Multi-center study on mortality in children, and adults with sickle cell anemia-risk factors and causes of death.

Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21-35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p < 0.05, Wilcoxon Signed Ranks test). All patients received antibiotics, whereas, 95.9% and 93.5% received simple blood transfusions, and exchange transfusions respectively, and 66.6% required non-invasive ventilation. Among the causes of death, ACS is seen in 32 (26%), sepsis in 49 (40%), and miscellaneous in 42 (34%). Sudden death was seen in 32 (26%) of patients. Male gender, with low HbF, rapid drop in Hb and platelet, and increased in WBC, LDH, ferritin, and CRP, correlated significantly with mortality in this cohort.

Influence of Voxelotor-hemoglobin complexes in the estimation of hemoglobin S levels by the current standard of care laboratory evaluation techniques.

Background: Sickle cell disease is an inherited disorder characterized by the presence of sickle hemoglobin (HbS). The process of Hb molecule polymerization is a pivotal step in the sickling process. Voxelotor, a recently approved novel therapeutic agent, is known to interfere with polymerization. We aim to study the impact of Voxelotor on Hb variants analysis using high performance liquid chromatography (HPLC). Material and methods: We are reporting the impact of Voxelotor on Hb variants analysis using HPLC after an informed consent and medical research committee approval. Data was collected from eight patients who are enrolled in the GBT440-034OL study using electronic medical records, to evaluate the Hb levels, hemolytic markers and the clinical response. Results: Our patients were well-balanced for gender, with a mean age of 31.1 years (19-50). Six patients showed a significant improvement in the Hb level, with reduced reticulocytes, bilirubin, LDH and an improved clinical outcome. Interestingly, these patients showed the appearance of a split band of Hb S and D on HPLC impacting significantly on HbS level. Two patients did not show any improvement on laboratory parameters, and no changes on their HPLC analysis. Conclusions: We report here eight patients on Voxelotor therapy, six of which showed improved hemolytic markers and anemia and demonstrated the appearance of HbD peak on the HPLC chromatogram. Therefore, the absence of HbD on HPLC or other laboratory methods for estimating HbS in patients on Voxelotor therapy, gives the clinician a possible hint regarding the patient's compliance with the drug.

Predicting risk factors for thromboembolic complications in patients with sickle cell anaemia - lessons learned for prophylaxis.

OBJECTIVE: To assess the clinical and laboratory predictors of venous thromboembolism (VTE) in patients with sickle cell anaemia (SCA) and its relationship to morbidity and mortality. METHODS: This retrospective case-control study analysed data from patients with SCA that experienced VTE compared with matched control patients with SCA but no VTE (2:1 ratio). RESULTS: A total of 102 patients with SCA were enrolled (68 cases with VTE and 34 controls). Amongst the 68 cases (median age, 29.5 years), 26 (38.2%) presented with isolated pulmonary embolism (PE). A higher prevalence of splenectomy (73.5% versus 35.3%) was observed in the cases compared with the controls. A significantly higher prevalence of central venous catheter (CVC) insertion (42.6% versus 8.8%) was observed in the cases compared with the controls. High white blood cell counts, serum lactic dehydrogenase (LDH), bilirubin and C-reactive protein (CRP) and low haemoglobin (Hb) and HbF were significant risk factors for VTE. Forty-two cases (61.8%) developed acute chest syndrome, 10 (14.7%) had a stroke and seven (10.3%) died. CONCLUSIONS: VTE in patients with SCA has a high impact on morbidity and mortality. PE was the leading presentation of VTE, with CVC insertion, high LDH, bilirubin, CRP and white blood cell counts along with low Hb and HbF constituting other significant risk factors.

Iron Overload in Patients With Heavily Transfused Sickle Cell Disease-Correlation of Serum Ferritin With Cardiac T2* MRI (CMRTools), Liver T2* MRI, and R2-MRI (Ferriscan®).

