Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study.

Ravulizumab (ALXN1210), a new complement C5 inhibitor, provides immediate, complete, and sustained C5 inhibition. This phase 3, open-label study assessed the noninferiority of ravulizumab to eculizumab in complement inhibitor-naive adults with paroxysmal nocturnal hemoglobinuria (PNH). Patients with lactate dehydrogenase (LDH) ≥1.5 times the upper limit of normal and at least 1 PNH symptom were randomized 1:1 to receive ravulizumab or eculizumab for 183 days (N = 246). Coprimary efficacy end points were proportion of patients remaining transfusion-free and LDH normalization. Secondary end points were percent change from baseline in LDH, change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score, proportion of patients with breakthrough hemolysis, stabilized hemoglobin, and change in serum free C5. Ravulizumab was noninferior to eculizumab for both coprimary and all key secondary end points (Pinf < .0001): transfusion avoidance (73.6% vs 66.1%; difference of 6.8% [95% confidence interval (CI), -4.66, 18.14]), LDH normalization (53.6% vs 49.4%; odds ratio, 1.19 [0.80, 1.77]), percent reduction in LDH (-76.8% vs -76.0%; difference [95% CI], -0.83% [-5.21, 3.56]), change in FACIT-Fatigue score (7.07 vs 6.40; difference [95% CI], 0.67 [-1.21, 2.55]), breakthrough hemolysis (4.0% vs 10.7%; difference [95% CI], -6.7% [-14.21, 0.18]), and stabilized hemoglobin (68.0% vs 64.5%; difference [95% CI], 2.9 [-8.80, 14.64]). The safety and tolerability of ravulizumab and eculizumab were similar; no meningococcal infections occurred. In conclusion, ravulizumab given every 8 weeks achieved noninferiority compared with eculizumab given every 2 weeks for all efficacy end points, with a similar safety profile. This trial was registered at www.clinicaltrials.gov as #NCT02946463.

Transfusion profile, clinical characteristics, comorbidities and outcomes of 3014 hospitalized patients diagnosed with COVID-19 in Brazil.

BACKGROUND: The novel coronavirus disease-2019 (COVID-19) caused a sudden and unexpected increase in the number of hospital admissions and deaths worldwide. The impact of social distancing on blood stocks was significant. Data on the use of blood products by patients with COVID-19 are scarce. MATERIAL AND METHODS: A retrospective observational study was conducted by analysing the medical records of 3014 hospitalized COVID-19 patients in 16 Brazilian hospitals. Individual data related to clinical, laboratory and transfusion characteristics and outcomes of these patients were collected. Patients characteristics association with mortality and transfusion need were tested independently by logistic regression models. RESULTS: Patients mean age was 57·6 years. In 2298 (76·2%) patients, there was an underlying clinical comorbidity. A total of 1657 (55%) patients required admission to intensive care unit (ICU), and 943 (31%) patients required ventilatory support and orotracheal intubation (OTI). There was a total of 471 (15·6%) deaths among all patients. 325 patients (10·7%) required blood transfusion; 3187 blood products were transfused: 1364 red blood cells in 303 patients, 1092 platelet units in 78 patients, 303 fresh frozen plasma in 49 patients and 423 cryoprecipitates in 21 patients. The mortality among patients who received transfusion was substantially higher than that among the total study population. CONCLUSION: Need for transfusion was low in COVID-19 patients, but significantly higher in patients admitted to ICU and in those who needed OTI. Knowledge of the transfusion profile of these patients allows better strategies for maintaining the blood stocks of hospitals during the pandemic.

Mutational Profile of Homozygous ß-Thalassemia in Rio de Janeiro, Brazil.

