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Home , Asplenia, Splenectomy, Splenic infarction

EJH 1270 Dispatch: 28.4.09 Journal: EJH CE: Anusha Journal Name Manuscript No. B Author Received: No. of pages: 3 PE: Meenakshi European Journal of Haematology

ORIGINAL ARTICLE 1 2 3 Acute splenic complications and implications of 4 in hemoglobin SC 5 Karthi Subbannan, Celalettin Ustun, Kavita Natarajan, Betsy Clair, Lisa Daitch, Sabine Fields, 6 Ferdane Kutlar, Abdullah Kutlar 7 8 Department of Medicine, Section of Hematology ⁄ Oncology, Sickle Cell Center, Medical College of Georgia, Augusta, Georgia, USA 9 10 11 12 13 Abstract 14 Splenectomy indications and outcome were evaluated in 124 adults with hemoglobin SC disease (Hb SC). 15 Twelve patients (9.6%) required splenectomy. There was a significant difference between the splenec- 16 tomy group and the non-splenectomy group, respectively, regarding Hb levels (median 7.2 g ⁄ dL vs. 17 12.5 g ⁄ dL, P < 0.0001), platelet counts (median 146 · 106 ⁄ L vs. 275 · 106 ⁄ L, P = 0.031), palpable 18 rate (66% vs. 16%, P = 0.0003%), acute chest syndrome frequency (75% vs. 12% P = 0.0004) and chole- 19 cystectomy rate (66% vs. 13%, P = 0.0004). No significant morbidity or mortality occurred postsplenecto- 20 my. There is a subgroup of Hb SC patients requiring splenectomy, in which splenectomy is effective. 21 Although it appears to be safe regarding short-term complications of , long-term adverse effects 22 such as have to be evaluated cautiously. 23 24 Key words Hemoglobin SC disease; splenectomy; splenic infarct; splenic hemorrhage 25 26 Correspondence Abdullah Kutlar, MD, Professor of Medicine, Director, Sickle Cell Center, Medical College of Georgia, 1521 Pope 27 Avenue, Augusta, Georgia 30912 USA. Tel: (706) 721 2171; Fax: (706) 721 7226; e-mail: [email protected] 28 29 Accepted for publication 17 April 2009 doi:10.1111/j.1600-0609.2009.01270.x 30 31 32 33 The spleen undergoes sickling-related damage with func- SC disease patients followed in the Sickle Cell Center at the 34 tional at a very early age, followed by fibrosis, Medical College of Georgia between 1975 and 2006. The 35 scarring and atrophy in patients with homozygous hemo- follow-up period for the non-splenectomy group (NSG) 36 globin (Hb) S gene (1–3). In contrast to patients with was 42 months (range; 1–121 months) and for the splenec- 37 homozygous HbS gene, 30–50% of Hb SC disease tomy group (SG) was 91 months (range; 1–324 months). 38 patients are reported to have persistent SC patients were not routinely evaluated for concomitant 39 into adulthood (1, 4). Complications like splenic seques- alpha unless they had a MCV of <70 fl. 40 tration, infarction and cytopenias are relatively common Approval for this study was obtained from the Medi- 41 in adults with Hb SC disease (1, 5–10). Acute splenic cal College of Georgia Institutional Review Board and 42 sequestration crisis (ASSC) can cause significant morbid- was in accordance with US federal regulations and the 43 ity or even mortality (2, 3, 9, 11). The recurrence of Declaration of Helsinki. 44 ASSC is common (2, 11). Splenectomy may be required 45 in the treatment of patients with ASSC or splenic infarct Statistics 46 (8, 9, 11). 47 Although there are several reports on splenectomy in Continuously valued endpoints were compared between 48 the pediatric population with Hb SC disease, little is the two groups by using Mann–Whitney U two-tailed 49 known in adults. test, and categorical factors were compared by using 50 Fisher’s exact two-tailed test. Presplenectomy complete 51 blood counts and chemistry results were available in 52 Patients and methods seven patients in the splenectomy group. Complete data 53 To evaluate splenectomy need and its outcome, we con- on the remaining five patients were not available because 54 ducted a retrospective analysis on 124 consecutive adult Hb splenectomy was performed at outlying hospitals.

