PO072 | DIAGNOSTIC CHALLENGES IN THROMBOTIC MICROANGIOPATHY: A CASE OF ATYPICAL HEMOLYTIC UREMIC SYNDROME

M. Moretti¹, R. Gervasi², E. Rossini², G.F. Romiti¹, P. Carfagna², S. Basili¹, P. Battisti² | ¹Azienda Ospedaliero-Universitaria Policlinico Umberto I, Roma, Italy; ²Azienda Ospedaliera San Giovanni Addolorata, Roma, Italy

Background. Atypical hemolytic uremic syndrome (aHUS), also known as complement-mediated HUS, is a form of thrombotic microangiopathy characterized by microangiopathic hemolysis, thrombocytopenia, and acute kidney injury (AKI). When central nervous system (CNS) manifestations occur, it is crucial to establish a differential diagnosis with thrombotic thrombocytopenic purpura (TTP) and typical HUS. We hereby present an illustrative case of aHUS, and the diagnostic workup.
Case Report. A 62-year-old Caucasian man was admitted to the Intensive Care Unit (ICU) with rapidly progressive neurological deterioration and coma. The patient was previously admitted to an Internal Medicine Unit for urinary tract infection; his hospital stay was complicated by an episode of C. difficile infection, and central venous catether-associated thrombosis of the right iliac and left jugular veins. During ICU stay, the patient developed anemia and thrombocytopenia; a spontaneous bleeding in the right kidney occurred, which required embolization, as well as multiple blood and plasma transfusions. Thrombophilia and antiphospholipid antibodies testing were negative. Following cognitive deterioration, a brain MRI was performed, showing no recent ischemic lesions but revealing symmetric T2 hyperintensity in the anteromedial thalami, mammillary bodies, mesencephalic tegmentum, and posterior columns of the medulla, findings suggestive of thiamine deficiency encephalopathy, for which pharmacological treatment was initiated. The patient was then transferred to our Unit with persistent thrombocytopenia (platelets 5,000/mm³) and Coombs-negative microangiopathic hemolytic anemia, consistent with thrombotic microangiopathy (PLASMIC score 5; French score 1). A whole-body CT scan ruled out malignancies; anti-PF4/heparin antibodies were negative, while ADAMTS13 activity was not severely reduced (21%), making TTP less likely. Further testing showed only isolated C3 consumption, in the absence of other microbiological or molecular findings. Given the initial TTP suspicion, the patient underwent plasma exchange, along with supportive care and transfusions as needed. The patient underwent dialysis due to worsening renal function; later, he developed COVID-19 and died due to septic complications.
Conclusions. The clinical overlap between HUS and TTP represents a diagnostic challenge in thrombotic microangiopathy. Microangiopathic hemolytic anemia, thrombocytopenia, AKI and acute CNS involvement are cardinal features of both conditions, yet none is pathognomonic. Although CNS involvement is more frequently observed in TTP, it has been reported in approximately 11% of aHUS cases. In these patients, CNS involvement is the leading cause of death, and most commonly affects the basal ganglia, although other brain regions can also be involved. Imaging findings may include cytotoxic, vasogenic, or mixed edema, sometimes associated with ischemic and/or hemorrhagic lesions, resulting in non-specific pattern. For a timely differential diagnosis, early blood sampling for microbiological (including stool cultures), serological, molecular, and immunological investigations (including ADAMTS13 activity) are essential. The timing of these investigations is crucial, as delayed testing may compromise interpretability, particularly if performed after the initiation of transfusion therapy. Their results play a decisive role in guiding therapeutic decisions and may significantly influence patient outcomes.