Current understanding of the pathophysiology of thrombotic thrombocytopenic purpura

Abstract

Several variants of TTP are recognised. Most cases are defined as single episode TTP: in these patients there is no identifiable precipitant and no subsequent recurrence. Because survival has improved with advances in treatment, it is now apparent that a few patients continue to relapse at infrequent intervals: in one study it was estimated that 11–36% fall into this category, known as intermittent TTP (fig 1), with relapses occurring up to eight years after the index episode.² In some instances, the index or subsequent episode might be precipitated by an identifiable cause, resulting in secondary TTP. Several drugs have been implicated including mitomycin C, ticlopidine, cyclosporin, oral contraceptives, and quinine. Perhaps those most closely linked are ticlopidine and cyclosporin. Ticlopidine characteristically results in TTP after two to four weeks of use,³ whereas cyclosporin is a recognised risk factor in post-allogeneic bone marrow transplant associated TTP, along with total body irradiation conditioning. Pregnancy and systemic lupus erythematosus (SLE) are other associations and might account, in part, for the female preponderance (male to female ratio, 1 : 2). Anecdotally, TTP also appears to be triggered by viral infections. However, because fever is one constituent of the defining pentad of TTP, such symptoms might actually represent a prodromal TTP illness. Nevertheless, certain infections are associated: HIV infection, especially when associated with a high viral load, is one example. Of interest, a TTP like illness in association with Bartonella bacilliformis like organisms adherent to 0.1–2% of circulating erythrocytes has been reported in five patients.⁴ It would appear, however, that infectious precipitants are relatively uncommon because TTP is not associated with seasonal variation and case clustering rarely occurs. Further research into this area is awaited.