Splenectomy for immune thrombocytopenic purpura:

Surgery for the 21st century

James P. Dolan,1* Brett C. Sheppard,2 and Thomas G. DeLoughery3

Although immune thrombocytopenic purpura (ITP) is the most common autoimmune hematological disor-
der, there is still controversy regarding the optimal management of this condition. Medical therapy may
cure a proportion of patients with ITP but there are still a significant number of these individuals who are at
risk for bleeding events. Surgery has become the least popular therapeutic option for ITP as other medical
therapies have become available that attempt to avoid splenectomy and its morbidity. However, the clinical
response to these therapies has not been overwhelming based on the fairly small number of trials con-
ducted to date. With current minimally invasive surgical techniques, splenectomy should be again regarded
as a viable therapeutic option in patients with ITP. The laparoscopic approach avoids much of the morbidity
and complications seen with the conventional open surgical approach and studies have demonstrated simi-
lar, if not better, outcomes. In addition, the risk of infection following splenectomy is not as high as may be
suspected, particularly with current vaccination regiments. It should be a priority for both the hematology
and medical community to advocate for clinical trials to rationally study alternatives to splenectomy. In the
interim, laparoscopic splenectomy should be considered as an additional front line therapeutic option in
ITP patients. Am. J. Hematol. 83:93–96, 2008. V C 2007 Wiley-Liss, Inc.

Despite being the most common autoimmune hematolog-
ical disease, with an estimated incidence of 1 in 50,000
persons, controversy exists concerning almost every aspect
of the management of immune thrombocytopenic purpura
(ITP). One of the main controversies concerns the role of
splenectomy. Over the past decade, splenectomy has
evolved from the cornerstone of ITP management to being
a therapy best avoided. In light of recent reports and surgi-
cal advances, we would like to make the argument that
splenectomy is again a therapy for serious consideration in
those patients who require chronic therapy for ITP.
The conventional wisdom in adult ITP was that most
patients who presented with acute thrombocytopenia went
on to have a chronic course. More recent studies, however,
have shown that this is not the case. In modern series, 20–
50% of patients are ‘‘cured’’ with steroids [1–4]. In addition,
it has been appreciated that even if patients have modest
thrombocytopenia, as long as their platelet counts are over
30,000/ll no therapy is required. Unfortunately, there are
still a considerable number of patients, with platelet counts
under 30,000/ll, who will still need some form of sustained
therapy for their ITP because they remain at risk for bleed-
ing events [5,6].
A number of therapeutic options have become available
that attempt to treat these patients and avoid the need for
splenectomy. One such approach has been to use frequent
doses of anti-D therapy. Bussel’s group reported that 68%
of patients could delay or defer splenectomy by receiving
multiple doses of anti-D. Ultimately, 28% of patients did
eventually undergo splenectomy and 25% of patients
required ongoing therapy with anti-D [5]. A randomized trial
by George et al. studied the idea that early use of anti-D
could avert splenectomy. When this treatment options was
compared with steroids, there was no difference in splenec-
tomy rate (38 vs. 42%) [7].
Anti-CD20 antibody therapy appears to represent another
advance in the medical management of ITP. Multiple
reports have indicated the utility of this agent for patients
with new onset and chronic refractory ITP but most of
these papers report only small numbers of patients. Only
two studies have reported a large number of patients. Stasi
et al. showed that 52% of patients responded to rituximab
[8]. The response rate in the 17 patients who had not yet
had splenectomy was 58%. Cooper’s series, with 63
patients, is the largest report to-date of anti-CD20 therapy
[5]. One-third of these patients were presplenectomy and
their outcomes appeared no different than the splenec-
tomy-refractory patients with 15 of 26 (58%) responses and
8 of 26 (31%) patients showing a complete response over
1 year. More recently, Arnold et al. reported on their sys-
temic review of the efficacy of anti-CD20 in 313 patients
from 19 eligible studies [9]. They reported a complete
response of 44% in the pooled analysis, where 54% of
patients had undergone splenectomy. The mortality rate
was 2.9%, leading the authors to recommend that providers
should avoid indiscriminate use of rituximab. To-date, the
available data appeared to show no difference in patient
response whether they had a splenectomy or not.
In parallel with the introduction of new medical therapies
for ITP, there has been a considerable evolution in the sur-
gical aspects of splenectomy as well. However, some of
these recent technical advances may be unfamiliar to most
medical and specialist practitioners who are more familiar
with the traditional approach. In the past, removal of the
1
Department of Surgery, Keesler Medical Center, Biloxi, Mississippi;
2
Department of Surgery, Division of General Surgery, Oregon Health and
Science University, Portland, Oregon; 3Department of Medicine, Division of
Hematology and Medical Oncology, Oregon Health and Science University,
Portland, Oregon
*Correspondence to: James P. Dolan, MD, Department of Surgery, Keesler
Medical Center, 301 Fisher St, 2A-217 Biloxi, MS 39534.
E-mail: james.dolan@keesler.af.mil
Received for publication 11 January 2007; Revised 4 June 2007; Accepted 5
June 2007
Am. J. Hematol. 83:93–96, 2008.
Published online 23 August 2007 in Wiley InterScience (www.interscience.
wiley.com).
DOI: 10.1002/ajh.21029

