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Thrombotic thrombocytopenic purpura (TTP) is a blood disorder and defined by the presence of microangiopathic haemolytic anaemia (MAHA) and moderate to severe thrombocytopenia, purpura or bleeding associated with thrombocytopenia, fever, neurological impairment and renal disease presenting with haematuria and/or proteinuria or elevated blood urea nitrogen.

Laboratory findings of platelet counts usually below 30 x 10⁹/L, increased lactate dehydrogenase [LDH] levels, reduced haemoglobin and haptoglobin concentrations, the presence of schistocytes on the peripheral blood smear, ‘unusually large’ (UL) multimers of von Willebrand factor (VWF), and plasma concentrations of ‘A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13’ (ADAMTS13) of below 10 % of the norm are highly specific for TTP in the presence of clinical features [1, 2].

The specific VWF-cleaving protease ADAMTS13 regulates the VWF multimers after secretion from the endothelial cells. It cleaves the Y1605-M1606 bond in the A2 domain. Under high shear forces, the VWF multimers secreted from the endothelial cells remain bound to the endothelium and are sustained by the shear stress. This makes the cleavage sites in the A2 domains accessible for the freely circulating ADAMTS13 to cleave the VWF multimers. Under normal, non-thrombotic conditions, the remaining VWF is not reactive. Due to its property as an acute phase protein, infections or inflammatory processes may lead to an increased release of VWF. In individuals with acquired or congenital ADAMTS13 deficiency, this can lead to the formation of microthrombi and the development of clinical signs of a TTP [3, 4].

It is important to distinguish TTP from other thrombotic microangiopathies (TMA). In patients with infection-associated TMA, MAHA and thrombocytopenia can develop due to systemic bacterial, viral or mycotic infections. Therefore, infection-associated TMA should always be considered during the evaluation of such patients, particularly elderly patients who have fever or chills associated with features of TTP. An infection can also trigger an acute episode of TTP, and it may be difficult to differentiate whether the infection is the cause or a trigger [5]. The ADAMTS-13 activity in patients with infection-associated TMA is usually discretely reduced to 20 % of the norm or even higher, with some exceptions in patients with e.g. severe sepsis causing a severe ADAMTS-13 deficiency in the absence of an inhibitor [6, 8]. Infection-associated TMA is triggered by endothelial damage caused by infection leading to increased VWF release and increased consumption of ADAMTS-13. Bacterial enzymes and cytokines lead to ADAMTS-13 proteolysis and inhibition [6]. Additionally, neutrophil extracellular traps (NETs) – chromatin fibres released from neutrophils during infection – may result in thrombosis because of their ability to cause platelet activation [3, 4, 7]. In patients positive for human immunodeficiency viruses (HIV), features of TMA may be due to multiple causes including coexisting TTP. These include advanced disease with opportunistic infections, malignancies and antiviral medications. In addition, the initiation of highly active antiretroviral therapy (HAART) may inhibit ADAMTS-13 activity and result in features of TMA [9, 10].