Tablet-based electroencephalography diagnostics for patients with epilepsy in the West African Republic of Guinea.

BACKGROUND AND PURPOSE: Epilepsy is most common in lower-income settings where access to electroencephalography (EEG) is generally poor. A low-cost tablet-based EEG device may be valuable, but the quality and reproducibility of the EEG output are not established. METHODS: Tablet-based EEG was deployed in a heterogeneous epilepsy cohort in the Republic of Guinea (2018-2019), consisting of a tablet wirelessly connected to a 14-electrode cap. Participants underwent EEG twice (EEG1 and EEG2), separated by a variable time interval. Recordings were scored remotely by experts in clinical neurophysiology as to data quality and clinical utility. RESULTS: There were 149 participants (41% female; median age 17.9 years; 66.6% ≤21 years of age; mean seizures per month 5.7 ± SD 15.5). The mean duration of EEG1 was 53 ± 12.3 min and that of EEG2 was 29.6 ± 12.8 min. The mean quality scores of EEG1 and EEG2 were 6.4 [range, 1 (low) to 10 (high); both medians 7.0]. A total of 44 (29.5%) participants had epileptiform discharges (EDs) at EEG1 and 25 (16.8%) had EDs at EEG2. EDs were focal/multifocal (rather than generalized) in 70.1% of EEG1 and 72.5% of EEG2 interpretations. A total of 39 (26.2%) were recommended for neuroimaging after EEG1 and 22 (14.8%) after EEG2. Of participants without EDs at EEG1 (n = 53, 55.8%), seven (13.2%) had EDs at EEG2. Of participants with detectable EDs on EEG1 (n = 23, 24.2%), 12 (52.1%) did not have EDs at EEG2. CONCLUSIONS: Tablet-based EEG had a reproducible quality level on repeat testing and was useful for the detection of EDs. The incremental yield of a second EEG in this setting was ~13%. The need for neuroimaging access was evident.

Delayed hemolytic transfusion reaction in the French hemovigilance system.

In France, reporting of adverse events related, or likely to be related, to transfusion is mandatory. Since its creation in 1993, the French hemovigilance system has contributed to a better recognition of unappreciated risks like delayed hemolytic transfusion reactions (DHTR) in sickle-cell disease (SCD) patients. Long under-reported or misclassified, reports of this serious complication of transfusion have improved, particularly through the dissemination of information within the hemovigilance network. To our knowledge, the French hemovigilance system has one of the largest series of DHTR in SCD patients. Guidelines for diagnosis and reporting to hemovigilance system as well as a specific reporting form are being developed, which should contribute to the quality of data essential for epidemiological studies.

[Study of 206 transfused sickle cell disease patients: immunization, transfusion safety and red blood cell supply]. / Etude d'une cohorte de 206 patients drépanocytaires adultes transfusés: immunisation, risque transfusionnel et ressources en concentrés globulaires.

BACKGROUND: Prevention of hemolytic transfusion reactions depends upon our capacity to prevent allo-immunization and conflicts between antigens of transfused red blood cells and antibodies produced by the recipient. In this study, we show that to secure transfusion of sickle cell disease patients, it is necessary to take into account their immunohematologic characteristics in the organization of transfusion. METHODS AND RESULTS: Immunohematological data of 206 chronically transfused patients have been collected as well as phenotypes of transfused units. In order to prevent allo-immunization against C and E antigens for patients typed D+C-E-c+e+ (56%), 26% of the transfused units were D-C-E-c+e+. We found that 47% of the patients had a history of allo-immunization, whereas only 15% produced an antibody the day of inclusion in the study. The non-detectable antibodies were frequently known as dangerous for transfusion. Finally, this study shows the frequency of anti-D in D+ patients and anti-C in C+ patients, pointing out the question of partial antigens. CONCLUSION: To insure optimal transfusion safety for sickle cell disease patients, three points have to be improved: blood donation within the Afro-Caribbean community living in France, access to history of immuno-hematological data, detection of variant antigens, especially within the RH blood system.

Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease.

Intracellular polymerization and sickling depend markedly on the cellular concentration of sickle hemoglobin (Hb S). A possible therapeutic strategy for sickle cell disease is based on reducing the cellular concentration of Hb S through prevention of erythrocyte dehydration. The K-Cl cotransporter is a major determinant of sickle cell dehydration and is inhibited by increasing erythrocyte Mg content. We studied 10 patients with sickle cell disease before treatment and after 2 and 4 wk of treatment with oral Mg supplements (0.6 meq/kg/d Mg pidolate). Hematological parameters, erythrocyte Na, K, and Mg content, erythrocyte density, membrane transport of Na and K, and osmotic gradient ektacytometry were measured. We found significant increases in sickle erythrocyte Mg and K content and reduction in the number of dense sickle erythrocytes. Erythrocyte K-Cl cotransport was reduced significantly. We also observed a significant reduction in the absolute reticulocyte count and in the number of immature reticulocytes. Ektacytometric analysis showed changes indicative of improved hydration of the erythrocytes. There were no laboratory or clinical signs of hypermagnesemia. Mild, transient diarrhea was the only reported side effect. We conclude that oral Mg supplementation reduces the number of dense erythrocytes and improves the erythrocyte membrane transport abnormalities of patients with sickle cell disease.

Rituximab for prevention of delayed hemolytic transfusion reaction in sickle cell disease.

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.

The natural history of asymptomatic osteonecrosis of the femoral head in adults with sickle cell disease.

BACKGROUND: Osteonecrosis 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. METHODS: One 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. RESULTS: At 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. CONCLUSIONS: Untreated 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.

[Symptomatic extramedullary haematopoiesis in ß-thalassemia: A retrospective single centre study]. / Hématopoïèse extra-médullaire symptomatique au cours des ß-thalassémies: étude rétrospective monocentrique.

INTRODUCTION: Symptomatic extramedullary hematopoiesis (EH) is a rare but potentially severe phenomenon which occurs in ß-thalassemia. There are no treatment guidelines. METHODS: Retrospective single centre study including the cases of symptomatic EH encountered between 1997 and 2014 in a unit specialised in red blood cell genetic disorders. Description of clinical, biological and radiological characteristics of the patients, treatments received, and outcomes. RESULTS: Among 182 ß-thalassemia patients followed during the study period, 7 cases of symptomatic EH were diagnosed. They were 5 men and 2 women, and their mean age was 37 years. Four patients were splenectomised, two patients were regularly transfused, and four patients had already received erythropoietin. EH was localised in intravertebral areas and responsible for dorsal spinal cord compression in 5 patients, in paravertebral dorsal area in 1 patient, and in presacral area in 1 patient. The mean hemoglobin level at diagnosis was 7.9 g/dL. Treatment administered included: red cell transfusion in 6 cases, associated with hydroxyurea in 5 cases and/or radiotherapy in 3 patients. One patient was treated with surgery and HU. After a median follow-up of 41 months, clinical recovery was complete in 2 patients and partial in 5 patients. CONCLUSION: EH must be suspected in ß-thalassemia in patients presenting clinical signs of organ compression, and a typical radiological aspect. The functional prognosis depends on the rapidity of treatment, which includes red blood cell transfusion, hydroxyurea, radiotherapy, and rarely surgery. Long-term outcome is uncertain.

Red cell membrane sialoglycoprotein beta in homozygous and heterozygous 4.1(-) hereditary elliptocytosis.