The treatment of sickle cell disease (SCD) is mainly supportive, except for a minority, who receive bone marrow transplantation (BMT). Serum ferritin (SF) is routinely available but is notoriously unreliable as a tool for iron-overload assessment since it is an acute-phase reactant. Although blood transfusion is one of the most effective ways to deal with specific acute and chronic complications of SCD, this strategy is often associated with alloimmunization, iron overload, and hemolytic reactions. This study, thus, aims to evaluate iron overload in patients with SCD on chronic blood transfusions and specifically, correlate SF with the current standard of care of iron-overload assessment using MRI-based imaging techniques. Amongst a historic cohort of 58 chronically transfused patients with SCD, we were able to evaluate 44 patients who are currently alive and had multiple follow-up testing. Their mean age (±SD) was 35 (9) years and comprised of 68.2% of women. The studied iron-overload parameters included cardiac T2* MRI, liver iron concentration (LIC) by Liver T2* MRI, and serial SF levels. Additionally, in a smaller cohort, we also studied LIC by FerriScan© R2-MRI. Chronic blood transfusions were necessary for severe vaso-occlusive crisis (VOC) (38.6%), severe symptomatic anemia (38.6%), past history of stroke (15.9%), and recurrent acute chest syndrome (6.9%). About 14 (24%) patients among the original cohort died following SCD-related complications. Among the patients currently receiving chelation, 26 (96%) are on Deferasirox (DFX) [Jadenu® (24) or Exjade® (2)], with good compliance and tolerance. However, one patient is still receiving IV deferoxamine (DFO), in view of the significantly high systemic iron burden. In this evaluable cohort of 44 patients, the mean SF (±SD) reduced marginally from 4,311 to 4,230 ng/ml, mean Liver T2* MRI dropped from 12 to 10.3 mg/gm dry weight, while the mean cardiac T2*MRI improved from 36.8 to 39.5 ms. There was a mild to moderate correlation between the baseline and final values of SF ng/ml, r = 0.33, p = 0.01; Cardiac T2* MRI ms, r = 0.3, p = 0.02 and Liver T2* MRI mg/kg dry weight, r = 0.6, p < 0.001. Overall, there was a positive correlation between SF and Liver T2* MRI (Pearson's r = 0.78, p < 0.001). Cardiac T2*MRI increased with the decreasing SF concentration, showing a negative correlation which was statistically significant (Pearson's r = -0.6, p < 0.001). Furthermore, there was an excellent correlation between SF ng/ml and LIC by FerriScan© R2-MRI mg/g or mmol/kg (Spearmen's rho = -0.723, p < 0.008) in a small subset of patients (n = 14) who underwent the procedure. In conclusion, our study demonstrated a good correlation between serial SF and LIC by either Liver MRI T2* or by FerriScan© R2-MRI, even though SF is an acute-phase reactant. It also confirms the cardiac sparing effect in patients with SCD, even with the significant transfusion-related iron burden. About 14 (24%) patients of the original cohort died over the past 15 years, indicative of a negative impact of iron overload on disease morbidity and mortality.

Red Cell Alloimmunization to Rhesus Antigen Among Pregnant Women Attending a Tertiary Care Hospital in Oman.

OBJECTIVES: The detection of maternal alloimmunization against red cell antigens is vital in the management of hemolytic disease of the fetus and newborn. We sought to measure the presence of allosensitization to Rhesus D (RhD) antibodies in antenatal women attending a tertiary care hospital and assess the fetal outcome in sensitized women. METHODS: We conducted a retrospective review of pregnant Omani women who registered at the Sultan Qaboos University Hospital between June 2011 and June 2013. Pregnant women were tested for ABO blood type and were screened for RhD antigen and antibodies at their first antenatal clinic visit. In women who tested positive for the RhD antibodies, an antibody titer was performed to evaluate the severity of their case. RESULTS: Data was available on 1,251 pregnant women who were managed and delivered at Sultan Qaboos University Hospital. The prevalence of RhD negative pregnant women was 7.3%. Blood group O was the most common followed by A, B, and AB. The rate of RhD negative alloimmunization was 10%, and anti-D was the most common antibody detected. There were no stillbirths or neonatal deaths. Postnatal transfusion was necessary for only one baby. CONCLUSIONS: The prevalence of RhD negativity was comparable to other Asian countries. Previous RhD alloimmunization and history of miscarriages were the most common maternal medical history.

