ADAMTS13 assays in thrombotic microangiopathy

Abstract

Thrombotic microangiopathy is featured by microangiopathic haemolytic anaemia, thrombocytopenia and the presence of peripheral fragmented red cells. Thrombotic thrombocytopenic purpura (TTP) is the major disease entity of concern, which is caused by a congenital or acquired deficiency of a von Willebrand factor (vWF) cleaving protease known as ADAMTS13 (A Disintegrin And Metalloprotease with Thrombospondin type 1 motif, member 13). Deficiency of this protease, leads to accumulation of uncleaved ultra-large hyperactive vWF multimers in peripheral circulation causing the extensive microvascular platelet aggregation in a TTP event.

However, the differential diagnosis is sometimes difficult because symptoms and signs can be non-specific and the condition may resemble a number of disorders. Early recognition and definite diagnosis of TTP is critical to enable prompt plasma exchange therapy. Specific and sensitive ADAMTS13 assays will be potentially helpful.

In this review, archive frozen plasma samples from six patients presented with prominent thrombotic microangiopathy were retrospectively analysed for ADAMTS13 by immunoassays. The relationship between ADAMTS13 antigen, activity and its autoantibodies and TTP was studied. Local reference ranges of these assays were also determined.

The assay results were validated by identifying the clinically-confirmed cases of TTP, with also prospective serial measurements of ADAMTS13 in a few cases. Patients presented with acute TTP were characterized by a severely deficient ADAMTS13 antigen and activity level, as well as a positive autoantibody titre detected for its acquired immune aetiology ; while patients with non-TTP conditions only had mildly reduced ADAMTS13 antigen but variably decreased activity level and a negative autoantibody titre . A pooled analysis of patients and normal subjects also demonstrated a positive correlation between ADAMTS13 antigen and activity.