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Subarna Chakravorty - One of the best experts on this subject based on the ideXlab platform.
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effectiveness of Hydroxycarbamide in children with sickle cell disease analysis of dose response metrics in a large birth cohort in a tertiary sickle cell centre
Pediatric Blood & Cancer, 2019Co-Authors: Hyun Park, S Bhatti, Subarna ChakravortyAbstract:BACKGROUND Despite the well-established efficacy of Hydroxycarbamide in the management of sickle cell disease (SCD), the paucity of real-world clinical data limits the establishment of a practical dosing strategy. The aim of this study was to analyse the dose-response metrics of Hydroxycarbamide associated with the minimum effective dose protocol - specifically, between dose groups and differing degrees of myelosuppression. DESIGN/METHODS A retrospective cohort study was conducted on 93 patients who were initiated on Hydroxycarbamide between 2005 and 2017 at a tertiary haemoglobinopathy centre in London, UK. The burden of acute SCD-related complications was defined by the annualised rates of emergency department attendances and hospital admissions. Secondary outcomes included haematological, biochemical, liver, renal and transcranial Doppler velocity status. Comparisons were performed upon stratification via dose (<20 mg/kg/day, 20-24 mg/kg/day and ≥25 mg/kg/day) and sustained absolute neutrophil count (ANC) values (ANC <4 × 109 /L and ANC ≥4 × 109 /L). RESULTS Clinical outcomes were not predicted by dose or ANC values. Whilst laboratory indices between dose groups were also non-statistically significant, patients maintained on ANC <4 × 109 /L were shown to achieve superior responses in haemoglobin, haemoglobin F, absolute reticulocyte count and liver function. Toxicities occurred idiosyncratically, with minimal reports of transient neutropaenia and thrombocytopaenia. CONCLUSIONS Objective clinical responses may be achievable without intensive dose escalation. Our finding that greater myelosuppression is associated with greater improvements in laboratory markers of clinical benefit is consistent with prior clinical trials, but ongoing effectiveness studies are needed to determine whether these benefits can be reliably demonstrated in routine clinical practice using different dosing protocols.
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g536 effectiveness of Hydroxycarbamide in children with sickle cell disease analysis of dose response metrics in a large birth cohort in a tertiary sickle cell centre
Archives of Disease in Childhood, 2019Co-Authors: Hyun Park, S Bhatti, Subarna ChakravortyAbstract:Background Hydroxycarbamide is an antimetabolite with known prophylactic efficacy in improving clinical and laboratory outcomes in sickle cell disease (SCD). Given its narrow therapeutic index, optimisation of the dosing strategy is a critical therapeutic goal. Current practice remains variable – some centres target the maximum tolerated dose (MTD) titred to absolute neutrophil counts (ANC), whilst others have maintained the minimum effective dose (MED). The paucity of real-life clinical studies represents a significant barrier to effective therapy. Aim To analyse the dose-response metrics of Hydroxycarbamide associated with the MED protocol, in respect to clinical, laboratory and toxicity outcomes; specifically between dose groups and differing degrees of myelosuppression, as marked by ANC levels. Methods A retrospective cohort study was conducted on 97 patients who were initiated on Hydroxycarbamide between 2005–2017 at a tertiary haemoglobinopathy centre in London, UK. The primary measure of outcome was the burden of acute SCD-related complications, as defined by the annualised rates of A and E attendances and hospital admissions. Secondary outcomes included haematological, biochemical, liver, renal and Transcranial Doppler velocity status. Comparative analysis was performed upon stratification via dose ( Results Clinical outcomes were not predicted by dose or ANC values. Whilst laboratory indices between dose groups were also non-statistically significant, patients maintained on ANC Conclusion Sufficient clinical responses may be achievable without intensive dose escalation. The implications of enhanced physiological responses achieved with greater myelosuppression remain to be investigated in prospective studies.
