Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients

Pallis, Flávia Rubia; Conran, Nicola; Fertrin, Kleber Yotsumoto; Saad, Sara T. Olalla; Costa, Fernando Ferreira; Franco‐Penteado, Carla F.

doi:10.1111/bjh.12628

Cited by 15 publications

(19 citation statements)

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“…HU therapy was also observed to significantly reduce HbS levels, which is consistent with results by Shome et al who also found an association between HU use and significantly reduced HbS levels in SCA patients [ 38 ]. We also detected significantly higher HbF levels in SCA-HU + patients compared to controls, which confirms results in previous studies regarding the efficacy of HU in inducing HbF synthesis [ 3 , 34 , 39 , 40 ].…”

Section: Discussionsupporting

confidence: 90%

“…SCA-HU − patients were used as the control group. HU therapy was found to be associated with higher values of MCH and MCV, similar to what was shown by Pallis et al [ 34 ]. On the contrary, Laurentino et al did not observe significant differences in MCH and MCV levels among SCA-HU + and SCA-HU − patients [ 3 ].…”

Section: Discussionsupporting

confidence: 88%

“…The present study found an association between HU therapy and significant reductions in leukocyte, eosinophil, and monocyte counts, confirming its cytoreductive effect. This effect can improve the inflammatory profile generally observed in SCA patients, which is mainly due to increases in eosinophil and monocyte counts [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

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Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

et al. 2018

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This study investigated associations between SNPs in genes encoding metabolizing drug enzymes and laboratory parameters in sickle cell anemia patients under hydroxyurea (SCA-HU+). We evaluated hematologic and biochemical parameters by electronic methods and SNPs by PCR-RFLP and multiplex PCR in 35 SCA-HU+ patients and 67 SCA-HU− patients. The HbS, total cholesterol, lactate dehydrogenase, aspartate aminotransferase, total bilirubin and fractions levels, and leukocyte, eosinophil, monocyte, and erythroblast counts were reduced in SCA-HU+ patients (p < 0.05). Moreover, they presented higher HbF, C-reactive protein, and ferritin levels and elevated MCH and MCV values (p < 0.05). Genotype frequencies of variants GA + AA of MPO −463G>A and c1c2 + c2c2 of CYP2E1 −1293G>C/−1053C>T were higher in SCA-HU+ patients (p < 0.05). Independent associations were found between the variant A allele and lower total cholesterol, between c2 allele and low alpha-1 antitrypsin and between the null GSTT1 variant and high indirect and total bilirubin in SCA-HU+ patients. In SCA-HU− patients, independent associations were found between the variant A allele and high uric acid and between c2 allele and high urea. Our results suggest that SNPs MPO −463G>A, CYP2E1 −1293G>C/−1053C>T, and GSTT1 can be associated with alterations in lipid, inflammatory, renal, hemolytic, and hepatic profiles. However, further studies are needed to elucidate these associations.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 88%

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Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

et al. 2018

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“…Several other authors are skeptical of a link between hydroxyurea and ulcers in SCD patients based on their own data [73][74][75], and many practical considerations preclude the randomized prospective trials needed for definitive evidence regarding this issue. There are many potential benefits of hydroxyurea use in SCD patients with ulcers: decrease in leukocyte count, decrease in inflammatory cytokines [76,77], increase in hemoglobin, increase in HbF, decrease in hemolysis, increase in oxygen carrying capacity, improved RBC rheology [78], and NO donor properties [79,80]. Our approach to the use of hydroxyurea in SCD is to aim for maximal fetal hemoglobin response, continue therapy unless there strong suspicion that hydroxyurea contributed to ulcer formation, and then consider switching to chronic transfusion therapy.…”

