Avatrombopag in immune thrombocytopenia: A real-world study of the Spanish ITP Group (GEPTI).

Avatrombopag is the newest thrombopoietin receptor agonist (TPO-RA) approved to treat immune thrombocytopenia (ITP). Real-world evidence regarding effectiveness/safety is limited. The Spanish ITP Group (GEPTI) performed a retrospective study with patients starting avatrombopag for the first time. A total of 268 ITP patients were recruited. The median (interquartile range [IQR]) follow-up time was 47.5 (30.4-58.9) weeks. Among the 193 patients with baseline platelet counts <50 × 109/L, 174 (90.1%) of them achieved response (PC ≥50 × 109/L), and 113 (87.6%) of the 129 who persisted on avatrombopag at last visit had platelet levels above such threshold. Results were similar when only those patients switching to avatrombopag due to previous treatment failure were considered (n = 104). Patients reached response in 13 (7-21) days. Among patients with baseline levels ≥50 × 109/L, 73/75 (97.3%) reported response, which was maintained by 53 (94.6%) of the 56 who continued on avatrombopag at the end of the study. Loss-of-response was always <10%. ITP duration did not influence response. Approximately 79% (34/43) of heavily pretreated (≥4 lines) patients with baseline platelet counts <50 × 109/L switching after previous failure achieved PC ≥50 × 109/L. Previous use of eltrombopag and/or romiplostim did not influence response, regardless of whether previous TPO-RA(s) succeeded or failed. Avatrombopag allowed dose-reduction/suspension of corticosteroids in 40/50 (80.0%) patients with baseline platelet counts <50 × 109/L. Overall, 40/268 (14.9%) thrombocytosis and 12/268 (4.5%) thromboembolic events were reported. Our real-world cohort supports the use of avatrombopag to manage ITP, regardless of disease severity and treatment history.

Activated prothrombin complex concentrate to treat bleeding events in acquired hemophilia A: BAHAS study.

OBJECTIVE: Activated prothrombin complex concentrate (aPCC) is a bypassing agent indicated to treat bleeds in patients with acquired hemophilia A (AHA). Nevertheless, its efficacy and safety in the real-world setting have not often been addressed. METHODS: We report the experience of Spanish reference centers for coagulation disorders and from acquired hemophilia Spanish Registry (AHASR) from August 2012 to February 2021. Follow-up period of 30 days after aPCC withdrawal. RESULTS: Thirty patients with a median age of 70 years old, suffering from 51 bleeds treated with aPCC were finally evaluated. As first-line treatment, aPCC stopped bleeding in 13 of 14 (92.9%) cases. aPCC as the second line after recombinant factor VIIa failure, stopped bleeding in all cases. In 17 patients, aPCC was used far from initial bleed control as prophylaxis of rebleeding with 94% effectiveness. No thromboembolic episodes were communicated. One patient developed hypofibrinogenemia, which did not prevent aPCC from halting bleeding. No other serious adverse events possibly or probably associated with aPCC were reported. CONCLUSIONS: This data support aPCC as hemostatic treatment in AHA with high effectiveness and excellent safety profile in acute bleeds and as extended use to prevent rebleedings, even in aging people with high cardiovascular risk.

Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy.

Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival.From all phenotypes investigated on leukemic cells, expression of the CD203c and/or CD22 basophil-associated markers showed the strongest association with the occurrence and severity of bleeding (p ≤ 0.007); moreover, aberrant expression of CD7, coexpression of CD34+/CD7+ and lack of CD71 was also more frequently found among patients with (mild and severe) bleeding at baseline and/or after starting treatment (p ≤ 0.009). Multivariate analysis showed that CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio: 5.4; p = 0.03) were the best independent predictors for cumulative incidence of severe bleeding after starting therapy. In addition, CD203c expression on leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative independent predictors for overall survival.In summary, our results show that the presence of basophil-associated phenotypic characteristics on leukemic cells from acute promyelocytic leukemia patients at diagnosis is a powerful independent predictor for severe bleeding and overall survival, which might contribute in the future to (early) risk-adapted therapy decisions.

Presence of acute and chronic renal failure in patients with paroxysmal nocturnal hemoglobinuria: results of a retrospective analysis from the Spanish PNH Registry.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening blood disease. With the advent of eculizumab treatment, renal function has substantially improved, although no data from real-world clinical practice are available. An observational, retrospective, multicenter study was conducted in Spain on clinical data obtained from outpatient visits of patients with PNH (Spanish PNH Registry) who had experienced acute (ARF) or chronic (CRF) renal failure. Of the 128 patients registered (April 2014), 60 were diagnosed with classic PNH. Twenty-seven (45.0%) patients with a mean age of 48.5 (±16.2) years had renal failure, ARF or CRF, and were included in this study. Near half of the patients (n = 13; 48.1%) presented with ARF alone, 33.3% (n = 9) had CRF with episodes of ARF, while 18.5% (n = 5) were diagnosed with CRF alone. For patients with diagnosis of PNH and renal failure (n = 27), the median time to the first ARF episode was 6.5 (CI 95%; 2.2, 14.9) years, whereas the median to the diagnosis of CRF was 14.5 (CI 95%; 3.8, 19.2) years after the diagnosis of PNH. Patients with ARF (n = 22) were treated with eculizumab and did not experience new episodes of ARF, except for one patient with sepsis. Of the patients with CRF, two received treatment without experiencing further episodes of ARF. Sixteen patients who completed treatment (11 with ARF and 5 with ARF + CRF) recovered from the episode of ARF or from CRF. Of the remaining patients treated with eculizumab, one patient improved from stages III to II, three patients stabilized without showing disease progression, and one patient progressed from stages III to IV. Treatment with eculizumab in PNH patients has beneficial effects on renal function, preventing ARF and progression to CRF.