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g15 p parental understanding and concerns regarding Hydroxycarbamide as a disease modifying agent in sickle cell disease within the paediatric population
Archives of Disease in Childhood, 2016Co-Authors: A J Whittaker, C Mkandawire, Subarna ChakravortyAbstract:Aims Robust clinical evidence of safety and efficacy supports the use of Hydroxycarbamide in children with sickle cell disease (SCD) leading to its use becoming globally accepted in clinical practice. Despite proven efficacy, low toxicity, clinical consensus and low cost, there are reports of underutilisation of Hydroxycarbamide in SCD. Possible causes include provider, patient and systems level barriers. Our project sought to determine whether parental barriers in the use of Hydroxycarbamide existed in the UK and whether its uptake has been affected as a result. Additionally we investigated clinicians’ views of Hydroxycarbamide utilisation and barriers to its use in children; parental knowledge and parental concerns regarding Hydroxycarbamide, and sources of drug information utilised by parents of children with SCD. Methods A multi-method approach was used, including a survey of clinicians, parent questionnaires and parent focus group meeting. Results We surveyed 150 members of the UK Forum of Haemoglobin Disorders in order to obtain clinician views of parental concerns regarding Hydroxycarbamide. Clinicians were asked to rank parental views on Hydroxycarbamide use. Of the 25 respondents, 68% ranked ‘concerned but willing to accept therapy’ as the commonest parental response, see Figure 1. Some clinicians indicated that a degree of provider barrier, in the form of highlighting of rare adverse effects discouraged parents to consent for treatment. Perceived concerns were its effect on fertility, potential carcinogenicity and need for frequent monitoring. We surveyed parents regarding their existing knowledge of Hydroxycarbamide by means of a questionnaire. We found knowledge to be limited despite being mainly derived from NHS sources. Additionally, some parents indicated that their concerns regarding the safety of the drug had affected their decision to consent for treatment, see Figure 2. Focus group discussions involving nine families echoed the clinician surveys with mixed views on efficacy and safety (Figure 3). Conclusion Our results indicate that parental concerns regarding safety and efficacy of Hydroxycarbamide is prevalent and may be creating a barrier to its uptake in the UK. More work is needed with larger number of participants to accurately understand the barriers to acceptance of Hydroxycarbamide therapy in order to improve Hydroxycarbamide uptake in children.
Gunnar Birgegård - One of the best experts on this subject based on the ideXlab platform.
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combination therapy of Hydroxycarbamide with anagrelide in patients with essential thrombocythemia in the evaluation of xagrid r efficacy and long term safety study
Haematologica, 2014Co-Authors: Luigi Gugliotta, Jean Jacques Kiladjian, Ruth Coll, Brihad Abhyankar, Carlos Besses, Claire N Harrison, Jonathan Smith, M Griesshammer, Gunnar BirgegårdAbstract:Available information is limited regarding the use of cytoreductive combination therapy in high-risk patients with essential thrombocythemia. This analysis aims to evaluate the clinical relevance and patterns of cytoreductive combination treatment in European high-risk patients with essential thrombocythemia in the Evaluation of Xagrid® Efficacy and Long-term Safety study. Of 3643 patients, 347 (9.5%) received combination therapy. Data were recorded at each 6-month update. Of 347 patients who received combination therapy, 304 (87.6%) received Hydroxycarbamide + anagrelide. Monotherapies received before this combination were Hydroxycarbamide (n=167, 54.9%) and anagrelide (n=123, 40.5%). Median weekly doses of Hydroxycarbamide and anagrelide were: 7000 and 10.5 mg when used as prior monotherapy; 3500 and 7.0 mg when used as add-on treatment. Overall, median platelet counts were 581×109/L and 411×109/L before and after starting Hydroxycarbamide + anagrelide, respectively. In patients with paired data (n=153), the number of patients with platelet counts less than 400×109/L increased from 33 (21.6%) to 74 (48.4%; P <0.0001), and with platelet counts less than 600×109/L, from 82 (53.6%) to 132 (86.3%; P <0.0001). Hydroxycarbamide + anagrelide was discontinued in 158 patients: 76 (48.1%) stopped Hydroxycarbamide, 59 (37.3%) stopped anagrelide, 19 (12.0%) stopped both and 4 (2.5%) had another therapy added. The most frequent reasons for discontinuation were intolerance/side-effects, lack of efficacy, and therapeutic strategy. Combination therapy, usually Hydroxycarbamide + anagrelide, is used in approximately 10% of all high-risk patients with essential thrombocythemia and may be a useful approach in treating patients for whom monotherapy is unsatisfactory. ( [Clinicaltrials.gov][1] identifier:[NCT00567502][2] ) [1]: http://Clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00567502&atom=%2Fhaematol%2F99%2F4%2F679.atom
