Abstract
Introduction Avatrombopag, a 2nd-generation thrombopoietin receptor agonist (TPO-RA), is approved for chronic immune thrombocytopenia (ITP) and thrombocytopenia in chronic liver disease prior to procedures. In fact, in Spain, its use has significantly increased over the past two years, reflecting a shift in prescribing trends supported by the AVESPA study (Pascual Izquierdo et al,Am J Hematol. 2024; 99:2328–2339DOI: 10.1002/ajh.27498). While established in these indications, emerging real-world data suggest its potential utility in broader, off-label clinical scenarios.
Objectives To report our center's experience and rationale for off-label use of Avatrombopag in four clinical scenarios.
Materials and Methods We retrospectively reviewed electronic medical records of patients treated with off-label Avatrombopag at our institution. Informed consent was obtained from all patients
Case 1 and 2: Newly Diagnosed ITP A 66-year-old female with ITP (18,000/ml platelets) and corticosteroid contraindication (intolerance) received Avatrombopag as first line of treatment: Avatrombopag was initiated at 40 mg/day, achieving rapid complete response (220,000/ml within 7 days). Treatment was gradually tapered and discontinued after 7 months, achieving complete remission. No adverse events were observed. 2nd case involved a male, 83 years old, with ITP, hypertension, and poorly controlled type 2 diabetes. Due to platelet count of 15,000/ml and the comorbidities, Avatrombopag was initiated at 20 mg/day: after 7 days, he showed complete response (158,000/ml). With progressive dose adjustments, after 3 months, platelet counts are 109,000/ml now, with dose of 100 mg/week. Well tolerated, no adverse events.
Case 3: Thrombocytopenia in Advanced Liver Disease A 45-year-old male with severe haemophilia A, prophylaxis 2 times per week with EHL-FVIII, cirrhosis, portal hypertension and severe thrombocytopenia (<20,000/ml). Due to the high bleeding risk, he received chronic low-dose Avatrombopag (40–60 mg/week) to maintain platelet counts between 40000/ml and 60000/ml.Treatment was well-tolerated over 6 months (contnue at this moment), minimizing bleeding risk, without thrombotic events.
Case 4: Preoperative Preparation for Surgery in Chronic ITP A 72-year-old female with chronic ITP (39,000/ml platelets) without indication to initiate treatment. She required meniscectomy. Avatrombopag was initiated at 40 mg/day for 5 days, following a regimen similar to the ADAPT-1 and ADAPT-2 trials: at day +8, the count of platelets was 109,000/ml. The procedure was complication-free, avoiding transfusions of platelets. She received antithrombotic prophylaxis with LMWH 14 days after in accordance with our protocol. At day +30, she presented platelets of 55000/mL. At this moment she remains off treatment, with stable platelet counts around 40000/ml and no bleeding events
Case 5: Thrombocytopenia Management in CCUS for Anticoagulation A 90-year-old female with CCUS (Clonal Cytopenia of Undetermined Significance, Deletion of 20q12, detected by FISH in 62% of cells). She had a count of platelets between 35,000−47,000/mL and she needed anticoagulation for newly diagnosed atrial fibrillation. Avatrombopag was initiated at 20 mg/day, increasing platelet counts to 40–90000/ml, enabling safe initiation of Dabigatran Etexilato. Platelet counts remain stable over 2 years, with different adjustments of dose as needed, good tolerability and no clonal progression
Conclusion This single-center experience supports potential off-label use of Avatrombopag in selected clinical scenarios. In newly diagnosed ITP, consistent with Virk et al. (Am J Hematol 2024; DOI: 10.1002/ajh.27080), Avatrombopag may effectively induce remission and help avoid corticosteroid-related adverse events. In chronic liver disease, low-dose use maintained safe platelet counts in high-risk patients as our severe haemophilia A patient. As preoperative management in chronic ITP, it facilitated safe surgery without transfusions, specially in patients without clinical indication to begin treatment. In CCUS, it enabled anticoagulation without hematologic progression. These encouraging observations underscore the need for prospective, controlled studies to validate the efficacy and safety of Avatrombopag in these off-label settings and to better define its role in personalized thrombocytopenia management. Ongoing real-world evidence is essential to inform the evolution of treatment guidelines
