Predictors of thalassaemia carriers in Trinidad and Tobago

OBJECTIVE: To determine possible predictors of thalassaemia carriers among prospective blood donors in Trinidad and Tobago. DESIGN AND METHODS: 460 prospective blood donors were screened for microcytosis (MCV<83fL) by performing a complete blood count (CBC) using a Sysmex XE-2100. The 86 samples with microcytosis further had a blood film analysis, iron studies, haemoglobin electrophoresis, haemoglonin F and A2 quantification, and DNA analysis for thalassaemia mutations. Statistical analysis was done using SPSS to determine predictors of thalassaemia trait. The variables tested were ethnicity, haemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin volume (MCHC), red blood cell (RBC), RBC distribution width (RDW-SD and RDW-CV). We looked at different mathematical formulae to predict thalassaemia trait ie the Mentzer Index, Shine and Lal Index, Green and King Index, Srivastava Index, RDW Index and the red cell indices tested were RDW-CV, RDW-SD and RCC. RESULTS: 86 (18.7%) subjects had microcytosis. 44(51.2%) of these had DNA results. 31(70.5%) had thalassaemia trait: 25(80.6%) with genotype –α/αα, 4(12.9%) α-/α-(all α3.7), one IVS I-5 G/C and one IVSII-666 T/C. The MCV, RDW-SD and RDW-CV were useful in predicting thalassaemia trait. RDW-SD identified 30 (96.8%) of the 31 carriers, the Green and King formula identified 27 (87.1%), and Ricerca index identified all 31 (100%). CONCLUSION: MCV, RDW-SD, Green and King formula and Ricerca index may be useful predictors of thalassaemia trait in Trinidad and Tobago.

Dental and maxillofacial investigation of a 9-year old thalassemic patient

We report a case of a 9 year-old Trinidadian girl of East Indian descent with thalassemia major presenting to the University of the West Indies Child Dental Health Clinic with two features of malocclusion as the chief complaints. Subsequent extra-oral radiographic findings included classical characteristics of Thalassemia major: enlargement of marrow spaces, expansion of the maxilla and 'hair-on-end" effect of the skull.

Anaemias of oral significance

Anaemia is not a disease in itself. It is a sign of a single or multiple diseases. Anaemia is said to exist when the haemoglobin concentration is below normal for the age and sex of an individual. The synthesis and normal circulatory level of haemoglobin in any given individual depend on factors such as an adequate supply of haemopoietic nutrients, normal functioning of bone marrow, and proper utilization of haemoglobin. Based on these factors anemia can be broadly grouped into three categories: 1. Anaemia due to lack of haemopoietic nutrients (nutritional anemia) 2. Anaemia due to bone marrow dysfunction (aplastic anaemia) 3. Anaemia due to excessive breakdown of red blood cells (haemolytic anaemia) (AU)

Influence of alpha thalassaemia on the retinopathy of homozygous sickle cell disease

Homozygous alpha+ thalassaemia (alpha-/alpha-) ameliorates some of the clinical manifestations of homozygous sickle cell (SS) disease but its effect on retinal complications remains unknown. This has been assessed by visual examination and flourescein angiography in 39 subjects with SS disease and homozygous alpha+ thalassaemia and in 39 age/sex matched controls with SS disease but with a normal alpha genotype (alpha alpha/alpha alpha). The results indicate that homozygous alpha+ thalassaemia reduces the extent of peripheral retinal vessel closure but has no apparent effect on the frequency of proliferative sickle retinopathy (AU)

Screening of cord blood for haemoglobinopathies and thalassaemia by high-performance liquid chromatography - abstract

