Summary

Thrombotic thrombocytopenic purpura (TTP) is an aggressive and life-threatening form of thrombotic microangiopathy (TMA; see this term) characterized by profound peripheral thrombocytopenia, microangiopathic hemolytic anemia (MAHA) and organ failure of variable severity and is comprised of congenital TTP and acquired TTP (see these terms).

The annual incidence estimates range from 1/250,000 to 1/1,000,000. The incidence in the U.K. is estimated at 1/166,000. Acquired TTP accounts for approximately 95% of all TTP cases.

Acquired TTP generally occurs in adulthood, whereas congenital TTP usually in the neonatal period or during childhood. Onset is usually acute but early symptoms may include fatigue, purpura or ecchymoses, abdominal pain, arthralgia and myalgia. Disseminated microvascular thrombosis leads to consumptive peripheral thrombocytopenia, MAHA and widespread organ injury associated with cerebral (headache, confusion, altered consciousness, coma, seizures, hemiparesis and visual disturbances), cardiac (arrhythmia, infarction, congestive heart failure and cardiac arrest) and gastrointestinal (nausea, vomiting, abdominal pain and diarrhea) manifestations. Purpura and petechiae are the most common bleeding manifestations. Renal anomalies may be mild in acquired TTP but oliguria, anuria, hemoglobinuria and acute renal insufficiency have been reported. Fever occurs in less than 50% of patients. Patients with acquired TTP may suffer from only one episode, but relapses can occur in 30 to 40% of cases while a chronic and frequently relapsing disease course is more typical in those with congenital TTP (without prophylactic treatment).

TTP is caused by a severely decreased activity of ADAMTS13, a metalloprotease involved in the cleavage of ultra-large von Willebrand factor multimers. In congenital TTP, ADAMTS13 deficiency is caused by homozygous or double heterozygous mutations in the 2 alleles of ADAMTS13 gene (9q34), whereas it is associated with the presence of anti-ADAMTS13 immunoglobulin G (IgG) antibodies in acquired TTP.

Congenital TTP is inherited autosomal recessively and genetic counseling is suggested.

Expert reviewer(s)

• Pr Paul COPPO