María Luisa Lozano

Whole‐blood donation and apheresis are the only ways to obtain blood components for human use. Tools are being developed to improve the efficiency of blood donation systems by reducing waste, increasing donations and preventing shortages. These tools also help manage the storage and distribution challenges posed by blood products with different expiry dates. The proposed approach focuses on identifying inefficiencies in the ‘blood transfusion chain’ and presents a renewed, practical model that differs from other theoretical ones. It outlines 11 processes across three periods: before donation (promotion), during donation and after blood processing. The goal is to optimize each process, reduce inefficiencies and propose improvements based on current scientific knowledge. While changes to healthcare policies are outside of its scope, the model aims to streamline existing donation processes. This paper emphasizes the need for a ‘vein‐to‐vein’ system, which tracks blood from donor to recipient, managed by a single entity controlling the blood centre's data infrastructure. Though limitations exist due to incomplete control over the transfusion chain, future work will demonstrate the model's application, focusing on areas like scheduling and monitoring pre‐donation haemoglobin levels for better optimization. Comprehensive tracking, including of the recipient, is essential for full system optimization.

Objective: This systematic review and meta‐analysis aimed to evaluate the risk of thromboembolic events and assess the overall safety and effectiveness of avatrombopag in adult patients with immune thrombocytopenia using real‐world evidence. Methods: A systematic search was conducted following the PRISMA 2020 guidelines. Observational studies (2020–2024) on adults with primary immune thrombocytopenia treated with avatrombopag were included. Primary outcomes were thromboembolic complications and treatment response; secondary outcomes included time to response, treatment discontinuation, and adverse events. Random‐effects meta‐analyses were performed to synthesise pooled proportions and rates. Risk of bias was assessed using the ROBINS‐Version 2 tool. Results: Fifteen studies were included. The pooled proportion of patients with thromboembolic events was 2.82% (95% confidence interval: 1.61%–4.27%), with an incidence rate of 3.29 per 100 patient‐years (95% CI: 1.81–5.08). Response and complete response were achieved by 80.0% and 92.0% of patients, respectively. The median time to response was 11 days, and the discontinuation rate was 18.9%. Adverse events occurred in 4.1% of patients. Conclusion: In real‐world practice, avatrombopag demonstrated high platelet response rates and a low pooled incidence of thrombotic events. These findings add real‐world evidence on avatrombopag outcomes in adult immune thrombocytopenia.

Iptacopan is a first‐in‐class, oral, selective inhibitor of complement factor B that has demonstrated positive efficacy across several complement‐driven diseases. Here we evaluate the efficacy and safety of iptacopan monotherapy in adult patients with primary immune thrombocytopenia (ITP) and primary cold agglutinin disease (CAD). We performed a global, multicenter, phase 2 basket study enrolling patients with primary ITP or CAD after failure of ≥ 1 unique prior therapies. Primary endpoints were platelet response (≥ 50 × 10 ⁹ /L) for ITP and hemoglobin response (≥ 1.5 g/dL increase) for CAD sustained for ≥ 2 consecutive weeks during the first 12 weeks of iptacopan treatment, without the use of rescue therapy. Other endpoints included time to first response, duration of response, pharmacokinetics, safety/tolerability, and FACIT‐Fatigue. Nineteen patients were treated with iptacopan (9 ITP, 10 CAD). Among patients with CAD, most showed improvements in hemoglobin levels, with a mean increase of 2.2 g/dL from baseline to week 12; five (50%) patients achieved the primary endpoint. Improvements were also observed for other outcomes in CAD, including lactate dehydrogenase, bilirubin, reticulocytes, and FACIT‐Fatigue. Conversely, no patients with ITP met the primary endpoint. Most treatment‐emergent adverse events (TEAEs) were mild, the most common being headache (21%), asthenia (16%), fatigue (16%), and petechiae (16%). Iptacopan monotherapy demonstrated encouraging preliminary efficacy in primary CAD, while no protocol‐defined responses were observed in primary ITP. Iptacopan may represent a promising oral option for CAD and was well tolerated in both ITP and CAD with no unexpected safety signals. Trial Registration: ClinicalTrials.gov identifier: NCT05086744

Inherited platelet function disorders (IPFDs) are rare diseases caused by defects in platelet surface receptors, enzymes, granules, or signaling proteins. In humans, GPVI and P2Y12 deficiency cause autosomal recessive bleeding disorders, while TBXAS1 deficiency is related to Ghosal hematodiaphyseal dysplasa, a rare autosomal recessive disorder characterized by increased long bone density and platelet dysfunction without bleeding. To date, at least 20 patients have been identified with molecular defects in P2RY12, 12 cases with molecular defects in GP6, and 34 cases with molecular defects in TBXAS1. Here, we report a novel nonsense and missense variants in P2RY12, a novel nonsense variant in GP6, and a novel missense variant in TBXAS1. These variants selectively affect the platelet reactivity to ADP and collagen/CRP, predisposing to bleeding. P2RY12 c.835 G>A [p.Val279Met] variant did not affect receptor expression whereas P2RY12 c.44delG [p.Ser15Ilefs*33] lead to decreased levels of the receptor in one of the patients. This was confirmed both by RT-qPCR and immunoblotting analysis. Decreased expression of both GPVI and FcRγ-chain was detected in patients carrying GPVI nonsense variant in heterozygosis. The deleterious effect of these variants was also confirmed in a transfected cell line model. TBXAS1 variant triggered decreased TxA₂ production using a cell line model. These variants expand the genetic landscape of P2RY12, GPVI and TBXAS1 inherited deficiency.

Summary: Inherited thrombocytopenia (IT) with germline variants in RUNX1, ETV6 or ANKRD26 carries a high risk (10%–45%) of developing haematological malignancy (IT‐HM). We evaluated the clinical, platelet and molecular characteristics in 37 patients with RUNX1‐related thrombocytopenia (RT), 9 with ETV6‐RT and 20 with ANRKD26‐RT. Genetic diagnosis was delayed by about 20 years from the identification of thrombocytopenia. Bleeding tendency was present in 25%–30% of RUNX1‐RT and ANKRD26‐RT patients. Platelet aggregation was impaired in 90% of all patients, while reduced activation and granule secretion were heterogeneous. Most RUNX1‐RT patients had low glycoprotein Ia (GPIa) levels, which may be a useful disease biomarker. Sixteen distinct genetic variants in RUNX1, four in ETV6 and four in ANKRD26 were identified in patients. The clinical profile showed immune, skin, gastrointestinal and other comorbidities in many patients. One third of the cases developed a malignancy: This included eight RUNX1‐RT patients with myelodysplastic syndrome (MDS), five with acute myeloid leukaemia (AML), and one with chronic myeloid leukaemia (CML) Ph+. One patient with ETV6‐RT subsequently developed B‐cell acute lymphoblastic leukaemia (B‐ALL) during childhood. Three cases with ANKRD26‐RT demonstrated a multifaceted clinical presentation, including B‐ALL Ph+, MDS and breast cancer. The high incidence of HM development highlights the importance of early diagnosis in life.