The mainstay of therapy for TTP is plasma exchange (see Table 91–3), which removes antibody inhibitors and replenishes ADAMTS13.
With the exception of factor H deficiency, and possibly APS and quinine-induced disease, no compelling evidence indicates that plasma therapy is effective for thrombotic microangiopathy caused by a mechanism other than ADAMTS13 deficiency. Regardless of mechanism, however, the clinical features are variable and overlapping. Consequently, plasma exchange may sometimes be used to treat apparent HUS or secondary thrombotic microangiopathy, particularly in adults, based on the possibility that such patients may have an atypical presentation of TTP that will respond.
After diagnosing TTP, or determining that the diagnosis is sufficiently likely to justify treatment, plasma exchange therapy should be started immediately. The optimal dose of plasma is not known, but a common practice is to perform plasma exchange once daily at a volume of 40 or 60 mL/kg, equivalent to 1 or 1.5 plasma volumes.
Prompt treatment is essential and if plasma exchange must be delayed more than a few hours, plasma should be given by simple infusion at 20 to 40 mL/kg total dose per day, consistent with the patient's ability to tolerate the fluid load.
Plasma exchange should be continued daily until the patient has a complete response, as shown by a platelet count greater than 150 × 109/L, lactic acid dehydrogenase (LDH) within the normal range, and resolution of nonfocal neurologic symptoms.
The optimal schedule for tapering and discontinuing therapy has not been determined. A typical (however, not evidence-based) strategy is to continue plasma exchange until a complete response is sustained for a minimum of 2 days, and then reduce the frequency of plasma exchange to every other day (or twice per week) for several days. If the disease remains quiescent, then treatment can be stopped and the patient monitored closely for recurrence.
The long-term mortality of TTP treated with plasma exchange ranges from 10 to 20 percent. Most deaths occur within a few days after presentation, and almost all occur within the first month.
The duration of illness is quite variable. Complete response occurs after an average of 9 to 16 days of plasma exchange, and almost all responders are encompassed by a range of 2 to 40 days.
Recurrences of disease more than 30 days after a complete response, occur in up to one-third of patients. Most relapses occur during the first year, but have been documented up to 13 years after diagnosis.
TTP often is an autoimmune disease and the use of glucocorticoids is logical, although a beneficial effect has not been demonstrated conclusively. Common practice is to give prednisone or equivalent at a total daily dose of 1 or 2 mg/kg, in one or two doses, for the duration of plasma exchange, followed by tapering. An alternative regimen is methylprednisolone 1 g intravenously daily for 3 days.
The use of antiplatelet agents in TTP is controversial. Aspirin and dipyridamole often are combined with plasma exchange but have not been shown conclusively to modify the course of TTP. Low-dose aspirin (e.g., 80 mg/day) has been suggested for thromboprophylaxis, once the platelet count exceeds 50 × 109/L.
Transfusion of platelets may sometimes correlate with the acute deterioration and death in TTP, although direct harm is difficult to establish. Consequently, platelet transfusions are relatively contraindicated and should be reserved for the treatment of life-threatening hemorrhage, preferably after plasma exchange treatment has been initiated.
TTP that is refractory to plasma exchange may respond to immunosuppression. Anecdotal experience suggests that vincristine may be beneficial, although its efficacy is difficult to assess. Dosing schedules have included 2 mg intravenously on day 1 followed by 1 mg on days 4 and 7, or 2 mg intravenously per week for 2 to 14 weeks. Cyclosporine has been used to treat TTP and may be effective in refractory disease. Apparent responses, with normalization of ADAMTS13 activity, have been observed with cyclosporine 2 to 3 mg/kg daily in two divided doses as an adjunct to plasma exchange, or without plasma exchange for early recurrences of TTP.
Rituximab (375 mg/m2 weekly for two to eight doses) resulted in an approximately 95 percent remission in patients with therapy-resistant TTP within 1 to 3 weeks of starting treatment, including a normal ADAMTS13 level and disappearance of anti–ADAMTS13 antibodies (if present).
Other immunosuppressive regimens have included oral or intravenous cyclophosphamide, oral azathioprine, combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and autologous stem cell transplantation.
Many reports suggest that splenectomy can result in lasting remissions or reduce the frequency of relapses for some patients with TTP who are refractory to plasma exchange or immunosuppressive therapy, presumably by removing a major site of anti–ADAMTS13 antibody production.
The cornerstone for treatment of secondary thrombotic microangiopathy is management of the underlying disorder. In most cases, this is sufficient to ameliorate the manifestations of the thrombotic microangiopathy.