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combination therapy of Hydroxycarbamide with anagrelide in patients with essential thrombocythemia in the evaluation of xagrid r efficacy and long term safety study
Haematologica, 2014Co-Authors: Luigi Gugliotta, Jean Jacques Kiladjian, Ruth Coll, Brihad Abhyankar, Carlos Besses, Claire N Harrison, Jonathan Smith, M Griesshammer, Gunnar BirgegårdAbstract:Available information is limited regarding the use of cytoreductive combination therapy in high-risk patients with essential thrombocythemia. This analysis aims to evaluate the clinical relevance and patterns of cytoreductive combination treatment in European high-risk patients with essential thrombocythemia in the Evaluation of Xagrid(®) Efficacy and Long-term Safety study. Of 3643 patients, 347 (9.5%) received combination therapy. Data were recorded at each 6-month update. Of 347 patients who received combination therapy, 304 (87.6%) received Hydroxycarbamide + anagrelide. Monotherapies received before this combination were Hydroxycarbamide (n=167, 54.9%) and anagrelide (n=123, 40.5%). Median weekly doses of Hydroxycarbamide and anagrelide were: 7000 and 10.5 mg when used as prior monotherapy; 3500 and 7.0 mg when used as add-on treatment. Overall, median platelet counts were 581 × 10(9)/L and 411 × 10(9)/L before and after starting Hydroxycarbamide + anagrelide, respectively. In patients with paired data (n=153), the number of patients with platelet counts less than 400 × 10(9)/L increased from 33 (21.6%) to 74 (48.4%; P<0.0001), and with platelet counts less than 600 × 10(9)/L, from 82 (53.6%) to 132 (86.3%; P<0.0001). Hydroxycarbamide + anagrelide was discontinued in 158 patients: 76 (48.1%) stopped Hydroxycarbamide, 59 (37.3%) stopped anagrelide, 19 (12.0%) stopped both and 4 (2.5%) had another therapy added. The most frequent reasons for discontinuation were intolerance/side-effects, lack of efficacy, and therapeutic strategy. Combination therapy, usually Hydroxycarbamide + anagrelide, is used in approximately 10% of all high-risk patients with essential thrombocythemia and may be a useful approach in treating patients for whom monotherapy is unsatisfactory. (Clinicaltrials.gov identifier:NCT00567502).
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a unified definition of clinical resistance and intolerance to Hydroxycarbamide in polycythaemia vera and primary myelofibrosis results of a european leukemianet eln consensus process
British Journal of Haematology, 2010Co-Authors: Giovanni Barosi, Gunnar Birgegård, Claire N Harrison, M Griesshammer, Guido Finazzi, Ruben A Mesa, Hans Carl Hasselbalch, Jean Jacques Kiladijan, Eva Lengfelder, Mary Frances Mc MullinAbstract:A unified definition of clinical resistance and intolerance to Hydroxycarbamide in polycythaemia vera and primary myelofibrosis : results of a European LeukemiaNet (ELN) consensus process
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Long-term management of thrombocytosis in essential thrombocythaemia
Annals of Hematology, 2009Co-Authors: Gunnar BirgegårdAbstract:Essential thrombocythaemia (ET) is an acquired myeloproliferative disorder with a prolonged clinical course and a near-normal life expectancy. Therapy is stratified according to risk of thrombohaemorrhagic events. In high-risk patients, platelet reduction is generally recommended. In intermediate-risk patients, therapy should be considered depending on the severity of associated risk factors, especially cardiovascular. In low-risk patients, a watch-and-wait approach is appropriate. Hydroxycarbamide is generally first-line therapy. Concerns for possible leukemogenicity make anagrelide or interferon-α possible choices in younger patients and those who are resistant or intolerant to Hydroxycarbamide. Each pharmacotherapy is associated with specific long-term risks and benefits. The potential risk of major bleeding is the main drawback of aspirin. Hydroxycarbamide is an established, effective drug for ET, but it may increase the risk of transformation to acute myeloid leukaemia and may give mucocutaneous ulcers. Anagrelide is a licensed treatment that also reduces platelet counts and is generally well tolerated, with evidence that some common side effects diminish over time. Anagrelide can have cardiac effects due to inhibition of phosphodiesterase III and therefore requires cautious use in patients with cardiac insufficiency. There is no evidence of leukaemogenicity with anagrelide or interferon-α therapy. Interferon-α is the only treatment suitable for use during pregnancy, although it is not licensed in ET. While it is effective for platelet reduction, the use of interferon-α is restricted by psychiatric side effects. Our knowledge of the optimum pharmacotherapy for each patient with ET continues to evolve through research and clinical trials, particularly into the molecular basis of the disease.
Russell E Ware - One of the best experts on this subject based on the ideXlab platform.
