or even the techniques used for the splenic artery embolization.

One corollary with the nonoperative management of blunt splenic trauma is the risk of delayed

rupture. Standard guidelines of conservative management are that patients should have stable

hemoglobin for 36 to 48 hours and have resolution of abdominal pain prior to discharge. The delayed

rupture rate in a large series of more than 1,900 patients showed that 27 patients were readmitted for

splenectomy within 180 days of discharge,42 a delayed rupture rate of 1.4%. The median time from

injury to readmission for splenectomy was 8 days with the range of 3 to 146 days. Similar results were

obtained in an institutional study of 450 patients with nonoperative management of blunt splenic injury.

In this group, 4% failed with eventual splenectomy due to delayed rupture.43 Both studies stress that

with the increased use of nonoperative management, the potential risks of delayed rupture require very

specific discharge instructions to patients regarding reonset of acute abdominal pain with other signs

and symptoms of hypotension requiring emergent transportation to the nearest emergency room or

hospital facility.

Another area of splenic trauma is atraumatic splenic rupture. This can be considered more

spontaneous rupture and it occurs primarily with enlargement of the spleen with malignant disorders

either primary or secondary metastases, infectious disease, or inflammatory diseases, or technical

disorders such as pregnancy or peripartum rupture. In a large series of more than 900 patients with

atraumatic spontaneous rupture of the spleen, only 6.4% had no pathologic or mechanical causes that

were identified.44

Autoimmune/Erythrocyte Disorders

There are two categories of disease in which abnormalities do not originate in terms of the histology,

pathology, or size of the spleen but rather are due to either autoimmune phenomenon or intrinsic

diseases within circulating cells that lead to their destruction. The most common and obvious example

of this is ITP in which antibodies to platelet antigens lead to destruction of platelets and

thrombocytopenia with the spleen being the primary source of platelet elimination. Related diseases

affecting erythrocytes and neutrophils with specific antibodies and splenic elimination occur to lesser

degrees.

A second category of disease is not an autoimmune phenomenon but rather an intrinsic cellular defect

that leads to a shortened half-life of this specific blood cell within the circulation primarily to

elimination within the spleen. As discussed in the physiology section given earlier, a normal role of the

spleen is to eliminate senescent erythrocytes and the anatomic structures of splenic circulation are well

suited to that task. If erythrocytes are altered in terms of their structure, this may lead to more rapid

elimination. In other diseases, genetic differences in the hemoglobin may result in splenic changes

particularly in the setting of hypoxia that occurs within the splenic sinusoids. The most obvious example

of this would be sickle cell anemia. A final example is an alteration in the cellular adhesion molecule

that leads to increased interaction and thrombocytopenia in the Wiskott–Aldrich syndrome.

Immune Thrombocytopenic Purpura

ITP is often a diagnosis of exclusion once all other causes such as drug-induced thrombocytopenia or

evidence of bone marrow failure are eliminated.45 ITP is a disease characterized by autoimmune

destruction of platelets with clinical manifestations of thrombocytopenia manifest by susceptibility to

easy or excess bleeding.46 ITP may be classified into an acute form and a chronic form. Acute ITP

generally occurs in children younger than 8 years following an upper respiratory viral illness. The

majority of children with acute ITP will have spontaneous remissions, whereas only a small minority of

adults who develop ITP have remission and most go on to develop chronic ITP. This disease is usually

self-limited and requires surgical intervention only in the case of intracranial bleeding. Chronic ITP

accounts for the vast majority of cases considered for splenectomy. Similar to autoimmune hemolytic

anemia, this disease may be idiopathic or may be secondary to a lymphoproliferative disorder,

connective tissue disorder such as systemic lupus erythematosus, or drug or bacterial exposure. The

average age at diagnosis is in the fourth decade of life and it affects women more commonly than men.

As HIV was identified in the mid-1980s, it was noted that patients with acquired immunodeficiency

syndrome (AIDS) were developing disease virtually identical to ITP.47 AIDS patients with newly

diagnosed ITP and risk factors for HIV should undergo screening.

