BackgroundOsteonecrosis of the femoral head is a frequent complication in adult patients with sickle cell disease. However, little is known about the natural history of asymptomatic ...lesions.MethodsOne hundred and twenty-one patients (121 hips) with sickle cell disease and asymptomatic osteonecrosis of the femoral head that was contralateral to a hip with symptomatic osteonecrosis were identified with magnetic resonance imaging between 1985 and 1995. The lesions were graded with use of the Steinberg classification system. The patients were followed with annual plain radiographs. The mean duration of follow-up was fourteen years.ResultsAt the time of the initial evaluation, fifty-six hips were classified as Steinberg stage 0, forty-two hips were classified as Steinberg stage I, and twenty-three hips were classified as Steinberg stage II. At the time of the most recent follow-up, pain had developed in 110 previously asymptomatic hips (91%) and collapse had occurred in ninety-three hips (77%). Symptoms always preceded collapse. Of the fifty-six hips that were classified as Steinberg stage 0 at the time of the initial evaluation, forty-seven (84%) had symptomatic osteonecrosis and thirty-four (61%) had collapse at the time of the most recent follow-up. Of the forty-two asymptomatic stage-I hips, forty (95%) became symptomatic within three years and thirty-six (86%) had collapse of the femoral head. Of the twenty-three asymptomatic stage-II hips, all became symptomatic within two years and all collapsed; the mean interval between the onset of pain and collapse was eleven months. At the time of the final follow-up, ninety-one hips (75%) had intractable pain and required surgery.ConclusionsUntreated asymptomatic osteonecrosis of the femoral head in patients with sickle cell disease has a high likelihood of progression to pain and collapse. Because of the high prevalence of complications after total hip arthroplasty in patients with this disease, consideration should be given to early surgical intervention with other procedures in an attempt to retard progression of the disease.Level of EvidencePrognostic Level II. See Instructions to Authors for a complete description of levels of evidence.
Background
Delayed haemolytic transfusion reaction (DHTR) is mainly caused by an immune response to transfused red blood cells (RBCs). Immunized patients have a high risk of producing antibodies in ...response to further transfusion. Controlling the immune response to RBCs is therefore a major goal in sickle cell disease (SCD).
Study design
We report an observational study of eight alloimmunized SCD patients with history of severe DHTR who were treated with rituximab before a new transfusion to prevent further immunization and DHTR.
Results
Five patients showed a good clinical outcome following transfusion preceded by preemptive treatment with rituximab. The remaining patients presented mild DHTR. In all patients, the results of post‐transfusion screening tests were identical to those of pretransfusion tests; no newly formed antibodies were detected.
Conclusion
These cases suggest that rituximab prevents at least occurrence of newly formed antibodies in high responders and minimizes the risk of severe DHTR. This study confirms that DHTR is complex in SCD and does not rely only on the classical antigens/antibodies conflict. Considering potentially serious adverse effect of rituximab, this treatment should be considered cautiously, and only when transfusion is absolutely necessary in patients with history of severe DHTR linked to immunization.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
To evaluate the effects of a prophylactic transfusion program (TP) on obstetric and perinatal outcomes in pregnant women with sickle cell disease (SCD).
This retrospective cohort study included all ...singleton pregnancies among women with SCD in a French university tertiary care center between 1 January 2004 and 31 December 2017. The TP group included patients selected according to the French guidelines who received regular red blood cell transfusions during pregnancy until delivery. The factors associated with TP indication year of birth, SCD genotype, history of acute chest syndrome and delayed hemolysis transfusion reaction (DHTR) risk score were taken into account in a propensity score. A composite obstetric adverse outcome was defined associating birth before 34 gestational weeks and/or pre-eclampsia and/or small for gestational age and/or abruption and/or stillbirth and/or maternal death and/or neonatal death.
In total, 246 pregnancies in 173 patients were analyzed. Twenty-two pregnancies with a history of DHTR were excluded. A higher frequency of TP was found before 2013 119/148 (80.4%) vs 38/76 (50%); p < 0.001. Rates of preterm birth before 34 gestational weeks (5.6% vs 19.7%; p = 0.001), vaso-occlusive crisis (36.5% vs. 61.8%; p < 0.001), and acute chest syndrome (6.1% vs. 14.5%; p = 0.04) during pregnancy were decreased significantly in the TP group. Among the groups with and without composite obstetric adverse outcomes, the frequency of TP was 52.6% and 74.7%, respectively odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09–1.02. The multivariate analysis shows that the TP was associated with a significant reduction in the risk of composite obstetric adverse outcomes (OR 0.28, 95% CI 0.08–0.97; p = 0.04).
