We describe the use of splenectomy in six patients who had had relapse of thrombotic thrombocytopenic purpura. In all cases, splenectomy was done while the patients were in hematologic remission.

Methods

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Since 1985, we have managed six patients with nonfamilial, relapsing thrombotic thrombocytopenic purpura. To receive a diagnosis of thrombotic thrombocytopenic purpura, patients had to have thrombocytopenia (platelet count <150 x 10⁹/L) and schistocytic hemolytic anemia and no condition other than thrombotic thrombocytopenic purpura (such as disseminated intravascular coagulation or sepsis) that could explain these symptoms. During periods of disease activity, patients received plasma exchange therapy on a frequent (usually daily) basis until remission was achieved. The day of remission was defined as the first day on which the platelet count exceeded 150 x 10⁹/L. Relapse was defined as a decrease in the platelet count (to less than 150 x 10⁹/L) and the return of schistocytic hemolytic anemia in patients who had had a normal platelet count (>150 x 10⁹/L) for more than 30 days and were receiving no medications other than acetylsalicylic acid. All patients received oral antiplatelet therapy (acetylsalicylic acid or dipyramidole) daily from the day of initial presentation, except on days when their platelet counts were less than 50 x 10⁹/L. All patients were receiving corticosteroid therapy (usually prednisone, 40 mg/d) at the time of relapse; this therapy was tapered and discontinued within 2 months of achievement of remission. No patient received cytotoxic chemotherapy.

At the time of splenectomy, all patients had normal platelet counts and no laboratory evidence of recurrent thrombotic thrombocytopenic purpura. Patients were followed for at least 6 months (range, 6 months to 8.0 years) for both clinical and laboratory evidence of recurrent thrombotic thrombocytopenic purpura.

Results

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Six patients with relapsing thrombotic thrombocytopenic purpura were managed during the 10-year period. At the time of initial presentation, no patient had clinically significant comorbid illness or was receiving long-term medical therapy. In these patients, a total of 26 acute episodes of thrombotic thrombocytopenic purpura occurred over a total of 22.3 patient-years before splenectomy (attack rate ± 1 SD, 2.3 ± 2.0 events per year). The duration of relapse ranged from 3 to 140 days. At no time did any patient develop severe renal impairment (creatinine level >200 µmol/L). The six patients received a total of more than 435 plasma exchange procedures before splenectomy. Splenectomy was done 8 days after remission of the second relapse in one patient, 10 days after remission of the tenth relapse in one patient, 22 days after remission of the fourth relapse in one patient, 48 days after remission of the third relapse in one patient, 80 days after remission of the third relapse in one patient, and 192 days after remission of the fifth relapse in one patient. Two patients had laparoscopic splenectomy. A total of 3 acute episodes, requiring 15 plasma exchange procedures, occurred during 22.7 patient-years of follow-up after splenectomy (attack rate ± 1 SD, 0.1 ± 0.1 events per year). No patient had a medical or surgical complication of splenectomy.

The clinical courses of the six patients are shown in Figure 1. Patient 1 was treated for 7 years with low-dose corticosteroid therapy, which was discontinued before splenectomy. Patient 2 had residual neurologic impairment (forgetfulness) secondary to a cerebrovascular accident that complicated the initial episode of thrombotic thrombocytopenic purpura. Patient 4 had presented with ptosis and hemiparesis while pregnant at 25 weeks' gestation; 16 plasma exchange procedures were required during the pregnancy to maintain a normal platelet count in this patient. Elective vaginal delivery of a healthy infant was induced at 36 weeks' gestation. One year later, this patient presented with a relapse of thrombotic thrombocytopenic purpura that had occurred at the time of a therapeutic termination of pregnancy. After splenectomy, she had two relapses of thrombotic thrombocytopenic purpura, at 6.5 and 9 years, that required a total of 10 plasma exchange procedures.

View larger version (16K): [in this window] [in a new window]   Figure 1. Timeline for six patients with relapsing thrombotic thrombocytopenic purpura (TTP). Each patient was followed until January 1996.

Patient 5 presented with a decreased level of consciousness and right hemiplegia and subsequently developed a coma that lasted for 3 weeks and resolved completely without residual deficit after 23 plasma exchange procedures. Relapse occurred 32 days after plasma exchange therapy was discontinued. Elective splenectomy was done 8 days after remission of the first relapse. On day 5 after splenectomy, microangiopathy recurred, and 5 plasma exchange procedures were required to achieve remission.

Discussion

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Elective splenectomy was done during hematologic remission in six patients who had had one or more relapses of thrombotic thrombocytopenic purpura. Splenectomy reduced the relapse rate from 2.3 ± 2.0 events per year to 0.1 ± 0.1 events per year. In addition, a total of more than 435 plasma exchange procedures were required to control the disease during the 22.3 patient-years before splenectomy, whereas only 15 plasma exchange procedures were required during the 22.7 patient-years of follow-up after splenectomy.

It is now estimated that more than 80% of patients with thrombotic thrombocytopenic purpura survive because of the effectiveness of plasma exchange therapy [1]. However, survival puts the patient at risk for relapse, which occurs in 20% to 40% of patients who have thrombotic thrombocytopenic purpura in remission [3, 4]. Plasma exchange therapy is usually effective in treating relapse, but the risk for death or persisting ischemic damage remains. In addition, plasma therapy is costly and inconvenient and exposes the patient to blood products from numerous donors. For these reasons, alternate therapies—including splenectomy—have been used. Splenectomy in patients with thrombotic thrombocytopenic purpura has been used primarily to treat patients with thrombocytopenia that is refractory to other therapy [3-11]. The success of splenectomy in this setting varies, and complications, including sudden death, have been well described elsewhere [3, 9]. We hypothesized that splenectomy done while patients were in remission would be less likely to result in illness and death.

In reviewing the medical literature, we identified three patients who appeared to have had elective splenectomy for relapsing thrombotic thrombocytopenic purpura while in remission [7, 12]. Their outcomes were similar to those of our patients, and no surgery-related deaths were reported.

The primary limitation of our study is that it is a case series from a single institution. However, given the marked difference in the rate of relapse before and after splenectomy, we feel that splenectomy done during hematologic remission requires further investigation and should be considered in patients with relapsing thrombotic thrombocytopenic purpura who require frequent or prolonged courses of plasma exchange therapy to control the disease. We conclude that splenectomy reduces the frequency of relapse and the associated need for plasma exchange therapy in patients with relapsing thrombotic thrombocytopenic purpura.

Ms. Heddle: Blood Bank, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.

Dr. Hayward: Pathology Department, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.

Dr. Warkentin: Hematology Department, Hamilton General Hospital, 237 Barton Street, Hamilton, Ontario L8L 2X2, Canada.

Dr. Kelton: McMaster University Medical Centre, 1200 Main Street West, HSC-3X28, Hamilton, Ontario L8N 3Z5, Canada.