Splenectomy – Open

Immune Thrombocytopenic Purpura

ITP, classically known as idiopathic thrombocytopenic purpura , is characterized by a low platelet count despite normal bone marrow and the absence of other causes of thrombocytopenia that could be responsible for the finding. Autoantibodies are responsible for the disordered platelet destruction mediated by the overactivated platelet phagocytosis within the reticuloendothelial system. Within the bone marrow, normal (or sometimes increased) amounts of megakaryocytes are present. There persists, however, a relative bone marrow failure in that production cannot match destruction to compensate sufficiently.

The typical presentation of ITP is characterized by purpura, epistaxis, and gingival bleeding. Less commonly, gastrointestinal bleeding and hematuria are noted. Intracerebral hemorrhage is a rare but sometimes fatal presentation. The diagnosis of ITP involves the exclusion of other relatively common causes of thrombocytopenia: pregnancy, drug-induced thrombocytopenia (e.g., heparin, quinidine, quinine, sulfonamides), viral infections, and hypersplenism ( Box 14-1-1 ). Mild thrombocytopenia may be seen in approximately 6% to 8% of otherwise normal pregnancies and in up to 25% of women with preeclampsia. Drug-induced thrombocytopenia is thought to occur rarely, in approximately 20 to 40 cases/million users of common medications, such as trimethoprim-sulfonamide and quinine. Other medications, such as gold salts, have a higher incidence, almost 1% of users. Viral infection (e.g., hepatitis C virus [HCV], HIV, rarely, Epstein-Barr virus [EBV]) can be responsible for thrombocytopenia independent of splenic sequestration. Once again, other processes must be ruled out but health care providers can be confident of these causative factors if platelet counts improve with successful treatment of the responsible infection. Bacterial infection, specifically Helicobacter pylori , has also been linked to infection-related thrombocytopenia that improves with eradication. Other causes are listed in Box 14-1-1 ; spurious laboratory values caused by platelet clumping or the presence of giant platelets should not be ignored.

ITP is predominantly a disease of young women; 72% of patients older than 10 years of age are women and 70% of affected women are younger than 40 years. ITP manifests somewhat differently in children: both genders are affected equally, onset is sudden, thrombocytopenia is severe, and complete spontaneous remissions are seen in approximately 80% of affected children. Girls older than 10 years with more chronic purpura are those in whom the disease seems to persist.

Management of ITP depends primarily on the severity of the thrombocytopenia. Asymptomatic patients with platelet counts higher than 50,000/mm ³ may be observed without further intervention. Platelet counts of 50,000/mm ³ and higher are rarely associated with clinical sequelae, even with invasive procedures. Patients with slightly lower platelet counts, between 30,000 and 50,000/mm ³ , may always be observed but with more routine follow-up because they are at increased risk for progressing to severe thrombocytopenia. Initial medical treatment for patients with platelet counts less than 50,000/mm ³ and symptoms such as mucous membrane bleeding, high-risk conditions (e.g., active lifestyle, hypertension, peptic ulcer disease), or platelet counts less than 20,000 to 30,000/mm ³ , even without symptoms, is glucocorticoid administration (typically, prednisone, 1 mg/kg body weight/day). Clinical response with increases in platelet levels to higher than 50,000/mm ³ is seen in up to two thirds of patients within 1 to 3 weeks of initiating treatment. Of patients treated with steroids, 25% will experience a complete response. Patients with platelet counts higher than 20,000/mm ³ who remain symptom-free, or who experience minor purpura as their only symptom, do not require hospitalization. Hospitalization may be required for patients whose platelet counts remain below 20,000/mm ³ with significant mucous membrane bleeding and is required for those who have life-threatening hemorrhage. Platelet transfusion is indicated only for those who experience severe hemorrhage. IV immunoglobulin is important for the treatment of acute bleeding, in pregnancy, or for patients being prepared for operation, including splenectomy. The usual dose is 1 g/kg body weight/day for 2 days. This dose usually increases the platelet count within 3 days; it also increases the efficacy of platelet transfusions.

