In April 2020, an 83-year-old Caucasian woman was admitted to the emergency room because of easy bruising, epistaxis, and gum bleeding. She also reported bloody urine and stools on one occasion. Laboratory exams performed on the day prior to admission revealed both thrombocytopenia (2000 mm3) and anemia (7.2 g/dl). The patient denied a personal or family history of bleeding and anemia and previous complete blood counts (CBCs) were normal. Her past medical history was unremarkable, and she did not take any medications except nebivolol for hypertension. However, 20 days prior to admission she developed fever, myalgia, and dyspnea, which were treated with azithromycin (5-day course). In April, there was a COVID-19 outbreak in Italy, but the patient denied close contact with confirmed or suspected cases of COVID-19. On examination, body temperature was 36.5 C. Oxygen saturation was 97% in room air, but then fell to 90%, and oxygen was administered through a nasal cannula (2 L/min). Diffuse ecchymosis on the skin and petechiae on the lips, oral cavity, and both lower limbs were observed. The rest of the physical examination was normal except for diminished breath sounds and rales at both lungs. Laboratory exams (Table 1) showed anemia, thrombocytopenia, leukocytosis, and lymphocytopenia. Levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), and fibrinogen were increased, while prothrombin time, partial thromboplastin time, and procalcitonin levels were in the normal range. No blasts, schistocytes, or platelet aggregates were found on repeated peripheral blood smears. A brain computed tomography (CT) scan revealed a left cortical microhemorrhage (5 mm). Moreover, chest CT showed bilateral consolidations and multiple patchy ground-glass opacities with peripheral distribution, suggesting COVID-19 pneumonia. However, molecular testing for SARS-CoV-2 was negative on two nasopharyngeal swabs (Diasorin assay). The patient was treated with two pools of platelets and a unit of packed red blood cells, intravenous prednisone (1 mg/kg), immunoglobulin (IVIG 400 mg/kg), antibiotics, and then transferred to our internal medicine ward. Reticulocytosis, haptoglobin consumption, and increased both LDH and indirect bilirubin suggested hemolytic anemia. The D-dimer value was elevated; however, normal antithrombin III activity, absence of both schistocytes and ADAMTS13 inhibitors, and normal ADAMTS13 activity made a diagnosis of thrombotic microangiopathy unlikely. Doppler ultrasound of both upper and lower extremities excluded venous thrombosis. Flow cytometry for CD55/CD59 including fluorescein-labeled proaerolysin (FLAER), triglycerides, ferritin, complement, anti-cardiolipin and anti-beta2-glycoprotein I antibodies were normal/absent, making paroxysmal nocturnal hemoglobinuria (PNH), hemophagocytic syndrome, and antiphospholipid syndrome (APS) unlikely. The direct antiglobulin test (DAT-IgG and C3D) and testing for irregular antibodies were negative, while anti-platelet antibodies were present. Screening for viral infections (HIV, hepatitis B virus (HBV)/hepatitis C virus (HCV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), parvovirus-B19) and autoimmunity was negative except for subclinical hypothyroidism. A bone marrow (BM) biopsy could not be performed because of the high bleeding risk, but peripheral blood cytometric immuno-phenotypic analysis was normal, although the absolute number of CD4+ T cells was reduced (369/mm3, normal range: 493-1666). The patient continued treatment with IVIG (5 days), oral prednisone (1-1.5 mg/kg), and platelet transfusions. Hemoglobin levels increased progressively, while thrombocytopenia did not respond to treatment (Figure 1). Moreover, a follow-up brain CT scan performed on day 5 showed the development of a thin frontal subdural hematoma. Meanwhile, a further molecular test for SARS-CoV-2 on sputum (Seegene's Allplex 2019-nCoV assay) confirmed the diagnosis of COVID-19 and the patient was transferred to a COVID-19 ward and treated with COVID-19 standard therapy. In the COVID-19 ward the patient was treated with oxygen therapy and she did not undergo anti-viral treatment. On day 6, treatment with the oral thrombopoietin receptor agonist (TPO-RA) eltrombopag was initiated (starting dose: 25 mg/day, maximal dose: 75 mg/day). The patient did not report any side effects and liver function remained unchanged. In the following days, the platelet count progressively increased (Figure 1) and the subdural hematoma resolved spontaneously. On day 24 after admission, the platelet count was normal and two consecutive nasopharyngeal swabs for SARS-CoV-2 were negative. The patient was discharged from the hospital on tapering doses of eltrombopag (50 mg/day) and prednisone (25 mg/day). At the follow-up visit 15 days after hospital discharge, the patient was asymptomatic, and the platelet count was in the normal range.