Molecular Diagnosis Is Vital to the Accurate Classification and Management of Thrombotic Thrombocytopenic Purpura in Children

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially life-threatening hematologic disease, presenting a myriad of diagnostic and management challenges in children. Here, we provide a review of this disorder and discuss 2 exemplary cases of TTP occurring in adolescents, emphasizing the need for consideration of late-onset congenital TTP (cTTP). We demonstrate the importance of early confirmation of ADAMTS13 enzyme deficiency and the presence or absence of ADAMTS13 inhibitor in order to rapidly initiate the appropriate life-saving therapies. Ultimately, molecular testing is paramount to distinguishing between congenital and acquired immune-mediated TTP.

Keywords: ADAMTS13; congenital TTP; immune-mediated TTP; inhibitor; pediatric.

Figure 1

Pathophysiology of TTP. Pathophysiology of TTP. In physiologic conditions, ultralarge VWF multimers released from endothelial cells are cleaved by ADAMTS13 in smaller VWF multimers, less adhesive to platelets. In TTP, because of the absence of functional ADAMTS13 (either absent by congenital defect or inhibited by specific autoantibodies), ultralarge VWF multimers are released into the blood and bind spontaneously to platelets to form aggregates within the arterial and capillary microvessels. The VWF platelet aggregates are large enough to form microthrombi inducing tissue ischemia, platelet consumption, and microangiopathic hemolytic anemia (schistocytes on blood smear).This figure was originally published in Blood, and re-printed with permission here. Bérangère S. Joly, Paul Coppo, and Agnès Veyradier. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. ^© the American Society of Hematology.