Predicting changes in hemoglobin S after simple transfusion using complete blood counts.

BACKGROUND: Hemoglobin S percentages are used in the management of patients who have sickle cell disease. However, hemoglobin S measurements often are not routinely or rapidly performed. Rapid and accurate methods to estimate hemoglobin S levels after simple transfusion may improve the care of patients with sickle cell disease. STUDY DESIGN AND METHODS: A comprehensive review of the electronic medical record identified 24 stable patients with sickle cell disease who received simple red blood cell transfusions and had hemoglobin S measurements before and after the transfusion that were less than 72 hours apart. Examination of these patients identified 62 separate transfusions that met our criteria. Three simple equations that utilized complete blood count values and readily available information from the medical record were used to predict the post-transfusion hemoglobin S level after transfusion (Equation 1: predicted post-transfusion hemoglobin = pre-transfusion hemoglobin S × [pre-transfusion hemoglobin/post-transfusion hemoglobin]; Equation 2: predicted post-transfusion hemoglobin S = pre-transfusion hemoglobin S × [pre-transfusion hematocrit/post-transfusion hematocrit]; and Equation 3: predicted post-transfusion hemoglobin S = pre-transfusion hemoglobin S × total pre-transfusion hemoglobin/[total pre-transfusion hemoglobin + (red blood cell volume × 20)]). RESULTS: The predicted hemoglobin S values for all three equations showed a highly significant correlation with the measured post-hemoglobin S value. The coefficient of determination (R2 ) for Equations 1, 2, and 3 was 0.95, 0.92, and 0.97, respectively. Predicting the post-transfusion hemoglobin S value using estimates of the patient's total hemoglobin and the transfused hemoglobin (Equation 3) was the most precise. CONCLUSION: Reductions in hemoglobin S values in patients with sickle cell disease who receive simple red blood cell transfusions can be reliably predicted using complete blood cell measurements and simple arithmetic equations.

Knowledge insufficient: the management of haemoglobin SC disease.

Although haemoglobin SC (HbSC) accounts for 30% of sickle cell disease (SCD) in the United States and United Kingdom, evidence-based guidelines for genotype specific management are lacking. The unique pathology of HbSC disease is complex, characterized by erythrocyte dehydration, intracellular sickling and increased blood viscosity. The evaluation and treatment of patients with HbSC is largely inferred from studies of SCD consisting mostly of haemoglobin SS (HbSS) patients. These studies are underpowered to allow definitive conclusions about HbSC. We review the pathophysiology of HbSC disease, including known and potential differences between HbSS and HbSC, and highlight knowledge gaps in HbSC disease management. Clinical and translational research is needed to develop targeted treatments and to validate management recommendations for efficacy, safety and impact on quality of life for people with HbSC.

Original Research: Use of hydroxyurea and phlebotomy in pediatric patients with hemoglobin SC disease.

Hydroxyurea is an excellent therapeutic agent for the pharmacological induction of HbF in patients with sickle cell disease (SCD). However, all completed clinical trials of hydroxyurea have excluded patients with hemoglobin SC (HbSC) disease. HbSC differs significantly in pathophysiology from HbSS, as HbC does not sickle, but instead causes cellular dehydration which potentiates sickling of HbS. Many severely affected HbSC patients have been placed on hydroxyurea on a case by case basis, but there are no large scale prospective data on safety or efficacy of hydroxyurea in this subset of patients with SCD. Here, we report a case series of 14 pediatric patients with HbSC treated to maximum tolerated dose (MTD) with hydroxyurea. Those who failed to show clinical improvement after at least six months at MTD were offered phlebotomy in addition to hydroxyurea. Five out of 11 patients with HbSC who achieved MTD failed to demonstrate clinical improvement on hydroxyurea. Of the four placed on dual hydroxyurea and phlebotomy therapy, all showed at least partial clinical improvement. Percent dense red blood cells (%DRBC) were measured via an ADVIA hematology analyzer. A marked rise in percent dense cells preceded clinical complications in three patients. Dual therapy with hydroxyurea and phlebotomy may be an effective approach to patients with HbSC that do not experience improvement with hydroxyurea alone. Monitoring of %DRBC may predict adverse events and aid in assessing hydroxyurea compliance. Large scale clinical trials are needed to evaluate the safety and efficacy of hydroxyurea and hydroxyurea with phlebotomy in patients with HbSC disease.

Psychological therapies for sickle cell disease and pain.