Sialoglycoprotein beta, a minor sialoglycoprotein of the red cell membrane, was studied in homozygous and heterozygous 4.1(-) hereditary elliptocytosis, a variety of hereditary elliptocytosis characterized by total or partial absence of protein 4.1. Erythrocytes were treated with the periodic acid-NaB3H4 procedure. Following polyacrylamide gel electrophoresis in the presence of SDS, labelled sialoglycoproteins were revealed by fluorography. (i) In the ghosts from the 4.1(-) homozygote, sialoglycoprotein beta was sharply decreased. It is not sure whether the residual material is sialoglycoprotein beta itself, or a distinct sialoglycoprotein migrating in the same place. In long exposure fluorograms, sialoglycoprotein gamma (a sialoglycoprotein related to sialoglycoprotein beta) also turned out to be reduced. In the homozygote's Triton-shells, sialoglycoprotein beta and gamma appeared completely absent. (ii) In the 4.1(-) heterozygote, sialoglycoprotein beta appeared slightly reduced, whereas sialoglycoprotein gamma appeared normal. Both of these proteins were extracted in seemingly normal amounts in the Triton-shells. These observations bring further support to the view that there is an interaction between skeletal membrane protein 4.1 and sialoglycoprotein beta, that is additional to other interactions between the former protein and the lipid bilayer and/or other transmembrane proteins.

The involvement of the Ca-dependent K channel and of the KCl co-transport in sickle cell dehydration during cyclic deoxygenation.

We have investigated the mechanisms involved in sickle cell dehydration upon continuous or cyclic deoxygenation: the Ca(2+)-activated K+ channel and the KCl co-transport system. Short-term continuous deoxygenation (1 h) of sickle cells in a Ca(2+)-containing medium promoted a stimulation of the efflux of K+ and cell dehydration. This latter was reduced by the replacement of Ca2+ in the medium by EGTA, but not by addition of [(dihydro-indenyl) oxy] alkanoic acid (DIOA), an inhibitor of the KCl co-transport. During cycles of deoxygenation-reoxygenation, cell dehydration was partly prevented by EGTA and significantly reduced by DIOA only in the presence of Ca2+. The present data support the view that sickle cell dehydration during deoxygenation arises from the stimulation of the Ca(2+)-dependent K+ permeability leading to water loss, whereas during reoxygenation periods, subsequent activation of the KCl co-transport also contributes to cell dehydration.

[Acute splenic sequestration: a rare and severe complication of sickle cell anemia in adults. A case report]. / La séquestration splénique aiguë: une complication rare et grave des syndromes drépanocytaires majeurs de l'adulte. A propos d'un cas.

INTRODUCTION: Acute splenic sequestration, a well-recognized complication of sickle cell syndromes, is characterized by a sudden decrease in haemoglobin concentration and marked painless splenomegaly. We report a case illustrating the outcome and the treatment options of this complication. CASE REPORT: A 45-year old homozygous woman developed acute splenic sequestration with severe anemia. Red blood cells transfusion led to transient improvement but a relapse-required splenectomy. Long-term outcome was favorable. CONCLUSION: Acute splenic sequestration is a severe complication mainly observed in children. Despite the severity of this complication, prompt diagnosis and appropriate therapy, and particularly red blood cells transfusions, led to a complete recovery. Splenectomy is required in the more severe form of the disease.

Acute chest syndrome in adults with sickle cell disease.

STUDY OBJECTIVES: Acute chest syndrome (ACS) is a frequent and potentially severe pulmonary illness in sickle cell disease (SCD). The aim of the study was to report the clinical features and outcome of consecutive ACS episodes in adult patients in a French SCD center. All patients were treated according to an uniform therapeutic protocol applying transfusion only in the more severe clinical form of ACS. RESULTS: There were 107 consecutive episodes in 77 adult patients (mean age, 29 +/- 7 years; 78% hemoglobin [Hb] SS; 14% Hb SC; and 8% Hb Sbeta + thalassemia) over a 6-year period. Seventy-eight percent of our patients had an associated vaso-occlusive crisis that preceded the chest signs in half of the cases. Comparison between acute and baseline levels showed a statistically significant difference in Hb levels (drop of 1.6 to 2. 25 g/dL depending on Hb genotype), WBC count (increase of 9.2 +/- 8. 3 x 10(9)/L); platelet count (increase of 67 +/- 209 x 10(9)/L); and lactate dehydrogenase values (increase of 358 +/- 775 IU/L) in ACS patients. Hypercapnia was detected in 42% of patients without sign of narcotic abuse. We identified a high percentage of alveolar macrophages containing fat droplets in 31 of 43 (77%) patients who underwent BAL. Bacterial culture findings were almost always negative, but were performed after starting antibiotic therapy that was administered in 96 episodes. Transfusion was required in 50 of 107 ACS events (47%). Five patients died, and all were transfused. CONCLUSIONS: These results confirm that fat embolism is probably a frequent mechanism of ACS in adult patients. However, fat embolism was not associated with a more severe clinical course, suggesting that bronchoscopy and BAL have little impact on the management of these patients. Restricting transfusion to the most severe ACS cases does not seem to increase the mortality rate.

