Journal of Pediatric Surgery: Contents Lists Available at
Journal of Pediatric Surgery: Contents Lists Available at
Journal of Pediatric Surgery: Contents Lists Available at
a r t i c l e
i n f o
Article history:
Received 30 September 2015
Accepted 7 October 2015
Key words:
Congenital hemolytic anemia
Splenectomy
Hematologic outcomes
Surgical technique
a b s t r a c t
Purpose: The purpose of this study was to dene the hematologic response to total splenectomy (TS) or partial
splenectomy (PS) in children with hereditary spherocytosis (HS) or sickle cell disease (SCD).
Methods: The Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium registry collected hematologic
outcomes of children with CHA undergoing TS or PS to 1 year after surgery. Using random effects mixed modeling,
we evaluated the association of operative type with change in hemoglobin, reticulocyte counts, and bilirubin.
We also compared laparoscopic to open splenectomy.
Results: The analysis included 130 children, with 62.3% (n = 81) undergoing TS. For children with HS, all
hematologic measures improved after TS, including a 4.1 g/dl increase in hemoglobin. Hematologic parameters
also improved after PS, although the response was less robust (hemoglobin increase 2.4 g/dl, p b 0.001).
For children with SCD, there was no change in hemoglobin. Laparoscopy was not associated with differences in
hematologic outcomes compared to open. TS and laparoscopy were associated with shorter length of stay.
Conclusion: Children with HS have an excellent hematologic response after TS or PS, although the hematologic
response is more robust following TS. Children with SCD have smaller changes in their hematologic parameters.
These data offer guidance to families and clinicians considering TS or PS.
2016 Elsevier Inc. All rights reserved.
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124
Table 1
Demographic, disease, and operative characteristics.
Variable
Overall
Total
splenectomy
Partial
splenectomy
N
Demographics
Gender
Male
Female
Race/Ethnicity
White
Black
Hispanic
Other
Diagnosis
Hereditary spherocytosis
Sickle cell disease
Indication for surgery
Splenic sequestration
Transfusion dependence
Splenomegaly
Hypersplenism
Aplastic crisis or anemia
Poor growth
Operative characteristics
Partial converted to total
Initial approach
Open
Laparoscopic
Laparoscopic converted
to open
130
81 (62.3%)
49 (37.7%)
67 (51.5%)
63 (48.5%)
42 (51.9%)
39 (48.1%)
25 (51%)
24 (49%)
52 (40%)
69 (53.1%)
7 (5.4%)
2 (1.5%)
26 (32.1%)
50 (61.7%)
4 (4.9%)
1 (1.2%)
26 (53.1%)
19 (38.8%)
3 (6.1%)
1 (2%)
61 (46.9%)
69 (53.1%)
33 (40.7%)
48 (59.3%)
28 (57.1%)
21 (42.9%)
74 (56.9%)
28 (21.5%)
22 (16.9%)
4 (3.1%)
7 (5.4%)
6 (4.6%)
54 (66.7%)
19 (23.5%)
9 (11.1%)
2 (2.5%)
4 (4.9%)
6 (7.4%)
20 (40.8%)
9 (18.4%)
13 (26.5%)
2 (4.1%)
3 (6.1%)
0 (0%)
p-Value
0.93
0.05
0.07
2 (4.2%)
0 (0%)
b0.01
0.64
0.04
0.63
0.99
0.08
2 (4.2%)
b0.001
37 (28.5%)
93 (71.5%)
9 (9.9%)
9 (11.1%)
72 (88.9%)
3 (4.2%)
28 (57.1%)
21 (42.9%)
6 (30.0%)
b0.01
hemoglobin compared to open surgery (p = 0.08), increasing their hemoglobin by only 3.3 g/dl. Children with HS who underwent PS had a
signicantly smaller hemoglobin rise compared to TS (p b 0.001), increasing by only 2.4 g/dl postoperatively. When examining the hemoglobin response over time, we found no changes through 1 year of
follow-up, indicating that after the initial increase associated with surgery values remained steady (p = 0.10).
In HS, the change in reticulocyte count after surgery was not associated with either PS vs. TS or laparoscopic vs. open technique, meaning
that the N8% decrease in reticulocytes was not signicantly different
among any subgroup. After the initial 8.3% drop in reticulocytes, there
was evidence of a rebound of 2.4% (0.7%4.3%; p = 0.01) over the rst
6 months; however, reticulocytes stabilized from 6 months to 1 year
(p = 0.87). Similar to the decrease in reticulocytes, the change in bilirubin was not associated with splenectomy type or surgical technique in
HS. These changes showed no trends over time (p = 0.34) through
1 year. No HS patients converted from partial to total splenectomy, so
no sensitivity analysis was required.
