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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydroxyurea may be the most promising drug suggested thus far as a treatment for patients with sickle cell anemia, but its safety and efficacy remain unproved, and it probably will not be evaluable for several years. It is not "the answer" for the disease, it seems likely that crises will not be eliminated by treatment, and at this time its use should be reserved for seriously affected adult patients who can participate in a controlled clinical trial. Every hematologist, internist, or pediatrician sees a few patients who are so severely afflicted by sickle cell anemia that their lives seem totally blighted. It is very tempting to consider treating them with hydroxyurea, because the drug is available in any pharmacy, but it is equally important to consider whether the treatment would accomplish any more than treating the physician's own sense of futility, or making the patient feel that "something was being done." If hydroxyurea were as safe as folic acid, treatment for these purposes would be reasonable. It is not, but its use may still be appropriate (although illegal unless used under an Investigational New Drug Agreement, because its use for this purpose is not approved by the FDA). Whether or not it is legal, prescription of hydroxyurea for patients with sickle cell anemia would be ethical or proper only if the potential risks, the variability of the Hb F response, and the lack of proof of clinical efficacy were clearly explained to potential recipients.
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PMID:Hydroxyurea as treatment for sickle cell anemia. 171 11

Sickle cell disease refers to a group of genetic disorders characterised by the predominance of hemoglobin S. This includes sickle cell anemia (SS) sickle hemoglobin C disease (SC), sickle beta thalassemia plus (S beta + Thal), sickle beta thalassemia zero (beta zero Thal), sickle with alpha thalassemia (SS alpha Thal) and rare combinations of sickle hemoglobin with Hb D, Hb O, etc. While pregnancy does carry risk for the woman with sickle cell disease (SCD) and for the fetus, pregnancy can be well tolerated by the major genotypes. Infants born from these pregnancies may tend to be small for gestational age and undergo premature delivery. While complications for both sickle-related events and for pregnancy are seen, data to date state that women are able to complete their pregnancies successfully. Counselling, regular prenatal visits and aggressive treatment of acute events are always indicated. There is no proof that prophylactic transfusion alters the outcome of pregnancy. Transfusion therapy should be reserved for those patients with previous perinatal mortality, pre-eclampsia, acute chest syndrome, new onset neurological event, severe anemia and in preparation for surgical intervention. Thus, blood transfusion will continue to have a role in management of obstetrical and medical indications accompanied by meticulous prenatal care and early detection of complications. In addition, newborn screening should be recommended for the early detection of infants with disease.
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PMID:Sickle cell disease and pregnancy. 856 17

The symptoms and signs of sickle cell disease are exacerbated in times of crisis, characterized by tissue infarction or worsening anaemia. Prompt medical intervention is required in these distressing situations to provide relief and comfort to the patient. Effective analgesia is crucial in treating the painful crisis of sickle cell disease. The haemoglobinopathy may cause hyposthenuria with reduced ability to excrete the sodium load in normal saline. A 5% dextrose solution or 5% dextrose in 25% normal saline is therefore recommended for intravenous hydration. As the leading cause of morbidity and mortality in sickle cell disease, infections call for vigorous antibiotic therapy. Oxygen administration should be reserved for hypoxic patients, and blood transfusion given only when really indicated. Acute chest syndrome and cerebrovascular accidents are life-threatening complications of sickle cell disease whereas priapism can cause important long-term sequelae; all deserve urgent attention. In the long term, comprehensive care is cost-effective in reducing the frequency and adverse effects of sickle cell crisis.
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PMID:The management of crisis in sickle cell disease. 945 21

Five years after the initiation of the first clinical trials of hydroxyurea in pediatric sickle cell anemia patients, there is firm evidence that this drug induces a significant and sustained increase in fetal hemoglobin (HbF) production and decreases the frequency of vasoocclusive crises in the overwhelming majority of cases. The mean dosage associated with clinical benefits is 20 mg/kg/d; the HbF increase is not perfectly correlated with clinical benefits, so that a dosage increase should be considered based on the absence of a clinical improvement after three months. The daily dose should not exceed 40 g/kg. Short- and medium-term safety has been acceptable, with the few episodes of bone marrow toxicity resolving after dose attenuation or temporary drug discontinuation. Many issues remain unsettled, most notably the long-term safety of this cytostatic medication. Current knowledge gaps should be fully disclosed to parents, and hydroxyurea therapy should be reserved for patients with severe pain. Because no randomized placebo-controlled trials are available, the potential role for hydroxyurea as a preventive or curative treatment for other complications of sickle cell disease remains unknown.
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PMID:[Hydroxyurea and other agents stimulating synthesis of fetal hemoglobin]. 1008 80

