ABSTRACT
INTRODUCTION: Periarteritis nodosa (PAN) is a vasculitis affecting medium-vessel and may be associated with myelodysplastic syndrome. This association needs a simultaneous treatment of the vascular and the hematological disease. However limited data are available on the benefit of hematological treatment, and in particular allogeneic stem cell transplantation, in this situation. CASE REPORT: A 32-year-old patient with refractory periarteritis nodosa and simultaneous myelodysplastic syndrome, was treated with chemotherapy followed by hematopoietic stem cell allograft. The symptoms relating to PAN improved, allowing to decrease the dose of prednisone down to 5mg/d. However, a hematological relapse occurred two months later leading to the patient's death. CONCLUSION: Hematopoietic stem cell allograft may represent a therapeutic option in the management of severe or refractory autoimmune diseases when the hematological indication is retained.
Subject(s)
Azacitidine , Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Polyarteritis Nodosa , Remission Induction , Humans , Myelodysplastic Syndromes/therapy , Myelodysplastic Syndromes/complications , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Adult , Polyarteritis Nodosa/diagnosis , Azacitidine/therapeutic use , Male , Transplantation, Homologous , Drug Resistance , Fatal OutcomeSubject(s)
Anemia, Sickle Cell , Disease Progression , Humans , Anemia, Sickle Cell/complications , Adolescent , Male , Female , Young Adult , Infant, Newborn , Adult , Cohort Studies , Risk Factors , Chronic DiseaseABSTRACT
The urine concentration impairment responsible for hyposthenuria in sickle cell nephropathy is currently thought to be a consequence of renal medulla lesions, which lead to nephrogenic diabetes insipidus. The objective of the present study was to investigate the mechanism of hyposthenuria in patients with sickle cell anemia. We performed an observational study of patients with homozygous SS sickle cell anemia and data available on the fasting plasma antidiuretic hormone (ADH) concentration. A total of 55 patients were analyzed. The fasting plasma ADH values ranged from 1.2 to 15.4 pg/mL, and 82% of the patients had elevated ADH values and low fasting urine osmolality (<505 mosmol/kgH2O). Plasma ADH was positively associated with plasma tonicity and natremia (P < 0.001). None of the patients experienced polyuria and fasting free water clearance was negative in all cases, thus, ruling out nephrogenic diabetes insipidus. The tertile groups did not differ with regard to fasting urine osmolality, plasma renin level, mGFR, or several hemolysis biomarkers. The negative fasting free water clearance in all cases and the strong association between 24-h osmolal clearance and 24-h diuresis favors the diagnosis of osmotic diuresis due to an impaired medullary gradient, rather than lesions to collecting tubule.NEW & NOTEWORTHY The urine concentration impairment in sickle cell anemia is an osmotic diuresis related to an impaired renal medullary gradient leading to an ADH plateau effect. The fasting plasma ADH was high in the context of a basic state of close-to-maximal urine concentration probably driven by short nephrons maintaining a cortex-outer medullary gradient (about 400 milliosmoles). The patients had a low daily osmoles intake without evidence of thirst dysregulation so no one experienced polyuria.
Subject(s)
Anemia, Sickle Cell , Diabetes Insipidus, Nephrogenic , Diabetes Insipidus , Diabetes Mellitus , Humans , Polyuria , Diuresis , Osmolar Concentration , Antidiuretic Agents , WaterABSTRACT
Not available.
ABSTRACT
DISEASE MODIFYING TREATMENTS FOR SICKLE CELL DISEASE. The two most widely available disease-modifying therapies, hydroxycarbamide and long-term redblood cells transfusions, are mostly introduced after the occurrence of complications. Hydroxycarbamide is mainly prescribed for the prevention of recurrent vaso-occlusive events (vaso-occlusive crisis and acute chest syndrome). Hydroxycarbamide efficacy and myelosuppressive effects are dependent on dose (usually 15 to 35 mg/kg/d) and patient compliance. Long-term transfusions are used for cerebral and end-organ damage protection or in second line after hydroxycarbamide for the prevention of recurrent vaso-occlusive events. The risks of each treatment should be weighed against the long-term risks and morbidity of the disease.