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Hydroxycarbamide treatment and brain mri mra findings in children with sickle cell anaemia
British Journal of Haematology, 2016Co-Authors: Kerri Nottage, Banu Aygun, Russell E Ware, Matthew P Smeltzer, Winfred C Wang, Jane S Hankins, Guolian Kang, Joseph Moen, Kathleen J HeltonAbstract:Summary Silent cerebral infarction (SCI) is the most common neurological abnormality among children with sickle cell anaemia (SCA). The effect of Hydroxycarbamide (also termed hydroxyurea) on the development and progression of SCI is unclear. We evaluated brain magnetic resonance imaging/angiography (MRI/MRA) in children with SCA receiving long-term Hydroxycarbamide therapy. Fifty participants (median 9·4 years, range 1·1–17·3) enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE; NCT00305175) underwent brain MRI/MRA and laboratory evaluations before Hydroxycarbamide initiation and after 3 and 6 years of treatment to maximum tolerated dose. SCI and vascular stenosis were evaluated. At baseline, 3 and 6 years, SCI were present in 19/50 (38%), 20/49 (41%), and 7/17 (41%), respectively. At 3 years, one child developed a SCI lesion, and another progressed (single lesion to multiple). Lower haemoglobin (Hb) (80 g/l vs. 86 g/l, P = 0·049), fetal Hb (5·0% vs. 10·4%, P < 0·001) and oxygen saturation (97% vs. 98%, P = 0·027) before Hydroxycarbamide initiation were associated with SCI. No patients had vascular stenosis identified on MRA, transient ischaemic attack or stroke. Our data indicate that children receiving Hydroxycarbamide over a 3- to 6-year period have a low rate of new or worsening cerebrovascular disease. Further studies are needed to confirm that Hydroxycarbamide can prevent the onset and progression of SCI.
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Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia tcd with transfusions changing to hydroxyurea twitch a multicentre open label phase 3 non inferiority trial
The Lancet, 2016Co-Authors: Russell E Ware, Banu Aygun, William H Schultz, Isaac Odame, Barry R Davis, Clark R Brown, Sharada A Sarnaik, Beng Fuh, Alex George, William OwenAbstract:Summary Background For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of Hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. Methods TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4–16 years and had abnormal TCD flow velocities (≥200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or Hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral Hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307. Findings Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to Hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140–146) in children who received standard transfusions and 138 cm/s (135–142) in those who received Hydroxycarbamide, with a difference of 4·54 (0·10–8·98). Non-inferiority (p=8·82 × 10 −16 ) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for Hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with Hydroxycarbamide and three events in one [2%] patient for transfusions). Interpretation For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, Hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. Funding National Heart, Lung, and Blood Institute, National Institutes of Health.
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Hydroxycarbamide clinical aspects
Comptes Rendus Biologies, 2013Co-Authors: Russell E WareAbstract:Due to its oral route of administration and mild toxicity profile, as well as its potent laboratory and clinical effects, hydroxyurea (or Hydroxycarbamide) has been the primary focus of fetal hemoglobin (HbF) induction strategies for the treatment of children with sickle cell anemia (SCA). When administered orally once a day, hydroxyurea treatment is very well tolerated with little short-term toxicity. Hydroxyurea has documented laboratory efficacy with increases in Hb and HbF; treatment also significantly reduces the number of painful episodes, acute chest syndrome, transfusions, and hospitalizations. Most young patients reach a maximum tolerated dose of hydroxyurea at 25-30 mg/kg/d, where they will achieve key laboratory thresholds (Hb ≥ 9 g/dL and HbF ≥ 20%) without excessive myelosuppression. Potential long-term toxicities continue to be of great concern and should be monitored in all patients with SCA who receive hydroxyurea therapy. To date, however, no increases in stroke, myelodysplasia, or carcinogenicity have been detected in SCA patient cohorts, with drug exposure now reaching 15 years for some treated children. Taken together, available evidence suggests that hydroxyurea represents an inexpensive and effective treatment option that should be offered to most, if not all, patients with SCA. As countries in Africa develop newborn screening programs to identify SCA, the widespread use of hydroxyurea may prove to be a useful treatment to help ameliorate the disease in resource-limited settings. Hydroxyurea is the only currently available disease-modifying therapy for SCA, and is emerging as a safe and effective treatment for all patients with SCA, in both developed and developing countries.