Fate of alpha-hemoglobin chains and erythrocyte defects in beta-thalassemia.

The fate of alpha-hemoglobin chains and the cause of membrane protein defects in thalassemic erythrocytes have been studied in: (1) human beta-thalassemia syndromes, (2) mouse beta-thalassemia, and (3) normal human erythrocytes loaded with purified alpha-hemoglobin chains. The similarity and differences observed in these three systems underline the importance of insoluble alpha chains and the direct relationship between the amount of these chains and the membrane protein defects. Indeed, in addition to the alpha/non-alpha ratio of globin chain synthesis, the proteolysis and instability of alpha chains are major factors in modulating the cellular defects.

Preventive treatment of priapism in sickle cell disease with oral and self-administered intracavernous injection of etilefrine.

OBJECTIVES: Priapism is a common and currently unsatisfactorily managed complication of sickle cell disease (SCD). In June 1994, 6 SCD patients received a new therapeutic regimen to prevent the occurrence and recurrence of priapism. METHODS: The patients (5 with SS and 1 with SC) were adults and had frequent episodes of stuttering priapism (SP), and two of them had had acute episodes (AP) lasting more than 3 hours. The treatment consists of preventive oral administration of the alpha-adrenergic agent etilefrine, and self-administered intracavernous injection (SICI) of the same agent to reverse episodes lasting more than 1 hour. RESULTS: Since the beginning of treatment, all patients were protected against AP, 4 patients had no recurrence with the oral treatment alone, 2 had to use SICI, 1 occasionally and 1 constantly. There was no modification of sexual activity and no complications. Blood pressure was unaffected. CONCLUSIONS: This treatment is simple, cheap, and self-administered. It should be proposed to all patients with SCD in all geographic areas as part of an educational program for active prevention of this severe complication.

The natural history of symptomatic osteonecrosis in adults with sickle-cell disease.

BACKGROUND: Adult patients with sickle-cell disease are at risk for the development of osteonecrosis of the hip. However, there is little information in the literature about the rate of progression of osteonecrosis once symptoms begin. The purpose of this study was to evaluate the natural history of the symptomatic hip in adult patients with osteonecrosis and sickle-cell disease. METHODS: Ninety-two symptomatic hips in sixty-four consecutive adult patients with sickle-cell disease were initially evaluated between 1980 and 1987. Sixty symptomatic hips had radiographic evidence of osteonecrosis at the initial evaluation: forty-three were classified as stage II; two, as stage III; and fifteen, as stage IV, according to the system of Steinberg et al. The other thirty-two hips had lesions (stage I) that were evident only on magnetic resonance imaging. All patients were evaluated after a mean duration of follow-up of seventeen years. RESULTS: Of the seventy-five hips without collapse of the femoral head at the initial evaluation, sixty-five demonstrated collapse within five years after the diagnosis. The average time between the diagnosis and collapse was forty-two months for stage-I hips and thirty months for stage-II hips. At the most recent follow-up examination, ninety hips had had collapse of the femoral head and eighty-eight of the ninety-two hips had had surgery because of intractable pain. CONCLUSIONS: Symptomatic osteonecrosis of the hip in sickle-cell disease has a high likelihood of leading to femoral head collapse, necessitating surgical intervention. When osteonecrosis develops, the deterioration is rapid and, in most patients, operative intervention is necessary because of intractable pain. LEVEL OF EVIDENCE: Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence.