Prevalence of methicillin resistant Staphylococcus aureus [MRSA] colonization or carriage among health-care workers.

In Oman, the prevalence of health care associated methicillin resistant Staphylococcus aureus [HA-MRSA] is unknown. Therefore, to estimate the prevalence of HA-MRSA, we collected nasal swabs and swabs from cell phones on sterile polyester swabs and immediately inoculated on the mannitol salt agar containing oxacillin from medical students and hospital health care providers. Antibiotic susceptibility testing of the isolates was then performed using the Kirby Bauer's disc diffusion method. Additionally, a brief survey questionnaire was used to acquire demographic data. Amongst the 311 participants enrolled, nasal colonization with HA-MRSA was found in 47 individuals (15.1%, 95% confidence interval [CI]=11.1%, 19.1%). HA-MRSA was also isolated from the cell phone surfaces in 28 participants (9.0%, 95% CI=8.6%, 9.3%). 5 participants (1.6%) showed positive results both from their nasal swabs and from their cell phones. Antibiotic resistance to erythromycin [48%] and clindamycin [29%] was relatively high. 9.3% HA-MRSA isolates were vancomycin resistant [6.6% nasal carriage]. There was no statistically significant correlation between HA-MRSA isolates and the demographic characteristics or the risk factors namely gender, underlying co-morbidities like diabetes, hypertension, skin/soft tissue infections, skin ulcers/wounds, recent exposure to antibiotics, or hospital visits (p>0.05, Chi-square test).

Comparison of Methicillin Resistant Staphylococcus Aureus in Healthy Community Hospital Visitors [CA-MRSA] and Hospital Staff [HA-MRSA].

BACKGROUND: The prevalence of community-associated methicillin-resistant Staphylococcus aureus [CA-MRSA] is unknown in Oman. METHODS: Nasal and cell phones swabs were collected from hospital visitors and health-care workers on sterile polyester swabs and directly inoculated onto a mannitol salt agar containing oxacillin, allowing growth of methicillin-resistant microorganisms. Antibiotic susceptibility tests were performed using Kirby Bauer's disc diffusion method on the isolates. Minimum inhibitory concentration (MIC) was determined for vancomycin and teicoplanin against the resistant isolates of MRSA by the Epsilometer [E] test. A brief survey questionnaire was requested be filled to ascertain the exposure to known risk factors for CA-MRSA carriage. RESULTS: Overall, nasal colonization with CA-MRSA was seen in 34 individuals (18%, 95% confidence interval [CI] =12.5%-23.5%), whereas, CA-MRSA was additionally isolated from the cell phone surface in 12 participants (6.3%, 95% CI =5.6%-6.98%). Nasal colonization prevalence with hospital-acquired [HA] MRSA was seen in 16 individuals (13.8%, 95% confidence interval [CI] =7.5%-20.06%), whereas, HA-MRSA was additionally isolated from the cell phone surface in 3 participants (2.6%, 95% CI =1.7-4.54). Antibiotic sensitivity was 100% to linezolid and rifampicin in the CA-MRSA isolates. Antibiotic resistance to vancomycin and clindamycin varied between 9-11 % in the CA-MRSA isolates. Mean MIC for vancomycin amongst CA- and HA-MRSA were 6.3 and 9.3 µg/ml, whereas for teicoplanin they were 13 and 14 µg/ml respectively by the E-test. There was no statistically significant correlation between CA-MRSA nasal carriage and the risk factors (P>0.05, Chi-square test). CONCLUSIONS: The prevalence of CA-MRSA in the healthy community hospital visitors was 18 % (95% CI, 12.5% to 23.5%) as compared to 13.8% HA-MRSA in the hospital health-care staff. Despite a significant prevalence of CA-MRSA, these strains were mostly sensitive. RECOMMENDATION: The universal techniques of hand washing, personal hygiene and sanitation are thus warranted.

