Complement in secondary thrombotic microangiopathy
Autor
Monteiro P. Palma, Lilian
Sridharan, Meera
Sethi, Sanjeev
Institución
Resumen
Thrombotic microangiopathy (TMA) is a condition characterized by thrombocytopenia and
microangiopathic hemolytic anemia (MAHA) with varying degrees of organ damage in the
setting of normal International Normalized Ratio (INR) and activated Partial Thromboplastin
Time (aPTT). Complement has been implicated in the etiology of TMA, which are classified as
Primary TMA - when genetic and acquired defects in complement proteins are the primary
drivers of TMA (complement-mediated TMA or atypical hemolytic uremic syndrome, aHUS) or
Secondary TMA, when complement activation occurs in the context of other disease processes,
such as infection, malignant hypertension, autoimmune disease, malignancy, transplantation,
pregnancy and drugs. It is important to recognize that this classification is not absolute as
genetic variants in complement genes have been identified in patients with secondary TMA,
and distinguishing complement/genetic-mediated TMA from secondary causes of TMA can be
challenging and lead to potentially harmful delays in treatment. In this review, we focus on data
supporting the involvement of complement in aHUS and in secondary forms of TMA associated
with malignant hypertension, drugs, autoimmune diseases, pregnancy and infections. In aHUS,
genetic variants in complement genes are found in up to 60% of patients, whereas in the
secondary forms the finding of genetic defects is variable, ranging from almost 60% in TMA
associated with malignant hypertension to less than 10% in drug-induced TMA. Based on these
findings, a new approach to management of TMA is proposed.