Twelve years of experience with miglustat in the treatment of type 1 Gaucher disease: The Spanish ZAGAL project.

We report data from a prospective, observational study (ZAGAL) evaluating miglustat 100mg three times daily orally. in treatment-naïve patients and patients with type 1 Gaucher Disease (GD1) switched from previous enzyme replacement therapy (ERT). Clinical evolution, changes in organ size, blood counts, disease biomarkers, bone marrow infiltration (S-MRI), bone mineral density by broadband ultrasound densitometry (BMD), safety and tolerability annual reports were analysed. Between May 2004 and April 2016, 63 patients received miglustat therapy; 20 (32%) untreated and 43 (68%) switched. At the time of this report 39 patients (14 [36%] treatment-naïve; 25 [64%] switch) remain on miglustat. With over 12-year follow-up, hematologic counts, liver and spleen volumes remained stable. In total, 80% of patients achieved current GD1 therapeutic goals. Plasma chitotriosidase activity and CCL-18/PARC concentration showed a trend towards a slight increase. Reductions on S-MRI (p=0.042) with an increase in BMD (p<0.01) were registered. Gastrointestinal disturbances were reported in 25/63 (40%), causing miglustat suspension in 11/63 (17.5%) cases. Thirty-eight patients (60%) experienced a fine hand tremor and two a reversible peripheral neuropathy. Overall, miglustat was effective as a long-term therapy in mild to moderate naïve and ERT stabilized patients. No unexpected safety signals were identified during 12-years follow-up.

Assessment of Bone Health in Patients With Type 1 Gaucher Disease Using Impact Microindentation.

Gaucher disease (GD), one of the most common lysosomal disorders (a global population incidence of 1:50,000), is characterized by beta-glucocerebrosidase deficiency. Some studies have demonstrated bone infiltration in up to 80% of patients, even if asymptomatic. Bone disorder remains the main cause of morbidity in these patients, along with osteoporosis, avascular necrosis, and bone infarcts. Enzyme replacement therapy (ERT) has been shown to improve these symptoms. This cross-sectional study included patients with type 1 Gaucher disease (GD1) selected from the Catalan Study Group on GD. Clinical data were collected and a general laboratory workup was performed. Bone mineral density (BMD) was measured at the lumbar spine and hip using dual-energy X-ray absorptiometry (DXA). Patients with bone infarcts or any other focal lesion in the area of indentation visible on imaging were excluded. Bone Material Strength index (BMSi) was measured by bone impact microindentation using an Osteoprobe instrument. Analysis of covariance (ANCOVA) models were fitted to adjust for age, sex, weight, and height. Sixteen patients with GD1 and 29 age- and sex-matched controls were included. GD1 was associated with significantly lower BMSi (adjusted beta -9.30; 95% CI, -15.18 to -3.42; p = 0.004) and reduced lumbar BMD (adjusted beta -0.14; 95% CI, -0.22 to -0.06; p = 0.002) and total hip BMD (adjusted beta -0.09; 95% CI, -0.15 to -0.03; p = 0.006), compared to GD1-free controls. Chitotriosidase levels were negatively correlated with BMSi (linear R2 = 51.6%, p = 0.004). Bone tissue mechanical characteristics were deteriorated in patients with GD1. BMSi was correlated with chitotriosidase, the marker of GD activity. Bone disorder requires special consideration in this group of patients, and microindentation could be an appropriate tool for assessing and managing their bone health. © 2017 American Society for Bone and Mineral Research.

The scintigraphic index spleen/liver at 30 minutes predicts the success of splenectomy in persistent and chronic primary immune thrombocytopenia.