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Hydroxycarbamide alters erythroid gene expression in children with sickle cell anaemia
British Journal of Haematology, 2012Co-Authors: Jonathan M Flanagan, Banu Aygun, Nicole A Mortier, Thad A Howard, Jane S Hankins, Shirley A Steward, Amy C Kimble, Geoffrey Neale, Russell E WareAbstract:Sickle cell anaemia (SCA) is a severe debilitating haematological disorder associated with a high degree of morbidity and mortality. The level of fetal haemoglobin (HbF) is well-recognized as a critical laboratory parameter: lower HbF is associated with a higher risk of vaso-occlusive complications, organ damage, and early death. Hydroxycarbamide treatment can induce HbF, improve laboratory parameters, and ameliorate clinical complications of SCA but its mechanisms of action remain incompletely defined and the HbF response is highly variable. To identify pathways of Hydroxycarbamide activity, we performed microarray expression analyses of early reticulocyte RNA obtained from children with SCA enrolled in the HydroxyUrea Study of Long-term Effects (NCT00305175) and examined the effects of Hydroxycarbamide exposure in vivo. Hydroxycarbamide affected a large number of erythroid genes, with significant decreases in the expression of genes involved in translation, ribosome assembly and chromosome organization, presumably reflecting the daily cytotoxic pulses of Hydroxycarbamide. Hydroxycarbamide also affected expression of numerous genes associated with HbF including BCL11A, a key regulator of baseline HbF levels. Together, these data indicate that Hydroxycarbamide treatment for SCA leads to substantial changes in erythroid gene expression, including BCL11A and other potential signalling pathways associated with HbF induction.
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Hydroxycarbamide in very young children with sickle cell anaemia a multicentre randomised controlled trial baby hug
The Lancet, 2011Co-Authors: Winfred C Wang, Scott T Miller, Zora R. Rogers, Russell E Ware, Caterina P Minniti, Rathi V Iyer, James F Casella, Sohail Rana, Courtney D Thornburg, Ram KalpatthiAbstract:Summary Background Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of Hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects. Methods This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin Sβ 0 thalassaemia, were aged 9–18 months at randomisation, and were not selected for clinical severity. Participants received liquid Hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for Hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on 99 Tc spleen scan) and renal function (glomerular filtration rate by 99m Tc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2–4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00006400. Findings 96 patients received Hydroxycarbamide and 97 placebo, of whom 83 patients in the Hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the Hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0·21; and a difference in the mean increase in DTPA glomerular filtration rate in the Hydroxycarbamide group versus the placebo group of 2 mL/min per 1·73 m 2 , p=0·84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0·002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p Interpretation On the basis of the safety and efficacy data from this trial, Hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia. Funding The US National Heart, Lung, and Blood Institute; and the National Institute of Child Health and Human Development.
Severine Ferdinand - One of the best experts on this subject based on the ideXlab platform.
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decrease of externalized phosphatidylserine density on red blood cell derived microparticles in sca patients treated with Hydroxycarbamide
British Journal of Haematology, 2018Co-Authors: Yohann Garnier, Nathalie Lemonne, Philippe Connes, Severine Ferdinand, Marie Garnier, Maryse Etiennejulan, Marc RomanaAbstract:Hydroxycarbamide (HC) treatment has been shown to improve the clinical course of patients with sickle cell anaemia (SCA), a haemoglobinopathy resulting from a single base substitution in the beta-globin gene (HBB). SCA is characterized by chronic haemolytic anaemia and recurrent vascular occlusions leading to multisystemic complications. Several beneficial biological effects of HC have been documented (Halsey et al, 2003) but its impact on the concentration of circulating microparticles (MPs), a subtype of extracellular vesicles released from cytoplasmic membrane of activated or apoptotic cells and detected at high levels in sickle plasma, remains controversial (Hebbel et al, 2016). The aim of the present study was to compare the MP pattern in a group of SCA patients treated by HC and followed for 2 years.
