Evaluation of sociodemographic, clinical, and laboratory markers of sickle leg ulcers among young nigerians at a tertiary health institution.

BACKGROUND: Sickle leg ulcer (SLU) is a chronic and debilitating complication of sickle cell disease (SCD) associated with huge physical and psychosocial discomfort. The occurrence of SLU has remained steady despite successful preventive strategies and advances in SCD care. Although multifactorial factors have been implicated in SLU, these are not fully understood, and data on how these relate to young Nigerian SCD patients are scanty. AIMS: This study aims to evaluate the sociodemographic, clinical, and laboratory markers of SLU in a young Nigerian SCD cohort. PATIENTS AND METHODS: This study involved 109 young SCD patients and 67 healthy peers. The sociodemographic and laboratory parameters of the participants were examined in addition to the evaluation of the SCD cohort for SLU. RESULTS: Only the HbSS patients had SLU. This was found in six of them giving a prevalence of 5.9% (6/101). Their median age was 17, range 14-21 years. There was a preceding history of trauma in 4 (66.7%), and this included a case of traditional scarifications for local therapeutic purposes. Two of the three (66.7%) males with SLU also had priapism (P = 0.0132). Patients with SLU were older, had less frequent bone pain crises, and significantly belonged to the low socioeconomic class (P < 0.05). Although patients with SLU had relatively higher lactate dehydrogenase, platelet count, aspartate transaminase, bilirubin, white blood cell, and lower Hb concentration and HbF, these did not attain statistical significance (P > 0.05). CONCLUSION: This study confirms that SLU is common among young SCD patients with HbSS genotype, low socioeconomic background, and older age. It also suggests that SLU could be more related to hemolysis-associated SCD phenotypes among the patients.

Sickle cell disease clinical phenotypes in children from South-Western, Nigeria.

BACKGROUND: The clinical phenotypes of children with sickle cell disease (SCD) are poorly described in many sub-Saharan countries including Nigeria. OBJECTIVES: The objective was to highlight various clinical phenotypes of SCD in children and investigate the influence of sociodemographic indices on the development of SCD complications. METHODS: We carried out a cross-sectional study of 240 pediatric patients attending the sickle cell clinic and the emergency room in a teaching hospital in South-Western Nigeria over a 12-month period. The clinical phenotypes and severity of the disease were documented, and the influence of sociodemographic variables was investigated. RESULTS: The five leading clinical phenotypes in our patients were significant pain episodes, that is, vaso-occlusive crisis in 159 (66.3%); anemic crisis in 62 (25.8%); severe bacterial infections, 57 (23.8%); acute chest syndrome (ACS), 27 (11.3%) and stroke, 7 (2.9%). Forty-two (33.1%) had a previous history of dactylitis (hand-foot syndrome). Other clinical phenotypes such as avascular necrosis of the femur, 4 (1.7%); nephropathy, 2 (0.8%); priapism, gallstone and chronic leg ulcer, one (0.4%) each, were not commonly seen. More children with a history of asthma had ACS. Furthermore, high steady-state white blood cell count was associated with severe disease. CONCLUSION: The clinical phenotypes of SCD in children from South-Western Nigeria are highly variable with the disease manifesting very early and about 10% having significant complications. Sociodemographic characteristics appear to have little influence on the development of SCD complications among our patients, but age and low-socioeconomic class are associated with anemic crisis.

Current sickle cell disease management practices in Nigeria.

BACKGROUND: Although Nigeria has the highest burden of sickle cell disease (SCD) worldwide, there is still variable and poor utilisation of standard-of-care practices for SCD patients in the country. METHODS: This was a questionnaire survey of doctors in some dedicated SCD clinics in Nigeria in order to document the facilities available and common management practices. RESULTS: There were responses from 18 clinics based in 11 institutions. The number of patients being followed in each centre ranged from 15 to approximately 11 000. All clinics provided malaria prophylaxis and folic acid routinely to their patients. Only eight clinics prescribe penicillin prophylaxis. Eight prescribe hydroxyurea to patients who can afford it when indicated. All of the centres except three have electronic cell counters, but all had access to haemoglobin electrophoresis. Three had high-performance liquid chromatography machines installed but none was being routinely used. One institution had a functioning molecular biology laboratory. There is no official newborn screening programme in the country. All had access to microbiology and chemistry laboratories. Nine institutions had CT, six had MRI and three had transcranial Doppler facilities. CONCLUSION: The care available for SCD in Nigeria is still suboptimal and there is an urgent need for concerted effort to tackle the problem, but to make a significant impact on the burden of the disease would require more focus at the primary care level. Some steps to achieving this are outlined.