UNLABELLED: Splenectomy is considered the second-line of treatment in patients with chronic primary immune thrombocytopenia (ITP) in whom glucocorticoids have failed. Some patients do not respond to splenectomy or they have postoperative complications. Based on our previous experience using kinetic and scintigraphic parameters, we did a retrospective study with the aim of comparing all these parameters as a means of predicting the success of splenectomy in persistent and chronic primary ITP. Forty-one consecutive patients with chronic primary ITP refractory to prednisone, who had been splenectomized, were included in the study. The response to splenectomy was assessed by evaluating bleeding and platelet counts before and at different times after surgery. A complete platelet kinetic study was performed before the splenectomy using autologous (111) In-labeled platelets. The scintigraphic parameters measured included different indices between spleen/heart, liver/hearth, and spleen/liver. Thirty-six patients gave a complete response after splenectomy and five patients did not respond. A statistically significant difference between both groups was found with initial platelet recovery and with some scintigraphic indices which also showed a variable prediction value for the success of splenectomy. Among these indices, the spleen/liver at 30 minutes demonstrated a predictive value with a 100% of sensitivity and a 100% of specificity. CONCLUSION: some platelet kinetic parameters and scintigraphic indices, in particular the spleen/liver at 30 minutes, were useful to predict the outcome of splenectomy in persistent and chronic primary ITP and, therefore, they should be taken into account when deciding whether or not to perform a splenectomy.

Low reticulocyte hemoglobin content is associated with a higher blood transfusion rate in critically ill patients: a cohort study.

BACKGROUND: Intensive care unit (ICU) patients often need blood transfusion, but no reliable predictors of transfusion requirements are available at ICU admission. The authors hypothesized that ICU patients with functional iron deficiency may be at higher risk for developing anemia, requiring blood transfusion. Their objective was to determine whether low reticulocyte hemoglobin content (CHr) was associated with transfusion requirements in ICU patients. METHODS: This is a prospective cohort study in a general ICU. The authors studied 62 patients, after excluding those transfused on or before ICU admission. The authors recorded age, diagnosis, severity score, presence of sepsis, ICU complications, ICU treatments, and transfusion-free interval. Threshold for low CHr was 29 pg. The authors also recorded ICU and hospital outcome. The statistical analysis included Cox proportional hazard function for transfusion. RESULTS: Twenty-three patients (37%) presented with low CHr on ICU admission and tended to be sicker and more likely to have sepsis than those with normal CHr. They were also more prone to complications, particularly acute renal failure (39 vs. 13% P = 0.02) and ICU-acquired infection (30 vs. 10% P = 0.04). The overall transfusion rate was 22.6%, being higher in low-CHr patients than in normal-CHr patients (39.1 vs. 12.8%, P = 0.02). After adjusting for severity of illness, age, trauma, and hemoglobin level, low CHr remained significantly associated with transfusion, with a hazard ratio of 3.6 (95% CI, 1.2-10.7; P = 0.02). Median ICU stay was also longer in patients with low CHr (8 vs. 5 days, P = 0.01). Differences in mortality did not reach statistical significance. CONCLUSION: Low CHr is common at ICU admission and is associated with higher transfusion requirements.

[Relationship between reticulated platelets and megacaryocyte number in thrombocytopenic patients]. / Relación entre plaquetas reticuladas y número de megacariocitos en pacientes con trombocitopenia.

BACKGROUND AND INTRODUCTION: Marrow aspiration is a test that helps the pathogenic diagnosis of thrombocytopenia. Our goal was to analyze the correlation between reticulated platelets (RP) values in peripheral blood with megakaryocytic number in bone marrow in a group of thrombocytopenic patients. PATIENTS AND METHODS: Prospective observational study in thrombocytopenic patients, between June 2002 and June 2005. RP determination was performed by flow cytometry using whole blood. We used a monoclonal anti-glycoprotein-IIIa antibody (CD61PerCP) for platelet identification and orange thiazole (Retic-count) as platelet mRNA stain. Marrow study was conducted by marrow aspiration. RESULTS: RP were measured in 54 thrombocytopenic patients with bone marrow study. Three were excluded from the study. Thirty-two patients had central thrombocytopenia with diminished megakaryocytes (MK) and/or dysplasia, mean of RP 9.5% (CI 95%:5.6%-13.4%). Thirteen patients had high MK,mean of RP 25.7%(CI 95%:13.1%-38.3%). Six patients had normal MK, mean of RP 13.6% (CI 95%:0.6%-26.8%). There were differences between the group of increased MK and the group of central thrombocytopenias (p=0001). A value of RP>or=11% showed a sensitivity of 70% and specificity of 81% for the diagnosis of marrow aspirate with increased MK. CONCLUSIONS: RP are an indirect marker of megakaryocyte number in bone marrow. A value of RP>or=11% in patients with thrombocytopenia, especially with an acute onset, would indicate regenerative thrombocytopenia, while in the presence of low levels of RP a marrow aspiration should be performed.

