Thrombocytopaenia and Down Syndrome - What about the Usual Suspects ?

Down syndrome is a chromosomal disorder renowned for conferring a predisposition to auto-immune and hematological conditions; hematological abnormalities in this population should prompt investigations to exclude malignancy, but comprehensive differential diagnosis should be broadened to other pathologies. A 15 months-old infant with Down syndrome presented with isolated moderate thrombocytopenia during an episode of upper respiratory tract infection. Clinical examination was unremarkable except for mild hepatomegaly and diffuse petechial rash. A bone marrow aspiration showed no malignant infiltration. Intravenous immunoglobulins showed little benefit over the course of the following 7 days. The patient secondarily developed hemolytic anemia. ADAMTS13 activity was undetectable, and plasmatic inhibitors were detected confirming the hypothesis of immune thrombotic thrombocytopenic purpura (TTP), triggered by an infection. Daily plasmapheresis were started with immediate but short-lived benefit, and TTP persistently recurred every 48h after interruption of exchanges, warranting initiation of treatment with Rituximab and enabling the achievement of long-term remission. Acquired TTP is an extremely rare entity in children below 9 years of age (<1/1.000.000), and can be life-threatening due to the formation of micro thrombi occluding terminal circulation leading to organ damage and dysfunction. Prompt recognition of this entity is important to avoid long-term damages. Altered IFN signaling in Down syndrome could theoretically predispose to immune TTP, although we couldn’t find any other report of cases of immune TTP in patients with Down syndrome.