BACKGROUND: Sickle cell disease comprises a group of genetic blood disorders. It occurs when the sickle haemoglobin gene is inherited from both parents. The effects of the condition are: varying degrees of anaemia which, if severe, can reduce mobility; a tendency for small blood capillaries to become blocked causing pain in muscle and bone commonly known as 'crises'; damage to major organs such as the spleen, liver, kidneys, and lungs; and increased vulnerability to severe infections. There are both medical and non-medical complications, and treatment is usually symptomatic and palliative in nature. Psychological interventions for individuals with sickle cell disease might complement current medical treatment, and studies of their efficacy have yielded encouraging results. This is an update of a previously published Cochrane Review. OBJECTIVES: To examine the evidence that psychological interventions improve the ability of people with sickle cell disease to cope with their condition. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and the Internet, handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 17 February 2015. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing psychological interventions with no (psychological) intervention in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed the risk of bias of the included studies. MAIN RESULTS: Twelve studies were identified in the searches and seven of these were eligible for inclusion in the review. Five studies, involving 260 participants, provided data for analysis. One study showed that cognitive behaviour therapy significantly reduced the affective component of pain (feelings about pain), mean difference -0.99 (95% confidence interval -1.62 to -0.36), but not the sensory component (pain intensity), mean difference 0.00 (95% confidence interval -9.39 to 9.39). One study of family psycho-education was not associated with a reduction in depression. Another study evaluating cognitive behavioural therapy had inconclusive results for the assessment of coping strategies, and showed no difference between groups assessed on health service utilisation. In addition, family home-based cognitive behavioural therapy did not show any difference compared to disease education. One study of patient education on health beliefs showed a significant improvement in attitudes towards health workers, mean difference -4.39 (95% CI -6.45 to -2.33) and medication, mean difference -1.74 (95% CI -2.98 to -0.50). Nonetheless, these results may not apply across all ages, severity of sickle cell disease, types of pain (acute or chronic), or setting. AUTHORS' CONCLUSIONS: Evidence for the efficacy of psychological therapies in sickle cell disease is currently limited. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions in sickle cell disease.

Red cell exchange transfusion halts progressive proliferative sickle cell retinopathy in a teenaged patient with hemoglobin SC disease.

A male with sickle SC disease presented at age 8 years with proliferative sickle cell retinopathy (PSCR) and bilateral vitreous hemorrhage which spontaneously resolved, then recurred at 13 years of age. Despite conventional therapy with repeated pan-retinal photocoagulation and pars plana vitrectomy, he developed progressive PSCR and recurrent vitreous hemorrhage over the next 30 months. We describe the successful use of chronic red cell exchange transfusion (RCE) to preserve his vision and stabilize the retinopathy.

Recommendations for the management of sickle cell disease in South Africa.

The spectrum of sickle cell disease (SCD) encompasses a heterogeneous group of disorders that include: (I) homozygous SCD (HbSS), also referred to as sickle cell anaemia; (ii) heterozygous SCD (HbAS), also referred to as sickle cell trait; and (iii) compound heterozygous states such as HbSC disease, HbSß thalassaemia, etc. Homozygous or compound heterozygous SCD patients manifest with clinical disease of varying severity that is influenced by biological and environmental factors, whereas subject with sickle cell trait are largely asymptomatic. SCD is characterized by vaso-occlusive episodes that result in tissue ischaemia and pain in the affected region. Repeated infarctive episodes cause organ damage and may eventually lead to organ failure. For effective management, regular follow-up with support from a multidisciplinary healthcare team is necessary. The chronic nature of the disease, the steady increase in patient numbers, and relapsing acute episodes have cost implications that are likely to impact on provincial and national health budgets. Limited resources mandate local management protocols for the purposes of consistency and standardisation, which could also facilitate sharing of resources between centres for maximal utility. These recommendations have been developed for the South African setting, and it is intended to update them regularly to meet new demands and challenges.

Sickle cell retinopathy: diagnosis and treatment.

Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.

Sickle cell retinopathy: diagnosis and treatment / Retinopatia falciforme: diagnóstico e tratamento

Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.

As hemoglobinopatias são um grupo de doenças hereditárias caracterizadas por mal-formações quantitativas ou qualitativas da hemoglobina (Hb). Algumas destas doenças podem apresentar fenômenos vaso-oclusivos, responsáveis por alta morbidade do ponto de vista clínico e/ou oftalmológico. O diagnóstico das hemoglobinopatias é feito exclusivamente através da eletroforese de hemoglobinas. Do ponto de vista oftalmológico, a representante mais importante deste grupo de doenças é a retinopatia falciforme, que pode apresentar um amplo espectro de manifestações fundoscópicas, podendo, inclusive, levar à perda visual irreversível se não for corretamente diagnosticada e tratada. O objetivo desta revisão é apresentar a classificação desta doença, a conduta no tratamento atual, bem como suas perspectivas futuras de tratamento, considerando-se as particularidades no manejo clínico destes pacientes.