A red blood cell TP may have an independent protective effect on maternal and perinatal adverse outcomes during pregnancy in women with SCD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Objective To describe pregnancy outcomes for pregnant women with sickle cell disease (SCD) receiving prophylactic transfusions. Study design This retrospective case–control study compared ...pregnancy outcomes among women with SCD receiving prophylactic transfusions and women without any hemoglobinopathy, matched for ethnicity, parity, age and hospital. Results The study included two groups of pregnancies: 128 in women with SCD (95 with SS phenotype and 33 with SC) and 128 in women with AA phenotype. No woman died. Two perinatal deaths (2.1%) and five alloimmunizations (5.3%) occurred, all in the SS group. Compared with the control group, HbSS disease was more often associated with pre-eclampsia (9.4% versus 2.3%, p = .03), preterm delivery (15.8% versus 6.2%, p = .01), birth weight <10th percentile (13.7% versus 3.9%, p = .008) and caesarean delivery (73.6% versus 26.4%, p < .01). Conclusion Despite prophylactic blood transfusions, SCD remains a severe complicating factor in pregnancy. The policy of systematic transfusions should be analyzed in a sufficiently large randomized trial.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose
Previous clinical trials suggested that inhaled nitric oxide (iNO) could have beneficial effects in sickle cell disease (SCD) patients with acute chest syndrome (ACS).
Methods
To determine ...whether iNO reduces treatment failure rate in adult patients with ACS, we conducted a prospective, double-blind, randomized, placebo-controlled clinical trial. iNO (80 ppm,
N
= 50) gas or inhaled nitrogen placebo (
N
= 50) was delivered for 3 days. The primary end point was the number of patients with treatment failure at day 3, defined as any one of the following: (1) death from any cause, (2) need for endotracheal intubation, (3) decrease of PaO
2
/FiO
2
≥ 15 mmHg between days 1 and 3, (4) augmented therapy defined as new transfusion or phlebotomy.
Results
The two groups did not differ in age, gender, genotype, or baseline characteristics and biological parameters. iNO was well tolerated, although a transient decrease in nitric oxide concentration was mandated in one patient. There was no significant difference in the primary end point between the iNO and placebo groups 23 (46 %) and 29 (58 %); odds ratio (OR), 0.8; 95 % CI, 0.54–1.16;
p
= 0.23. A post hoc analysis of the 45 patients with hypoxemia showed that those in the iNO group were less likely to experience treatment failure at day 3 7 (33.3 %) vs 18 (72 %); OR = 0.19; 95 % CI, 0.06–0.68;
p
= 0.009.
Conclusions
iNO did not reduce the rate of treatment failure in adult SCD patients with mild to moderate ACS. Future trials should target more severely ill ACS patients with hypoxemia.
Clinical trial registration
NCT00748423.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
1 Etablissement Français du Sang, Ile de France, Hôpital Henri Mondor, Créteil;
2 Centre de Référence des Cytopénies Auto-Immunes, Hôpital Henri Mondor, Créteil;
3 Service des Maladies Génétiques du ...Globule Rouge, Hôpital Henri Mondor Créteil;
4 Service de Médecine Interne, Hôpital Henri Mondor, Créteil;
5 Laboratoire dImmunologie, Hôpital Henri Mondor, Créteil;
6 Université de Poitiers, EA 3806, CHU de Poitiers
Correspondence: France Noizat-Pirenne, MD, PhD, Etablissement Français du Sang dIle de France, 51 Avenue du Maréchal de Lattre de Tassigny, 94000, Créteil, France. Tel: 331 56 72 76 37; Fax: 331 56 72 76 01, E-mail: france.noizat-pirenne{at}efs.sante.fr
Delayed hemolytic transfusion reaction (DHTR), a life-threatening transfusion complication in sickle cell disease (SCD), is characterized by a marked hemoglobin drop with destruction of both transfused and autologous red blood cells (RBCs) and exacerbation of SCD symptoms. One mechanism of RBCs destruction is auto-antibody production secondary to transfusion. As rituximab specifically targets circulating B cells, we thought that it could be beneficial in preventing this immune-mediated transfusion complication. We report the case of a SCD patient who previously experienced DHTR with auto-antibodies and who needed a new transfusion. DHTR recurrence was successfully prevented by rituximab administration prior transfusion, supporting the safe use of rituximab to prevent DHTR in SCD patients as a second line approach when other measures failed.
Key words: Sickle cell disease, rituximab, transfusion, auto-antibodies.
Summary
Background
Leg ulcers (LUs) are a chronic and severe complication of sickle cell disease (SCD). A prospective study in patients with SCD to identify factors associated with complete healing ...and recurrence of LUs is lacking.
Objectives
To determine clinical and biological factors associated with SCD‐LU complete healing and recurrence.