Aetiological profile of women presenting with premature ovarian failure to a single tertiary care center in Oman.

BACKGROUND: Premature ovarian failure is estimated to affect at least 1%-3% of adult women. There are several aetio-pathogenic factors that may cause premature ovarian failure including iatrogenic causes, genetic, autoimmune, infectious and idiopathic. The aim of this study was to identify the aetiological profile of women with premature ovarian failure presenting to Sultan Qaboos University hospital. METHOD: A retrospective medical record review was conducted from June 2006 to October 2012. All women diagnosed with symptoms and/or laboratory evidence of premature ovarian failure (follicle stimulating hormone ≥40 UI/L and less than 40 years of age) were enrolled in this study. Possible causes of premature ovarian failure were obtained and classified into main aetiological factors. RESULTS: There were 90 patients during the study period, of which, 39 (43%) were following chemotherapy and bone marrow transplant. The second most common reason was idiopathic (n = 29; 31%) followed by autoimmune diseases (n = 8; 9%) and genetic disorders (n = 7; 8%). Most chemotherapy cases (69%) were among the young age group, while in the older age group idiopathic was the commonest (48%). CONCLUSION: Compared to the world literature, the most common cause of premature ovarian failure in this study was chemotherapy induced, especially in young girls undergoing bone marrow transplantation. This is due to high prevalence of transplantable hereditary haematological disorders like thalassemia and sickle-cell disease in this part of the world. Current standard of care recommends cryopreservation of ovarian tissue to preserve ovarian function in young girls undergoing bone marrow transplantation for such disorders.

A stepwise α-thalassemia screening strategy in high-prevalence areas.

INTRODUCTION: Coinheritance of α-thalassemia influences the clinical and hematological phenotypes of ß-hemoglobinopathies (ß-thalassemia and sickle cell disease) and when present together in significant frequency within a population, a spectrum of clinical forms is observed. Precise molecular characterization of α-thalassemia is important in understanding their disease-modifying role in ß-hemoglobinopathies and for diagnostic purposes. PATIENTS AND METHODS: Because currently used approaches are labor/cost-intensive, time-consuming, error-prone in certain genotype combinations and not applicable for large epidemiological screening, we developed a systematic stepwise strategy to overcome these difficulties. We successfully applied this to characterize the α-globin gene status in 150 Omani cord blood samples with Hb Barts and 32 patients with HbH disease. RESULTS: We observed a good correlation between α-globin genotypes and level of Hb Bart's with the Hb Bart's levels significantly higher in both deletional and non-deletional α-globin genotypes. The most common α-globin genotype in HbH cases was α(TSaudi) α/α(TSaudi) α (n = 16; 50%) followed by -α(3.7) /-(MED) (n = 10; 31%). This approach detects also the α-globin gene triplication as exemplified by the study of a family where the ß-globin gene defect failed to explain the ß-thalassemia intermedia phenotype. CONCLUSION: Molecular characterization of α-thalassemia is complex due to high sequence homology between the duplicated α-globin genes and to the existence of a variety of gene rearrangements (small and large deletions of various sizes) and punctual substitutions (non-deletional alleles). The novelty of our strategy resides, not in the individual technical steps per se but in the reasoned sequential order of their use taking into consideration the hematological phenotype as well.

Warfarin pharmacogenetics: polymorphisms of the CYP2C9, CYP4F2, and VKORC1 loci in a genetically admixed Omani population.