Deformities of the hip in adults who have sickle-cell disease and had avascular necrosis in childhood. A natural history of fifty-two patients.

We report the natural course of the hip in fifty-two patients (ninety-five hips) who had sickle-cell disease and had had avascular necrosis in childhood. There were twenty-one African, twenty-one West Indian, and ten Mediterranean patients. At the most recent follow-up examination (at an average duration of nineteen years after the onset of the disease), 80 per cent of the hips that had been affected by avascular necrosis during childhood were painful and had permanent damage with regard to decreased mobility, limb-length discrepancy, and an abnormal gait. When the patients were evaluated, at an average age of thirty-one years, fifteen hips (16 per cent) had had an operation for progressive disability and sixty (63 per cent) had major problems because of pain. Of the twenty hips (21 per cent) that were not painful, five were in patients who had an abnormal gait, with decreased agility. The mean Iowa hip-rating score at the most recent follow-up examination was 73 points (range, 30 to 100 points). Correlations were found between the hip score and the patient's age at the onset of the disease and at the latest follow-up, between the hip score and degenerative changes in the hip, and between degenerative changes and radiographic evidence of deformity of the hip.

Vascular lesions of the liver in sickle cell disease. A clinicopathological study in 26 living patients.

BACKGROUND: Hepatic lesions in sickle cell disease have been studied essentially in autopsy series. Previous reports on living patients are rare and concern a limited number of cases. The aim of the present study is to report the clinical, biochemical, and hepatic histological findings in 26 living patients with sickle cell disease and hepatobiliary disease. PATIENTS AND METHODS: Twenty-six of 510 patients with sickle cell disease, in whom liver tissue was available for histological analysis, were selected. In 21 patients, biopsy was obtained during laparotomy for cholecystectomy; 5 patients underwent needle biopsy for hepatomegaly and/or liver test abnormalities. RESULTS: Twenty of the 21 cholecystectomized patients, as well as the 5 other patients, had liver vascular lesions consisting of sinusoidal dilatation (23 cases), perisinusoidal fibrosis (19 cases), and acute ischemic necrosis (5 cases). It is of interest that the 21 cholecystectomized patients had clinical signs of complicated cholelithiasis, and that 20 of them had gallbladder stones, with common bile duct lithiasis in only 1 case. In the 25 patients without common bile duct obstruction, symptoms might have been due to vascular lesions, but it must also be noted that in the cholecystectomized patients they did not persist or recur following surgery. In one cirrhotic patient, marked sinusoidal lesions might have favored severe hepatocellular failure that led to liver transplantation. In another patient, fatal hepatocellular insufficiency was possibly due to ischemia. The nonvascular lesions that were observed, ie, chronic persistent or mildly active hepatitis (11 cases) and cirrhosis (2 cases), were always associated with vascular lesions. CONCLUSION: These results suggest that in sickle cell disease: (1) hepatic lesions are mainly vascular; (2) these lesions can be responsible for acute and/or chronic ischemia that may be severe; (3) symptoms suggestive of acute cholecystitis and/or biliary tract obstruction might be, at least in part, explained by vascular lesions; and (4) biliary tract surgery indications should be considered more carefully.

Avascular necrosis of the femoral head in sickle-cell disease. Treatment of collapse by the injection of acrylic cement.