Haptoglobin gene polymorphisms in sickle cell disease patients with different ßS-globin gene haplotypes.

OBJECTIVE: To investigate the prevalence of haptoglobin (Hp) gene alleles in Kuwaiti sickle cell disease (SCD) patients, who generally have a mild phenotype, and compare the pattern to Nigerian SCD patients whose SCD phenotype is more severe. SUBJECTS AND METHODS: Hp genotyping was carried out in a group of 82 and 54 SCD patients from Kuwait and Nigeria, respectively, and appropriate Hb AA controls. The Hp genotyping was done using a PCR technique followed by agarose gel electrophoresis. RESULTS: The frequency of the Hp-2 allele was 73.8% among Kuwaiti SCD patients, while the Hp-1 allele predominated among Nigerian patients (60.7%). However, the differences were not significant (p > 0.05) when the allele distributions were compared between Kuwaiti SCD and their AA counterparts or between Nigerian SCD and their AA controls. There was no association of Hp-2 allele with frequent vaso-occlusive crisis among the Kuwaiti SCD patients. CONCLUSION: The distribution of Hp alleles appears to follow ethnic and geographical trends. Their role in the pathophysiology of pain crisis is not clear.

Chromosome 22q11.2 deletion presenting with immune-mediated cytopenias, macrothrombocytopenia and platelet dysfunction.

OBJECTIVE: To report a case of chromosome 22q11.2 deletion presenting with large platelets, platelet dysfunction, immune-mediated thrombocytopenia and neutropenia, in addition to other features of the disease. CASE PRESENTATION AND INTERVENTION: The patient presented in the neonatal period with tetralogy of Fallot, subtle dysmorphic features and thrombocytopenia. Fluorescent in situ hybridization analysis confirmed the diagnosis of chromosome 22q11.2 deletion. Further investigations showed immune thrombocytopenia and neutropenia in addition to reduced expression of platelet GPIb and abnormal platelet aggregation studies. CD4:CD8 ratio was reversed. His cardiac abnormality was successfully corrected surgically. He had mild recurrent bacterial infections. Recurrent epistaxis was becoming increasingly more severe, and he had cognitive developmental and speech delay. His serum calcium, phosphorus and parathormone have remained normal. CONCLUSIONS: Immune thrombocytopenia can coexist with macrothrombocytopenia and platelet dysfunction in chromosome 22q11.2 deletion and may present with significant bleeding episodes.

HLA-DRB1 alleles in Hb SS patients with avascular necrosis of the femoral head.

Strong associations have been established between various HLA alleles and different complications of sickle cell disease (SCD). Recently, the HLA-DRB1*03 allele was shown to be associated with susceptibility to stroke while the HLA-DRB1*02 allele may be protective. While stroke and silent brain infarcts (SBI) are unusual in Kuwaiti children with SCD, avascular necrosis of the femoral head (AVNFH) is quite common. The modulatory association factors must still be elucidated. An investigation of HLA-DRB1 alleles was carried out in a group of 68 Kuwaiti SS patients, of age 7-44 years, of whom 20 (29.4%) had AVNFH, confirmed by magnetic resonance imaging. A group of 167 apparently healthy age- and sex-matched individuals served as controls. Comparison of the HLA alleles between the whole SS group and the controls showed a significant over-representation of DRB1*01 (P < 0.01) and DRB1*10 (P < 0.05) in the patient group. No significant differences in the allele frequencies in the SS patients with or without AVNFH were observed. It therefore appears that the HLA-DRB1 locus does not play a significant role in the pathogenesis of AVNFH Kuwaiti patients.

Pulmonary function studies in Kuwaiti children with sickle cell disease and elevated Hb F.

