured clinical parameters

Table (4): Multivariate analysis of SSC and measured clinical parameters

Regression analysis also revealed that none of the studied variables were correlated with the recurrence of SSC except for the steady-state HB which was negatively correlated (OR: 0.42, CI: 0.20–0.78; p.02).

The aim of this study was to determine the prevalence of SSC and study the clinical and hematological features of SSC in two groups of children with SCD. These groups are related to two different ancestries with the AI and African haplotypes of the sickle gene and live in the Eastern province of SA. The analysis revealed that SSC was common among SCD children, but the difference between the two groups was not significant. The clinical features of the episodes among the African haplotype–related children (SWs) were more severe than those among their peers with the AI haplotypes. Notably, children with Sβ thalassemia and those who had splenomegaly prior to the occurrence of SSC were more prone to develop SSC. There was no mortality in this study, reflecting increased awareness and successful parental education in addition to easy access and free medical services in SA.

Prevalence

The overall prevalence of SSC in the current study was 14.7% in SCD patients, in accordance with previous reports from different countries (1–35%)[4, 8, 13–15]. This figure is almost the same as that reported in a tertiary hospital(14.5%) in Riyadh (central region of SA) [16]. The patients’ ancestries were not specified in that study.

In the present study, the prevalence among Eastern children (with the AI haplotype) was 12.7%, which is in line with other reports from India where SCD patients genuinely carry the AI haplotype[17–19]. This figure is higher than that reported in an earlier study from the same Eastern Saudi Region (1.7%)[20]. However, in that study, the patients were younger than 4 years (in an area known to have SSC mainly in older children) [9, 21] and even in adulthood. Zakaria et al. reported a prevalence of 7.8% of SSC among adults (older than 17) in the same Eastern area[22].

The prevalence of 15.5% among SW children (with the African haplotypes) is greater than the 7% reported earlier by Hawsawi et al. in the Western region in 2001.[8] This could be explained by increased awareness and parents’ knowledge of disease complications over time, resulting in increased numbers of patients diagnosed with SSC. On the other hand, it is less common than what has recently been reported in SCD children by Basuni et al. (31%)[23] in the Western area, and Alsultan et al. (23%) in SCD patients at all ages in the SW region. The variability in prevalence in different regions could be attributed to the possible variation in genetic mutations and the environmental differences as the Eastern province is approximately 1500 km from these areas.

In concordance with other studies, our analysis revealed a significantly greater prevalence of SSC among SCD children with HBS/β-thalassemia genotype than among their peers with homozygous SS disease[4, 19, 24]. The reason for this is unknown, however, some authors have suggested that HBS/β-thalassemia patients may have maintained some of the splenic function necessary for sequestration to occur[4].

The SSC relapse rate in our patients was high (78%) which is in accordance with other studies [4, 15]. In contrast, in older studies the recurrence rate was only 49–50%[8, 25]. This difference was hypothesized to be due to increased rates of survival after the first SSC and increased numbers of diagnosed patients[15]. The risk factors for SSC recurrences have not yet been established. In our statistical analysis, the only factor significantly associated with recurrence was steady-state HB. Brousse et al. reported a lower risk when the first episode occurred after 2 years of age[15]. In another study, a baseline splenic size ≥ 3 cm and the age of the 1st SSC between 2 and 5 years were predictive, whereas HBS > 72% at the time of diagnosis of SCD, vaso-occlusive crisis (VOC) as a revealing sign of SCD and neutrophil count ≥ 5400 / mm3 at the time of diagnosis were associated with a lower risk of recurrence[4].

Features of the 1 st SSC

Studies have shown that the clinical features of SCD are relatively mild in places where the AI haplotype is predominant, namely India and Eastern SA. The exact reason for this is not fully understood. This may be due to higher levels of HBF and the co-inheritance of alpha thalassemia[26]. Information about SSC in these places is scarce.

Studies on SSC in the Eastern, Western and SW regions of SA, where SCD is most prevalent, are scarce, with limited details[8, 9, 21, 27]. Our study suggested that the 1st splenic sequestrations were severe among SW children (African haplotype group). They occurred at a young age with a low steady-state HB which decreased to lower levels and in three occasions were accompanied by circulatory collapse. In addition, they recurred more frequently. Table (5) shows that these findings are comparable to the available data in previous studies on similar population but in their original provinces (Western and SW regions)[8]. They are also similar to episodes that occur in SCD patients of African origin in other countries, including Jamaica[5], Tunisia[4] and France[15].