ª 2009 John Wiley & Sons A/S 1 Splenectomy in Hb SC patients Subbannan et al.

1 Results patients in the SG had MCV < 70 which is against the 2 Twelve (9.6%) patients underwent splenectomy (SG) for coexistence of thalassemia. There was no difference in 3 the following indications: splenic in 3 ⁄ 12 terms of Hb S, C and F levels and stroke rate between 4 (25%), hypersplenism and sequestration in 5 ⁄ 12 (41.6%), the SG and NSG. 5 subcapsular in 1 ⁄ 12 (8%) and information not In the SG, the median Hb levels and counts 6 available in 3 ⁄ 12 patients (25%). significantly increased after splenectomy (Hb level from ⁄ ⁄ P 7 Splenectomy group and non-splenectomy group (NSG) 7.2 g dL to 11.4 g dL, = 0.007; platelet count from · 6 ⁄ · 6 ⁄ P 8 were compared in terms of patients demographics, clini- 146 10 L to 416 10 L, = 0.007) (Table 2). 9 cal and laboratory findings and sickle cell complications All patients undergoing splenectomy tolerated the 10 (Table 1). procedure well with no severe complications reported. The 11 There was no significant difference in terms of age and median follow up after splenectomy was 96 months 12 gender in these two groups. The majority of the patients (range;1–302 months). Mortality rate was similar between 13 undergoing splenectomy were in their third and fourth the splenectomy and non-splenectomy group (Table 1). 14 decade (7 ⁄ 12, 58%). Twenty-six patients (21%) had 15 splenomegaly and that observation was more common in Discussion 16 the patients who required splenectomy compared with The prevalence of palpable splenomegaly in adults with 17 those who did not (16%, 18 ⁄ 112 vs. 66%, 8 ⁄ 12, Hb SC disease is more common compared to adults with 18 P = 0.0003) (Table 1). The patients in the SG had sig- HbSS disease (1, 4). For the same reason, adults with 19 nificantly lower median Hb levels and platelet counts as Hb SC are more prone to have complications like splenic 20 compared with the NSG (Hb 7.2 g ⁄ dL vs. 12.5 g ⁄ dL, sequestration and (1, 4–8, 11). In our 21 P < 0.0001; platelet count 146 · 106 ⁄ L vs. 275 · 106 ⁄ L, study, the splenectomy rate was 9.6% (12 ⁄ 124). Splenec- 22 P = 0.031) (Table 1). Acute chest