Prior to the establishment of glucocorticoids as treatment for ITP in 1950, splenectomy was the treatment of choice. For those two thirds of patients in whom glucocorticoids result in the normalization of platelet counts, no further treatment is necessary. For patients with severe thrombocytopenia, with counts less than 10,000/mm ³ for 6 weeks or longer, those with thrombocytopenia refractory to glucocorticoid treatment, or those who require toxic doses of steroid to achieve remission, the treatment of choice is to proceed to splenectomy. Splenectomy is also the treatment of choice for patients with incomplete response to glucocorticoid treatment and for pregnant women in the second trimester of pregnancy who have also failed steroid treatment or IVIg therapy with platelet counts less than 10,000/mm ³ without symptoms or less than 30,000/mm ³ with bleeding problems. It is not necessary to proceed to splenectomy for patients who have platelet counts higher than 50,000/mm ³ , have had ITP for longer than 6 months, are not experiencing bleeding symptoms, and who are not engaged in high-risk activities. A recent review of short-term and long-term failure of laparoscopic splenectomy has reported an overall approximate failure rate of 28% at 5 years after splenectomy.

A systematic review of 436 published articles from 1966 to 2004 has reported that 72% of patients with ITP had a complete response to splenectomy. Relapse occurred in a median of 15% of patients (range, 1% to 51%), with a median follow-up of 33 months.

In addition to relapse rates, predictors of successful splenectomy were examined. Of the variables in the multivariate model, age at the time of splenectomy was an independent variable that was most correlated with response. Younger patients had improved responses. Preoperative indium-111 ( ¹¹¹ In)–labeled platelet scintigraphy with platelets sequestered predominantly within the spleen had a significantly higher response rate than those noted to have hepatic sequestration.

Most patients will exhibit improved platelet counts within 10 days postoperatively and durable platelet responses are associated with patients who have platelet counts of 150,000/mm ³ by postoperative day 3 or more than 500,000/mm ³ by the postoperative day 10. Even with splenectomy, however, some patients may relapse (~12%; range, 4% to 25%). A recent review of 1223 ITP patients has estimated the long-term failure rate of laparoscopic splenectomy at approximately 8% and approximately 44/1000 patient-years of follow-up. Another study has estimated the complete response of ITP patients postsplenectomy to be 66%.

Although a thorough search for accessory spleens is completed during the initial surgery, evaluation for a missed accessory spleen must be undertaken in patients who experience a relapse. In their evaluation of 394 patients treated with laparoscopic splenectomy, Katkhouda and colleagues noted 15% of patients with accessory spleens. In those with accessory spleens, examination of a peripheral blood smear will lack the characteristic red cell morphology resulting from excision of the spleen. Radionuclide imaging may also be helpful in locating the presence and location of any accessory splenic tissue. Patients with chronic ITP in whom an accessory spleen is identified should have this removed, as long as the patient can withstand the surgical risk.

Other treatment options for these patients include observation of stable nonbleeding patients with platelet counts higher than 30,000/mm ³ , long-term glucocorticoid therapy, and treatment with azathioprine or cyclophosphamide. Recent evidence regarding thrombopoietin receptor agonists may offer a novel medical therapy for patients with no response to steroids, IV immunoglobulin therapy, or splenectomy.

Other conditions linked to thrombocytopenia include thrombotic thrombocytopenic purpura, chronic disseminated intravascular coagulation, congenital thrombocytopenia, myelodysplasia, autoimmune disorders (e.g., systemic lupus erythematosus), and lymphoproliferative disorders (e.g., chronic lymphocytic leukemia, non-Hodgkin's lymphoma).

Approximately 10% to 20% of otherwise asymptomatic patients with HIV will develop ITP. Splenectomy is a safe treatment option for this cohort of patients and may actually delay HIV disease progression.