ß-Thalassemia (ß-thal) is a hemolytic anemia that is caused by point mutations in most cases. The Brazilian population is highly heterogeneous and knowledge of the mutations that make up the genotypic profile of individuals can contribute information about the formation of the population and clinical condition of patients. In this study, we evaluated the mutations present in homozygous ß-thal patients from Rio de Janeiro, Brazil. We analyzed 24 samples of peripheral blood of patients with homozygous ß-thal. To identify the mutations, we carried out allele-specific-polymerase chain reaction (AS-PCR) and DNA sequencing. We found 11 different mutations on the ß-globin gene. Among the most frequent mutations observed were HBB: c.92 + 6T>C, followed by HBB: c.93-21G>A, HBB: c.118C>T and HBB: c.92 + 1G>A. We also identified the rare mutation HBB: c.75T>A that was reported in an individual carrying Hb S (HBB: c.20A>T)/ß-thal (HBB: c.75T>A) but not in Brazilian thalassemic patients, thus, this is the first report of this mutation in Brazilian ß-thal patients. For its multiethnic character, Brazil has different mutations that cause ß-thal and that are distributed with different frequencies according to the regions of the country. Our findings contribute to the description of the mutational profile of Brazilian thalassemic patients, showing wide heterogeneity and genetic variability.

Right and left ventricular function and myocardial scarring in adult patients with sickle cell disease: a comprehensive magnetic resonance assessment of hepatic and myocardial iron overload.

BACKGROUND: Patients with Sickle cell disease (SCD) who receive regular transfusions are at risk for developing cardiac toxicity from iron overload. The aim of this study was to assess right and left cardiac volumes and function, late gadolinium enhancement (LGE) and iron deposits in patients with SCD using CMR, correlating these values with transfusion burden, ferritin and hemoglobin levels. METHODS: Thirty patients with SCD older than 20 years of age were studied in a 1.5 T scanner and compared to age- and sex-matched normal controls. Patients underwent analysis of biventricular volumes and function, LGE and T2* assessment of the liver and heart. RESULTS: When compared to controls, patients with SCD presented higher left ventricular (LV) volumes with decreased ejection fraction (EF) with an increase in stroke volume (SV) and LV hypertrophy. The right ventricle (RV) also presented with a decreased EF and hypertrophy, with an increased end-systolic volume. Although twenty-six patients had increased liver iron concentrations (median liver iron concentration value was 11.83 ± 9.66 mg/g), only one patient demonstrated an abnormal heart T2* < 20 msec. Only four patients (13%) LGE, with only one patient with an ischemic pattern. CONCLUSIONS: Abnormal heart iron levels and myocardial scars are not a common finding in SCD despite increased liver iron overload. The significantly different ventricular function seen in SCD compared to normal suggests the changes in RV and LV function may not be due to the anemia alone. Future studies are necessary to confirm this association.

Comparison of myocardial T1 and T2 values in 3 T with T2* in 1.5 T in patients with iron overload and controls.

Myocardial iron quantification remains limited to 1.5 T systems with T2* measurement. The present study aimed at comparing myocardial T2* values at 1.5 T to T1 and T2 mapping at 3.0 T in patients with iron overload and healthy controls. A total of 17 normal volunteers and seven patients with a history of myocardial iron overload were prospectively enrolled. Mid-interventricular septum T2*, native T1 and T2 times were quantified on the same day, using a multi-echo gradient-echo sequence at 1.5 T and T1 and T2 mapping sequences at 3.0 T, respectively. Subjects with myocardial iron overload (T2* < 20 ms) in comparison with those without had significantly lower mean myocardial T1 times (868.9 ± 120.2 vs. 1170.3 ± 25.0 ms P = 0.005 respectively) and T2 times (34.9 ± 4.7 vs. 45.1 ± 2.0 ms P = 0.007 respectively). 3 T T1 and T2 times strongly correlated with 1.5 T, T2* times (Pearson's r = 0.95 and 0.91 respectively). T1 and T2 measures presented less variability than T2* in inter- and intra-observer analysis. Native myocardial T1 and T2 times at 3 T correlate closely with T2* times at 1.5 T and may be useful for myocardial iron overload quantification.