Relación entre plaquetas reticuladas y número de megacariocitos en pacientes con trombocitopenia / Relationship between reticulated platelets and megacaryocyte number in thrombocytopenic patients

Fundamento y objetivo: El aspirado medular es un test de gran valor para el diagnóstico patogénico de las trombocitopenias. El objetivo fue analizar la correlación entre los valores de plaquetas reticuladas (PR) en sangre periférica con el número de megacariocitos en médula ósea en un grupo de pacientes con trombocitopenia. Pacientes y método: Estudio prospectivo observacional en pacientes con trombocitopenia entre junio de 2002 y junio de 2005. La determinación de PR se realizó mediante citometría de flujo con el uso de sangre total. Se utilizó un anticuerpo monoclonal anti-glucoproteína-IIIa (CD61 PerCP®) para la identificación de plaquetas y naranja de tiazol (Retic-count®) para la tinción del ácido ribonucleico plaquetario residual. El estudio medular se realizó mediante aspirado medular. Resultados: Se determinaron las PR en 54 pacientes con trombocitopenia que tenían estudio medular. Tres pacientes se excluyeron del estudio. Treinta y dos pacientes tenían trombocitopenias centrales con megacariocitos disminuidos o displasia, con una media de PR del 9,5% (intervalo de confianza [IC] del 95%: del 5,6 al 13,4%). Trece pacientes tenían megacariocitos elevados, con una media de PR del 25,7% (IC del 95%: del 13,1 al 38,3%). Seis pacientes tenían megacariocitos normales, con una media de PR del 13,6% (IC del 95%: del 0,6 al 26,8%). Se observaron diferencias entre el grupo con megacariocitos aumentados y el grupo de trombocitopenias centrales (p=0,001). Un valor de PR superior o igual al 11% mostró sensibilidad del 70% y especificidad del 81% para el diagnóstico de aspirado medular con megacariocitos aumentados. Conclusiones: Las PR son un marcador indirecto de la producción de megacariocitos en médula ósea. La presencia de PR superior o igual al 11% en pacientes con trombocitopenia, especialmente de inicio agudo, indicaría trombocitopenia regenerativa, mientras que ante la presencia de valores bajos de PR sería recomendable realizar un aspirado medular (AU)

Background and Introduction: Marrow aspiration is a test that helps the pathogenic diagnosis of thrombocytopenia. Our goal was to analyze the correlation between reticulated platelets (RP) values in peripheral blood with megakaryocytic number in bone marrow in a group of thrombocytopenic patients. Patients and methods: Prospective observational study in thrombocytopenic patients, between June 2002 and June 2005. RP determination was performed by flow cytometry using whole blood. We used a monoclonal anti-glycoprotein-IIIa antibody (CD61PerCP) for platelet identification and orange thiazole (Retic-count®) as platelet mRNA stain. Marrow study was conducted by marrow aspiration. Results: RP were measured in 54 thrombocytopenic patients with bone marrow study. Three were excluded from the study. Thirty-two patients had central thrombocytopenia with diminished megakaryocytes (MK) and/or dysplasia, mean of RP 9.5% (CI 95%:5.6% 13.4%). Thirteen patients had high MK,mean of RP 25.7%(CI 95%:13.1% 38.3%). Six patients had normal MK, mean of RP 13.6% (CI 95%:0.6% 26.8%). There were differences between the group of increased MK and the group of central thrombocytopenias (p=0001). A value of RPe11% showed a sensitivity of 70% and specificity of 81% for the diagnosis of marrow aspirate with increased MK. Conclusions: RP are an indirect marker of megakaryocyte number in bone marrow. A value of RPe11% in patients with thrombocytopenia, especially with an acute onset, would indicate regenerative thrombocytopenia, while in the presence of low levels of RP a marrow aspiration should be performed (AU)