[Transitory acute atrioventricular block in an African patient: consider sickle cell anemia]. / Bloc auriculoventriculaire complet transitoire chez un africain: la drépanocytose comme cause.

This case report shows a rare cardiac complication of sickle cell anemia in a young African patient which was an acute paroxysmal atrio-ventricular block. Acute paroxysmal atrioventricular block is a rare complication of polymerization of hemoglobin S during sickle cell disease. Hence, sickle cell anemia should be considered as a cause of auriculoventricular block in black African patients. Cardiac complications of sickle cell anemia are presented in this article.

Psychological therapies for sickle cell disease and pain.

BACKGROUND: Sickle cell disease comprises a group of genetic blood disorders. It occurs when the sickle haemoglobin gene is inherited from both parents. The effects of the condition are: varying degrees of anaemia which, if severe, can reduce mobility; a tendency for small blood capillaries to become blocked causing pain in muscle and bone commonly known as 'crises'; damage to major organs such as the spleen, liver, kidneys, and lungs; and increased vulnerability to severe infections. There are both medical and non-medical complications, and treatment is usually symptomatic and palliative in nature. Psychological interventions for individuals with sickle cell disease might complement current medical treatment, and studies of their efficacy have yielded encouraging results. OBJECTIVES: To examine the evidence that psychological interventions improve the ability of people with sickle cell disease to cope with their condition. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and the Internet, handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 28 July 2011. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing psychological interventions with no (psychological) intervention in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed the risk of bias of the included studies. MAIN RESULTS: Eleven studies were identified in the searches and six of these were eligible for inclusion in the review. Four studies, involving 223 participants, provided data for analysis. One study showed that cognitive behaviour therapy significantly reduced the affective component of pain, mean difference -3.00 (95% confidence interval -4.63 to -1.37), but not the sensory component, mean difference 0.00 (95% confidence interval -9.39 to 9.39). One study of family psycho-education was not associated with a reduction in depression. Another study evaluating cognitive behavioural therapy had inconclusive results for the assessment of coping strategies, and showed no difference between groups assessed on health service utilisation. AUTHORS' CONCLUSIONS: Evidence for the efficacy of psychological therapies in sickle cell disease is currently limited. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions in sickle cell disease.

Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and ß-thalassemia major.

Red blood cell alloimmunization is a major complication of transfusion therapy. Host immune markers that can predict antibody responders remain poorly described. As regulatory T cells (Tregs) play a role in alloimmunization in mouse models, we analyzed the Treg compartment of a cohort of chronically transfused patients with sickle cell disease (SCD, n = 22) and ß-thalassemia major (n = 8) with and without alloantibodies. We found reduced Treg activity in alloantibody responders compared with nonresponders as seen in mice. Higher circulating anti-inflammatory IL-10 levels and lower IFN-γ levels were detected in non-alloimmunized SCD patients. Stimulated sorted CD4+ cells from half of the alloimmunized patients had increased frequency of IL-4 expression compared with nonresponders, indicating a skewed T helper (Th) 2 humoral immune response in a subgroup of antibody responders. All patients had increased Th17 responses, suggesting an underlying inflammatory state. Although small, our study indicates an altered immunoregulatory state in alloantibody responders which may help future identification of potential molecular risk factors for alloimmunization.

Recurrent intrahepatic pigmented stones after liver transplantation in a patient with hemoglobin SC disease: case report and review of the literature.

Patients with hemoglobinopathies may have hepatic involvement, which if severe, can lead to chronic liver disease and a need for liver transplant. Here, we present a case of a 16-yr-old female adolescent who presented to our center with hemoglobin SC disease, obstructive jaundice because of pigmented intrahepatic biliary stones, and progressive liver disease. She underwent a successful liver transplant but a few years later, she developed recurrent cholangitis and graft dysfunction because of recurrent intrahepatic biliary stones. Recurrent formation of intrahepatic stones after liver transplant is a rare and severe complication in patients with hemoglobinopathies. We recommend hypertransfusion therapy and surveillance imaging studies after liver transplant for early detection and prevention of this complication.

Ovarian sickling as a proposed mechanism for premature ovarian failure necessitating ovum donation.

