Thrombotic thrombocytopenic purpura (TTP)

TTP is characterized by the presence of widespread hyaline thrombi in small vessels. Young adults are most commonly affected. Microangiopathic haemolysis, renal failure and evidence of neurological disturbance are characteristically found. It is now believed that the pathogenesis of TTP differs from that of HUS. In TTP only, there is deficiency of (or the presence of autoantibody to) the protease enzyme which cleaves von Willebrand factor.

TTP is a rare, but very serious condition, in which platelet destruction leads to profound thrombocytopenia. There is a characteristic symptom complex of florid purpura, fever, fluctuating cerebral dysfunction and haemolytic anaemia with red cell fragmentation, often accompanied by renal failure. The coagulation screen is usually normal but lactic dehydrogenase (LDH) levels are markedly raised as a result of haemolysis.

Controlled trials are lacking but there is a consensus that repeated plasma exchange is beneficial in TTP. Infusion of fresh plasma may also be of benefit. Some patients with TTP have underlying SLE or polyangiitis.

Cause of Thrombotic thrombocytopenic purpura (TTP)

The underlying cause is not fully understood but TTP seems to be due to endothelial damage associated with the presence in the circulation of very-high-molecular-weight multimers of von Willebrand factor (vWF) which accumulate owing to the absence of a protease which is normally responsible for vWF degradation. This absence is due to mutations in the ADAMTS 13 gene. In some cases there is a true deficiency of the protease while in others an immune response appears to reduce protease activity temporarily.

The related condition of haemolytic uraemic syndrome (HUS), in which renal failure is a prominent feature, probably has a different cause. TTP is associated with pregnancy, oral contraceptives, systemic lupus erythematosus, infection and drug treatment, including the use of ticlopidine and clopidogrel, but many cases have no obvious cause.

Treatment of Thrombotic thrombocytopenic purpura (TTP)

Treatment consists of plasma exchange using cryoprecipitate-depleted FFP (cryo-poor supernatant) or solvent detergent-treated FFP, both of which contain reduced amounts of high-molecular-weight vWF multimers. It is also thought that FFP supplies the missing protease.

Most patients are also treated with prednisone 1 mg/kg daily and low-dose aspirin 75 mg daily is often given as the platelet count rises above 50 × 10 9 /L. Platelet concentrates are contraindicated.

The untreated condition has a mortality of up to 90% but modern management has reduced this figure to about 10%. Recurrent and relapsing TTP occurs, often associated with a persistent lack of vWF protease. Disease activity is monitored by measuring the platelet count and serum LDH.