In ten patients with sickle-cell disease, we used a new technique of cement injection for the treatment of 16 painful hips with a radiographic crescent line or flattening of the articular surface due to avascular necrosis. The necrotic bone and overlying cartilage are elevated by the injection to restore the sphericity of the femoral head. Five days after the operation, full weight-bearing was allowed with the help of crutches for three weeks. The time in hospital averaged eight days; the average blood loss was 100 ml. There was early pain relief and postoperative radiographs showed improvement in the shape of the femoral head. At a mean follow-up of 5 years (3 to 7), 14 of the 16 hips were still improved although some gave slight pain. Only two hips had required revision to total hip arthroplasty, at one year and two years respectively. The increasing longevity of patients with sickle-cell disease means that avascular necrosis will be an increasing problem. Total hip replacement has a poor prognosis because of the risks of infection, high blood loss, and early loosening. Cement injection does not have these problems and allows for earlier, more conservative surgery.

[Potential alternatives to erythrocyte transfusion in hemoglobinopathies: hydroxyurea (HU), erythropoietin (EPO), butyrate derivatives, blood substitutes]. / Alternatives potentielles à la transfusion érythrocytaire dans les hémoglobinopathies: hydroxyurée (HU), érythropoïétine (EPO), dérivés du butyrate, substituts du sang.

Transfusion is associated with improvement of life expectancy in beta thalassemia and sickle cell disease (SCD). Bone marrow transplantation concerns only a few patients. Among potentially useful therapeutic agents which can induce fetal hemoglobin (HbF) production, hydroxyurea (HU) stands out in particular for SCD. In our sickle cell center, 10 patients with SCD received HU for chronic leg ulcer with good results in terms of healing (7 among 10, who required no additional transfusion). A few patients, most of them over 30 years, received HU for chronic organ failure at the onset. HU on long term therapy over one year improved general status, Hb level, in 7 patients with beta thalassemia intermedia. A major challenge in the coming years will be the effective evaluation of clinical efficiency and the comparison of risks and benefits of such compounds versus transfusion.

[Transfusion and alloimmunization in sickle cell anemia patients]. / Transfusion et alloimmunisation chez les patients drépanocytaires.

Transfusion therapy for sickle cell anemia is limited by the development of antibodies to red cell antigens. The aim of this study was to evaluate whether transfusion of blood matched for antigens Rh and Kell would reduce the incidence of alloimmunization. We determined the transfusion history, red cell phenotype and development of alloantibodies in 173 patients with sickle all anemia who received transfusions. Forty nine patients were transfused exclusively with frozen red blood cells (RBL) matched for antigens Rh and Kell; the rate of alloimmunization was 8.2%; antibodies to the Jkb, Jka, Fya and S were developed; 1 patient developed 2 antibodies. In a control group of 124 patients who received standard red blood cells, the rate of alloimmunization was significantly increased to 30.6% (p < 0.05); antibodies against C, E, K, Fya were the most frequently developed and 19 patients (16%) developed antibodies reacting with different antigens. In the 2 groups, alloimmunization occurred after receiving a significantly different number of transfusions: mean 9 in the patients transfused with matched RBC and 32 in the control group. The influence of the kinetics of transfusion was not demonstrated. To assess the effect that racial differences might have on alloimmunization, comparison of the red cell phenotype of patients with that of a panel of unselected blood bank donors was performed: the patients had a significant decrease in the frequency of red cell antigens corresponding to most of the detected alloantibodies JkB, C, S. Fyb, Fya and Kell.(ABSTRACT TRUNCATED AT 250 WORDS)

[Extensive bone marrow necrosis and major sickle cell syndromes]. / Nécrose médullaire étendue et syndromes drépanocytaires majeurs.

Three cases of extensive bone marrow necrosis in patients with sickle cell disease are reported. All three patients presented severe bone pains with severe anaemia (haemoglobin value less than 5 g/dl) and high increased of LDH serum values (upper than 20 fold normal value). Bone marrow aspirate and biopsy showed typical signs of necrosis. The extent of necrosis was evaluated by reticuloendothelial scan obtained with 111In chloride. Treatment required transfusions of phenotyped red blood cell concentrates. Favourable outcome was observed in all patients.