TRAITEMENT DE FOND ET SUIVI DE LA DRÉPANOCYTOSE. Le traitement de fond de la drépanocytose regroupe le traitement médicamenteux par hydroxycarbamide (HC), et les transfusions régulières de globules rouges, dits programmes transfusionnels, traitements atténuateurs de la maladie pour lesquels on dispose de données d'efficacité et de tolérance solides dans les formes génétiques sévères homozygotes SS et Sß°. Le traitement par HC, longtemps prescrit après la récurrence des complications, notamment vaso-occlusives (crises vaso-occlusives ou syndromes thoraciques aigus), est actuellement proposé plus précocement après la survenue des premières complications, voire en prévention des complications dès la petite enfance. L'efficacité du traitement par HC est étroitement liée à la dose (posologies habituelles utilisées entre 15 et 35 mg/kg/j) et à l'observance (une prise orale quotidienne). La posologie doit être adaptée à la tolérance hématologique (myélosuppression dose-dépendante). Le programme transfusionnel régulier reste indiqué, en première intention pour prévenir les complications cérébrales de la maladie, et en seconde ligne après l'HC pour prévenir la récurrence des complications vasoocclusives. La balance bénéfices-risques de chaque traitement doit être évaluée en regard de la morbidité de la maladie drépanocytaire.
Subject(s)
Anemia, Sickle Cell , Humans , Hydroxyurea , Patient ComplianceSubject(s)
Anemia, Sickle Cell , Cardiomyopathies , Heart Failure , Humans , Heart Failure/complications , Myocardium , FibrosisABSTRACT
INTRODUCTION: The effect of coronavirus disease (COVID-19) on pregnancy outcome in women with sickle cell disease (SCD) is unknown. OBJECTIVES: To analyze the severity of the SARS-CoV-2 infection in pregnant women with SCD and its impact on pregnancy. METHODS: This retrospective cohort study included SCD pregnant women tested positive for COVID-19 between March 2020 - February 2021. The primary endpoint was the severity of the COVID-19 infection. Secondary endpoints were pregnancy complications and fetal outcomes. RESULTS: During the study period among 82 pregnant women with SCD, 8 have presented symptoms suggestive of COVID-19 and were tested positive. A common mild clinical presentation was observed in 6 women (75%), one woman was asymptomatic and one required oxygen. The latter was admitted to the Intensive Care Unit and a cesarean section was performed in the context of an ongoing vaso-occlusive crisis and acute chest syndrome together with incidental preeclampsia. Labor was induced in another patient who developed a vaso-occlusive crisis after COVID-19 remission. Fetal outcomes were good with an average Apgar score of 10 and normal umbilical blood pH at birth. Two newborns were small-for-gestational-age as expected on the ultrasound follow-up before occurrence of COVID-19. CONCLUSION: COVID-19 infection in our population of pregnant women with SCD had typical presentation and rarely triggered a sickle cell crisis or other complications. Fetal outcomes were good and did not seem to be directly influenced by the SARS-CoV-2 virus. Further studies are required to confirm these observations as compared to the population of women with SCD without COVID-19 infection.
Subject(s)
Anemia, Sickle Cell , COVID-19 , Pregnancy Complications, Infectious , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/epidemiology , Cesarean Section , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Outcome/epidemiology , Pregnant Women , Retrospective Studies , SARS-CoV-2ABSTRACT
Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.
