Correlates of pulmonary function in children with sickle cell disease and elevated fetal hemoglobin

Objective: The current study was carried out to compare pulmonary function tests [PFTs] in pediatric Kuwaiti sickle cell disease [SCD] patients to age-matched normal controls and to investigate the association of PFTs with selected clinical and laboratory parameters

Subjects and Methods: There were 38 patients with SCD and 36 controls in the study. The patients were recruited from the Pediatric Hematology Clinics of Mubarak AI-Kabeer and AI-Amiri Hospitals, Kuwait, and were studied in steady state. The controls were healthy, non-sickle cell siblings of the patients. Forced expiratory volume in 1 s [FEV], forced vital capacity [FVC], total lung capacity, and other PFT parameters were obtained using a constant-volume, variable-pressure, body plethysmograph. Hemoglobin, fetal hemoglobin, serum bilirubin, and lactate dehydrogenase were determined using standard methods

Results: The mean ages of the patients and controls were 10.5+/- 3.2 and 10.5 +/-3.5 years, respectively. The FEV/o predicted of 84.1 +/- 15.4% among the patients was significantly lower than the 92.1 =/- 11.8% in the controls [p = 0.003]. The FVC% predicted was also significantly lower [p = 0.022] in the patients than in the controls, although the values were generally within the normal range. There was no association of FEV] with pain phenotype, acute chest syndrome [ACS], or blood transfusions. Also, there was nosignificant correlation with reticulocytes, bilirubin, or lac-tate dehydrogenase

Conclusions: In this study, changes in PFT, especially FEV1; developed early in the SCD patients. There was no demonstrable association with frequent vaso-occlusive crisis, ACS, and other variables. Hence, there is a need for follow-up studies with serial PFTs to identify vulnerable patients, who might need intervention to prevent early mortality

Acquired multiple clotting factor inhibitors in children

Acquired childhood multiple clotting factor inhibitors are rare especially in the absence of lupus anticoagulants. They may represent multiple specific inhibitors or may be non-specific, resulting from molecular mimicry or cross-reacting antibodies. Their exact nature and natural history are not well known. To report our experience with seven children presenting with prolonged activated partial thromboplastin time [APTT], with or without bleeding, not corrected by mixing, and showing deficiency of > one clotting factor. Prospective review. Mubarak Hospital, Kuwait. Patients referred to the pediatric hematology unit between 2010 and 2012 with deranged coagulation profiles with or without bleeding, without a previous or family history of a bleeding disorder. They all had multiple clotting factor deficiencies. Prothrombin time [PT] and APTT assay. Control of bleeding and normalization of coagulation factors and APTT. The patients were aged 6 months to 8 years; three presented with mild to moderate bleeding and five had preceding viral infections. Factor IX was decreased in all cases in addition to deficiencies of factors VIII, X and / or XI in various combinations. There was spontaneous recovery in five patients in whom the factors and APTT normalized within two to five months. One patient died from massive pulmonary hemorrhage and another with nephropathy remains the same after two years. Multiple acquired inhibitors are not uncommon in children, tend to follow viral infections, and are usually transient and not associated with severe bleeding

Hepatic crisis in a ten-year-old Kuwaiti boy with sickle cell disease

Hepatic sickle crisis [HSC] is a rare complication of sickle cell disease [SCD] which responds to proper hydration, simple transfusion, or exchange blood transfusion. We describe the case of a ten-year-old boy who presented with severe right upper quadrant abdominal pain, jaundice, and elevated liver enzymes. Abdominal ultrasonography showed only sludge, with no gallstones or abnormal biliary tree. He did not respond to initial management with analgesics and intravenous fluids. There was prompt resolution of symptoms and biochemical derangement following exchange blood transfusion

Acquired hemophilia in a child: response to rituximab

Acquired hemophilia, secondary to factor VIII inhibitors, is very rare especially in childhood. We present the case of an otherwise healthy Kuwaiti boy who presented with spontaneous factor VIII inhibitors at the age of two years, making him one of the youngest to be reported. There was no associated acute illness, recent vaccination or drug intake except a history of mild bronchial asthma. He presented with multiple ecchymoses, but no frank bleeding. His lowest factor VIII level was 8% and highest inhibitor level was 400 Bethesda units [BU]/ml. He initially responded to a combination of intravenous immunoglobulin, prednisolone and azathioprine. However he relapsed and later became refractory to treatment. He had a trial of mycophenolate, to which he did not respond. He eventually received rituximab 375 mg/m[2] as a six-week IV course, to which he had a prompt response without any major side effects. More than two years later, his factor VIII level is about 150% and inhibitor is not detectable. It appears therefore, that even in childhood, rituximab is useful for the management of acquired factor VIII inhibitors