Table (5) [Supplementary file]: Saudi studies showing SSC in SCD children with African haplotypes in the western and SW regions.

On the other hand, the study demonstrated milder attacks among Eastern children with the AI haplotype, which is in line with previous studies on similar populations in the Eastern region (Table 6)[9, 21]. SSC is considered an important SCD complication in India, and the details of its prevalence and natural history are lacking.[28]

Table (6) [Supplementary file]: Saudi studies showing SSC in SCD children with AI haplotypes in the Eastern Region.

A comparison of the 1st episode characteristics in this report supports our hypothesis that SSC is more severe among the SW children (African haplotype group) than among their Eastern peers (the AI haplotype group). Interestingly, the splenic enlargement characteristic of these episodes was more marked in the Eastern patients. The reason for this could be related to the characteristic late persistence of splenomegaly and possibly some splenic function in Eastern patients.[29]

These differences between the two groups could be explained by genetic and/or environmental factors affecting the sickling process. Both groups of children were living in the same environment in the Saudi Eastern province. They shared the climate (temperature, air quality, humidity, rainfall, and wind speed), altitude, exposure to infection, medical care, and socio-economic status (all of them are military personnel dependent). This finding supports the theory that SW children retain the severity of their African haplotype of the sickle gene despite living in an environment of mild SCD[10]. Additionally, the severity of their SSC is likely related to genetic rather than environmental factors as shown in the present study.

Splenomegaly

Splenomegaly in SCD is assumed to be caused by a moderate amount of stiff RBC entrapment, which results in limited splenic enlargement with minimal hematological alterations. Its prevalence varies according to genetic and environmental factors[30]. In areas where its prevalence is high (> 50%), it is considered a risk factor for the occurrence and recurrence of SSC[4, 14]. In our cohort, 84% of patients with SSC had splenomegaly before the first episode which was predictive for SSC in multivariate analysis.

The concentrated sickled RBCs are unable to pass through the small endothelial slits of the splenic venous sinuses and rejoin the intravascular system[30, 31]. This condition typically resolves spontaneously, but occasionally, the obstruction may spread, leading to rapid splenic filling with RBCs that cannot flow out. A large blood volume may become acutely retained within the spleen, leading to SSC[3]. The reason for this rapid spread of small occlusive events in the spleen rather than spontaneous resolution is still unknown. In the present study, there was no significant difference in the steady state splenic size between the two groups of patients. However, the rate of splenic enlargement increased more significantly during the 1st SSC in Eastern SA (AI haplotype group) than in their SW peers (African haplotype group). After stabilization and a reduction in the size of the spleen upon discharge from the hospital, a significant difference in the splenic size persisted.

Earlier studies have shown that patients in the Eastern region (with the AI haplotype) have a unique splenic characteristic of SCD as they have fibro-congestive pathology, rendering large spleens persist for longer periods[29]. It has been reported that a high level of HBF can be an important factor contributing to the persistence of splenomegaly and predisposing patients to SSC[4]. However, the higher HBF in Eastern children than in their SW peers was not statistically significant. The difference in splenic size appeared in this study only after the patients experienced the 1st SSC, which may have triggered this change in the spleen. Surgical splenectomy was performed in 50% of our patients. Splenectomy may be needed if SSCs are difficult to manage or if they recur[32]. The remaining patients either refused the operation or underwent auto-splenectomy.

Limitations of the study and future directions

There are several limitations to this study. The first is the retrospective nature of the study, with difficulty in obtaining all the precise important data. Second, this was a single-center study with a small number of patients, particularly Eastern children, which limits its generalizability. Third, there is a paucity of literature, particularly Saudi studies, on SSC. Fourth, other episodes may have been treated in other hospitals and were not included in this study. Further prospective multi-center studies in different regions of SA with more representative samples are needed to enhance our understanding of the natural history of SSC in children with SCD. This will be helpful in developing appropriate care models.

SSC is common in Saudi children with SCD living in the Eastern region of SA but the prevalence of SSC is not significantly different between SW children (African haplotype group) and their Eastern peers (the AI group). Comparatively, the episodes appeared more severe in the former group, likely due to the retained genetic effect of their sickle gene African haplotype rather than environmental impact.