In children with SCD, there was no signicant increase in hemoglobin
(0.1 g/dl; 0.8 to 1.9 g/dl; p = 0.77) after surgery and no differences
when comparing PS to TS or laparoscopy to open splenectomy. Reticulocytes did decrease by 4.2% (0.8%7.6%; p = 0.02). Use of laparoscopy was
not associated with a difference in reticulocytes compared to open
surgery; however, PS was associated with a smaller reticulocyte improvement by 3.4% (0.3%6.5%; p = 0.03) compared to TS. In addition,
there was a small decrease in bilirubin by 1.0 mg/dl (0.31.7 mg/dl;
p = 0.01) after surgery. Laparoscopy showed no difference, although
PS resulted in a smaller bilirubin decrease by 0.8 mg/dl (0.11.4 mg/dl;
p = 0.03) compared to TS. No changes were found over time. In a sensitivity analysis grouping children by procedure performed rather than intention to treat, the same trends were seen; however, the difference in
reticulocytes was not statistically signicant (p = 0.07), indicating that
these results may be sensitive to the rate of conversion from PS to TS.
2.3. Secondary outcomes
PS appeared to have greater estimated blood loss than TS (28% with
EBL 100 ml vs. 14%), but perioperative transfusions were similar (6.2%
vs. 3.8%; p = 0.67) (Table 2). LOS was 1.5 days longer in the PS group
(3.5 vs. 2 days, p b 0.001). Long-term transfusion requirements through
1 year were similar between PS and TS (2.1% vs. 5.6%; p = 0.65). By
surgeon estimate, patients undergoing PS were left with a median
splenic volume of 15% of original (IQR: 10%15%), with two children
(4.2%) converted from PS to TS. PS was also less likely to be done
laparoscopic (43% vs. 89%, p b 0.001) and more likely to be converted
to open if started laparoscopic compared to TS (30% vs. 4%, p =
0.003). Although there were no deaths in this cohort through 1 year of
follow-up, 3 children (4.2%) undergoing total splenectomy experienced
postsplenectomy sepsis compared to 0 children undergoing partial
splenectomy (p = 0.28).
Laparoscopic splenectomy had higher blood loss than open splenectomy (24% vs. 5.8% of children losing 100 ml of blood), but perioperative transfusions showed no difference with 5.6% vs. 2.8% requiring
125
the low rates of clinical events allow limited sensitivity to identify subtle
differences between procedures; therefore, we used random effects
mixed models to examine these differences and better understand expected hematologic outcomes from various procedures and diagnoses.
All types of splenectomy improve hemoglobin, reticulocyte, and bilirubin measures in children with HS. The hematologic outcomes from
the mixed modeling analysis (Fig. 3) correlate well with those displayed
in the unadjusted analysis (Figs. 1 and 2). Our current ndings conrm
most prior studies examining PS for children with HS, which have
shown good clinical and hematologic responses to surgery, although
the hematologic response to TS is more robust than PS [2,5,10,1416].
This difference between TS and PS is not unexpected given the remaining splenic remnant effect on hemolysis following PS. In addition, both
adjusted and unadjusted analyses demonstrated initial postoperative
improvements that remained stable over time. The exception was reticulocyte count which demonstrated a rebound after initial improvement
in HS; however, the 6-month and 1-year values continued to be lower
than baseline.
Although no signicant difference was found in postsplenectomy
sepsis, the higher rate of this complication following TS underlines the
complexity of the decision to undergo PS or TS. The most appropriate
procedure for a given child depends on many variables, such as age, disease severity, genotype, risk of adverse events, and long-term hematologic control, and not all were addressed in this study. The decision
between TS and PS is dependent on clinician and family preferences,
taking into account all expected risks and benets. Our current report
provides estimates of hematologic response following TS or PS, which
should help all stakeholders through this decision-making process.
For children with SCD, our ndings conrm most studies which suggest that hemoglobin levels do not change after TS or PS [12]. However
these ndings are likely confounded by articially elevated hemoglobin
preoperatively because of the common practice of chronic transfusions
following sequestration events in very young children with SCD. While
reticulocyte count and bilirubin may be more sensitive measures for hematologic improvement in SCD, the small differences that we found in
these measures support previous studies in suggesting that splenectomy in SCD should focus on outcomes such as quality of life or adverse
events rather than hematologic parameters. We and others have previously conrmed control of important select clinical symptoms in these
children with regard to transfusion dependence and sequestration
following either TS or PS, which is a major goal for both families and
clinicians caring for these children [3,12,17].
