26th June 2023

Thrombotic thrombocytopenic purpura

Like HUS, thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by damage to endothelial cells of small blood vessels and subsequent intravascular thrombosis. The key contrast from HUS is that the brain is more commonly involved in TTP and neurological symptoms such as reduced GCS or seizures are often present.

TTP is an autoimmune disorder caused by antibodies against ADAMTS-13, an enzyme involved in regulating platelet aggregation. This enzyme normally cleaves von Willebrand factors (vWF) and its deficiency results in large multimers which crosslink platelets.

Higher circulating levels of vWF lead to the formation of multiple thrombi as well as the depletion of platelets which in turn can cause bleeding. Red blood cells passing these microthrombi in the capillary circulation are subject to shear stress and trauma, which in turn leads to microangiopathic haemolytic anaemia and schistocyte formation. The small thrombi cause reduced blood flow and cell death; the kidney is particularly susceptible to damage as a result, due to its microcirculation and high blood flow.

TTP is characterised by a pentad of clinical features:

1. Thrombocytopenia
2. Microangiopathic haemolytic anaemia
3. Fever
4. Renal impairment
5. Neurological involvement

Untreated, mortality rates are 90% within ten days. The gold standard of treatment is emergency plasma exchange, however, corticosteroids, aspirin, and rituximab all have a role in management.