Thrombocytopenia and
microangiopathic hemolytic anemia are the hallmark of the
thrombotic microangiopathies (TMAs)
thrombotic thrombocytopenic purpura (
TTP) and
hemolytic uremic syndrome (HUS).
TTP, inherited or autoimmune, is mainly caused by the plasma deficiency of the
von Willebrand factor cleaving protease ADAMTS13, owing to gene mutations or
autoantibodies. Typical HUS is often caused by
infections with Shiga-Toxin-producing Escherichia coli and thus is called STEC-HUS. The rarer atypical form of HUS is often associated with
complement dysregulation, owing to the inherited deficiency or dysfunction of
factor H or other
complement proteins. In the past the distinction between these TMAs was almost exclusively based on clinical grounds, the term
TTP being used for cases with predominant neurological involvement, STEC HUS for cases presenting with bloody
diarrhea and atypical HUS identifying patients with severe renal damage. However the clinical presentation may not easily distinguish
TTP from atypical HUS. A more accurate differential diagnosis has clinical implications, because
plasma exchange (the treatment of choice in
TTP) is much less effective in atypical HUS, which shows dramatic short- and long-term therapeutic benefits from
eculizumab, a
monoclonal antibody that inhibits complement activation. This article will point out that the measurement of ADAMTS13 is able to diagnose accurately the majority of
TTP cases, and that very simple tests such as the platelet count and serum
creatinine can predict the deficiency of the
protease with a good degree of accuracy. In atypical HUS, new methods were recently developed that not only demonstrate the activation of the
complement system, i.e., the main disease mechanism, but also help to tailor the short- and long-term treatment with
eculizumab.