The role of bone marrow examination is controversial.17 Patients with a classic presentation of ITP (young woman, normal blood smear) do not require a bone marrow exam before therapy is initiated, although patients who do not respond to initial therapy should have a bone marrow aspiration. The rare entity amegakaryocytic thrombocytopenia can present with a clinical picture similar to that of ITP, but amegakaryocytic thrombocytopenia will not respond to steroids. Bone marrow aspiration reveals the absence of megakaryocytes in this entity. It is rare, however, that another hematologic disease is diagnosed in patients with a classic clinical presentation of ITP.
In the future, measurement of thrombopoietin and reticulated platelets may provide clues to the diagnosis.4 Patients with ITP paradoxically have normal or only mildly elevated thrombopoietin levels. The finding of a significantly elevated thrombopoietin level should lead to questioning of the diagnosis. One can also measure “reticulated platelets,” which are analogous to red cell reticulocytes. Patients with ITP (or any platelet destructive disorders) will have high levels of reticulated platelets. These tests are not recommended for routine evaluation, but may be helpful in difficult cases.
Treatment
In general, therapy in ITP should be guided by the patient’s signs of bleeding and not by unquestioning adherence to measuring platelet levels,15 as patients tolerate thrombocytopenia well. It is unusual to have life-threatening bleeding with platelet counts greater than 5 × 103/µL in the absence of mechanical lesions. Despite the low platelet count in patients with ITP, the overall mortality is estimated to be only 0.3% to 1.3%.18 It is sobering that in one study the rate of death from infections was twice as high as that from bleeding.19 Rare patients will have antibodies that interfere with the function of the platelet, and these patients can have profound bleeding with only modestly lowered platelet counts.20 A suggested cut-off for treating newly diagnosed patients is 30 × 103/µL.21
Initial Therapy
The primary therapy of ITP is glucocorticoids, either prednisone or dexamethasone. In the past prednisone at a dose of 60 to 80 mg/day was started at the time of diagnosis (Table 1).
Most patients will respond by 1 week, although some patients may take up to 4 weeks to respond. When the platelet count is greater than 50 × 103/µL, the prednisone should be tapered over the course of several weeks. An alternative that is being used more frequently is dexamethasone 40 mg/day for 4 days, which offers the advantage of requiring patients to take medication for only 4 days. In European studies better responses were seen with multiple cycles of dexamethasone: 4-day pulses every 28 days for 6 cycles (overall response was 89.2% and relapse-free survival at 15 months was 90%) or 4-day pulses every 14 days for 4 cycles (85.6% response rate with 81% relapse-free survival at 15 months).22 Two randomized trials have shown higher response rates with pulsed dexamethasone repeated 2 or 3 times every 2 weeks, and this is now the preferred option.8,23
For rapid induction of a response, there are 2 options. A single dose of intravenous immune globulin (IVIG) at 1 g/kg or intravenous anti-D immunoglobulin (anti-D) at 50 to 75 µg/kg can induce a response in more than 80% of patients in 24 to 48 hours.21,24 IVIG has several drawbacks. It can cause aseptic meningitis, and in patients with vascular disease the increased viscosity can induce ischemia. There is also a considerable fluid load delivered with the IVIG, and it needs to be given over several hours.
The use of anti-D is limited to Rh-positive patients who have not had a splenectomy. It should not be used in patients who are Coombs positive due to the risk of provoking more hemolysis. Rarely anti-D has been reported to cause a severe hemolytic disseminated intravascular coagulation syndrome (1:20,000 patients), which has led to restrictions in its use.25 Although the drug can be rapidly given over 15 minutes, due to these concerns current recommendations are now to observe patients for 8 hours after their dose and to perform a urine dipstick test for blood at 2, 4, and 8 hours. Concerns about this rare but serious side effect have led to a dramatic decrease in the use of anti-D.
For patients who are severely thrombocytopenic and do not respond to initial therapy, there are 2 options for raising the platelet counts. One is to use a combination of IVIG, methylprednisolone, vincristine, and/or anti-D.26 The combination of IVIG and anti-D may be synergistic since these agents block different Fc receptors. A response of 71% has been reported for this 3- or 4-drug combination in a series of 35 patients.26 The other option is to treat with a continuous infusion of platelets (1 unit over 6 hours) and IVIG 1 g/kg for 24 hours. Response rates of 62.7% have been reported with this combination, and this rapid rise in platelets can allow time for other therapies to take effect.27,28