V
C 2007 Wiley-Liss, Inc.

American Journal of Hematology 93 http://www3.interscience.wiley.com/cgi-bin/jhome/35105

Figure 1. Laparoscopic dissection. Laparoscopic view of the
lower pole of the spleen under gentle retraction (left) as the
splenocolic ligament is divided (center). [Color figure can
be viewed in the online issue, which is available at www.
interscience.wiley.com.]
Figure 2. Laparoscopic retraction. Laparoscopic view of the
splenic hilum (center) as the spleen is elevated superiorly by
the assistant surgeon. [Color figure can be viewed in the online
issue, which is available at www.interscience.wiley.com.]

spleen had been performed by open surgery with the surgi-

cal approach made through a midline abdominal incision.
The surgical wound has been responsible for much of the
morbidity associated with open splenectomy leading to diffi-
culty in mobilization after surgery and increased risk of
both thromboembolic and pulmonary events. After dis-
charge, patients usually require several weeks of convales-
cence before returning to normal activities or work and
have an average 10–15% risk per year of developing bowel
obstruction due to adhesions as a result of surgery. Finally,
the wound itself, as a function of its size, is also at
increased risk of developing infection or herniation.
Because many patients with ITP have presented for sur-
gery in a debilitated state, or as failed medical treatment,
the overall complication rates have been reported to be as
high as 20–25% [3,10].
Modern surgical approaches to splenectomy for ITP have
sought to minimize these complications and maximize
response to treatment by utilizing minimally invasive (lapa- Figure 3. Laparoscopic transection. With the spleen elevated,
roscopic) techniques. The benefits of laparoscopic surgery, a surgical stapling and cutting device is passed around the
in terms of less postoperative pain, shorter duration of hos- splenic vessels at the hilum. The device is deployed and the
pital stay, decreased wound complication rates, and shorter vessels transected, freeing the spleen for removal from the ab-
duration of convalescence, have now been well established domen. [Color figure can be viewed in the online issue, which
by a multitude of reports in the past 20 years. Delaitre and is available at www.interscience.wiley.com.]
Maignien reported the first successful laparoscopic sple-
nectomy for hematological disease in 1991 [11]. Since that
time, refinements in optics, camera technology, instrumen-
tation, and surgeon training and experience have brought approach is now considered the standard technique for lap-
this method to the forefront as the current preferred aroscopic splenectomy.
approach to splenectomy for hematological disease [12,13]. Because the benefits of laparoscopic surgery have been
ITP, with no splenomegaly or hypervascularity and with well established for a number of different conditions, the
no need to preserve gross splenic architecture, is a disease application and refinement of this technique for splenec-
process that is particularly suited to a laparoscopic tomy in ITP has been quickly accepted as the ‘‘gold stand-
approach, which differs considerably from the conventional ard’’ [13,14]. A meta-analysis of laparoscopic splenectomy
open procedure. This operation is performed with the examined 51 published series with a total of 2,940 patients
patient under general anesthesia and positioned in the right and reported outcomes from laparoscopic and open sple-
lateral decubitus position. A pneumoperitoneum of 14 mmHg nectomy in the treatment of benign and malignant hemato-
pressure of carbon dioxide gas is established and a series logical disease [15]. This analysis concluded that laparo-
of laparoscopic working ports are placed. The spleen is scopic splenectomy was associated with significantly
freed from its intraabdominal attachments (Fig. 1), allowing reduced procedure-related morbidity and a shorter hospital
it to be elevated with the splenic hilum clearly visualized stay than the open method. Seven contemporary studies,
(Fig. 2). The hilum is then transected with a laparoscopic most also contained in the larger meta-analysis, have com-
stapling device (Fig. 3). Within the surgical community, this pared laparoscopic to open splenectomy for the treatment