Conflicting ventilatory defects have been reported in children with sickle cell disease (SCD). In Kuwait, the disease is relatively mild with a low incidence of acute chest syndrome and other complications, presumably due to the Arab-Indian haplotype chromosomal background and elevated Hb F levels. There have been no previous studies of pulmonary function in patients with this haplotype. Pulmonary function test (PFT) was carried out on 28 steady state children with SCD (21 homozygous sickle cell (SS), seven S beta(o) thal) and two group of controls: 17 age- and sex-matched healthy children and 10 children with HbH disease. The charts of the SCD patients were reviewed for frequency of acute chest syndrome and vaso-occlusive crisis. The mean values of forced vital capacity (FVC) (83.2 +/- 11.9 vs. 91.2 +/- 11.7) and vital capacity (VC) (81.5 +/- 11.8 vs. 90.5 +/- 10.9) were significantly lower in the SS patients compared with healthy controls (p < 0.05). Similarly, these values were significantly lower than in those of the HbH group (p < 0.001 for VC and p < 0.01 for FVC). The mean forced expiratory volume in 1 s (FEV1) was lower in SS patients (86.4 +/- 11.5) compared with healthy controls (94.2 +/- 14.2), but the difference was not significant (p = 0.07). Also, the FEV1 was significantly lower in SS patients than in the HbH group (p < 0.001). There was no significant difference in the PFT parameters between SS patients with acute chest syndrome and those without. Although patients with frequent vaso-occlusive crisis had lower PFT parameters, the differences were not significant in comparison to those with infrequent crisis. This study revealed an early restrictive and obstructive pulmonary function pattern in steady state children with SCD. The finding also indicates that the changes of PFT parameters in SS patients could not be attributed to anaemia per se as patients with HbH who also have chronic anaemia did not show similar changes. This observation underscores the early occurrence of pulmonary involvement, even in patients with an otherwise relatively mild SCD.

Avascular necrosis of the femoral head in adult Kuwaiti sickle cell disease patients.

While sickle cell disease (SCD) is generally mild in most Kuwaitis, because of their elevated fetal Hb levels, avascular necrosis of the femoral head (AVNFH) appears to be a common complication. It was recently documented in 26.7% of Kuwaiti children with SCD. There have, however, been no previous studies of adult patients. This is a 1-year study of consecutive, steady-state SCD patients seen in the hematology clinic of Mubarak Al-Kabeer Hospital. The patients' charts were reviewed for frequency of hospitalizations, any documented complications and steady-state complete blood count (CBC). MRI was performed using T1- and T2-weighted FATSAT sequences in coronal and axial planes with 4-mm-thick slices on a 1.5-tesla GE super-conducting magnet. Thirty-five patients were studied, consisting of 25 SS and 10 Sbeta(0)Thal patients aged between 17 and 44, with a mean age of 26.7 +/- 9.3 years. Seventeen (48.6%) had varying degrees of AVNFH; among the 70 hips examined, 29 (41.1%) were affected. Of the 17 patients affected, 11 (64.7%) were SS, while 6 (35.3%) were Sbeta(0)Thal. There were 14 (82.4%) males and 3 (17.6%) females (chi(2) = 8.6, p < 0.01). The mean age of those affected, 27.5 +/- 10.7 years, was not significantly higher than that of the unaffected (26.3 +/- 8.0 years). Eleven (64.7%) of those affected had a history of frequent vaso-occlusive crisis. No significant differences could be demonstrated in the mean CBC and Hb F values of the two groups; coexistent alpha-thal trait was not a factor in the SS group. Male gender was the only significant predisposing factor identified. While more patients with frequent vaso-occlusive crises were affected, the difference was not significant. AVNFH is, indeed, quite common among Kuwaiti SCD patients and there is a need for early institution of preventive and therapeutic protocols.

Silent brain infarcts in adult Kuwaiti sickle cell disease patients.

Although overt stroke is a common complication of sickle cell disease (SCD), its incidence is very low in Kuwaiti patients. On the other hand, the prevalence of silent brain infarcts, which is reported to be about 17-20% in American patients, has not been documented in adult Kuwaiti patients. This is a 1-year study of consecutive, asymptomatic SCD patients seen in the hematology clinic of Mubarak Al-Kabeer Hospital. Patients with a past history of seizure or any other neurological abnormality were excluded. The patients' charts were reviewed for frequency of hospitalizations, any documented complications, and steady-state CBC. MRI was done with a 1.5-Tesla unit with super-conducting magnet. T1- and T2-weighted sagittal and axial sections and proton-density axial images were obtained in 5-mm-thick sections. Thirty-five patients were studied, made up of 25 SS and 10 Sbeta(0)Thal, aged between 17 and 44 years, with a mean age of 26.9 +/- 9.3 years. MRI findings consistent with infarcts were found in 7 (20.0%) patients-6 SS and 1 Sbeta(0)thal-with a mean age of 31.8 +/- 8.2 years, which was significantly higher (P < 0.05) than the mean age of the unaffected group (25.1 - 9.0 years). There were also no differences in the mean Hb, Hb F, or any other hematological parameter in the two groups. Among the affected 6 SS, 2 had co-existent alpha-thal trait. It is interesting that, while silent infarcts are prevalent in young American patients, it is in the older age group that they occur in Kuwaiti patients. Further studies are needed to investigate the factors modulating this heterogeneity.