Children with sickle cell anemia (HbSS) are at high risk for neurologically overt cerebral infarcts associated with stroke and neurologically silent cerebral infarcts correlated with neuropsychometric deficit. We used complete magnetic resonance imaging (MRI) histories from 266 HbSS children, aged 6 through 19 years, who were enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) to examine silent infarct prevalence, localization, recurrence, and progression. We report a baseline prevalence of 21.8%, marginally higher than previously reported due to improved imaging technologies. Although we observed no overall sex difference in prevalence, most lesions in girls occurred before age 6, whereas boys remained at risk until age 10. Silent infarcts were significantly smaller and less likely to be found in the frontal or parietal cortex than were infarcts associated with stroke. Children with silent infarct had an increased incidence of new stroke (1.03/100 patient-years) and new or more extensive silent infarct (7.06/100 patient-years) relative to stroke incidence among all children in our cohort (0.54/100 patient-years). Both events were substantially less frequent than the risk of stroke recurrence among children not provided chronic transfusion therapy. Although chronic transfusion is known to decrease occurrence of new silent infarcts and strokes in children with elevated cerebral arterial blood flow velocity, further study is required to determine its risk-benefit ratio in children with silent infarct and normal velocities. Until safe and effective preventive strategies against infarct recurrence are discovered, MRI studies are best reserved for children with neurologic symptoms, neuropsychometric deficits, or elevated cerebral artery velocities.
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PMID:Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease. 1192 94

Priapism is a common complication of sickle cell anemia. Two different patterns are described: acute priapism, a prolonged painful erection generally lasting more than 6 hours, and stuttering priapism, which consist of brief repeated self-resolving episodes. Until 1990, priapism in sickle-cell patients has relied on measures aimed at lowering blood viscosity and acidosis and reducing the level of circulating hemoglobin S (alcalinization, hyperhydration, exsanguinotransfusion). But these means are not consistently successful. Surgical cavernous-venous shunt was proposed after 12 to 24 hours when conservative treatment failed. These therapeutic modalities are based on the pathophysiology of sickle-cell priapism. Priapism in sickle-cell disease may be due to sequestered sickled red cells in the corpus cavernosum with venous outflow obstruction. For some years, the treatment of priapism in sickle-cell anemia was changed by the use of alpha-adrenergic agonists. These therapeutics (mainly etilefrine and epinephrine) were first reserved for priapism resulting from intrapenile injections of vasoactive drugs which are used for the treatment of impotence. In acute priapism, alpha-adrenergic agonists are used in intracavernous injections (ICI). In stuttering priapism, treatment consists in an oral administration associated, if necessary, with self-administered ICI. ICI results mainly depend on when treatment occurs. Detumescence is achieved in patients treated within 30 hours, as opposed to the few patients treated beyond this delay. This finding is in agreement with experimental findings demonstrating histological evidence of necrosis of endothelial cells and cavernous smooth muscle fibers after 24 hours. Surgery is only used after failure of ICI. The result of oral treatment is not very satisfactory because many patients do not respond well or are dependent on ICI. However, self-administered ICI associated with the oral treatment protects patients with stuttering priapism against acute strokes. The safety of alpha-adrenergic agonists is good as both oral and ICI have few side-effects. The excellent efficacy of ICI in sickle-cell priapism leads to suggest that the pathogenic mechanism could involve a neuromuscular dysfunction.
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PMID:[Management of priapism in sickle-cell diseases with alpha-adrenergic agonists]. 1247 31

Allogeneic haematopoietic cell transplantation (HCT) is presently the only treatment which offers the possibility of a cure for patients with sickle cell disease (SCD). While approximately 84% of patients survive disease-free after human leukocyte antigen (HLA)-identical sibling donor HCT, this therapy has traditionally been reserved for patients who have suffered serious complications due to the risk of transplant-related morbidity and mortality. Typically, these sickle-related complications have included recurrent episodes of acute chest syndrome, recurrent vaso-occlusive episodes and stroke. The future of HCT for haemoglobinopathies undoubtedly will evolve as transplant-related complications are reduced and as the process of selecting patients for HCT is refined.
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PMID:Haematopoietic cell transplantation in the treatment of sickle cell disease. 1464 Sep 47