6 The pathophysiology of ITP is development of an IgG antibody to a platelet antigen. This is felt to

be most commonly directed against the fibrinogen receptor (glycoprotein IIb/IIIa and IR/IX).48 The

spleen plays a predominant role in this disease as it may be the site of initial antibody production.49 It is

1998

almost certainly the site of continued antibody production, and in the majority of patients the spleen is

the primary site of platelet destruction. Since the targeted antigen is an intravascular cell, and since the

spleen stores large numbers of platelets, it is felt that the initial reaction to the platelet cell antigen may

occur in the spleen. Studies on antibody levels have indicated that overall IgG production in spleens

from patients with ITP is markedly increased over individuals with normal spleens. Similarly, following

splenectomy the amount of IgG antibody is somewhat decreased. The spleen is also the predominant site

of platelet destruction. As noted earlier, the macrophages located in the cords of Billroth have receptors

for the Fc portion of the IgG and will bind and phagocytize the antibody-coated platelets. A second

more recently described component of the pathophysiology is an inappropriately decreased level of

production of thrombopoietin for that level of thrombocytopenia. Cloning of the thrombopoietin

receptor or the megakaryocytes has led to several new agents that can alter this aspect of the

pathophysiology of ITP.50,51

To be considered to have ITP, the platelet count has to at least be <100,000, but typically patients do

not become symptomatic unless platelet counts are <50,000. Platelet counts in this disorder may drop

to very low levels, well below 10,000 on occasion. Assays are now available to identify the IgG

antiglobulin on the platelet surface verifying the disease, but over one third of the patients have no

clear identification of antiplatelet antibodies. Bone marrow analysis shows an increased megakaryocytes

production as compensatory mechanism to the thrombocytopenia. In this disorder, there is often no

splenomegaly and the spleen may be somewhat smaller than typical. Only 2% of patients with ITP have

palpable spleens. For this reason, there is virtually no leukopenia or anemia associated with ITP due to

hypersplenism. There may be anemia secondary to chronic blood loss. The risk of a fatal hemorrhage in

patients with ITP overall is 0.0162 and 0.0389 cases/patient year and predicted 5-year mortality rates

are 2.2% for patients <40 years of age and 47.8% for patients older than 60 years.52

The treatment of ITP includes standard measures to treat any ongoing bleeding, medical therapies

designed to increase platelet count, and splenectomy. First-line medical therapy options include platelet

transfusion, corticosteroids, gamma-immunoglobulin, and the recently approved Rho (d)

immunoglobulin.53 Platelet transfusions should be discouraged unless patients are actively bleeding as

platelets will become rapidly coated with IgG and will be sequestered and destroyed in the spleen.

High-dose corticosteroids produce an initial response in the majority of patients but this is unfortunately

not sustained. Approximately 75% of the patients will have an increase in platelet count that is

significant within 24 hours of starting high-dose steroids.54 However, only 15% to 25% of patients will

have a sustained remission with chronic ITP following steroid therapy. A second aspect of initial

medical treatment for chronic ITP has been administration of intravenous IgG immunoglobulin. This

treatment takes only between 3 and 5 days to show an effect and generally does not put patients into

complete remission. The mechanism of action of immune gamma globulin is felt to be saturation of the

Fc receptors on the splenic macrophages.55 The administered gamma globulin may coat red cells and

they may provide a competitive interference such that platelet destruction is decreased. A new available

drug is the recently approved Rho (d) immunoglobulin that specifically targets the Fc receptors.

In patients who have not achieved a sustained remission with medical therapy, which is the majority

of patient with chronic ITP, an elective splenectomy is recommended. A large series analyzed 135 case

series between 1966 and 200456 and reported results in terms of normalization of platelet counts,

predictive features evaluating which patients would likely achieve complete response following

splenectomy, and reported complications of the procedure including morbidity and mortality (Table 73-

8). Among the case series analyzed reporting only on adults (1,731 patients), the complete response

upon splenectomy was noted to be 66% (median follow-up of 29 months). Response rates tended to be

higher among children, and when cases series evaluating adults and children (2,463 patients) were

included in analysis, the complete response rate was noted to be 72% (median follow-up 23 months).56

Among cases series that included a multivariate analyses in the systematic review, age (younger) was

associated with an increased likelihood of response to splenectomy. Response to prior medical therapy

was not found as an independent predictor in those studies, and site of platelet sequestration also was

variably reported among the case series evaluated with regard to its predictive role on response to

splenectomy. A proportion of patients with initial response to splenectomy (15% to 20%) develops

relapse with long-term follow-up. One cause for a failed splenectomy for ITP would be residual splenic

tissue most commonly in the form of a missed accessory spleen but also in the form of splenosis.17

While earlier reports expressed concerns of laparoscopy splenectomy demonstrating a high number of

failure rates secondary to residual splenic tissue,57 more recent studies suggest similar efficacy of the

laparoscopic and open approaches in the management of patients with ITP.58

1999