Hemoglobin electrophoresis and hemoglobinopathies in Kuwait.

OBJECTIVES: To analyze the results of hemoglobin electrophoresis (HE) in the routine laboratory of a tertiary hospital in Kuwait and to review the common types of hemoglobinopathies prevalent in the country. METHODS: This was a prospective study of HE performed on 2,386 samples in Mubarak Al-Kabeer Hospital, which serves more than 30% of the population of Kuwait, from June 1997 to May 1998. RESULTS: Of the 2,386 HE tests, only 561 (23.5%) had abnormal hemoglobin genotypes. The most commonly identified hemoglobinopathies were beta-thalassemia minor (14%), sickle cell trait (6%), sickle cell anemia (0.9%), S beta zero thal (0.8%) and S beta + thal (0.8%). Two rare hemoglobin variants, Hb DPunjab and Hb E, were encountered. CONCLUSION: HE yielded only 23.5% abnormal results, thus indicating the need to streamline requests for the test. The test should be limited to patients with hematological and clinical features suggestive of hemoglobinopathies or to individuals with a positive family history.

Silent brain infarcts are rare in Kuwaiti children with sickle cell disease and high Hb F.

Overt stroke is rare among sickle cell disease (SCD) patients in Kuwait. However, there are no previous studies of silent cerebral infarcts, which have been described in up to 20% of American children with Hb SS. We have carried out a prospective brain MRI study among otherwise normal SCD patients, who were consecutive patients seen in a 1-year period to document the prevalence of silent cerebral infarcts in children with sickle cell disease in Kuwait. Any patient with a previous seizure or other neurological abnormality was excluded. MRI was done with a 1.5 Tesla unit with super-conducting magnet. T1- and T2-weighted sagittal and axial sections and proton density axial images were obtained in 5-mm thick sections. The study group consisted of 30 (23 SS and 7 Sbeta(0)Thal) patients-19 males and 11 females-whose ages ranged from 6 to 17 (mean of 9.8 +/- 3.5) years. Hb F ranged from 11% to 35% with a mean of 22.8% +/- 5.7%. Only one patient, a 10-and-a-half-year-old boy with Hb SS, showed hyperintense signals in the parietal white matter, consistent with small infarcts, thus giving a prevalence of 3.3%. Silent brain infarcts are uncommon in our patients, and the protective factors remain to be fully elucidated.

Temporal sequence of splenic dysfunction in sickle cell disease.

Sickle cell patients develop splenic dysfunction early in the course of their disease as shown by failure to visualize the organ on technetium-99m colloid scintigraphy. However, preliminary studies from our center have shown that, when the spleen is not demonstrable on colloid uptake, it may be visualized on technetium-99m heat-denatured RBC scintigraphy. With time, however, the spleen can no longer be visualized with both tests in many patients. We have studied 46 patients aged 2 to 16 years, which included 36 SS, 7 Sbeta(0) thal, and 3 SD. Eighteen (39.1%) had normal splenic colloid uptake (Group 1), 15 (32.6%) had partial uptake (Group 2), and 13 (28.3%) had absent uptake (Group 3). When the patients in Group 1 were compared to those in the two other groups, there was no significant difference in the mean age and Hb F values. However, the mean Hb of 10.2 g/dl in Group 1 was significantly higher than the value of 9.0 g/dl in the other two groups. In addition, 60% of the SS patients with normal uptake and 40% of those with partial or absent uptake had co-existing alpha-thal trait; the difference in this proportion is significant (chi(2) = 85, P < 0.0001). Heat-denatured RBC scintigraphy was carried out on five patients in Group 2, and the spleen was visible in all, while of 12 children in Group 3, the spleen was visible only in 4 patients. This study demonstrates that the phagocytic function of the spleen, which is tested by colloid uptake, is the first to be lost while the filtration function, tested by denatured RBC uptake, persists for much longer. This finding may have significant implications for the clinical symptomatology and therapeutic strategies of sickle cell disease.