Subject(s)
Occupational Exposure , Sarcoidosis , Adult , Child , Dust , Environmental Exposure/adverse effects , Humans , Occupational Exposure/adverse effects , Occupations , TalcABSTRACT
Because of chronic anemia, hypogonadotropic hypogonadism, and iron chelation, pregnancy in homozygous and heterozygous compound beta-thalassemia patients stays a challenge. Pregnancies of transfused beta-thalassemia women registered in the French National Registry, conducted between 1995 and 2015, are described. These pregnancies were compared with pregnancies in healthy women and to data previously published in the literature. Fifty-six pregnancies of 37 women were studied. There were 5 twin pregnancies. Assisted reproductive technologies (ART) were used in 9 pregnancies. Median term at delivery was 39 amenorrhea weeks, and median weight at birth was 2780 g. Cesarean section was performed in 53.6% of the pregnancies. There were 6 thromboembolic events, 6 serious infections, 6 pregnancy-induced hypertensions (PIH), 6 intrauterine growth retardations (IUGR), 5 severe hemorrhages, 4 gestational diabetes, 3 alloimmunizations, 2 heart diseases, and 1 pre-eclampsia. There were 5 infections and 4 osteoporosis in the first year of post-partum. ART and cesarean sections were more often used in the beta-thalassemia group, compared to control subjects. Thromboembolic events, PIH, hemorrhage at delivery, and IUGR were more frequent in the beta-thalassemia group. Time to delivery was not different, but infant weight at birth was significantly smaller in the beta-thalassemia group. In the post-partum period, global maternal complications were more frequent in the beta-thalassemia group. Pregnancy in transfused beta-thalassemia women is safe with rare obstetrical and fetal complications. Cesarean section remains often chosen, and infant weight at birth remains smaller than that in the general population, despite delivery at full term.
Subject(s)
Pregnancy Complications, Hematologic/therapy , beta-Thalassemia/therapy , Adult , Cesarean Section , Cross-Sectional Studies , Erythrocyte Transfusion , Female , Fetal Growth Retardation/etiology , France/epidemiology , Humans , Infant, Newborn , Pregnancy , Pregnancy Complications, Hematologic/epidemiology , Pregnancy Outcome , Retrospective Studies , beta-Thalassemia/complications , beta-Thalassemia/epidemiologyABSTRACT
BACKGROUND: The underlying mechanisms of exercise intolerance in sickle cell anaemia (SCA) patients are complex and not yet completely understood. While latent heart failure at rest could be unmasked upon exercise, most previous studies assessed cardiac function at rest. We aimed to investigate exercise cardiovascular reserve as a potential contributor to exercise intolerance in adult SCA patients. METHODS: In this observational prospective study, we compared prospectively 60 SCA patients (median age 31 years, 60% women) to 20 matched controls. All subjects underwent symptom-limited combined exercise echocardiography and oxygen uptake (VO2 ) measurements. Differences between arterial and venous oxygen content (C(a-v)O2 ) were calculated. Cardiac reserve was defined as the absolute change in cardiac index (Ci) from baseline to peak exercise. RESULTS: Compared to controls, SCA patients demonstrated severe exercise intolerance (median peakVO2 , 34.3 vs. 19.7 ml/min/kg, respectively, p < .0001). SCA patients displayed heterogeneously increased Ci from rest to peak exercise (median +5.8, range 2.6 to 10.6 L/min/m²) which correlated with peakVO2 (r = 0.71, p < .0001). In contrast, the C(a-v)O2 exercise reserve was homogenously reduced and did not correlate with peakVO2 (r = 0.18, p = .16). While haemoglobin level and C(a-v)O2 were similar in SCA subgroups, SCA patients in the lower VO2 tertile had chronotropic incompetence and left ventricular diastolic dysfunction (left atrial peak longitudinal strain was reduced, and both E/e' ratio and left atrial volume index were increased) and were characterized by a reduced cardiac reserve, +5.0[4.2-5.5] compared to +6.7[5.5-7.8] L/min/m² for the rest of the patient cohort, p < .0001. CONCLUSIONS: Altered cardiac reserve due to chronotropic incompetence and left ventricular diastolic dysfunction seems to be an important determinant of exercise intolerance in adult SCA patients.