Methods
This prospective, observational cohort study was conducted at two adult SCD referral‐centre sites (2009–2015) and included 98 consecutive patients with at least one LU lasting ≥ 2 weeks. The primary end points compared patients with healed vs. nonhealed LUs at week 24, and patients with vs. without recurrence during follow‐up.
Results
The median (interquartile range) LU area, duration and follow‐up were, respectively, 6·2 cm2 (3–12·8), 9 weeks (4–26) and 65·8 weeks (23·8–122·1). At week 24, LUs were healed in 47% of patients, while 49% of LUs recurred. Univariate analyses identified inclusion LU area < 8 cm2 (82% vs. 35%; P < 0·001), inclusion LU duration < 9 weeks (65% vs. 35%; P = 0·0013) and high median fetal haemoglobin level (P = 0·008) as being significantly associated with complete healing at week 24, and low lactate dehydrogenase level (P = 0·038) as being associated with recurrence. Multivariate analyses retained LU area < 8 cm2 (odds ratio 6·73, 95% confidence interval 2·35–19. 31; P < 0·001) and < 9 weeks’ duration (OR 3·19, 95% confidence interval 1·16–8·76; P = 0·024) as being independently associated with healing at week 24. Factors independently associated with recurrence could not be identified.
Conclusions
SCD‐LU complete healing is independently associated with the clinical characteristics of LUs rather than the clinical or biological characteristics of SCD.
What's already known about this topic?
Factors predictive of sickle cell disease (SCD)‐related leg‐ulcer (LU) healing are not known, although their identification would seem to be essential for therapeutic decisions and clinical research.
What does this study add?
At week 24, LUs were completely healed in 47% of the patients, with 15 weeks being the median time to healing.
Healing prognosis was independently linked to LU area < 8 cm2 and duration < 9 weeks, but not to SCD characteristics.
Respond to this article
Linked Comment: Aractingi. Br J Dermatol 2017; 177:15–16
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Objective To describe maternal mortality among women with sickle-cell disease in France. Study design Data from the national confidential enquiry into maternal deaths and from reference ...centres for sickle-cell disease were examined to identify women with this disease who died in France during 1996–2009. The maternal mortality ratio among women with sickle-cell disease was estimated and compared with the ratio in the general population. Characteristics of these women and their pregnancies and circumstances of their deaths were examined in detail. Results Fifteen maternal deaths occurred among an estimated 3300 live births to women with sickle-cell disease, for a maternal mortality ratio of 454 per 100 000 live births (95% CI 254; 750), versus 9.4/100 000 in the general population. Ten women were homozygous (SS) for sickle-cell disease, and five were composite heterozygotes. The episode leading to death appeared in the antepartum period for seven women (47%). Two women died of septic shock during pregnancy, one at 6 weeks, the other at 24 weeks. The other 13 women (87%) died postpartum. Thirteen deaths were directly attributable to sickle-cell disease. The other two maternal deaths, both considered direct obstetric causes, were due to amniotic fluid embolism and septic shock after post-amniocentesis chorioamnionitis. The expert committee on maternal mortality judged seven of these 15 deaths (47%) to be avoidable. Conclusion Sickle-cell disease is responsible for a major excess risk of maternal death in France, due mainly to direct complications of the disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Objectives To evaluate the concept that iron depletion (ID) induced by bloodletting and followed by recombinant human erythropoietin (rhEPO) administration could be a therapeutic strategy in ...progressive multiple sclerosis (PMS) and that it could be assessed by neurophysiological measurements. Patients and methods In four patients with PMS, bloodletting was performed until ID was induced, and then rhEPO was administered (300 UI/kg/week). The changes induced by the treatment were assessed by clinical scores, biological tests, and neurophysiological study of cortical excitability using transcranial magnetic stimulation techniques. Results The treatment was well tolerated except for muscle cramps and one popliteal vein thrombosis in a patient confined to chair. ID was obtained within 28 weeks and was associated with endogenous production of EPO. No bloodletting was further required during a six-month period after introduction of rhEPO. At the end of the follow-up (up to one year), fatigue and walking capacities tended to improve in two patients. Neurophysiological changes were characterized by an increased cortical excitability, including a decrease of motor thresholds and an enhancement of intracortical facilitation and cerebellothalamocortical inhibition. Conclusions The combined ID-rhEPO therapy could authorize a prolonged administration of rhEPO in PMS patients, able to modify cortical excitability of the glutamatergic and gabaergic circuits. These preliminary data are encouraging to design a larger, controlled therapeutical trial to assess the value of such a strategy to improve functional symptoms in PMS patients, and maybe to prevent axonal degeneration. Neurophysiological measurements based on cortical excitability studies could provide sensitive parameters to evaluate treatment-induced changes in this context.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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