Rituximab in severe refractory autoimmune hemolytic anemia in children

Rituximab, an anti-CD20 monoclonal antibody, is a relatively new drug for autoimmune diseases, and its use in childhood autoimmune hemolytic anemia [AIHA] is still limited. We report our experience with two children who presented with acute severe AIHA not responding to standard treatment modalities. The first patient was a 4-month-old infant with severe AIHA who did not respond to steroids, intravenous immune gammaglobulin [IVIG], cyclophosphamide and plasmapheresis, but responded well to rituximab. The second patient was an 8-year-old with a similar presentation who did not respond to all modalities of treatment including rituximab. He eventually required a splenectomy to control his hemolysis. While rituximab is a useful addition to the treatment regime in AIHA, it is not always effective and the occasional patient may still require splenectomy

Ten-year review of hospital admissions among children with sickle cell disease in Kuwait

This study was designed to document the common causes and patterns of hospitalization among sickle cell disease [SCD] patients in Kuwait. Subjects and The case files of all SCD patients admitted to the hospital between 1995 and 2004 were studied. Their personal data, hemoglobin genotype, diagnosis on admission, complete blood count, treatment received, length of stay and outcome were documented. Fifty SCD patients aged from 10 months to 14.8 years [mean: 8.7 +/- 2.8 years] had 351 admissions over the 10-year period accounting for 0.6% of all admissions to the pediatric wards. The 50 patients were made up of 18 Hb SS, 28 Sb beta0 thal and 4 Hb SD patients. Common causes of admission were vaso-occlusive crisis: 222 [63.2%], acute splenic sequestration crisis: 32 [9.1%], hemolytic crisis: 31 [8.8%] and acute chest syndrome: 23 [6.6%]. Stroke was seen in only 1 patient, and bacteriologically proven [Salmonella] acute osteomyelitis in 1 patient. There were no deaths during the study period. Vaso-occlusive crisis was the commonest cause of hospitalization among our SCD patients. Efforts should be intensified to give advice on preventive measures. The use of hydroxyurea should be encouraged in patients with frequent severe pain crises

Hemoglobin F concentration as a function of age in Kuwaiti sickle cell disease patients

This study aimed to document the transition of hemoglobin [Hb] F levels from early childhood to adulthood in Kuwaiti sickle cell disease patients, investigating its relationship to sex, Hb genotype and coexistence of alpha-thalassemia trait. The following parameters were extracted from the patients' records: age, sex, Hb, mean corpuscular volume, mean corpuscular Hb, red blood cell count, Hb F, Hb S, Hb A 2 and alpha-globin genotype. Hb quantitation was performed with cation exchange HPLC, while alpha-globin genotype was determined by PCR. Records were available for 149 patients, made up of 94 SS and 55 S beta-thal; 83 males and 66 females, aged 3 months to 60 years [mean 10.5 +/- 1.8]. The mean Hb F level in the whole popula-tion was 21.5 +/- 8.1% and was not significantly different between males and females, and SS or S beta thal. When the age groups were analyzed, the Hb F level was highest [28.9 +/- 10.9%] in those below 5 years. Indeed, patients

Mutations associated with beta-thalassemia intermedia in Kuwait

To identify the beta -globin gene mutations associated with beta -thalassemia [beta -thal] intermedia in Kuwait. Eighteen patients from 13 unrelated families, mean age 12.7 +/- 8.1 years, range 4-31 years, were involved in the study. They did not require regular blood transfusion. Complete blood count and cation exchange high-performance liquid chromatography hemoglobin quantitation were carried out using standard techniques. beta -Thal mutations were identified with a combination of PCR amplification, allele- specific oligonucleotide hybridization or direct DNA sequencing. The patients were also screened for the alpha 2-globin gene [-3.7 kb] deletion. Of the 13 families, 4 were homozygous for the IVS-I-II [G[rightwards arrow]A] and 4 for the IVS-I-6 [T[rightwards arrow]C] mutations, while 1 each was a compound heterozygote for the following mutation combinations: CD 8 [-AA] and -101 [C[rightwards arrow]T]; IVS-I-6 [T[rightwards arrow]C] and CD 19 [A[rightwards arrow]G]; IVS-II-1 [G[rightwards arrow]A] and -28 [A[rightwards arrow]C]; IVS-I-110 [G[rightwards arrow]A] and delta beta[0] deletion. Therefore, homozygosity for two typically mild mutations [IVS-II-1 and IVS-I-6] accounted for 61% of the genotypes in our patients. Our results indicate that screening should commence with these two common alleles in Kuwaiti patients presenting with beta -thal syndrome. Early identification of intermedia patients will avoid the complications following an unnecessary hypertransfusion program