Section: Systemic and Local Therapiesmentioning

confidence: 99%

Critical Reviews: How we treat sickle cell patients with leg ulcers

Minniti

Kato

2015

American J Hematol

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The past five decades have seen an improvement in the mortality and morbidity of sickle cell disease (SCD) because of prophylaxis against infectious complications, improved and expanded red cell transfusions, implementation of hydroxyurea therapy, and advances in supportive care. Now that the majority of patients in the western hemisphere reaches adulthood, end organ diseases are frequent, which include vasculopathic complications such as chronic leg ulcers. The management of patients with leg ulcers requires the hematologist to lead a team of health care professionals, and investigates the presence of associated, but potentially still occult signs of vasculopathy, such as pulmonary hypertension, renal disease, priapism and retinopathy. These complications may be asynchronous, and long term careful screening is indicated, in order to ensure early diagnosis and intervention. It is crucial to address both the immediate consequences of pain, infection and disability, and long term effects on quality of life, employment and stigma associated with chronic ulceration. Recent insights into their pathophysiology may have practical implications. We propose a holistic approach to the management of patients' physical and emotional problems and mechanisms of ulcers formation and delayed healing. An overview of topical and systemic therapies for chronic ulcers is given, with the understanding that wound care therapy is best left to the wound specialists, medical and surgical, with whom the hematologist must keep an open line of communication. In the absence of evidence-based guidelines, our opinion is based on both a critical review of the literature and our personal clinical and research experience. Am. J. Hematol. 91:22-30, 2016. V C 2015 Wiley Periodicals, Inc. Clinical CasesCase 1. A 49 year old African American woman with sickle cell anemia, bilateral hip replacements for avascular necrosis of the femoral head, pulmonary arterial hypertension documented by pulmonary artery catheterization, and history of laser treatment and vitrectomy for proliferative retinopathy and vitreous hemorrhage, presented with a very painful ulcer at the right malleolus. She has had three previous ulcers, on both legs, the first at age 32 years, attributed to excessive standing at her job, no trauma, which had responded to topical care and healed within few months of presentation. At that time she was not taking hydroxyurea, but has been taking it now for longer than 10 years with good fetal hemoglobin response: 17%. This current ulcer developed while she was experiencing high personal stress but no physical trauma. She rarely experiences vaso-occlusive pain crisis and has very infrequent hospitalizations. She was referred to the wound care service and after 7 months of unfruitful therapies, including surgical debridement, MIST ultrasound therapy, antibiotics, and compressions, she was started on monthly transfusions and her ulcer healed 5 months later. She has had consistently elevated serum lactate dehydrogenase (LDH) (>600 IU/L), serum dire...

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“…HU therapy is associated with lowering of the absolute count, adhesion and the degranulation of eosinophils (185). Interestingly, HU does not impact eosinophil expression of eotaxin-2, 3 and RANTES, or the production of ROS suggesting that the major influence of the drug on this cell is adhesion.…”

Section: Hydroxyureamentioning

confidence: 99%

Inflammatory targets of therapy in sickle cell disease

Owusu-Ansah

Ihunnah

Walker

et al. 2016

Translational Research

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Sickle cell disease (SCD) is a monogenic globin disorder characterized by the production of a structurally abnormal hemoglobin (Hb) variant Hb S, which causes severe hemolytic anemia, episodic painful vaso-occlusion and ultimately end-organ damage. The primary disease pathophysiology is intracellular Hb S polymerization and consequent sickling of erythrocytes. It has become evident over several decades that a more complex disease process contributes to the myriad of clinical complications seen in SCD patients with inflammation playing a central role. Drugs targeting specific inflammatory pathways therefore offer an attractive therapeutic strategy to ameliorate many of the clinical events in SCD. In addition they are useful tools to dissecting the molecular and cellular mechanisms that promote individual clinical events, and for developing improved therapeutics to address more challenging clinical dilemmas such as refractoriness to opioids or hyperalgesia. Here, we discuss the prospect of targeting multiple inflammatory pathways implicated in the pathogenesis of SCD with a focus on new therapeutics, striving to link the actions of the anti-inflammatory agents to a defined pathobiology, and specific clinical manifestations of SCD. We also review the anti-inflammatory attributes and the cognate inflammatory targets of hydroxyurea, the only FDA approved drug for SCD.

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Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients

Cited by 15 publications

References 61 publications

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

Critical Reviews: How we treat sickle cell patients with leg ulcers

Inflammatory targets of therapy in sickle cell disease

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