15 research outputs found
AMH type II receptor and AMH gene polymorphisms are not associated with ovarian reserve, response, or outcomes in ovarian stimulation
Thirty-year experience in preventing haemoglobinopathies in Greece: Achievements and potentials for optimisation
Objectives: Beta thalassaemia major (β-TM) and sickle-cell disease (SCD) are severe haemogobinopathies requiring life-lasting, advanced medical management. In the Mediterranean region, both conditions occur with high frequency. We assessed the efficacy of the National Program for the Prevention of Haemoglobinopathies in Greece during the last 30 yrs. Methods: Data of affected births between 01/01/1980 and 31/12/2009 were collected in a nationwide scale, and expected vs. observed rates of new births were calculated and compared. In a subpopulation of affected births of Greek origin, the causes for occurrence of the new affected birth were also collected and analysed. Results: Overall, the reduction in new cases was 81.1% and 84.6% for β-TM and SCD, respectively. For β-TM, a constant declining trend was recorded over the 30-yr period, whereas for SCD, a transient reversal was observed in the mid-1990s probably due to the significant influx of immigrants of African origin. Programme failure was 2.2 times more common among new β-TM births of Greek origin compared to new SCD cases (P < 0.001). Unawareness and parental choice were more frequent in SCD compared to β-TM (unawareness: OR = 1.4, P = 0.05, parental choice: OR = 1.9, P = 0.01). The main cause for programme failure was carrier misidentification and incorrect genetic advice for β-TM and SCD, respectively. Conclusions: The β-TM and SCD prevention programme in Greece has significantly reduced the numbers of new affected births. The outcomes could be optimised in groups of non-Greek origin, in carrier identification and by offering specialised genetic counselling. © 2013 John Wiley & Sons A/S
Pseudoxanthoma elasticum lesions and cardiac complications as contributing factors for strokes in β-thalassemia patients
Background and Purpose: Pseudoxanthoma elasticum (PXE) lesions, which lead to intracranial hemorrhages and cardiac complications, predisposing to thrombotic strokes, are frequent findings in β-thalassemia. Nevertheless, the association of these lesions with strokes in thalassemic patients has not been previously discussed. Methods: Ten β-thalassemic patients who developed an intracranial hemorrhage or a thrombotic stroke were reviewed. Results: In the group of the four patients presenting with hemorrhage, one had PXE lesions, one had cardiac abnormalities, and one both PXE and cardiac disorders. In the group presenting with thrombotic stroke, all six patients had cardiac abnormalities and platelet count elevation due to splenectomy. Three also had PXE findings. No other predisposing factor for stroke was present. Conclusions: Cardiac complications and PXE may be risk factors for strokes in β-thalassemia. Their frequent coexistence leads to a therapeutic dilemma in patients requiring antithrombotic therapy
Thalassernia heart disease - A comparative evaluation of Thalassemia major and Thalassemia intermedia
Background: Heart disease represents the main determinant of survival in
beta-thalassemia, but its particular features in the two clinical forms
of the disease, thalassemia major (TM) and thalassemia intermedia (TI),
are not completely clarified.
Methods: We compared clinical and echocardiographic global parameters in
131 TM patients who received regular chelation transfusions and were
highly compliant with treatment (mean age, 28 +/- 6 years [+/- SD%
and 74 age-matched, TI patients who did not receive chelation
transfusions.
Results: Congestive heart failure was encountered in five patients with
TM (3.8%; age range, 25 to 29 years) and in two patients with TI
(2.7%; age range, 37 to 40 years). Systolic left ventiricular (LV)
dysfunction (ejection fraction < 55% or shortening fraction < 35%) was
only encountered in patients with TM (8.4%). Considerable pulmonary
hypertension (systolic tricuspid gradient > 35 mm Hg) was only present
in TI (23.0%). In the remaining patients without evident heart disease,
cardiac dimensions, LV mass, LV shortening and ejection fractions, and
cardiac output were significantly higher in patients with TI. LV
afterload was higher in patients with TM. LV diastolic early transmitral
diastolic peak flow velocity (E)/late transmitral diastolic peak flow
velocity (A) ratio was also higher in TM. Systolic and mean pulmonary
artery pressures and total pulmonary resistance were higher in both
young and old TI patients.
Conclusion: Regular lifelong transfusion and chelation therapy in TM
prevented premature heart disease and pulmonary hypertension, although
LV dysfunction still occurred and led to heart failure. The absence of
regular therapy in TI, in contrast, preserved systolic LV function but
allowed pulmonary hypertension development, which also led to heart
failure, starting within the fourth decade of fife, a decade later
compared to TM
Unusual phenotypic observations associated with a rare HbH disease genotype (--(Med)/alpha(TSaudi)alpha): implications for clinical management
A single patient with a rare Haemoglobin H (HbH) disease genotype
(–(Med)/alpha(TSaudi)alpha) was observed to have exceptionally high
levels of HbH (> 60%) and paradoxically high total haemoglobin levels.