Avascular necrosis of the hip in children with sickle cell disease and high Hb F: magnetic resonance imaging findings and influence of alpha-thalassemia trait.

Avascular necrosis (AVN) of the hip is a common cause of morbidity in sickle cell disease (SCD). Its prevalence increases with age and predisposing factors include coexistent alpha-thalassemia trait, frequent vaso-occlusive crisis and a high hematocrit (Hct). SCD is relatively mild among Kuwaiti patients because of their elevated Hb F levels, but a subset exists with severe recurrent vaso-occlusive crises. We carried out a prospective magnetic resonance imaging (MRI) study of the hip in a group of patients being followed in the Pediatric Hematology clinics of Al-Mubarak and Al-Amiri Hospitals. The association of AVN with age, frequency of hospitalization, alpha-thal trait, steady-state Hb, Hct, Hb F, WBC and platelet counts was investigated. MRI was carried out with a 1.5-tesla GE unit with a super-conducting magnet. Thirty patients (19 males, 11 females) (23 SS and 7 SbetaThal) were studied. Their ages ranged from 6 to 17 years, with a mean of 9.8 +/- 3.5 years, and Hb F from 11 to 35% with a mean of 22.8 +/- 5.7%. Among the SS patients, 11 (47.8%) had coexistent alpha-thal trait (-3.7-kb deletion). A total of 8 (26.7%) patients (6 SS and 2 SbetaThal) had varying degrees of osteonecrosis of the hip. Four (36.4%) of the 11 SS patients with alpha-thal trait and 2 (16.7%) of those without alpha-thal trait had osteonecrosis. This difference is, however, not statistically significant (chi(2) = 0.3, p = 0.5). While there was also no significant difference in the mean age and hematological parameters (Hb, Hct, Hb F, WBC, platelets), the SS patients with osteonecrosis had a significantly higher number of hospitalizations for vaso-occlusive crisis in the preceding 3 years than those without osteonecrosis.

Frequency of the 677 C-->T mutation of the methylenetetrahydrofolate reductase gene among Kuwaiti sickle cell disease patients.

Sickle cell disease (SCD) is relatively mild among Kuwaiti Arabs. However, an atypical subset of patients exists with frequent, severe vaso-occlusive crisis and osteonecrosis. The thermolabile variant of MTHFR, resulting from a C-->T mutation at nucleotide 677, has been shown to be associated with hyperhomocysteinemia, which is an important risk factor for premature vascular disease. We have screened an unselected group of 41 Kuwaiti SCD patients (33 SS and 8 Sbeta(0)-thal) attending the Hematology Clinic of Kuwait University Teaching Hospital for the MTHFR mutation, using a PCR-RFLP method. The patients were aged 2-41 years (mean of 12.8 +/- 8.6). One (2.4%) individual was homozygous for the mutation while 15 (36.6%) were heterozygous, giving an allele frequency of 20.7%. Twenty-one patients (14 SS and 7 Sbeta(0)-thal) were screened for osteonecrosis using MRI of the hip (spin-echo T1- and T2-weighted images). Seven (33.3%) had varying degrees of osteonecrosis, among whom the frequency of the 677 C-->T allele was 21.4%. The frequency was identical among those without osteonecrosis. Although the allele frequency is higher among our patients compared to American SS patients, our results do not suggest an association with osteonecrosis.

Th1 and Th2 cytokine profiles in sickle cell disease.

We have investigated the levels of Th1 (IL-2 and IFN-gamma) and Th2 (IL-4) cytokines in the plasma and supernatants following peripheral blood mononuclear cell culture and mitogen stimulation in a group of 39 patients with sickle cell disease (SCD) made up of 29 SS, 8 Sbeta-thal and 2 Hb SD in steady state. Five SS patients were studied during 7 episodes of vaso-occlusive crisis. Twenty-four control (3 Hb AS and 21 Hb AA) were also studied; 10 were acutely ill while 14 were healthy at the time of the study. The plasma levels of IL-2 and IFN-gamma were similar in the patients and the controls. However, plasma IL-4 was significantly higher among the steady-state SS patients than in the controls. While there was no significant difference in cytokine levels following mitogen stimulation in the different groups, plasma IL-2 to IL-4 and IFN-gamma to IL-4 ratios were significantly lower among the steady-state SS patients, indicating a possible Th2 bias in our sickle cell patients and suggesting a possible mechanism to explain the predisposition of SCD patients to bacterial infections. However, SS patients with good splenic function showed a relative Th1 bias, which may be an additional explanation for the protection against bacterial infections in such patients.