This is the first study to evaluate the spectrum and prevalence of dose-predictive genetic polymorphisms of the CYP2C9, CYP4F2 and VKORC1 loci together, in a geographically defined, ethnically admixed healthy adult Omani population sharing common lifestyle/environmental factors. Since the present-day Omani population is the result of an admixture of Caucasian, African and Asian ancestries, we compared the pharmacogenetic profile of these three loci in this population. Interestingly, the Omani pharmacogenetic profile, in terms of allele and genotype distribution, has values that are intermediate between Caucasians and African Americans, the African admixture further substantiated by the presence of the CYP2C9*8 allele. However, limitations and usefulness of such comparisons warrant caution, as the data from pharmacogenetic literature do not always represent bona fide population categories. Furthermore, definition of study population based on microgeographical scale would be more appropriate in pharmacogenetic research rather than the flawed racial, ethnic, or social categorizations since pharmacogenetic variation is clinal, and genetic influences will be further altered by lifestyle and environmental factors.

Tumor necrosis factor-α and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis.

AIM: To evaluate the role of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis (SBP). METHODS: We prospectively studied 120 cirrhotic patients with SBP and 80 cirrhotic patients with sterile ascitic fluid. They included 144 males and 56 females with ages ranging between 34 and 62 years. The diagnosis of cirrhosis was established by clinical and laboratory criteria that did not require histological confirmation. The severity of underlying liver disease was evaluated using Pugh's modification of Child's criteria (Child-Pugh scores). Ascitic fluid was sent to the laboratory for cell count, culture, sensitivity testing, and measurement of chemical elements (i.e., albumin, glucose). Specimens were inoculated into aerobic and anaerobic blood culture bottles. Serum and ascitic fluid were also collected in sterile tubes at study entry (before the initiation of antibiotic treatment) and 48 h later. Assays for TNF-α and IL-6 in the serum and ascitic fluid were performed with an immunoenzymometric assay using manufacture's instructions. RESULTS: Cytokine levels in serum and ascitic fluid were significantly higher in the patients with SBP. (plasma TNF-α: 135.35 ng/mL ± 11.21 ng/mL vs 92.86 ng/mL ± 17.56 ng/mL, P < 0.001; plasma IL-6: 32.30 pg/mL ± 7.07 pg/mL vs 12.11 pg/mL ± 6.53 pg/mL, P < 0.001; ascitic fluid TNF-α: 647.54 ± 107.11 ng/mL vs 238.43 ng/mL ± 65.42 ng/mL, P < 0.001); ascitic fluid IL-6: 132.84 ng/mL ± 34.13 vs 40.41 ± 12.85 pg/mL, P < 0.001). About 48 (40%) cirrhotic patients with SBP developed renal and hepatic impairment and showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection. [(plasma TNF-α: 176.58 ± 17.84 vs 135.35 ± 11.21 ng/mL) (P < 0.001) and (IL-6: 57.83 ± 7.85 vs 32.30 ± 7.07 pg/mL) (P < 0.001); ascitic fluid TNF-α: 958.39 ± 135.72 vs 647.54 ± 107.11 ng/mL, (P < 0.001), ascitic fluid IL-6: 654.74 ± 97.43 vs 132.84 ± 34.13 pg/mL, (P < 0.001)]. Twenty nine patients (60.4%) with SBP and renal impairment died whereas, only four patients (5.55%) with SBP but without renal impairment died from gastrointestinal hemorrhage (P < 0.0005). CONCLUSION: It appears that TNF-α production may enhance liver cell injury and lead to renal impairment. This correlated well with the poor prognosis and significantly increased mortality associated with SBP in cirrhotic patients.

dRTA and hemolytic anemia: first detailed description of SLC4A1 A858D mutation in homozygous state.

Mutations in the anion exchanger 1 (AE1) gene encoding the erythroid and kidney anion (chloride-bicarbonate) exchanger 1 may result in familial distal renal tubular acidosis (dRTA) in association with membrane defect hemolytic anemia. Seven children presenting with hyperchloremic normal anion gap metabolic acidosis, failure to thrive, and compensated hemolytic anemia were studied. Analysis of red cell AE1/Band 3 surface expression by Eosin 5'-maleimide (E5M) was performed in patients and their family members using flow cytometry. Genetic studies showed that all patients carried a common SLC4A1 mutation, c.2573C>A; p.Ala858Asp in exon 19, found as homozygous (A858D/A858D) mutation in the patients and heterozygous (A858D/N) in the parents. Analysis by flowcytometry revealed a single uniform fluorescence peak, with the mean channel fluorescence (MCF) markedly reduced in cases with homozygous mutation, along with a left shift of fluorescence signal but was only mildly reduced in the heterozygous state. Red cell morphology showed striking acanthocytosis in the homozygous state [patients] and only a mild acanthocytosis in heterozygous state [parents]. In conclusion, this is the first description of a series of homozygous cases with the A858D mutation. The E5M flowcytometry test is specific for reduction in the Band 3 membrane protein and was useful in conjunction with a careful morphological examination of peripheral blood smears in our patient cohort.