A high-performance liquid chromatography (HPLC) method for the screening of haemoglobins in cord blood was evaluated and the gene frequencies of the structural haemoglobin variants HbS and HbC and the synthesis variants O- and á+ -thalassaemia were studied in babies born on the Caribbean island of Curacao, the Netherlands Antilles. In 3 months, 67.2 percent of all (748) newborns were screened and 122 (24.3 percent) had an abnormal haemoglobin pattern, of which 53 (43.4 percent) had a haemoglobinopathy (HbS or HbC), 64(52.2 percent) O-thalassaemia (Hb Barts > 0.5 percent, corresponding with heterozygous or homozygous O-thalassaemia-2) and 5 (4.1 percent) a haemoglobinopathy plus O-thalassaemia. None of the newborns with heterozygous HbS and HbC had concomitant á+-thalassaemia. The population genotype frequency of heterozygous O-thalassaemia -2 remain undetected. The data are in excellent agreement with comparable published results. The HPLC method proved pre-eminently suitable for the screening of cord blood samples. (AU)

Comparison of homozygous sickle cell disease in Northern Greece

The clinical and hematological features of homozygous sickle cell (SS) disease were compared in 30 Greek and 310 Jamaican patients. Deletional O-thallassaemia, which modifies SS disease, is rare among Greek patients, so only Jamaican patients with four O-globin genes were included in the control group. Greek patients had higher total haemoglobin concentration and red cell counts, and lower mean cell haemoglobin concentration (MCHC) and reticulocyte counts. They also had a more normal body build and more adults had persistent splenomegaly. Fewer had a history of leg ulceration or priapism but more reported acute chest syndrome. The comparitively mild disease in Greek patients is consistent with less haemolysis and sickling and therefore less bone marrow expansion. In the absence of amelioriating factors such as high HbF concentration or O-thalassaemia, these findings may be explained by the low MCHC. (AU)

Clinical and laboratory features of sickle cell disease in the Netherlands

Out of about 200 patients with sickle cell disease (SCD) in the Netherlands, 6 percent are non-negroid patients from Turkey. 83 were assessed clinico-haematologically regarding the type of SCD, ethnic origin, concurrent O-thalassaemia (O-thal), and type of sickle cell gene (á-chromosome). 54 patients had homozygous sickle cell (SS),1 sickle cell haemoglobin D (SD) Punjab, 5 sickle cell á§-thalassaemia (Sá§-thal), 5 sickle cell á+-thalassaemia (Sá+-thal) and 18 sickle cell haemoglobin C (SC) disease. 14 percent of the 83 patients were from Turkey, the others were of West Indian and African origin, most (73 percent) of whom were from Surinam. The Netherlands may be the only country in the world where non-negroid SCD patients are present in such a proportion to negroid SCD patients. O-thal was detected in 16 patients and in 14 of their relative with sickle cell trait. Four main types of ás-chromosomes were identified: Benin, Central African Republic, Senegal and Saudi Arabia types. SS and Sá§-thal disease ran a more severe course than Sá+ +-thal and SC disease. No clinical difference was ascribable to ethnic origin, O-thal or HbF-level but in each ethnic group there were some patients with a remarkably mild course of SS disease, which was related to the type of ás-chromosome. These were the Senegal and Saudi Arabia ás-chromosomes. Proper differentiation between genotypes is of prognostic and therapeutic relevance,especially in SC disease as it is sometimes discovered too late. A proper screening program is encouraged not only for all negroid inhabitants or immigrants, but also for non-negroid immigrants especially from Turkey.(AU)

Fetal hemoglobin levels and beta s globin haplotypes in an Indian population with sickle cell disease

To further explore the cause for variation in hemoglobin F (HbF) levels in sickle cell disease, the á globin restriction-fragment length polymorphism haplotypes were determined in a total of 303 (126SS, 141AS, 17Sá§, 7Aá§, and 12AA) Indians from the state of Orissa. The ás globin gene was found to be linked almost exclusively to a ás haplotype (+++-++-), which is also common in Saudi Arabian patients from the Eastern province (referred to as the Asian ás haplotype). By contrast, the majority of áA and ᧠thalassemia globin genes are linked to hoplotypes common in all European and Asian populations (+-----[+/-];--++-++). Family studies showed that there is a genetic factor elevating HbF levels dominantly in homozygotes (SS). This factor appears to be related to the Asian ás globin haplotype, and a mechanism for its action is discussed. There is also a high prevalence of an independent Swiss type hereditary presistance of fetal hemoglobin (HPFH) determinant active in both the sickle cell trait and in sickle cell disease.(AU)