Subject(s)
Anemia, Sickle Cell/physiopathology , Exercise Tolerance , Heart/physiopathology , Adult , Anemia, Sickle Cell/complications , Female , Humans , Male , Prospective Studies , Ventricular Dysfunction, Left/complications , Young AdultABSTRACT
Chronic interstitial lung abnormalities have been described in sickle cell disease (SCD) and attributed to repetitive episode of acute chest syndrome. We report a series of 22 cases of diffuse cystic lung disease in SCD with a case-control study to hunt for mechanism. On pathological analysis of a surgical lung biopsy of the index case, the bronchioles had the appearance of constrictive bronchiolitis. Pulmonary function test results revealed lower forced expiratory flow from 25% to 75% of vital capacity in cases versus controls. These findings suggest a bronchiolar mechanism that was not associated with more acute chest syndrome.
Subject(s)
Anemia, Sickle Cell , Lung Diseases, Interstitial , Anemia, Sickle Cell/complications , Case-Control Studies , Humans , Lung/diagnostic imaging , Vital CapacityABSTRACT
Primary hyperparathyroidism (pHPT) has been reported to have a higher prevalence in sickle cell disease (SCD) patients, including a high rate of recurrence following surgery. However, most patients are asymptomatic at the time of diagnosis, with surprisingly infrequent hypercalciuria, raising the issue of renal calcium handling in SCD patients. We conducted a retrospective study including (1) 64 hypercalcemic pHPT non-SCD patients; (2) 177 SCD patients, divided into two groups of 12 hypercalcemic pHPT and 165 non-pHPT; (3) eight patients with a diagnosis of familial hypocalciuric hypercalcemia (FHH). Demographic and biological parameters at the time of diagnosis were collected and compared between the different groups. Determinants of fasting fractional excretion of calcium (FeCa2+) were also analyzed in non-pHPT SCD patients. Compared to non-SCD pHPT patients, our data show a similar ionized calcium and PTH concentration, with a lower plasmatic calcitriol concentration and a lower daily urinary calcium excretion in pHPT SCD patients (p < 0.0001 in both cases). Fasting FeCa2+ is also surprisingly low in pHPT SCD patients, and thus inadequate to be considered hypercalcemia, recalling the FHH phenotype. FeCa2+ is also low in the non-pHPT SCD control group, and negatively associated with PTH and hemolytic biomarkers such as LDH and low hemoglobin. Our data suggest that the pHPT biochemical phenotype in SCD patients resembles the FHH phenotype, and the fasting FeCa2+ association with chronic hemolysis biomarkers strengthens the view of a potential pharmacological link between hemolytic by-products and calcium reabsorption, potentially through a decreased calcium-sensing receptor (CaSR) activity.
ABSTRACT
This study sought to link cardiac phenotypes in homozygous Sickle Cell Disease (SCD) patients with clinical profiles and outcomes using cluster analysis. We analyzed data of 379 patients included in the French Etendard Cohort. A cluster analyses was performed based on echocardiographic variables, and the association between clusters, clinical profiles and outcomes was assessed. Three clusters were identified. Cluster 1 (n = 123) patients had the lowest cardiac output, mild left cardiac cavities remodeling, mild diastolic dysfunction, and higher tricuspid regurgitation velocity (TRV). They were predominantly female and displayed the most altered functional limitation. Cluster 2 (n = 102) patients had the highest cardiac output and the most remodeled cardiac cavities. Diastolic function and TRV were similar to cluster 1. These patients had a higher blood pressure and a severe hemolytic anemia. Cluster 3 (n = 154) patients had mild left cardiac cavities remodeling, normal diastolic function and lowest TRV values. They were younger with the highest hemoglobin value. Right heart catheterization was performed in 94 patients. Cluster 1 (n = 33) included the majority of pre-capillary PH whilst cluster 2 (n = 34) included post-capillary PH. No PH was found in cluster 3 (n = 27). After a follow-up of 11.4 ± 2 years, death occurred in 41 patients (11%). Cluster 2 patients had the worst prognosis with a 19% mortality rate versus 12% in cluster 1 and 5% in cluster 3 (p log-rank = 0.003). Cluster analysis of echocardiography variables identified three hemodynamic and clinical phenotypes among SCD patients, each predicting a different prognosis.
