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Bleeding diathesis’ diagnosis can be challenging due to the high number of disorders with hemorrhagic symptomatology. Sitosterolemia is a rare disease characterized by increased sterols plasma levels and cardiovascular, cutaneous, articular, and hematological manifestations, including anemia and macrothrombocytopenia. The disorder is caused by ABCG5 and ABCG8 mutations. We present a case of a patient with bleeding diathesis, macrothrombocytopenia, a moderate defect of primary hemostasis and a pathological platelet aggregation analysis, with an initial diagnosis of Bernard-Soulier variant syndrome. After performing a genetic study using an exome analysis, the patient had two ABCG8 gen variants, one pathogenic ( NP_071882.1:p.Trp536Ter (NM_022437.2:c.1608G > A) variant, ClinVar ID: 499930) and the other one probably pathogenic ( NP_071882.1:p.Leu465Arg (NM_022437.2:c.1394T > G) variant), changing the diagnosis to sitosterolemia, which has its own therapeutic approach. This case report shows the importance of the genetic analysis. Sitosterolemia should be suspected in the presence of macrothrombocytopenia, stomatocytes in the blood smear and hemolytic anemia, performing a genetic study including ABCG5 and ABCG8 gene variants.

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.

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.

Background/objectives: Fostamatinib is a spleen tyrosine kinase (SYK) inhibitor approved for the treatment of adult patients with chronic immune thrombocytopenia (ITP). There is little information about dose tapering and sustained remission after discontinuation in ITP. In this retrospective multicenter study, we evaluated efficacy and safety of fostamatinib in adult patients with ITP before, during, and after tapering/discontinuation (T/D). Methods: T/D was performed on subjects who achieved complete platelet response (CR) with progressive, conditional dose reduction every four weeks. Results: Sixty-one patients were included from 14 reference centers between October 2021 and May 2023. In subjects that completed T/D (n = 9), the median time from treatment initiation to response was 21 days (IQR: 7.5–42), median time from treatment initiation to CR was 28 days (IQR: 28–42), median time from treatment initiation to the start of tapering was 116 days (IQR: 42–140), and duration of tapering was 112.5 days (IQR: 94.5–191). The median platelet count was 232 × 109/L (IQR: 152–345 × 109/L) at tapering and 190 × 109/L (IQR: 142.5–316.5 × 109/L) at discontinuation. With a median follow-up since discontinuation of 263 days (IQR: 247–313 days), only two patients have relapsed (at 63 and 73 days). Fostamatinib was restarted, achieving a new CR. Platelet counts higher than 100 × 109/L in week 12 were the only positive predictive factors for successful tapering and discontinuation. Conclusions: Sustained response in patient with ITP treated with fostamatinib could be developed. The prognostic factors and recommended scheme of tapering still have to be evaluated.