Protein Z levels in pregnant Omani women: correlation with pregnancy outcome.

Placental insufficiency resulting in fetal loss has been recognized in women with thrombophilic predisposition. Recent studies indicate that there is a high prevalence of protein Z (PZ) deficiency in patients with unexplained fetal loss. The objective of this study was to measure the PZ levels in pregnant Omani women in the first, second and third trimesters and correlate with the pregnancy outcome. The study enrolled 126 consecutive pregnant women after an informed consent prospectively. PZ was estimated in the first, second and third trimester in 15, 97 and 66 pregnant women respectively and they were followed for pregnancy outcomes including live birth, still birth, spontaneous abortion/induced abortion, maternal complications, fetal complications and health risks/complications in the newborn. The median PZ level (Mean ± SD) in the first, second and third trimester were 0.98 (1.07 ± 0.46), 1.3 (1.36 ± 0.61) and 1.44 (1.43 ± 0.69) (P < 0.05, Student's t-test, between first vs. second and first vs. third trimester). PZ deficiency defined as PZ level below 0.54 µg/ml (below 10th centile in the Omani population) was observed in 4 (4.7%) women, but interestingly all had a normal pregnancy outcome. Amongst the 43 subjects in whom paired PZ estimations were available, reducing PZ levels were observed from baseline values in 8 (33%) with normal pregnancy outcome; 5 (55%), with diabetes; 3 (50%) with hypertension and 2 (50%) with low birth weight respectively (P < 0.05, chi square test). PZ values increased progressively during the three trimesters of pregnancy. However, this increase is blunted in patients with abnormal pregnancy outcome like low birth weight babies or pregnancies associated hypertension or diabetes. Isolated PZ deficiency alone did not result in an abnormal outcome in this cohort of subjects.

Sensorineural hearing loss in sickle cell disease--a prospective study from Oman.

BACKGROUND: Sickle cell disease (SCD) is characterized by intermittent episodes of vascular occlusion and end-organ damage. Neurologic symptoms are frequent and auditory involvement is not unexpected. AIM: To study the prevalence and pattern of hearing loss in Omani patients with SCD. METHODS: We conducted a prospective case control study on SCD patients attending the outpatient department. Age and sex matched normal volunteer blood donor controls were recruited after an informed consent and Medical Ethics Committee approval. Pure tone audiometry was performed in all cases studied. RESULTS: Forty-six SCD patients (15 males, 32.6%) aged 16-45 years with a mean age of 26 years ± 6.9 and 29 controls (10 males, 34.4%) aged 16-39 years with a mean age of 25.24 ± 8.2 were enrolled in this study. The average hearing thresholds of SCD patients were consistently higher than controls in all frequencies tested in both ears. Of the 92 ears tested in SCD patients, 29.34% had SNHL. Ten patients had bilateral SNHL; whereas 3 and 4 cases had SNHL in left and right ears, respectively. All the control subjects had hearing thresholds within normal limits. SUMMARY/CONCLUSIONS: The study reveals a significant incidence of sensorineural hearing loss (SNHL) in SCD patients (36.95%), although the patients were clinically asymptomatic. The hearing loss was worse in the right ears and had a female preponderance. Also, the hearing loss was more severe at the higher frequencies, 2,000-8,000 Hz in SCD patients. HbS, HbF, or low hemoglobin levels did not discriminate SCD patients with SNHL, and the role of hemoglobin F in the cochlea is still not clear. Regular audiometric assessment should therefore be recommended in SCD patients routinely.