Sickle cell disease in Orissa State, India

A study of 131 patients with homozygous sickle cell (SS) disease in Orissa State, India, indicated that, compared with Jamaican patients, Indian patients have higher frequencies of alpha thalassaemia, higher fetal haemoglobin, total haemoglobin, and red cell counts, and lower mean cell volume, mean cell haemoglobin concentration, and reticulocyte counts. Indian patients have a greater frequency and later peak incidence of splenomegaly, and hypersplenism is common. Painful crises and dactylitis are not uncommon in Indian patients but chronic leg ulceration is rare. Homozygous sickle cell disease in Orissa is similar to that in the Eastern Province of Saudi Arabia and is very different from that in populations of West Africa origin.(Summary)

Alpha thalassemia and the hematology of homozygous sickle cell disease in childhood

Alpha thalassemia modifies the gematolic expression of homozygous sickle cell (SS) disease, resulting in increased total hemoglobin and HbA2 and decreased HbF, mean cell volume, reticulocytes, irreversibly sickled cells, and biliru-bin levels. The age at which these changes develop in children with SS disease is unknown. Ascertainment of globin gene status in a large representative sample of study the gematologic indices in nine children homozygous for Alpha thalassemia 2 (two-gene group), 90 children heterozygous for Alpha thalassemia 2 (three-gene group), and 167 children with a normal Alpha globin gene complement (four-gene group). The two-gene group had significantly lower mean cell volumes from birth, higher red cell counts from one month, lower reticulocytes from three months, and higher HbA2 levels from one year, as compared with the four-gene group. Children with three genes had intermediate indices but resembled more closely the four-gene group. Differences in total hemoglobin or in fetal hemoglobin between the groups were not apparent by eight years of age. The most characteristic differences of the two-gene group were the raised proportional HbA2 level and low mean cell volume, the latter having some predictive value for Alpha thalassemia status at birth.(AU)

Haematological change in sickle cell-haemoglobin C disease and in sickle cell-beta thalassaemia: a cohort study from birth

The haematological changes in early years following neonatal diagnosis have been observed in representative groups of children with sickle cell-haemoglobin C (SC) disease, sickle cell-á+ thalassaemia, and in sickle cell-á Thalassaemia. Most haematological indices in SC disease were intermediate between previously published values in SS disease and in AA controls, generally being closer to values in normal children, Eceptions were microcytosis which may be genetically determined and a striking elevation of mean cell haemoglobin cocentration from age 2 months to 4 years. The combination of a raised MCHC and a lowered MCV is unusual and may be characteristic of SC disease. Features in sickle cell-á thalassaemaia generally differed accordingly to the type of á thalassaemia gene. Sickle cell-B degree thalassaemia had lower levels of haemoglobin, MCHC, red cell count, MCV, and higher reticulocytes, most differences being significant before 1 year. No differences between SB degree thalassaemia and Sá+ thalassaemia were apparent in HbF levels (which resembled those in SS disease) or in HbA2 levels (which exceeded those in SS disease by 1 year of age).(AU)