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men with sickle cell anemia and priapism exhibit increased hemolytic rate decreased red blood cell deformability and increased red blood cell aggregate strength
PLOS ONE, 2016Co-Authors: Nathalie Lemonne, Kizzyclara Cita, L Brureau, Marie Billaud, Philippe Connes, Severine Ferdinand, Benoit Tressieres, Vanessa TarerAbstract:Objectives To investigate the association between priapism in men with sickle cell anemia (SCA) and hemorheological and hemolytical parameters. Materials and Methods Fifty-eight men with SCA (median age: 38 years) were included; 28 who had experienced priapism at least once during their life (priapism group) and 30 who never experienced this complication (control group). Twenty-two patients were treated with Hydroxycarbamide, 11 in each group. All patients were at steady state at the time of inclusion. Hematological and biochemical parameters were obtained through routine procedures. The Laser-assisted Optical Rotational Cell Analyzer was used to measure red blood cell (RBC) deformability at 30 Pa (ektacytometry) and RBC aggregation properties (laser backscatter versus time). Blood viscosity was measured at a shear rate of 225 s-1 using a cone/plate viscometer. A principal component analysis was performed on 4 hemolytic markers (i.e., lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), total bilirubin (BIL) levels and reticulocyte (RET) percentage) to calculate a hemolytic index. Results Compared to the control group, patients with priapism exhibited higher ASAT (p = 0.01), LDH (p = 0.03), RET (p = 0.03) levels and hemolytic indices (p = 0.02). Higher RBC aggregates strength (p = 0.01) and lower RBC deformability (p = 0.005) were observed in patients with priapism compared to controls. After removing the Hydroxycarbamide-treated patients, RBC deformability (p = 0.01) and RBC aggregate strength (p = 0.03) were still different between the two groups, and patients with priapism exhibited significantly higher hemolytic indices (p = 0.01) than controls. Conclusion Our results confirm that priapism in SCA is associated with higher hemolytic rates and show for the first time that this complication is also associated with higher RBC aggregate strength and lower RBC deformability.
Philippe Connes - One of the best experts on this subject based on the ideXlab platform.
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decrease of externalized phosphatidylserine density on red blood cell derived microparticles in sca patients treated with Hydroxycarbamide
British Journal of Haematology, 2018Co-Authors: Yohann Garnier, Nathalie Lemonne, Philippe Connes, Severine Ferdinand, Marie Garnier, Maryse Etiennejulan, Marc RomanaAbstract:Hydroxycarbamide (HC) treatment has been shown to improve the clinical course of patients with sickle cell anaemia (SCA), a haemoglobinopathy resulting from a single base substitution in the beta-globin gene (HBB). SCA is characterized by chronic haemolytic anaemia and recurrent vascular occlusions leading to multisystemic complications. Several beneficial biological effects of HC have been documented (Halsey et al, 2003) but its impact on the concentration of circulating microparticles (MPs), a subtype of extracellular vesicles released from cytoplasmic membrane of activated or apoptotic cells and detected at high levels in sickle plasma, remains controversial (Hebbel et al, 2016). The aim of the present study was to compare the MP pattern in a group of SCA patients treated by HC and followed for 2 years.
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men with sickle cell anemia and priapism exhibit increased hemolytic rate decreased red blood cell deformability and increased red blood cell aggregate strength
PLOS ONE, 2016Co-Authors: Nathalie Lemonne, Kizzyclara Cita, L Brureau, Marie Billaud, Philippe Connes, Severine Ferdinand, Benoit Tressieres, Vanessa TarerAbstract:Objectives To investigate the association between priapism in men with sickle cell anemia (SCA) and hemorheological and hemolytical parameters. Materials and Methods Fifty-eight men with SCA (median age: 38 years) were included; 28 who had experienced priapism at least once during their life (priapism group) and 30 who never experienced this complication (control group). Twenty-two patients were treated with Hydroxycarbamide, 11 in each group. All patients were at steady state at the time of inclusion. Hematological and biochemical parameters were obtained through routine procedures. The Laser-assisted Optical Rotational Cell Analyzer was used to measure red blood cell (RBC) deformability at 30 Pa (ektacytometry) and RBC aggregation properties (laser backscatter versus time). Blood viscosity was measured at a shear rate of 225 s-1 using a cone/plate viscometer. A principal component analysis was performed on 4 hemolytic markers (i.e., lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), total bilirubin (BIL) levels and reticulocyte (RET) percentage) to calculate a hemolytic index. Results Compared to the control group, patients with priapism exhibited higher ASAT (p = 0.01), LDH (p = 0.03), RET (p = 0.03) levels and hemolytic indices (p = 0.02). Higher RBC aggregates strength (p = 0.01) and lower RBC deformability (p = 0.005) were observed in patients with priapism compared to controls. After removing the Hydroxycarbamide-treated patients, RBC deformability (p = 0.01) and RBC aggregate strength (p = 0.03) were still different between the two groups, and patients with priapism exhibited significantly higher hemolytic indices (p = 0.01) than controls. Conclusion Our results confirm that priapism in SCA is associated with higher hemolytic rates and show for the first time that this complication is also associated with higher RBC aggregate strength and lower RBC deformability.