Iron overload in female patients with sickle cell disease (SCD) has been reported to result in gonadal dysfunction. To date there has been no report in the literature of ovarian sickling being a reason for gonadodysgenesis (premature ovarian failure [POF]) in women. This case report describes POF in a woman with SCD and suggests ovarian sickling as its cause. We propose that frequent episodes of intravascular sickling, vessel occlusion and infarction as well as tissue hypoxia associated with chronic anaemia could account for the ovarian dysgenesis and hence POF.

Mobilization, collection, and transplantation of peripheral blood hematopoietic progenitor cells in a patient with multiple myeloma and hemoglobin SC disease.

BACKGROUND: The use of granulocyte-colony-stimulating factor (G-CSF) for mobilization, collection, and transplantation of autologous hematopoietic progenitor cells (HPCs) in patients with hemoglobinopathies can be complicated by severe vasoocclusive crises. Erythrocytapheresis before G-CSF administration may help prevent these complications. To date, no cases regarding the safety and outcome of erythrocytapheresis followed by autologous high-dose G-CSF mobilization in hemoglobinopathy populations have been reported. STUDY DESIGN AND METHODS: A patient with hemoglobin (Hb) SC disease and multiple myeloma underwent erythrocytapheresis followed by high-dose (16 microg/kg) G-CSF in preparation for HPC mobilization and collection. RESULTS: Erythrocytapheresis reduced the patient's combined Hb S and C levels to less than 20 percent. Subsequent HPC mobilization and peripheral blood harvesting using high-dose G-CSF yielded approximately 9 x 10(6) CD34+ HPCs per kg over 3 days of collection. Mobilization and leukapheresis were completed without vasoocclusive complications. Two weeks after collection, and after myeloablative chemotherapy, 5.33 x 10(6) CD34+ HPCs per kg were infused to the patient; platelet and white cell engraftment occurred, respectively, on Days +9 and +10 posttransplant. The patient experienced no vasoocclusive complications in the posttransplant period. CONCLUSIONS: The results of this case demonstrate that erythrocytapheresis before high-dose G-CSF HPC mobilization and collection appears to be an effective means for prevention of vasoocclusive crisis in patients with hemoglobinopathies undergoing autologous stem cell transplantation.

Third-trimester erythrocytapheresis in pregnant patients with sickle cell disease.

OBJECTIVE: To evaluate the effects of prophylactic transfusion by means of erythrocytapheresis at the beginning of the third trimester of pregnancy in women with sickle cell disease (SCD). METHODS: A cohort of 14 pregnant women with SCD who received prophylactic erythrocytapheresis transfusions at the beginning of the third trimester was retrospectively compared with a cohort of 17 pregnant women who received simple prophylactic transfusions for no indication other than SCD severity. RESULTS: Prophylactic erythrocytapheresis transfusions were associated with a lower risk of intrauterine growth restriction (OR, 0.11; 95% confidence interval, 0.01-1.00) and oligohydramnios (OR, 0.65; 95% confidence interval, 0.45-0.92) in pregnant women with SCD. CONCLUSION: These results suggest that erythrocytapheresis transfusions are beneficial in women with SCD who are in the third trimester of pregnancy. Given the decrease in transfusion risks, this therapy deserves further evaluation in future trials.

[Sickle cell disease and retinal damage: a study of 38 cases at the African Tropical Ophthalmology Institute (IOTA) in Bamako]. / Drépanocytose et atteintes rétiniennes: etude de 38 cas a l'Institut d'Ophtalmologie Tropicale de l'Afrique de Bamako--(IOTA).

The purpose of this prospective study was to evaluate retinal damage in patients with sickle cell disease and its links with the different genotypic forms of the disease in patients consulting at the African Tropical Ophthalmology Institute (IOTA). A total of 38 patients with the HbS gene were included over a 12-month study period. Retinal damage was assessed by a computerised angiofluorography in 31 patients. Of the 38 patients studied, 71% had sickle cell disease (SC), 21% had sickle cell trait (AS) and 8% had sickle cell anemia (SS). Sixty-eight percent of patients (n = 21) presented sickle cell retinopathy. The age group with the highest prevalence of proliferative neovascularisation was between 26 and 35 years. Retinopathy was more frequent in SC patients than AS patients: 90% (n = 19) versus 10% (n = 2). None of the 3 SS patients presented retinopathy. Retinal neovascularisation was the most common finding in the 27 affected eyes. This study confirms the frequency and severity of retinal damage in patients with the HbS haemoglobin, particularly among young people with double heterozygous disease (SC) in the tropical African environment. Treatment of this disorder is largely unavailable to patients in sub-Saharan Africa except at the major eye care centres. An early screening and management programme for retinal damage related to SC would reduce ocular complications and optimise visual efficiency in these young active patients.