Acute deterioration following an apparently uncomplicated vaso-occlusive episode in sickle cell disease poses significant diagnostic challenges. When respiratory failure, neurological impairment, and progressive cytopenias develop abruptly, distinguishing between infectious, inflammatory, and thrombotic mechanisms becomes critical. We describe a 20-year-old woman with sickle cell/thalassaemia admitted for severe limb pain consistent with vaso-occlusion. Within 24 hours, she developed acute respiratory failure, encephalopathy, and thrombocytopenia requiring intensive care support. Initial management targeted presumed sepsis. However, evolving laboratory abnormalities including disproportionate lactate dehydrogenase elevation, extreme hyperferritinaemia, and marked peripheral erythroblastosis without schistocytosis , prompted reconsideration of the differential diagnosis. Brain magnetic resonance imaging revealed a characteristic pattern supported by futher assessment such as bronchoalveolar lavage and bone marrow biopsy establishing the final diagnosis. Treatment with red cell exchange and therapeutic plasma exchange was followed by progressive haematological and neurological recovery. This case underscores the importance of stepwise diagnostic reasoning in sickle cell disease and highlights how dynamic laboratory interpretation and early referral to specialised centres may be decisive in rare but life-threatening complications.

Background and Aims. Avatrombopag, a second-generation thrombopoietin receptor agonist (TPO-RA), represents an effective treatment option for chronic immune thrombocytopenia (ITP). In clinical practice, its use is increasingly embedded in a personalized treatment strategy, in which dosing is progressively adjusted to the individual patient in order to optimize platelet count control while minimizing the risk of adverse events and toxicity. In this context, defining the minimal effective dose plays a central role within a tailored approach to ITP management. The aim of this study was to evaluate the minimal maintenance dose of avatrombopag required to sustain a platelet count >50,000/µL while also analyzing clinical characteristics, treatment response, and safety profile. Methods. We retrospectively analyzed 37 patients treated at our center with avatrombopag (26 females, 11 males), either currently on therapy or previously exposed to the drug. Median age was 47 years (range 19–86). At diagnosis, median platelet count was 10,000/µL, with bleeding manifestations in 56% of patients. Patients had received a median of 3 prior lines of therapy; all had been treated with first-line corticosteroids and 78.38% with intravenous immunoglobulins (IVIG). Twenty-seven patients had received a prior TPO-RA, and among them, 24 underwent a direct switch to avatrombopag. Reasons for switching included lack or loss of response in 62.5% of cases, significant platelet count fluctuations in 8.33%, adverse events in 8.33%, and patient preference for a better tolerability profile. We assessed time to response, number of dose adjustments, minimal effective maintenance dose, and safety outcomes. Results. During follow-up, a median of 3 dose adjustments was required before reaching a stable effective dose capable of maintaining platelet counts >50,000/µL. In 5 patients (13.5%), temporary treatment interruption due to thrombocytosis during the tapering phase was required, with subsequent reintroduction of therapy. The median stable maintenance dose of avatrombopag was 50 mg/week, associated with a median platelet count of 151,000/µL. At the time of analysis, 25 patients (67.6%) remained on active treatment, while 12 (32.4%) had permanently discontinued therapy. Among these, the median dose at discontinuation was 210 mg/week, with a median platelet count of 21,500/µL. Reasons for discontinuation included loss or lack of response in 6 cases (50%), marked platelet count fluctuations in 4 cases (33.3%), one major adverse event (NSTEMI, 8.3%), and achievement of sustained off-treatment response (SROT, 8.3%). Regarding safety, 14 patients (37.8%) experienced treatment-related adverse events, including thrombocytosis in 5/37 patients (13.5%), thrombotic events (NSTEMI) in 1/37 (2.7%), platelet count fluctuations in 4/37 (10.8%), hepatotoxicity in 3/37 (8.1%), bleeding events in 2/37 (5.4%), and asthenia in 1/37 (2.7%). Conclusions. In our real-world experience, avatrombopag confirms its effectiveness as a rapid-acting treatment for chronic ITP. The variability in maintenance dose highlights the need for a highly individualized approach, in which the minimal effective dose is often lower than the initial dosing regimen. Dose tapering represents a key step in clinical practice, transforming ITP management into a truly tailored model in which both efficacy and safety are optimized on a patient-specific basis.

Background and Aims. The introduction of thrombopoietin receptor agonists (TPO-RAs) has significantly improved response rates in patients with immune thrombocytopenia (ITP). In a subset of patients, a sustained response can be achieved despite progressive dose reduction and even after treatment discontinuation, defined as sustained response off treatment (SROT). We analyzed patients from our center who achieved SROT, evaluating response duration, tapering strategies, and relapse rates, with the aim of contributing to process standardization. Methods. Seventeen patients (9 males, 8 females) were included, with a median age at diagnosis of 63 years (range 21–73). Before TPO-RA initiation, 12/17 patients (70.6%) had received one prior treatment line, 3/17 (17.6%) two lines, and 2/17 (11.8%) ≥3 lines. TPO-RAs were started within 3 months from diagnosis in 2/17 patients, during the persistent phase in 5/17, and in the chronic phase in 10/17. Six patients received eltrombopag, ten romiplostim, and one avatrombopag. Results. Median duration of TPO-RA therapy was 24 months (range 3–79), with a median peak platelet count of 308×10⁹/L. Tapering was performed over a median of 12 months; median platelet count at tapering initiation was 223.5×10⁹/L, with a nadir of 119×10⁹/L during dose reduction. In 2/17 patients, treatment was discontinued without tapering due to adverse events; both maintained SROT for more than 10 years. Median dose at discontinuation was 25 mg/week for eltrombopag, 0.065 mL/week for romiplostim, and 10 mg/week for avatrombopag. Median platelet count at discontinuation was 139×10⁹/L. Median follow-up after discontinuation was 53 months. Relapse occurred in 4/17 patients: two were successfully treated with corticosteroids, while two resumed TPO-RA therapy; one of these regained SROT after a second tapering attempt, while the other remains on treatment. Conclusions. SROT is an achievable goal in a subset of ITP patients treated with TPO-RAs, with relevant clinical and psychological impact, although relapse may occur in a minority of cases. Our monocentric experience is consistent with available literature and supports the need for standardized tapering strategies. Data on avatrombopag remain limited, and further studies are warranted to identify predictive factors for SROT