Ultrastructural pathology of the heart in patients with beta-thalassaemia major.

Patients with beta-thalassaemia major frequently suffer from hypersiderosis which leads to hemochromatosis of major organs such as the heart and liver. Little information exists about the ultrastructural pathology of the human heart in beta-thalassaemia patients. Five Cypriot patients with elevated blood ferritin and intractable heart failure were investigated. Cardiac biopsies from these patients were studied by light and electron microscopy, as well as by X-ray microanalysis. Ultrastructural examination revealed the presence of disrupted myocytes showing loss of myofibers, dense nuclei, and a variable number of pleomorphic electron dense granules. These cytoplasmic granules or siderosomes consisted of iron-containing particles as confirmed by X-ray microanalysis. It is likely that the ultrastructural changes observed in myocytes of patients with beta-thalassaemia are largely due to iron deposition.

Hydroxyurea therapy in thalassemia.

The clinical effectiveness of Hydroxyurea in thalassemia is still controversial. The present paper puts together the authors' experience in two groups of patients with thalassemia intermedia and sickle cell/beta-thalassemia treated with varying dosages of hydroxyurea over several months. A third group received hydroxyurea along with recombinant human erythropoietin. Our observations are summarized in that treatment with hydroxyrea results in a significant increase of fetal hemoglobin with no change of the total hemoglobin levels. The drug causes also a considerable increase of the erythrocyte volume and hemoglobin content while the MCHC values remain unchanged. As a rule, and without objective criteria so far, patients state feeling better and having more energy. The authors postulate that this feeling may reflect the significant decrease of ineffective erythropoiesis resulting by the replacement of the poorly hemoglobinized, prematurely dying erythroid progenitor and red cell population by another population of cells with higher hemoglobin content and longer survival, the regeneration of which requires less energy and consumption. As expected, patients with sickle cell/beta-thalassemia have also fewer crises and painful episodes. The above findings are in keeping with the few available reports in the literature.

Bone pain in thalassaemia: assessment of DEXA and MRI findings.

An increasing number of adult thalassaemics have been complaining of aches and pains of varying degrees of severity. In a minority the pains are debilitating and there is stiffness in movement. This study is an attempt to understand the osteoporosis of thalassaemia using DEXA and MRI as the main investigative tools. 122 patients with homozygous beta-thalassaemia were examined by DEXA. It was found that almost half had BMD below two standard deviations from the mean for the normal population, especially in the lumbar spine. There was no marked worsening with age. However the proportion of patients who had their first transfusion after the 3rd year (especially after the 6th) was significantly greater in those with the low BMD. There is also an excess of hypogonadic thalassaemics amongst those with low BMD. 72 thalassaemics were examined by MRI of marrow. Hypercellular, dark marrow on T1 weighted images found in young patients (20-30 yr) was replaced by fatty marrow in later life (30-40 yr). In a group of 21 older thalassaemics (33-62 yr) extreme bone marrow expansion was expressed by the reappearance of hypercellular areas, giving the impression of patchiness which affects not only the diaphyses but also the metaphyses. These patients mostly (66%) had thalassaemia intermedia and had started irregular transfusion after the 6th year of life. About 75% had a BMD below 2 SD. The conclusion is that patients who were late in receiving blood and especially those with thalassaemia intermedia had a more expanded bone marrow with pressure on cortical bone which caused pain in several cases. An attempt was made in 10 patients to reduce marrow hyperplasia by using hydroxyurea. Results showed a relief of pain and modification of magnetic signal intensity.

Transfusional transmitted viruses in pregnancy.