Subject(s)
Anemia, Sickle Cell/physiopathology , Heart/physiopathology , Adult , Anemia, Sickle Cell/diagnosis , Cardiac Output , Cluster Analysis , Echocardiography , Female , Humans , Male , Prognosis , Tricuspid Valve Insufficiency/diagnosis , Tricuspid Valve Insufficiency/physiopathology , Young AdultABSTRACT
Glomerular hyperfiltration alone or associated with albuminuria is a well-known feature of sickle cell associated nephropathy. Though, glomerular hyperfiltration is currently considered to be related to a high renal plasma flow and chronic hemolysis, cardiac output influence on measured glomerular filtration rate (mGFR) have not been investigated so far. Thirty seven homozygous sickle cell patients (SCA) from the RAND study investigated before and under angiotensin converting enzyme inhibitor (ACEI) were included. Both mGFR and cardiac index (CI) were high (> 110 ml/min/1.73 m2 and > 3.5 l/m2 in 81% and 97% of cases) with low systemic vascular resistance (SVR) (< 700 dynes/s/cm-5) in 38% of cases. mGFR association with CI and SVR were significant at baseline (respectively ρ: 0.44, p = 0.008 and ρ: - 0.37, p = 0.02) and under ACEI (p = 0.007 and 0.01 respectively), in accordance with previous data showing that hyperfiltration was linked to an increased glomerular perfusion and a glomerulomegaly rather than increased capillary hydrostatic pressure. Of notice, after adjustment on CI, mGFR remained associated with reticulocyte count and albuminuria under ACEI (p = 0.006 and 0.02 respectively). Our results suggest that hyperfiltration is tightly linked to an increased cardiac output which may account for an increased renal blood flow. Chronic hemolysis could be a relevant factor accounting for hyperfiltration potentially acting on glomerular enlargement which appears as a key factor. Our data suggest that cardiac output assessment is a relevant tool in the routine management and monitoring of SCA nephropathy.
Subject(s)
Anemia, Sickle Cell/blood , Anemia, Sickle Cell/complications , Glomerular Filtration Rate , Hemodynamics , Kidney Diseases/etiology , Kidney Diseases/physiopathology , Kidney Glomerulus/physiopathology , Adult , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Biomarkers , Female , Glomerular Filtration Rate/drug effects , Hemodynamics/drug effects , Humans , Kidney Diseases/diagnosis , Kidney Diseases/drug therapy , Kidney Glomerulus/drug effects , Male , Renin-Angiotensin System/drug effects , Treatment Outcome , Young AdultABSTRACT
The long-term consequences of pre-eclampsia (PrE) for renal function have never been determined in patients with sickle cell disease (SCD). Between 2008 and 2015, we screened 306 pregnancies in women with SCD and identified 40 with PrE (13%). The control group consisted of 65 pregnant SCD patients without PrE. In multivariable analysis, PrE events were associated with an increase of 1 log of lactate dehydrogenase level (adjusted odds ratio, aOR = 3·83, P = 0·05), a decrease of 10 g/l of haemoglobin levels (aOR = 2·48, P = 0·006) and one or more vaso-occlusive crisis during pregnancy (aOR = 16·68, P = 0·002). Estimated glomerular filtration rate (eGFR) was similar in the two groups at steady state but was significantly lower in the PrE group after one year of follow-up and at last follow-up (130 vs 148 ml/min/1·73 m2 , P < 0·001 and 120 vs 130 ml/min/1·73 m2 , P < 0·001, respectively). In multivariable analysis, eGFR had returned to steady-state levels one year after pregnancy in patients without PrE but continued to decrease in patients with PrE (ß = -18·15 ml/min/1·73 m2 , P < 0·001). This decline was more marked at the end of follow-up (ß = -31·15 ml/min, P < 0·001). In conclusion, PrE episodes are associated with a significant risk of subsequent renal function decline in SCD patients.