syndrome (ACS) tomized patients had significantly lower Hb levels and 23 occurred significantly more in the SG compared with the platelet counts compared with those who did not 24 NSG (75% vs. 12%, P = 0.0004) (Table 1). These undergo splenectomy. Moreover, this group had more 25 patients also had a significantly higher cholecystectomy complications of such as acute chest 26 rate (66% vs. 13%, P = 0.0001). Only two patients had syndrome and cholecystectomy. These patients were also 27 splenectomy and cholecystectomy at the same time. The more likely to be on hydroxyurea therapy (4 ⁄ 12 vs. 28 SG patients were more likely to be on hydroxyurea ther- 6 ⁄ 112, P = 0.007). This may indicate that the patients 29 apy (4 ⁄ 12 vs. 6 ⁄ 112, P = 0.007). Five of 112 patients in who require splenectomy represent a subset with more 30 the NSG had an MCV of 60–69. Only one of them had severe disease. 31 documented HB SC ⁄ alpha thalassemia. None of the 32 33 34 Table 1 Demographic, clinical and laboratory 35 Splenectomy Non- Group Prior to Splenectomy P comparisons between the splenectomized and 36 splenectomy P#12 Group P#112 non-splenectomized patients 37 38 Age 31(18–59) 26 (15–74) 0.5 ⁄ ⁄ ⁄ 39 Gender (female male) 8 45260 0.23 WBC · 106 ⁄ L median (range) 11.4 (4.9–30.9) 8.3 (2.5–21.5) 0.2 40 Hb (g ⁄ dL) median (range) 7.2 (5.8–12) 12.5 (10.6–15.6) <0.0001 41 Plt (·106 ⁄ L) median (range) 146 (91–470) 275 (64–856) 0.031 42 Reticulocyte count (%) median (range) 4 (1–15.5) 3.8 (0.06–21.5) 1 43 T. Bili (mg ⁄ dL) median (range) 1 (0.6–3.3) 1.3 (0.5–7.6) 0.8 1 44 Palpable spleen (%) 66 (8 ⁄ 12) 16 (18 ⁄ 112) 0.0003 45 HU treatment (%) 33 (4 ⁄ 12) 5% (6 ⁄ 112) 0.007 46 Hb S (%) median (range) 47.4 (45.1–49.4) 47.7 (39.6–55.6) 0.6 Hb C (%) median (range) 45.7 (39.9–50) 46.7 (39.7–69.9) 0.5 47 Hb F (%) median (range) 1.4 (0.5–12.3) 1.8 (0.5–16) 0.6 48 Acute chest (%) 75 (9 ⁄ 12) 22% (25 ⁄ 112) 0.0004 49 Priapism % 0 (0 ⁄ 4) 10% (6 ⁄ 60) 1 50 AVN (%) 25 (3 ⁄ 12) 17 (20 ⁄ 112) 0.69 51 Leg ulcer (%) 0 (0 ⁄ 12) 0.8 (1 ⁄ 112) 1 52 Cholecystectomy (%) 66 (8 ⁄ 12) 13 (15 ⁄ 112) 0.0001 ⁄ ⁄ 53 Stroke (%) 8 (1 12) 0.8 (1 112) 0.18 Mortality (%) 0 (0 ⁄ 12) 5 ⁄ 112 (4%) 1 54