Clinical presentation of homozygous sickle cell disease

The pattern of initial clinical symptoms and signs developing in a representative sample of 305 children with homozygous sickle cell (SS) disease diagnosed at birth was analyzed. Specific symptoms were present by age 6 months in 6 percent of the group, and had developed by the first to eighth birthdays in 32 percent, 61 percent, 78 percent, 86 percent, 90 percent, 92 percent, 94 percent and 96 percent, respectively. Inclusion of nonspeccific symptoms in the analyst led to earlier recognition by a mean of 3 months in the first year and by a mean of approximately 1 year between the ages of 2 and 4 years. Dactylitis was the most common initial symptom, noted in 40 percent of the group overall and in 50 percent in the first 2 years. Painful crisis was the first symptom in more than one fourth of the patients and was the most frequent symptom after the age of 2 years. Acute splenic sequestration led to presentation in one-fifth of the group overall and in one third of the patients younger than 2 years. The most common nonspecific symptom was pneumonia. There was a significant trend of earlier presentation in children with low fetal hemoglobin levels. The age of presentation did not appear to be affected by O-thalassemia status. (AU)

Alpha-Thalassemia changes erythrocyte heterogeniety in sickle cell disease

Homozygous alpha thalassemia has the beneficial effect in sickle cell anaemia of reducing the hemolytic severity while changing several other hematological parameters. We examined in detail some of these hematological alterations. We find that the broad distribution in erythrocyte density and the large proportion of dense cells associated with sickle cell anaemia are both reduced with co-existing alpha-thalassemia. Measurements of glycosylated hemoglobin levels as a function of cell density indicate that the accelerated increase in cell density, beyond normal cell ageing, in sickle cell anaemia is also reduced with alpha thalassemia. The patients with homozygous alpha-thalassemia and sickle cell disease have slightly lower levels of hemoglobin F than non-thalassemic patients. Examination of hemoglobin F production revealed that the proportion of hemoglobin F containing reticulocytes remained unchanged, as did the proportion of hemoglobin F in cells containing hemoglobin F (F cells). Preferential survival of F cells occurs in sickle cell anaemia, with or without alpha-thalassemia, and the slight difference in hemoglobin F levels appear to reflect differences in numbers of circulating F cells. Thus in sickle cell disease with co-existing alpha-thalassemia, the change in the erythrocyte density profile, possibly due to inhibition of polymerisation-related increases in cell density, explains the hematological improvement.(Summary)

Effect of alpha thalassaemia on the rheology of homozygous sickle cell disease

A study of rheological determinants (plasma viscosity, whole-blood viscosity, and erythrocyte deformability) was made in 24 matched pairs of patients with homozygous sickle cell disease, with and without homozygous x-thalassaemia. Patients with coexisting x-thalassaemia showed a significant increase in erythrocyte deformability measured as filtration of washed erythrocytes through 5 um diameter pores and also as viscosity of whole blood at high shear rate (230s-1) and standard haematocrit (0.45). This rheological advantage may explain the beneficial effect of x-thalassaemia 2 on haematological parameters and clinical events in homozygous sickle cell disease (AU)

The interaction of alpha-thalassemia and homozygous sickle-cell disease

Patients with homozygous sickle-cell disease may be homozygous for alpha-thalassemia 2 (O-/O-), may be heterozygous for alpha-thalessemia 2 (O-/OO), or may have a normal alpha-globin-gene complement (OO/OO). We compared the clinical and hematologic features of 44 patients who had sickle-cell disease and homozygous alpha-thalassemia 2 with those of controls with the two hematologic conditions. The patients with homozygous alpha-thalassemia 2 had significantly higher red-cell counts and levels of hemoglobin and hemoglobin Aý, as well as significantly lower hemoglobin F, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, reticulocyte counts, irreversibly-sickled-cell counts, and serum total billirubin levels, than those with a normal alpha-globin-gene complement. Heterozygotes (O-/OO) had intermediate values. In the group with homozygous alpha-thalassemia 2, fewer patients had episodes of acute chest syndrome and chronic leg ulceration and more patients had splenomegaly, as compared with patients in the other two subgroups. These data confirmed previous suggestions that alpha-thalassemia inhibits in vivo sickling in homozygous sickle-cell disease and may be an important genetic determinant of its hematologic severity.