94 American Journal of Hematology DOI 10.1002/ajh

TABLE I. Results of Selected Series of Laparoscopic Versus Open Splenectomy for the Treatment of ITP in Adult Patients

Major Accessory Platelet Postoperative

OR time Mortality morbidity spleens response stay
Author Year Procedure N (min) (%) (%) (%) (%) (days) Cure (%)
a
Friedman et al. [13] 1996 Lap 29 122 0 (0) 1 (3.4) 6 (21) 27 (93) 2.9 NR
Open 18 103 0 (0) 0 (0) 2 (11) 15 (83) 6.9 NR
Watson et al. [21] 1997 Lap 13 88 0 (0) 0 (0) 2 (15) 12 (92) 2a
Open 47 87 0 (0) 9 (19) 3 (6) 39 (83) 10
Lozano-Salazar 1998 Lap 22 270 1 (5) 6 (27) 2 (9) 19 (86) 4a 15 (68) at 15 months
et al. [17] Open 27 162a 2 (7) 10 (37) 3 (11) 24 (88) 6 19 (70) at 35 months
Marassi et al. [18] 1999 Lap 14 146 0 (0) 1 (7.1) 3 (21) 13 (93) 5a 13 (93) at 19 months
Open 15 90a 0 (0) 2 (13) 4 (27) 12 (80) 8.7 11 (73) at 39 months
Tanoue et al. [19] 1999 Lap 35 205 0 (0) 4 (11)a 4 (11.4) 31 (89) 9.6a 25 (70) at 60 months
Open 41 100a 0 (0) 19 (46) 5 (12.2) 32 (78) 20.1 NR
Shimomatsuya 1999 Lap 14 203 0 (0) 3 (21) 4 (28.6) 13 (93) 8.9a 11 (79) at 6 months
et al. [20] Open 20 126a 0 (0) 3 (15) 4 (20) 13 (81) 15 11/16 (69) at 6 months
Cordera et al. [22] 2003 Lap 42 167 NR 10 (24) 2 (5) NR 3.3a 35 (83) at NR
Open 44 119a NR 17 (39) 7 (16) NR 5.3 29 (66) at NR

NR, not reported; Lap, laparoscopic splenectomy; Open, open splenectomy.

a
Significant difference.