Subject(s)
Anemia, Sickle Cell/physiopathology , Kidney Diseases/physiopathology , Kidney/physiopathology , Pre-Eclampsia/physiopathology , Adult , Anemia, Sickle Cell/complications , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Kidney Diseases/etiology , PregnancyABSTRACT
Prevalence of renal impairment is increasing with aging in sickle cell anemia (SCA) patients, and is responsible for a high morbidity and mortality. However, sickle cell nephropathy's natural course remains mostly unknown. We conducted a prospective observational cohort study aimed to identify risk factors for CKD stage II in a cohort of SCA patients. Baseline clinical and biological parameters were collected. Renal parameters were updated at each visit. Risk factors were analyzed using the Cox model. Five-hundred and thirty-five SCA patients were included with a median follow-up of 5.33 (IQR:2.10-8.13) years. Median age was 22 (IQR:19-30) years old. Glomerular hyperfiltration was detected in 299 (55.9%) patients, microalbuminuria and macroalbuminuria in 180 (34%) and 67 (12.7%) patients respectively. During follow up, CKD stage II onset was detected in 39 patients (7.3%). Risk factors for CKD stage II after adjustment on baseline eGFR and age were macroalbuminuria HR: 3.89 [95% CI: 1.61;9.43], diastolic blood pressure (DBP) above 70 mm Hg HR: 2.02 [1.02-3.971], LDH (for 100 IU/L increase) HR: 1.28 [1.12;1.48] and tricuspid regurgitation velocity >2.5 m/sec HR: 2.89 [1.20-6.99]. Multivariate analysis also found age as a strong independent risk factor with HR: (per year increase) 1.13 [1.09;1.16] and a 13.3-fold increase above 30 years (p < 0.001). Our results show a high incidence of CKD stage II with aging, with a strong significant risk increase after 30-years-old, and pinpoint baseline DBP, macroalbuminuria and increased LDH as independent risk factors raising the issue of optimal blood pressure targets for SCA patients.
Subject(s)
Anemia, Sickle Cell/complications , Renal Insufficiency, Chronic/etiology , Adult , Age Factors , Albuminuria/diagnosis , Albuminuria/etiology , Albuminuria/physiopathology , Anemia, Sickle Cell/physiopathology , Blood Pressure , Female , Glomerular Filtration Rate , Humans , Incidence , Male , Proportional Hazards Models , Prospective Studies , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Risk Factors , Young AdultABSTRACT
OBJECTIVE: To assess psychosocial risk factors for increased emergency hospital utilization by sickle cell patients. INTRODUCTION: Emergency hospital utilization by sickle cell disease patients is high but heterogeneous between patients and in a given patient over time. Psychosocial factors affect emergency hospital utilization and are a possible target to improve the management of sickle cell disease. INCLUSION CRITERIA: This review will include all original quantitative studies evaluating the impact of psychosocial risk factors on emergency hospital utilization by sickle cell disease patients. There will be no language restriction. METHODS: PubMed, Embase, CINAHL, PubPsych, LiSSa, and Web of Science will be searched using a peer-reviewed search strategy. Study selection and extraction of data will be performed independently by two authors. Discrepancies will be solved by consensus or, if needed, by a third author. The authors will assess study quality, as well as perform a narrative synthesis of included studies, and where possible, meta-analyses with evaluation of heterogeneity and publication bias. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019140435.