More than 25 years after the discovery of the parvovirus B19 (B19), the issue of the safety of blood components and the screening of this virus in blood donations is still debated. Although more often transmitted by respiratory route, B19 may also be transmitted by transfusion of blood components. This risk of exposure has been estimated to a frequency ranging from 1/625 to 1/50,000, according to the sensitivity of the detection methods and to seasonal epidemiologic circumstances. Usually, B19 is responsible for benign pathologies. However, such an infection can have a serious clinical outcome in three categories of susceptible recipients: (i) patients with shortened red cell survival (thalassemia major, sickle cell disease, other hemolytic diseases); (ii) immunocompromised patients (previously exposed to B19 or not) (iii) and pregnant women (not previously exposed the B19), with a risk of hydrops fetalis or of intrauterine death. Selected blood components, not collected during the short but highly viremic pre-seroconversion phase, could be reserved for these three groups of at-risk recipients. The screening of such viremic donations could be performed with nucleic acid testing (NAT), but an alternate strategy could be the selection of B19 immunised donors far from the primo-infection (positive for B19 IgG and negative for B19 IgM, or only positive for IgG at two controls distant of several months). However, the existence of persistently B19-infected individuals carrying B19 DNA despite the presence of specific IgG (estimated at 1% of blood donors) could constitute a potential threat for transfused immunocompromised recipients. The screening of such donors, which could be performed through a very highly sensitive NAT, would be justified only if the infectivity of such blood donations is demonstrated. If not, a screening of blood donors positive for B19 IgG would be a sufficient preventive measure.
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PMID:[Safety of blood products and B19 parvovirus]. 1682 87

Acute chest syndrome describes new respiratory symptoms and findings, often severe and progressive, in a child with sickle cell disease and a new pulmonary infiltrate. It may be community-acquired or arise in children hospitalized for pain or other complications. Recognized etiologies include infection, most commonly with atypical bacteria, and pulmonary fat embolism (PFE); the cause is often obscure and may be multifactorial. Initiation of therapy should be based on clinical findings. Management includes macrolide antibiotics, supplemental oxygen, modest hydration and often simple transfusion. Partial exchange transfusion should be reserved for children with only mild anemia (Hb > 9 g/dL) but deteriorating respiratory status. Therapy with corticosteroids may be of value; safety, efficacy and optimal dosing strategy need prospective appraisal in a clinical trial. On recovery, treatment with hydroxyurea should be discussed to reduce the likelihood of recurrent episodes.
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PMID:How I treat acute chest syndrome in children with sickle cell disease. 2140 23

The basis of allogeneic hemopoietic stem cell (HSC) transplantation in thalassemia consists in substituting the ineffective thalassemic erythropoiesis with and allogeneic effective one. This cellular replacement therapy is an efficient way to obtain a long lasting, probably permanent, clinical effective correction of the anaemia avoiding transfusion requirement and subsequent complications like iron overload. The first HSC transplant for thalassemia was performed in Seattle on Dec 2, 1981. In the early eighties transplantation procedure was limited to very few centres worldwide. Between 17 December 1981 and 31 January 2003, over 1000 consecutive patients, aged from 1 to 35 years, underwent transplantation in Pesaro. After the pioneering work by the Seattle and Pesaro groups, this therapeutic approach is now widely applied worldwide. Medical therapy of thalassemia is one of the most spectacular successes of the medical practice in the last decades. In recent years advances in knowledge of iron overload patho-physiopathology, improvement and diffusion of diagnostic capability together with the development of new effective and safe oral chelators promise to further increase success of medical therapy. Nevertheless situation is dramatically different in non-industrialized countries were the very large majority of patients live today. Transplantation technologies have improved substantially during the last years and transplantation outcome is likely to be much better today than in the '80s. Recent data indicated a probability of overall survival and thalassemia free survival of 97% and 89% for patients with no advanced disease and of 87% and 80% for patients with advanced disease. Thus the central role of HSC in thalassemia has now been fully established. HSC remains the only definitive curative therapy for thalassemia and other hemoblobinopathies. The development of oral chelators has not changed this position. However this has not settled the controversy on how this curative but potentially lethal treatment stands in front of medical therapy for adults and advanced disease patients. In sickle cell disease HSC transplantation currently is reserved almost exclusively for patients with clinical features that indicate a poor outcome or significant sickle-related morbidity.
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PMID:Hematopietic stem cell transplantation in thalassemia and related disorders. 2141 93


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