2 ª 2009 John Wiley & Sons A/S Subbannan et al. Splenectomy in Hb SC patients

1 Table 2 Changes in hematologic values with splenectomy In conclusion, Hb SC is considered to be a relatively 2 Presplenectomy Postsplenectomy P mild form of sickle cell disease, especially in adults. 3 However, these patients can experience severe anemia 4 Hb (g ⁄ dL) (median) 7.2 11.4 0.007 and due to splenomegaly and · 6 ⁄ 5 WBC ( 10 L) (median) 11.4 10.3 0.9 related complications. Of interest, these particular (·106 ⁄ L) 146 416 0.007 6 (median) patients may also have other severe complications 7 Reticulocyte count % 4 2.8 0.4 mostly seen in patients with Hb SS disease. Splenec- 8 (median) tomy in these adult patients appears to be effective. 9 T. Bilirubin (mg ⁄ dL) 1 1 0.48 Long-term adverse effects of splenectomy remain to be 10 (median) observed. 11 Hb S% (median) 47.4 48.5 0.87 12 Hb C% (median) 45.7 46.3 0.67 Hb F% (median) 1.4 2 0.35 References 13 14 1. Orringer EP, Fowler VG, Owens CM, Johnson AE, et al. ⁄ 15 Aquino reported a 6% (16 271) rate of acute Mauro MA, Dalldorf FG, Croom RD. Case report: 16 splenic complications in children with Hb SC disease (2). Splenic infarction and acute splenic sequestration in ⁄ Am J Med Sci 17 The majority of these patients (13 16) experienced adults with hemoglobin SC disease. 18 ASSC. The first episode of ASSC occurred at a mean 1991;302:374–9. 19 age of 8.9 years. Forty-six percent of these children were 2. Aquino VM, Norvell JM, Buchanan GR. Acute splenic 20 noted to have splenomegaly before the initial episode of complications in children with sickle cell-hemoglobin C ⁄ disease. J Pediatr 1997;130:961–5. 21 ASSC. Acute drop in hemoglobin (median 3.6 g dL) and 3. Michel JB, Hernandez JA, Buchanan GR. A fatal case 22 in platelet counts were common with ASSC. Eight of acute splenic sequestration in a 53-year-old woman 23 patients (3%) underwent a splenectomy (three patients with sickle-hemoglobin C disease. Am J Med 1992;92: 24 for the first episode of ASSC and three patients for 97–100. 25 recurrent episodes of ASSC and two for splenic hemor- rhage) at the median age of 9.5 years. The recurrence of 4. Koduri PR, Agbemadzo B, Nathan S. Hemoglobin S-C 26 Am J ASCC was common, 33% within 12 months of the first disease revisited: clinical study of 106 adults. 27 Hematol 2001;68:298–300. 28 episode. In another study of 100 children with Hb SC disease, 5. Koduri PR, Nathan S. Acute splenic sequestration crisis 29 in adults with hemoglobin S-C disease: a report of nine palpable splenomegaly was 34% (12). The median age was 30 cases. Ann Hematol 2006;85:239–43. 11 years (range; 2–23.8 years). The presence of spleno- 31 6. Geola F, Kukreja SC, Schade SG. Splenic sequestration megaly was associated with lower average mean Hb levels 32 with sickle cell -C disease. Arch Intern Med 1978;138: (10.3 vs. 10.8 g ⁄ dL, P = 0.011) and lower platelet counts 33 307–8. · 9 ⁄ · 9 ⁄ P 34 (237 10 L vs. 314 10 L, < 0.001). ASSC occurred 7. Solanki DL, Kletter GG, Castro O. Acute splenic seques- 35 in 12% of these children. The median age of splenic seques- tration crises in adults with sickle cell disease. Am J Med 36 tration was 5.4 years. 1986;80:985–90. 37 The study limitation is the small number of patients in 8. Berry RA, Odumakinde EA, Lewis JP. Massive splenic 38 the splenectomy group. On the other hand, the control infarction in doubly abnormal heterozygous sickling 39 group is quite large, and comparing these two groups disorders. West J Med, 1991;155:531–2. 40 statistically indeed indicated that the splenectomy group 9. Shao SH, Orringer EP. Case report. Splenic sequestration 41 may represent a clinically distinct subgroup of patients and multiorgan failure as the presenting manifestation of Am J Med Sci 42 with Hb SC that had more severe complications. These hemoglobin SC disease. 1996;311:139–41. 43 splenic complications do not seem to be contributed 10. Habibi A, Khellaf M, Bachir D, Schaeffer A, Galacteros F, Godeau B. Acute splenic sequestration: a rare and 44 by an additional such as severe complication of sickle cell anemia in adults. A case 45 when we used MCV as a surrogate marker. The follow report. Rev Med Interne 2005;26:339–42. 46 up period for the NSG was shorter compared with 11. Wang-Gillam A, Lee RS, Hsi ED, Brotman DJ. Acute 47 the SG. This difference basically resulted from the retrospective nature of the trial. Some of the patients splenic sequestration crisis resembling in an adult 48 with hemoglobin SC disease. South Med J 2004;97:413– 49 underwent splenectomy out of our center, in particular the earlier patients. The decision was made by local 5. 50 12. Zimmerman SA, Ware RE. Palpable splenomegaly in chil- 51 and surgeons. Therefore, the discrepancy among indications of splenectomy basically reflects this dren with hemoglobin SC disease: haematogical and clini- 52 cal manifestations. Clin Lab Haematol 2000;22:145–50. 53 fact. 54

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