SCD: sickle cell disease

SSC: splenic sequestration crisis

SA: Saudi Arabia

AI: Arab-Indian

SW: southwest

HB: hemoglobin

HPLC: high performance liquid chromatography

MCV: mean corpuscular volume

Retic%: Reticulocytes%

VOC: vaso-occlusive crisis

HU: hydroxyurea.

Acknowledgment

We would like to thank Rehab Abdalla Zayed for her contribution in preparation of the graphs and completion of the manuscript.

Clinical Trial Number: Not applicable

Ethical Considerations:

The study received scientific and ethical approval from the Armed Forces Hospitals Eastern Province Institutional Review Board (IRB): IRB (Protocol No. AFHER-IRB-2021-008). This study was conducted in accordance with good clinical practice and the declaration of Helsinki. According to the study's design, there was no direct interaction with patients or use of tissue samples, eliminating the need for parental or guardian informed consent for minors. In recognition of this, our Ethics Review Board granted a waiver for informed consent.

Authors contribution:

All authors contributed significantly to this research and reviewed the final version. All were involved in the conception and design of the study, data collection, analysis and interpretation.

Data availability

The raw data of this study contain protected health information. They are therefore not publicly available. Deidentified data may be provided by the corresponding author upon reasonable request, after approval from the ethical review board at King Fahad Military Medical Complex. Any data shared will be fully anonymized for protection of patient confidentiality and privacy according to the regulations.

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Table (1): Comparison between the SW and Eastern groups of SCD children.

Parameter

Splenic Sequestration crisis (n.= 50)

Total

P value

SW area

(n=38)

Eastern area

(n=12)

Gender:

Male
Female

25 (73.5%)

13 (81.3%)

9 (26.5%)

3 (18.7%)

34 (68%

16 (32%)

0.727

Consanguinity:

Positive
Negative

23 (85.2%)

15 (65.2%)

4 (14.8%)

8 (34.8%)

27 (54%)

23 (46%)

0.182

G6PD:

Deficient
Normal
Not done

7 (77.8%)

11 (68.8%)

20 (80.0%)

2 (22.2%)

5 (31.2%)

5 (20.0%)

9 (18%)

16 (32%)

25 (50%)

0.706

Genotype:

SS
Sβ⁰

28 (71.8%)

10 (90.9%)

11 (28.2%)

1 (9.1%)

39 (78%)

11 (22%)

0.256

Blood transfusion program:

Yes
No

16 (88.9%)

22 (68.8%)

2 (11.1%)

10 (31.2%)

18 (36%)

32 (64%)

0.170

Follow- up splenic status:

Surgical splenectomy
Auto-splenectomy
Persistent splenomegaly

19 (76.0%)

8 (80.0%)

11 (73.3%)

6 (24.0%)

2 (20.0%)

4 (26.7%)

25 (50%)

10 (20%)

15 (30%)

0.930

Table (2): Comparison between the SW and Eastern groups of SCD children according to features of the 1^st SSC

Parameter	All	Southwest (N:38)	East (N:12)	P Value
Age at SCD diagnosis: Median (IQR)	10 (6-21)	8.5 (6-11)	30.5 (24-36)	0.00*
Steady state HB Median (IQR)	8.5 (7.5-9)	8 (7.5-9)	9 (8-10)	< 0.01*
Steady state Retic (%): Mean ± SD	6.2±2.4	6.3± 2.1	6.0 ± 2.1	0.75
Age in months at 1^st SSC: Median (IQR)	35(14.7-60)	25(12-48)	72(39-134)	< 0.01*
HB at 1^st SSC: Median (IQR)	5.7 (4.5-6.1)	5.1 (4.4-5.9)	6.1 (5.9-6.4)	0.01*
Retic % at 1^st SSC: Mean ± SD	15.5±8.1	17.6 ± 5.8	14.8 ± 8.8	0.31
Steady state splenic size: Median (IQR)	2.9 (2-3.3)	2.47±1.65	4.25±3.36	0.11
Splenic size on admission: Median (IQR)	6 (4-8)	5.5 (3-8)	8 (6-9.5)	0.01*
Splenic size on discharge: Median (IQR)	3 (2-5)	3 (2-5)	5 (3.5-5.5)	0.02 *
Number of recurrences	3 (2-5)	3.5 (2-6)	2 (1.5-2.5)	0.03 *
Interval between crisis: Median (IQR)	3 (1-5)	3(1-4)	4.5(0.5-5)	0.34
HBS (%): Mean ± SD	69.5±10	69.7 ± 10.7	68.6 ± 7.5	0.30
HBF (%): Mean ± SD	14.9±9	14.2 ± 9.5	17.3 ± 7.4	0.15