Isochromosome 9q as a sole anomaly in an Omani boy with acute lymphoblastic leukaemia.

This report describes a case of acute lymphoblastic leukaemia in which isochromosome 9q (i(9q)) was the sole acquired cytogenetic abnormality. The Immunophenotype showed positivity for CD3, CD4, CD5, CD7, CD8, CD10, CD71, CD117 and TdT, consistent with T cell acute lymphoblastic leukaemia (ALL). The chromosomal analysis of bone marrow showed 46,XY,i(9)(q10) in all the metaphases analysed. The bone marrow morphology was ALL-L2 as per the French-American-British criteria. Isochromosomes are rare chromosomal abnormalities in childhood ALL and the effect of i(9q) is not well established. The patient's good response to therapy with normal cytogenetics within a month of induction, and disease-free survival after bone marrow transplant are indicative of a good prognosis in such cases.

Haematological and clinical features of beta-thalassaemia associated with Hb Dhofar.

Hb Dhofar is a variant haemoglobin (beta(29 (GGC-GGT) gly-gly), beta(58 (CCT-CGT) pro-arg)) associated with a thalassaemic phenotype and unique to the Sultanate of Oman. We report clinical and haematological data on 54 subjects with Hb Dhofar (37 heterozygotes, 14 homozygotes and three compound heterozygotes with a different beta-thalassaemia mutation). In heterozygotes, the level of Hb Dhofar ranged from 8.8% to 21.5%. All heterozygotes had Hb A2 > 3.5%, consistent with beta-thalassaemia trait. Hb Dhofar in homozygotes and compound heterozygotes ranged from 26% to 59.7%, with a peripheral film consistent with homozygous beta-thalassaemia. Age at presentation in homozygotes ranged between 6 months and 8 yr, with a majority presenting before 5 yr of age. All had splenomegaly and six (43%) had undergone splenectomy. All had some degree of frontal bossing and in particular, two patients with infrequent transfusions had marked thalassaemic facies and stunting of growth. Hb Dhofar can be mistaken for Hb D as the electrophoretic mobility is similar, but differs from it by a variable and reduced quantity of variant Hb in both heterozygotes and homozygotes. Clinical and haematological data suggest that this mutation behaves like a moderately severe beta(+) thalassaemia allele resulting in a thalassaemia intermedia phenotype.

Recurrent priapism in sickle cell trait with protein S deficiency.

We report the case of a young Omani man, a regular blood donor, who presented twice in two months, with painful penile erection lasting more than 12 hours. The patient is known to have sickle cell trait [HbS 34.6%]. Although the first episode of penile erection settled with aspiration of blood and local injection of epinephrine, on the second occasion necessitated cavernosal glandular shunting. A subsequent investigation revealed a mild protein S deficiency. Although priapism is known to occur in sickle cell disease, it is unusual in sickle cell trait. Association of mild protein S deficiency with erythrocytosis could have precipitated the onset of priapism.

Trisomy 21 as a sole acquired abnormality in an adult Omani patient with CD7- and CD9-positive acute myeloid leukemia.

We describe a case of acute myeloid leukemia (AML) in which trisomy 21 was the sole acquired cytogenetic abnormality. The immunophenotype showed positivity for CD7 and CD9 along with CD13, CD33, and CD34. The chromosomal analysis of bone marrow showed 47,XY +21 in all the metaphases analyzed. The constitutional karyotype was normal. The patient was an adult and did not have any features of Down's syndrome. The bone marrow morphology was AML-M2 as per the French-American-British (FAB) criteria. A final diagnosis of CD7- and CD9-positive AML-M2 was established with trisomy 21 as a sole cytogenetic abnormality. The patient responded remarkably well to chemotherapy and achieved complete clinical remission. This is the first case of CD7- and CD9-positive AML with trisomy 21 as a sole abnormality. A putative role for the co-expression of abnormal lymphoid markers in achieving quick remission is discussed.