Studies of haematological parameters, blood biochemistry and oxygen
transport properties revealed a severe functional anaemia, associated
with marked erythropoietic stimulation and a markedly raised cardiac
output. This rare case illustrates the complexity of interactions that
may be associated with the clinical course of HbH disease, highlighting
that haematological parameters alone may lead to spurious evaluation of
clinical status. Issues related to the therapeutic management of unusual
cases are raised
Distribution of serum lipids and lipoproteins in patients with beta thalassaemia major; an epidemiological study in young adults from Greece
Background: Beta-thalassaemia major (b-TM) has been defined as a combination of chronic hemolytic anemia, iron storage disease and myocarditis, and it has been associated with premature death especially due to heart failure. To the best of our knowledge the status of blood lipids in these patients has rarely been investigated. Thus, we assessed the levels of lipids and lipoproteins in a sample of cardiovascular disease free adult men and women with b-TM. Methods: During 2003 we enrolled 192 consecutive patients with b-TM that visited our Institution for routine examinations. The Institution is considered the major reference center for b-TM in Greece. Of the 192 patients, 88 were men (25 ± 6 years old) and 104 women (26 ± 6 years old). Fasting blood lipid levels were measured in all participants. Results: Data analysis revealed that 4% of men and 2% of women had total serum cholesterol levels > 200 mg/dl, and 11% of men and 17% of women had triglyceride levels > 150 mg/dl. In addition, mean HDL cholesterol levels were 32 ± 11 mg/dl in men and 38 ± 10 mg/dl in women, lipoprotein-a levels were 8.3 ± 9 mg/dl in men and 8.8 ± 9 mg/dl in women, apolipoprotein-A1 levels were 111 ± 17 mg/dl in men and 123 ± 29 mg/dl in women, and apolipoprotein-B levels were 60 ± 20 mg/dl in men and 59 ± 14 mg/dl in women. Total-to-HDL cholesterol ratios were 3.7 ± 1.2 and 3.8 ± 1.5 in men and women, respectively. Conclusions: The majority of the patients had blood lipid levels (by the exception of HDL-cholesterol) within the normal range, and consequently the prevalence of lipid and lipoprotein abnormalities was much lower as compared to the general population of the same age. Interestingly, is that the total - to HDL cholesterol ratio was high in our patients, and may underline the importance of this index for the prognosis of future cardiac events in these patients
Rapid and accurate quantitation of Hb Bart's and Hb H using weak cation exchange high performance liquid chromatography: Correlation with the alpha-thalassemia genotype
The Bio-Rad Variant(TM) Hemoglobin testing system is an automated high
performance liquid chromatography analyzer marketed with a
beta-thalassemia short program to quantify Hbs F and A(2), and assist in
detecting Hbs A, S, D, C, and E, Although the two hemoglobins present in
Hb H disease, Hb Bart’s and Hb H, are separated by the system, they are
not quantitated, In this study we modified the P-thalassemia short
program in order to facilitate quantitation of Hb Bart’s and Hb H. Blood
samples from 60 patients with Hb a: disease, with various underlying
genotypes, were studied. Analyses were performed on the day of blood
collection or an hemolysates stored at -80 degrees C in cyanide or
carbomonoxy forms. The mean sum of Hb Bart’s and Hb H levels in all
patients was found to be 12% (range 1.8-35%). Patients with
nondeletional mutations (or association of alpha(0) deletion and
nondeletional mutations) had notably higher Hb Part’s and Hb H levels
when compared to patients with deletional genotypes
Interaction of an alpha(+)-thalassemia deletion with either a highly unstable alpha-globin variant (alpha 2, codon 59, G(G)under-barC -> G(A)under-barC) or a nondeletional alpha-thalassemia mutation (AATAA(A)under-bar -> AATAA(G)under-bar): Comparison of phenotypes illustrating “dominant” alpha-thalassemia
Thalassemia syndromes and unstable hemoglobins traditionally represent
two phenotypically separate disorders of hemoglobin synthesis. Highly
unstable hemoglobin variants, however, often have phenotypic
characteristics associated with both ineffective erythropoiesis
(thalassemias) and peripheral hemolysis (unstable hemoglobins). Many
highly unstable beta chain variants cause a dominant thalassemia-like
phenotype, in which simple heterozygotes for such mutations have a
clinical expression similar to thalassemia intermedia. The phenotypic
expression of highly unstable alpha-globin variants is usually less
severe, due mainly to a gene dosage effect, and they are often only
characterized on interaction with other alpha-thalassemia mutations,
whence they are classified as nondeletional alpha-thalassemia
determinants. This study reports the clinical and hematological findings
in five cases with rare alpha-thalassemia genotypes: a single patient
with the thalassemic alpha 2-globin gene codon 59 Gly–>Asp hemoglobin
variant in trans to an alpha(+)-thalassemia deletion, and four compound
heterozygotes for the nondeletional alpha-thalassemia polyadenylation
mutation (alpha 2 gene AATAAA–>AATAAG or alpha(T-Saudi)alpha/-alpha)
and an alpha(+)-thalassemia deletion. Evaluation of the clinical and
hematological features in these two analogous genotypes clearly
demonstrates the more severe clinical expression associated with the
alpha-thalassemic unstable hemoglobin variant. In addition, the case in
this study with the codon 59 alpha chain variant provides a further
example illustrating the spectrum of phenotypes associated with the
alpha-thalassemic hemoglobinopathies
PSEUDOXANTHOMA-ELASTICUM-LIKE SKIN-LESIONS AND ANGIOID STREAKS IN BETA-THALASSEMIA
One hundred patients with homozygous or doubly heterozygous
beta-thalassemia (62 with the major form and 38 with beta-thalassemia
intermedia) were examined for signs of Pseudoxanthoma elasticum (PXE).
Diagnostic skin lesions were found in 16 patients with either form of
the basic disease. Twenty percent of all patients had angioid streaks
(AS); both PXE skin lesions and AS were found in 10% of the patients;
in all, 26% had either one or both of these manifestations. A positive
correlation was found between the presence of one or both types of
lesion and age of the patients (P = 0.032); there were no differences as
regards ferritin and hematocrit levels, number of transfused units,
chelation therapy, and splenic status between patients with PXE/AS
findings and those without. The pathogenesis of these connective tissue
manifestations at such a high frequency in beta-thalassemia is not
clear; the possibilities of it’s being acquired or inherited are
discussed, the former being considered to be the more economical
interpretation