Thrombotic microangiopathy in children: Redefining hemolytic uremic syndrome, thrombotic thrombocytopenic purpura and related disorders

Abstract

Thrombotic microangiopathy (TMA) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemic damage. The primary mechanism involved is the occurrence of microthrombi due to deficient activity of ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats, member 13). The most common types of TMA in children are Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) followed by complement-mediated (CM) TMA, Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS) and hereditary thrombotic thrombocytopenic purpura (hTTP) and other rare causes. Since the outcomes are dismal if appropriate treatment is not promptly initiated, there is a need to have a high clinical suspicion. Additionally, urgently performing ADAMTS13 functional activity and autoantibody levels can help differentiate hTTP, immune thrombotic thrombocytopenic purpura (iTTP), and CM-TMA. The etiological differentiation is crucial as eculizumab is a specific therapy with exceedingly good results in CM-TMA. While plasma exchanges are required for iTTP, besides corticosteroids and/or rituximab, plasma infusions suffice for hTTP. This review focuses on the commonly encountered congenital and acquired types of TMA in children and their varied presentations while briefly touching upon the rarer disorders causing TMA.

Keywords

• Thrombotic microangiopathy (TMA)
• Hemolytic uremic syndrome (HUS)
• Thrombotic thrombocytopenia purpura (TTP)
• ADAMTS13
• Upshaw schulman syndrome (USS)