A comparative study of perception of sickle cell anaemia by married Nigeria rural and urban women.

Environmental factors may influence perception of or attitude to chronic disorders. The perception of sickle cell anaemia (SCA by 165 married Nigerian rural and 507 urban women was studied to determine how living in an urban or rural environment may influence perception. None of the subjects had children with SCA. The instrument used for data collection was a structured questionnaire designed to enquire into their knowledge about the cause, precipitating factors for crises, clinical features of SCA and their opinions regarding traditional and modern treatment options for the disorder. As a group, urban women had better knowledge about SCA than rural women probably because their social environment afforded a wider scope for interaction with and information exchange among people. For most respondents, the educational institutions attended the health institutions in the locality and the electronic media were poor sources of information on SCA. The study showed a serious lack of information about important aspects of SCA among rural women. We think the training of primary health care providers as counsellors on SCA, the inclusion of instruction about SCA in the curriculum of schools and sustained outreach programmes on SCA on the electronic media would ensure early education of people in both rural and urban communities and help to improve perception of the disorder.

Tumor necrosis factor-alpha is undetectable in the plasma of SS patients with elevated Hb F.

Steady-state sickle cell disease (SCD) patients may have increased plasma levels of acute phase reactants and pro-inflammatory cytokines because of subclinical inflammation. We have estimated TNF-alpha levels in the plasma and in supernatants following peripheral blood mononuclear cell (PBMC) activation with phytohemagglutinin (PHA) in a group of Kuwaiti SCD patients using ELISA. The group consisted of 28 SS, 8 Sbeta-thal, and 2 SD patients all in steady state; 5 SS patients were studied during 7 episodes of painful crisis. The subjects were aged 2 to 16 years, with a mean of 7.3 +/- 3.5 years. The beta(S)-globin gene cluster haplotype, alpha-tha1 status, and spleen function were determined in the SS group using standard techniques. Most (82%) were homozygous for the Saudi Arabia/India haplotype and had elevated Hb F levels ranging from 15% to 35%. There were 24 controls (Hb AA or AS), of whom 14 were healthy and 10 were acutely ill at the time of the study. None of the children with SCD (either in steady state or crisis) had detectable plasma TNF-alpha, but four controls (3 acutely ill and one healthy) had levels ranging from 61.7 to 249.8 pg/mL. Following PHA stimulation most subjects responded with high levels of TNF-alpha, with the median level among the steady-state SS patients being significantly higher than that in the controls (both the acutely ill or healthy). It therefore appears that because of the mild disease among our Arab SS children, TNF-alpha is not detectable in their plasma in steady state; these children, however, had a significantly higher response than controls following PBMC activation.

GM-CSF in sickle cell anemia patients with elevated Hb F.

We estimated plasma GM-CSF levels in a group of 28 steady-state sickle cell anemia (SS) patients in Kuwait, using an ELISA technique. There were 24 age-matched Hb AA controls, 14 of whom were healthy while 10 were acutely ill at the time of the study. Five SS patients were also studied during 6 episodes of painful crisis. Among the SS patients, 82.1% were homozygous for the Saudi Arabia/India (SAI) haplotype with Hb F ranging from 15 to 35% and total Hb from 8.5 to 11 g/dl. Three patients (siblings) were SAI/Benin compound heterozygotes with Hb F of 9-23% and total Hb >10 g/dl. One patient each was homozygous for the Benin or the Bantu haplotype; they had Hb F <2% and total Hb of 6.6 and 7.2 g/dl, respectively. Four (14. 3%) steady-state SS patients had detectable plasma GM-CSF ranging from 75 to 1,817.6 pg/ml. These included the 2 patients with Hb F <2. 0% and 2 with the SAI/Benin compound heterozygotes with Hb F of 11 and 9%, respectively. Four (66.7%) SS patients in crisis, 6 (42.9%) healthy controls and 6 (60%) acutely ill controls had detectable plasma GM-CSF. A clearcut association of GM-CSF with Hb F level or degree of anemia in steady-state SS patients could not be established. The appearance of GM-CSF in the plasma of patients in crisis and also among control subjects raises the possibility that other factors are involved in the production of this cytokine in the subjects studied.