of ITP (Table I). Overall, laparoscopic splenectomy con-
sumed significantly more operating room time than the
open procedure in almost all studies. However, case mor-
tality and major morbidity associated with the procedure
are comparable, if not better with the laparoscopic
approach. Likewise, it has been difficult to determine a pro-
hibitive platelet level for safe operative intervention until
recently. Keidar et al. found a significant increase in length
of hospital stay, blood transfusion requirements, and opera-
tive complications in their series of 110 consecutive patients
with platelet counts below 20,000/ll who underwent laparo-
scopic splenectomy for ITP [16]. It would not be unreason-
able to expect that these results would be representative of
the open approach as well. It is important to note that the
discovery of accessory splenic tissue and the postoperative
platelet response are also comparable between the proce-
dures across all the studies, irrespective of origin. A total of
four accessory spleens were missed in two of the seven
studies (two in the laparoscopic groups and two in the open
groups) [21,22]. Overall, the current evidence suggests that
laparoscopic splenectomy is superior to the open approach
in terms of safety, efficacy, and cost.
Consistent with these smaller reports are the results of a
large and definite review of splenectomy for ITP recently
published by George’s group [23]. In this review, the com-
plete response rate for adults was 66% and the complete
or partial response rate was 88%. Over time, relapse
occurred in a median of 15% of patients. The consistent
theme of reports over the last 50 years is that, although it
will not cure every patient with ITP, splenectomy is the ther-
apy with the most reported patients, the longest follow-up,
and the most consistent rate of cure.
The one major and feared complication associated with
splenectomy is the specter of overwhelming postsplenec-
tomy sepsis (OPSS). Recent data suggest an eight-fold
increase in sepsis in splenectomy patients. This may be
due, in part, to the increased isolation of gram-negative
bacteria as the causative organism with an associated
higher mortality rate than that seen with the ‘‘traditional’’
pneumococcal infections. A literature review of 6,942 sple-
nectomy cases reported before 1996 found 1.2% mortality
due to invasive infection after splenectomy for ITP [24].
However, more current series report a lower rare with one
case seen in 357 patients [25–28]. This may be due to the
fact that vaccination has decreased the risk of OPSS [29]
and suggests that our older conception of OPSS in adult
patients undergoing splenectomy for ITP may be over-
stated, particularly at the current time when vaccination is
readily available. In a meta-analysis of 17 studies, the age-
adjusted risk of fatal hemorrhage at platelet counts persis-
tently less than 30,000/ll was estimated to be 0.4%, 1.2%,
and 13% per patient per year for those younger than 40,
40–60, and older than 60 years of age, respectively [6].
Predicted 5-year mortality ranged from 2.2% for patients
younger than 40 years to 47.8% for those older than
60 years. These data should be compared against the
0.2% surgical mortality rate for laparoscopic splenectomy
and 1% lifelong mortality from OPSS [6,23].
The widely known complication rate associated with open
splenectomy for ITP in the past, the paucity of surgical out-
come data disseminated in the medical literature, and the
availability of new treatment options have made medical ther-
apy the preferred treatment for ITP over surgery. This has
made it difficult to initiate large scale trials of splenectomy as
a therapeutic option due to the concerns of many in the he-
matology community and the referral or selection bias (physi-
cian or patient) that may hinder recruitment into prospective
trials. In addition, randomization to a surgical arm of a pro-
spective study would be impossible to blind and would require
patient consent to undergo surgery. Raising the awareness
of the status of the current surgical outcomes data and
highlighting the availability of laparoscopic surgical options for
the treatment of ITP should be the major first step in over-
coming these difficulties. In the future, it is conceivable that
prospective studies will be initiated comparing medical versus
surgical therapy for ITP, much as has been done with other
disease processes such as gastroesophageal reflux.
It appears that the popularity of splenectomy has
decreased dramatically in the past few years despite
increasing reports of the high and durable rate of response
with surgery [30]. One interesting finding in the anti-D trial
was that the rate of splenectomy fell from 50 to 30% as the
trial progressed [23]. Data on the alternatives therapies to
splenectomy suffer from small numbers of patients and in-
ferior responses. As evident from current reports, the
aggressive use of anti-D does not prevent splenectomy.
Likewise, the early anti-CD20 data is also inferior to out-
comes seen after splenectomy and the long-term effects of
CD20 depletion is largely unknown at this time. This
becomes an important consideration in treating a disease

American Journal of Hematology DOI 10.1002/ajh 95

process that affects a large proportion of young patients.
Finally, splenectomy remains the most cost-effective ap-
proach when compared to intravenous immunoglobulin anti-
D or anti-CD20 [8,13,31].
It is distressing to note that despite the large number of
patients who suffer from ITP there has only been one
randomized clinical trial of therapy and very few papers
that report on more than 20 patients [30]. It should be a pri-
ority for both the hematology and medicine community to
advocate for clinical trials to rationally study alternatives to
splenectomy. Years of accumulated data have shown us
that patients who fail or relapse after initial therapy of ITP
benefit from splenectomy, particularly if their platelet counts
are consistently below 30,000/lL. Patient education is also
an important aspect of the management of these patients,
and it should be realized that the attitudes, ideas, and
beliefs of the patient toward splenectomy also play a role in
the decision-making process. In this regard, until clinical tri-
als have adequately studied alternatives to splenectomy,
physicians need to begin to have an honest discussion with
the patient about splenectomy as an additional treatment
option.
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