Numerous previous studies have compared laparoscopic to open
splenectomy in children, nding advantages in postoperative pain control and decreased length of stay (LOS) for children undergoing laparoscopy [4,79]. The single study comparing hematologic outcomes for
laparoscopic vs. open PS showed similar postoperative hemoglobin
but less favorable results in reticulocytes [11]. This prior study also demonstrated a larger splenic remnant in laparoscopy vs open splenectomy,
raising concerns that hematologic benets may depend on the amount
of spleen resected, and that extensive resection may not be as easily
achieved in laparoscopic technique. Our current study offers reassurance that the hematologic outcomes following laparoscopy for TS or
PS are similar to an open approach, and that the retained spleen size is
not different between approaches for children undergoing PS. We did
conrm the longer LOS for open splenectomy compared to laparoscopy
as previously reported [4]. PS has a low but real risk of conversion to
total splenectomy estimated at 4%. In addition, this study demonstrates
a signicantly higher conversion from laparoscopic to open surgery in
PS compared to TS (30% vs. 4%), which surgeons and families need to
understand when considering these procedures.
This study has the advantage of generalizable results due its
prospective and multi-institutional design. Because random effects
models allow the use of multiple data points per patient [13], this
analytic approach can identify differences among subgroups, as we
used an average of 250 data points per hematologic outcome and
126
Fig. 3. Postsplenectomy changes in hematologic parameters for children with congenital hemolytic anemias. Results represent differences in postoperative hematologic values at 4, 24, and
52 weeks (versus baseline), laparoscopic (versus open) splenectomy, and partial (versus total) splenectomy as indicated. Results produced from random-effects mixed modeling including
the following covariates: gender, race/ethnicity, laparoscopic vs. open technique, partial vs. total splenectomy. Hereditary spherocytosis and sickle cell disease were analyzed separately.
Blue squares represent point estimates and black lines represent 95% condence intervals. Results are additive such that estimating the change in postoperative hemoglobin after laparoscopic partial splenectomy, the point estimates for postoperative, laparoscopy, and partial splenectomy would need to be added. For example, the postoperative hemoglobin increase in HS
is estimated at 4.1 g/dl in open, total splenectomy. This estimate is decreased by 1.7 g/dl in partial splenectomy compared to total splenectomy (estimate displayed) indicating that the
expected postoperative hemoglobin in partial splenectomy would only be 2.4 g/dl (equal to 4.11.7; not displayed).
Table 2
Secondary outcomes total vs. partial splenectomy.
Variable
Overall
Total splenectomy
Partial splenectomy
N
Estimated blood loss (ml)
Estimated blood loss
b30 ml
3099 ml
100199 ml
200 ml
Perioperative blood transfusion
Splenic volume retained, surgeon estimate (%)
Length of stay (days)
Long-term transfusion (through 1 year)
Sepsis (through 1 year)
130
15 (10, 50)
81 (62.3%)
15 (10, 30)
49 (37.7%)
25 (10, 100)
81 (65.3%)
19 (15.3%)
11 (8.9%)
13 (10.5%)
6 (4.8%)
0 (0, 10)
3 (2, 4)
5 (4.2%)
3 (2.5%)
57 (74%)
9 (11.7%)
6 (7.8%)
5 (6.5%)
3 (3.8%)
0 (0,0)
2 (1,3)
4 (5.6%)
3 (4.2%)
24 (51.1%)
10 (21.3%)
5 (10.6%)
8 (17%)
3 (6.2%)
15 (10,15)
3.5 (3,4)
1 (2.1%)
0 (0%)
p-Value
0.03
0.05
0.67
b0.001
b0.001
0.65
0.27
127
Table 3
Secondary outcomes laparoscopic vs. open splenectomy.
Variable
Overall
Open splenectomy
Laparoscopic splenectomy
N
Estimated blood loss (ml)
Estimated blood loss
b30 ml
3099 ml
100199 ml
200 ml
Perioperative blood transfusion
Splenic volume retained, surgeon estimate (%)
Length of stay (days)
Splenic volume retained, 4 weeks (%)
Splenic volume retained, 24 weeks (%)
Splenic volume retained, 52 weeks (%)
Long-term transfusion (through 1 year)
130
15 (10, 50)
37 (28.5%)
10 (10, 12.5)
93 (71.5%)
20 (10, 75)
81 (65.3%)
19 (15.3%)
11 (8.9%)
13 (10.5%)
6 (4.8%)
15 (10, 15)
3 (2, 4)
16 (10, 22)
15 (11, 27)
17 (10, 29)
5 (4.2%)
30 (85.7%)
3 (8.6%)
1 (2.9%)
1 (2.9%)
1 (2.8%)
15 (10, 20)
3 (3, 4)
16 (10, 25)
15 (8, 26)
22 (9, 31)
1 (2.7%)
51 (57.3%)
16 (18%)
10 (11.2%)
12 (13.5%)
5 (5.6%)
15 (10, 15)
2 (1, 4)
15 (11, 19)
15 (13, 24)
12 (12, 12)
4 (4.8%)
p-Value
b0.01
0.03
0.67
0.38
b0.01
0.78
0.78
0.77
0.99
Continuous data represented by median and interquartile range (IQR). Patients with total splenectomies were excluded from analysis on retained splenic volume.
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