Immune Thrombocytopenia

Patients with severe thrombocytopenia who relapse with reduction of steroids or who do not respond to steroids have several options for further management. Repeated doses of IVIG can transiently raise the platelet count, and some patients may only need several courses of therapy over the course of many months. One study showed that 60% of patients could delay or defer therapy by receiving multiple doses of anti-D. However, 30% of patients did eventually receive splenectomy and 20% of patients required ongoing therapy with anti-D.²⁹ In a randomized trial comparing early use of anti-D to steroids to avoid splenectomy, there was no difference in splenectomy rate (38% versus 42%).³⁰ Finally, an option as mentioned above is to try a 6-month course of pulse dexamethasone 40 mg/day for 4 days, repeated every 28 days.

Options for Refractory ITP

There are multiple options for patients who do not respond to initial ITP therapies. These can be divided into several broad groups: curative therapies (splenectomy and rituximab), thrombopoietin receptor agonists, and anecdotal therapies.

Splenectomy

In patients with severe thrombocytopenia who do not respond or who relapse with lower doses of prednisone, splenectomy should be strongly considered. Splenectomy will induce a good response in 60% to 70% of patients and is durable in most patients. In 2 recently published reviews of splenectomy, the complete response rate was 67% and the total response rate was 88% to 90%%.^8,31 Between 15% and 28% of patients relapsed over 5 years, with most recurrences occurring in the first 2 years. Splenectomy carries a short-term surgical risk, and the life-long risk of increased susceptibility to overwhelming sepsis is discussed below. However, the absolute magnitude of these risks is low and is often lower than the risks of continued prednisone therapy or of continued cytotoxic therapy.

Timing of splenectomy depends on the patient’s presentation. Most patients should be given a 6-month trial of steroids or other therapies before proceeding to splenectomy.³¹ However, patients who persist with severe thrombocytopenia despite initial therapies or who are suffering intolerable side effects from therapy should be considered sooner for splenectomy.³¹ In the George review, multiple factors such as responding to IVIG were found not to be predictive of response to splenectomy.⁸

Method of splenectomy appears not to matter.²¹ Rates of finding accessory spleens are just as high or higher with laparoscopic splenectomy and the patient can recover faster. In patients who are severely thrombocytopenic, open splenectomy can allow for quicker control of the vascular access of the spleen.

Rates of splenectomy in recent years have decreased for many reasons,³² including the acceptance of lower platelet counts in asymptomatic patients and the availability of alternative therapies such as rituximab. In addition, despite abundant data for good outcomes, there is a concern that splenectomy responses are not durable. Although splenectomy will not cure every patient with ITP, splenectomy is the therapy with the most patients, the longest follow-up, and the most consistent rate of cure, and it should be discussed with every ITP patient who does not respond to initial therapy and needs further treatment.

The risk of overwhelming sepsis varies by indications for splenectomy but appears to be about 1%.^33,34 The use of pneumococcal vaccine and recognition of this syndrome have helped reduce the risk. Asplenic patients need to be counseled about the risk of overwhelming infections, should be vaccinated for pneumococcus, meningococcus, and Haemophilus influenzae, and should wear an ID bracelet.^35–37 Patients previously vaccinated for pneumococcus should be re-vaccinated every 3 to 5 years. The role of prophylactic antibiotics in adults is controversial, but patients under the age of 18 should be on penicillin VK 250 mg orally twice daily.

Rituximab

Rituximab has been shown to be very active in ITP. Most studies used the standard dose of 375 mg/m² weekly for 4 weeks, but other studies have shown that 1000 mg twice 14 days apart (ie, on days 1 and 15) resulted in the same response rate and may be more convenient for patients.^38,39 The response time can vary, with patients either showing a rapid response or requiring up to 8 weeks for their counts to go up. Although experience is limited, the response seems to be durable, especially in those patients whose counts rise higher than 150 × 10³/µL; in patients who relapse, a response can be re-induced with a repeat course. Overall the response rate for rituximab is about 60%, but only approximately 20% to 40% of patients will remain in long-term remission.^40–42 There is no evidence yet that “maintenance” therapy or monitoring CD19/CD20 cells can help further the duration of remission.