Apheresis and the thrombotic thrombocytopenic purpura syndrome: current advances in diagnosis, pathophysiology, and management. Brailey LL, Brecher ME, Bandarenko N. Therapeutic Apheresis 1999;3(1):20-24.

Endeavors to optimize the management of thrombotic thrombocytopenic purpura (TTP) syndrome and improve mortality and relapse rates are hindered by its poorly understood pathophysiology. Variability in the application of therapeutic plasma exchange (TPE), including replacement fluid strategies, desirable endpoints in the platelet count, serum lactate dehydrogenase concentration, and the use of a TPE taper, limit comparisons among published studies. The diversity of adjunctive therapies such as antiplatelet agents, steroids, and splenectomy further clouds comparisons. Recent progress in the diagnosis, pathophysiology, and management of TTP syndrome are summarized in this paper. Most relevant is the overview of TTP management. The current standard of care is the administration of plasma. The improved survival with TPE is unquestionable, but the mechanism of its effect is still not well understood. The significant mortality seen even with TPE indicates that current therapy can be further improved. To optimize the management of TTP, alternatives to fresh-frozen plasma (FFP) have been investigated. Cryo poor plasma (CPP) has shown to provide improved response rates and increased survival. Of interest is the recently licensed solvent-detergent treated plasma (SDP). Limited reports indicate that SDP is at least comparable in efficacy to FFP, and at least one case report indicated that a patient refractory to TPE with FFP achieved a sustained remission following treatment with SDP. Preliminary data from a retrospective study suggest that using 5% albumin as replacement for the initial half of TPE and plasma for the second half may be equivalent or better than using plasma alone as replacement fluid. This finding requires further study. Other treatment regimens include steroids and/or antiplatelet agents. For refractory cases, intravenous immune globulin, splenectomy, and other agents have been employed with variable results. Platelet transfusions should be avoided unless the patient is at risk of a life-threatening hemorrhage. Relapses occur in 30-60% of survivors of TTP. One hypothesis is that the initial episode of TTP may continue subclinically, that is without signs or symptoms. Late recurrences may best represent true reactivation of the disease. The role of splenectomy is preventing relapses has yet to be defined in the initial episode of TTP, but several small studies have described patients with multiple recurrences who have benefited from splenectomy. Prompt recognition and intervention are critical in TTP due to the high and early mortality rate. Current progress toward the delineation of the pathophysiology of TTP, with future clinical trials to define optimal management, hold promise for decreasing TTP mortality and relapse rates.