Modern management of congenital thrombotic thrombocytopenic purpura (cTTP).

Congenital thrombotic thrombocytopenic purpura (cTTP) arises from an inherited deficiency of ADAMTS13, causing a thrombotic microangiopathy with multisystemic sequelae. Acute cTTP relapse can cause arteriovascular thrombosis, and registry data suggest that later diagnosis and commencement of treatment are associated with increased morbidity. Undiagnosed or "nonovert" cTTP may also be associated with end-organ damage. Treatment is based on ADAMTS13 replacement, previously limited to plasma and factor VIII concentrates and now expanded to recombinant ADAMTS13, which can achieve higher peak and trough levels with smaller volumes. Now that treatment options are improved, we need to focus on prophylaxis and the clinical impact of this lifelong condition. Beyond treatment of acute TTP relapses, symptoms such as headaches, abdominal pain, and lethargy without overt laboratory relapse may reflect subacute TTP and herald later end-organ damage. We need further longitudinal data on how to optimize care. Key questions remain about prophylaxis and how to target optimal control of this condition through the alliance of improved treatment delivery and measures of clinical outcome.