*Significant

SD: standard deviation, IQR: interquartile range

Age: months, HB: gm/dL, Splenic size: cm

Table (3) Univariate analysis of SSC and measured clinical parameters

Variable	OR	95% CI	P
Age	0.94	0.88-1.01	0.90
VOC	2.00	0.91-4.20	0.08
Splenomegaly	20.29	8.32-49.5	0.02*
Hemolytic crisis	3.70	1.9-7.2	0.00*
Steady state HB	0.65	0.48-0.87	0.005*
MCV	0.99	0.97-1.01	0.46
HBF	0.99	0.96-1.02	0.60
HU use	1.32	0.72-2.40	0.37

*Significant

OR: Odds Ratio, CI: Confidence interval, VOC: vaso- occlusive crisis, MCV: Mean corpuscular volume, HBF: Hemoglobin F, HU: Hydroxyurea

Table (4): Multivariate analysis of SSC and measured clinical parameters

Variable	OR	95% CI	P
Splenomegaly	18.69	7.56-46.23	0.00*
Hemolytic crisis	3.04	1.58-6.67	0.01*
Steady state HB	0.80	0.58-1.10	0.17

*Significant

Table (5) Saudi studies showing SSC in SCD children with African haplotypes in the western and SW regions.

Region

Prevalence/Description

Characters of 1^st episode

Al-Hawsawi et al. [8]

Western

Prevalence: 7%

Number: 8/120

Age: children <13y

7-year-study

From 1993-2000

F/M: 3.1

Genotype: SS 7, Sβ⁰ 1

- Mean age: 2.5y (2m-6y)

- All patients: collapse, no death

- Steady state HB: 6-10.5 gm/dL

- baseline retics: 4-8%

- HBF:15-30%

- SSC recurrences: 50%

Current study (SW)

Southwestern

Prevalence: 15.5%

Patients’ number:

38/340

From 01.2010 to 12/2020

M>F: 1.9

Genotype: HB SS 28, HB Sβ⁰ 10

- Mean age: 2y (1-4y)

- 3 patients presented with circulatory collapse

- Steady state HB: 8.3 ± 1.08 gm/dL

- HB at 1st SSC: 5.1 ± 1.2 gm/dL

- Baseline Retics (%):6.3 ± 2.1

- HBF (%):14.2 ± 9.5

Table (6) Saudi studies showing SSC in SCD children with AI haplotypes in the Eastern Region.

Study	Region	Prevalence/Description	Characters of 1^st episode
Salamah et al. [9]	Eastern	Prevalence? 17 patients with SSC From 09.1981-09.2085 Males: 11/17 Genotype: HB SS 14/17, HB Sβ⁰ 3/17	- mean age 4 9/12 y - No major episodes. - spleen: 5-13 cm - HB: 4.5 gm/dL (2-7gm/dL) - Retics: 20% (mean) - HBF:30% - Recurrences: 4/17
Al-Salem et al. [21]	Eastern	Prevalence? 19 patients 5 years study from 1989 to 1993 M/F:14/19 Genotype: HBSS 17/19, HB Sβ⁰ 2/19	- Median age: 10 y (range 4-32) - 2 patients: collapse - HB: 1.4- 6.4 gm/dL - Retics: 6.8-47.8% - HBF: 9-34% - Spleen: 207-1200 gm - number of recurrences:2-8
Current study (East)	East	Prevalence: 12.7% 12/50 patients From 01.2010 to 12/2020 M/F: 3 Genotype: HBSS 11, HB Sβ⁰ 1	- Median age: 6y (IQR: 3-11y) - One patient: fainting. - HB: 8.8 ± 1.3 gm/dL - HB at 1st SSC: 6.0 ± 0.6 gm/dL - Retic % at 1st SSC: 14.8 ± 8.8 - HBF (%):17.3 ± 7.4 - Splenic size: 8.53±4.07 cm - Recurrence: 1.75±0.45(75%)

No competing interests reported.

Splenic sequestration crisis in children with sickle cell disease in the Eastern Region of Saudi Arabia

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Abstract

Figures

Introduction

Methods

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Tables

Additional Declarations

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