Blood has long been recognized as a vehicle for transmission of infectious organisms and as molecular laboratory technology has advanced, a seemingly endless array of infectious agents has occasionally been documented to be blood transmitted. Transfusion associated hepatitis (TAH) has been the most common serious consequence of blood transfusion although in recent years this has been significantly reduced (blood donor screening, blood processing, etc.). Thalassaemia major is classically associated with increased susceptibility to infections caused by those agents that are blood transmitted such as HBV, HCV, HIV, CMV, HPV B-19 (frequency rates vary from country to country). Monitoring the prevalence of transfusion transmitted infections in thalassaemics has been in recent years an indispensable part of their clinical management protocol. As a number of these viruses have been documented to be efficiently transmitted through the vertical route, the issue of blood transmitted viral infection monitoring becomes particularly important in order to provide protection or treatment both to the pregnant thalassaemic patient herself and to her foetus/newborn. Hepatitis (mainly B and C) and HIV in the obstetric thalassaemic is what the clinician is faced with most frequently. Although preventative measures have been very successful in the case of HBV infection and recently to an encouraging extent in the case of HIV (recommendations have been constructed), the mechanisms and frequency of HCV vertical transmission as well as the clinical outcome of children born to HCV carriers are not yet completely clarified. No vaccines are available and HIGB or antivirals do not appear to offer protection to the foetus against infection with HCV. Thalassaemics are frequently seropositive to markers of other transfusion transmitted viruses, such as CMV and HPV B-19, particularly by the age of pregnancy. Infection with a second or multiple strains as well as reactivation of existing CMV strain(s) are possible events in thalassaemics. However, the frequency of "recurrency" episodes, their implication in vertical transmission and clinical outcome for the foetus/newborn are issues requiring further investigation.

Fertility in female patients with thalassemia.

With recent therapeutic advances, thalassemic patients can now reach adulthood and attain reproductive capacity. Endocrine complications due to hemosiderosis and especially hypogonatotropic hypogonadism, which present either with sexual infantilism and primary amenorrhea or with secondary amenorrhea, are common in thalassemic women. The aim of this study was to estimate the frequency of fertility among our female thalassemic patients. Our population included 50 married women with thalassemia major (TM) and 12 with thalassemia intermedia (TI) who are regularly followed in our thalassemic centers. Of the 50 patients with TM, 7 had primary amenorrhea (PA), 9 had secondary amenorrhea (SA), and 34 had normal menstrual function (NM), as did all the patients with TI. Overall we had 62 women who were able to achieve 90 pregnancies and give birth to 87 healthy babies. Most of our patients became pregnant around the age of 25 years. Associated endocrine complications were rare except in the group of patients with PA, as expected. In all patients with PA and SA, the 17 pregnancies were induced (intercourse 10, insemination 3, IVF 4). In the patients with NM and TI, 66 pregnancies were achieved spontaneously and 7 following induction (insemination 3, IVF 4). There were four twin and one triple pregnancies, which all resulted in premature deliveries. Among the seven couples in which both partners had thalassemia major, sperm donation was used in 5 cases, ovum donation in one case, and one pregnancy was achieved spontaneously. These 90 pregnancies resulted in 69 full-term, 12 pre-term, 7 abortions and 2 stillbirths. No severe obstetric complication was observed except for two patients with preeclampsia. One patient with PA who carried the triple pregnancy developed severe cardiac failure, which was successfully treated. Transfusion requirements were increased during pregnancy. Discontinuation of desferrioxamine resulted in elevation of ferritin levels during the second and third trimesters of pregnancy and after delivery. Nine patients who were examined with cardiac echo had a transient increase of ESD and EDD during pregnancy, with return to normal after delivery. Labor was performed by Caesarian section in 26 births (26%) out of the 81 successful pregnancies. These collected data represent the largest number of pregnancies in thalassemic females reported so far and are clearly encouraging for the ultimate improvement of the quality of life in thalassemic patients.

Effect of pentoxifylline on treatment of lower limb ulcers in patients with thalassemia major.

The possible healing effect of deferoxamine and pentoxifylline on persisting lower limb ulcers was studied in 51 patients with thalassemia major. The results indicated that the regular use of deferoxamine at an intravenous dose of 20 mg/kg did not affect the healing progress and the recurrence rate of these ulcers significantly. On the contrary, the oral administration of pentoxifylline at a dose of 1,200 mg daily during the ulcer's healing time and at a low long-term maintenance dose of 400 mg daily during the ulcer-free intervals improved their healing ability impressively and diminished their recurrence rate significantly.