Understanding thrombotic microangiopathies in children

Excerpt

Thrombotic microangiopathy (TMA) is an ultra-rare syndrome. The incidence in children is estimated to be ~ 3.0 cases/10⁶ population per year (Fig. 1). Very importantly, TMA belongs to the Thrombocytopenia Associated-Multi Organ Failure (TAMOF) syndromes and, therefore, its diagnosis should be considered in critically-ill children. Thus, intensive care physicians and nurses should be familiar with this rare but specific cause of TAMOF. TMA is life-threatening, resulting from ischemic multi-organ failure and characterised by its diversity and high ICU mortality rate, ~ 20%, despite appropriate treatment [1, 2]. The common features for TMA are microangiopathic haemolytic anemia (haemolysis, elevated lactate dehydrogenase, reduced haptoglobin, and fragmentation of red blood cells) and thrombocytopenia. Organ injury, associated with disseminated thrombi in the microcirculation, further supports the diagnosis of TMA. Differential diagnosis includes idiopathic thrombocytopenic purpura (ITP), Evans syndrome or malignancy-associated haematological abnormalities, in which organ injury is uncommon. Also, in contrast to disseminated intravascular coagulation (DIC), TMA are usually associated with normal prothrombin time (PT), activated partial thromboplastin time (aPTT), factor V and fibrinogen. Despite overlapping clinical and biological features, TMA has its distinct pathophysiology and therapeutic management [3]. The most frequent TMA syndromes reported in children are haemolytic uraemic syndrome (HUS), in which renal impairment is the prominent clinical feature. Thrombotic thrombocytopenic purpura (TTP), another TMA syndrome, also occurs in children, often associated with cerebral involvement. Secondary TMA are defined as TMA occurring with other comorbidities serving as the triggering events. These include severe infections, autoimmunity, haematopoietic progenitor cells or solid organ transplantations, malignancy and drugs. Therefore, the diagnosis of secondary TMA can be extremely challenging [1]. In this review, HUS and TTP will be discussed in more detail.

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